Pocket Drug Guide

Posts Tagged ‘HIV’

Zyloric 100 mg and 300 mg tablets

Allopurinol

1 What Zyloric is and what it is used for

Zyloric tablets contain a medicine called Allopurinol. It works by slowing down the speed of certain chemical reactions in your body. Zyloric is used:

•  to prevent gout. This is a disease where your body produces too much of a substance called ‘uric acid’. The uric acid builds up in your joints and tendons as crystals. These crystals cause an inflammatory reaction. The inflammation causes the skin around certain joints to become swollen, tender and sore when only slightly touched. You can also fine you get severe pain when the joint is moved.

•  to prevent other conditions where there is a build up of uric acid in the body. These include kidney stones and certain other types of kidney problem and when you are having treatment for cancer.

2 Before you take Zyloric

Do not take Zyloric if:

•  you are allergic (hypersensitive) to Allopurinol or any of the other ingredients of Zyloric. Do not take Zyloric if the above applies to you. If you are not sure, talk to your doctor or pharmacist before taking Zyloric.

Take special care with Zyloric

Check with your doctor or pharmacist before taking your medicine if:

•  you have problems with your liver or kidneys. Your doctor may give you a lower dose or ask you to take it less often than each day. They will also monitor you more closely

•  You have heart problems or high blood pressure

•  you are currently having an attack of gout

•  you have been told by your doctor that you have an intolerance to lactose. Zyloric tablets contain a small amount of lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

If you are not sure if any of the above applies to you, talk to your doctor or pharmacist before taking Zyloric.

Taking other medicines

Tell your doctor or pharmacist if you are taking any of the following:

•  aspirin

•  theophylline, used for breathing problems

•  medicines used for fits (epilepsy)

•  antibiotics

•  didanosine, used to treat HIV infection

•  medicines for cancer

•  medicines used to reduce your immune response (immunosuppressants)

•  medicines used to treat diabetes

•  medicines for heart problems or high blood pressure such as ‘ACE inhibitors’ or water tablets (diuretics)

•  medicines used to thin your blood (anticoagulants), such as warfarin

•  any other medicine to treat gout.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Zyloric can affect the way some medicines work. Also some other medicines can affect the way Zyloric works. Taking Zyloric with food and drink Take Zyloric with food and water.

Pregnancy and breast-feeding

Talk to your doctor before taking this medicine if you are pregnant, might become pregnant or are breast-feeding.

Driving and using machines

You may feel drowsy, giddy or have problems with your co-ordination. If this happens, do not drive or use any tools or machines.

3 How to take Zyloric

Always take Zyloric exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Taking this medicine

•  Swallow the tablet with a drink of water.

•  Take with or just after food. Children (under 15 years)

•  The usual dose ranges from 100 to 400 mg each day. Adults (over 18 years)

•  The usual dose ranges from 100 to 900 mg each day.

You will usually start on a dose of 100 to 300 mg each day. Elderly (over 65 years)

•  Your doctor will prescribe the lowest dose of Zyloric tablets that best controls your symptoms.

If you have a serious kidney problem

•  you may be asked to take less than 100 mg each day

•  or you may be asked to take 100 mg at longer intervals than one day.

If you have dialysis two or three times a week, your doctor may prescribe a dose of 300 or 400 mg which is to be taken straight after your dialysis.

If you take more Zyloric than you should

If you take more Zyloric than you should, talk to a doctor or go to hospital straight away. Take the medicine pack with you.

If you forget to take Zyloric

•  If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose.

•  Do not take a double dose to make up for a forgotten dose. If you stop taking Zyloric

Do not stop taking your Zyloric without talking to your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4.  Possible side effects

Like all medicines, Zyloric can cause side effects, although not everybody gets them. The following side effects may happen with this medicine:

Allergic reactions (affects less than 1 in 10,000 people) If you have an allergic reaction, stop taking Zyloric and see a doctor straight way. The signs may include:

•   skin rash, flaking skin, boils or sore lips and mouth

•   very rarely signs may include sudden wheeziness, fluttering or tightness in the chest and collapse.

Do not take any more tablets unless your doctor tells you to do so.

If you experience any of the following, stop your tablets and tell your doctor as soon as possible:

Rare (affects less than 1 in 1000 people)

•  joint pain or painful swelling in your groin, armpits or neck

•   yellowing of the skin and eyes (jaundice)

• liver or kidney problems

•   feeling sick (nausea) or being sick (vomiting), occasionally    with blood

. •   you notice any changes to your skin, for example blisters or   peeling

•   fever and chills, aching muscles and generally feeling unwell

•   bleeding in the lips, eyes, mouth, nose or genitals Very rare (affects less than 1 in 10,000 people)

•   bruising more easily than usual, or you may develop a sore throat or other signs of an infection. Tell your doctor as soon as possible. Occasionally Zyloric tablets may affect your blood or lymph system. These effects usually occur in people with liver or kidney problems

•   high temperature

•   blood in your urine (haematuria)

•   high levels of cholesterol in your blood (hyperlipidaemia)

•   a general feeling of being unwell

•   weakness, numbness, unsteadiness on your feet, feeling unable to move muscles (paralysis) or loss of consciousness

•   headache, dizziness, drowsiness or disturbance of your vision

•   chest pain, high blood pressure or a slow pulse

•   male infertility or erectile dysfunction

•   enlargement of the breasts, in men as well as women

•   a change in your normal bowel habit

•   a change in taste

•   cataracts

•   hair loss or discolouration

•   fits (convulsions)

•   depression

•   build up of fluid leading to swelling (oedema) particularly of your ankles

•   feeling thirsty, tired and losing weight; these may be symptoms of diabetes. Your doctor may wish to measure the level of sugar in your blood to check if this is happening.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. How to store Zyloric

•   Keep out of the reach and sight of children.

•   Do not use Zyloric after the expiry date which is stated on the carton after ‘EXP’. The expiry date refers to the last day of that month.

•   Keep your tablets in the original packaging.

•   Do not store above 25°C.

•   Medicines should not be disposed of via wastewater or household waste.

•   Return any unused or unwanted tablets to your pharmacist for disposal. Only keep them if your doctor tells you to. These measures will help to protect the environment.

6. Further information

What Zyloric contains

•  The active substance is Allopurinol.

•  The other ingredients are lactose, maize starch, povidone and magnesium stearate.

What Zyloric looks like and contents of the pack

Zyloric tablets contain 100 or 300 mg Allopurinol. Each 100 mg tablet is white, round and marked with a score line, ‘GXCM2′.

Each 300 mg tablet is white, round and marked with a score line, ‘GXCM7′.

Zyloric 100 mg tablets come in 4 strips of 25 tablets.

Zyloric 300 mg tablets come in calendar packs of 2 x 14 tablets.

 

Zerit 20 mg hard capsules

Zerit 30 mg hard capsules

Zerit 40 mg hard capsules

Stavudine

1. WHAT ZERIT IS AND WHAT IT IS USED FOR

Zerit belongs to a group of antiviral medicines, also known as antiretrovirals, called nucleoside reverse transcriptase inhibitors (NRTIs).

These are used to treat Human Immunodeficiency Virus (HIV) infection.

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies between patients. Your doctor will therefore be monitoring the effectiveness of your treatment.

Zerit may improve your condition, but it is not a cure for your HIV infection. Treatment with Zerit has not been shown to reduce the risk of passing HIV infection on to others by sexual contact or by blood transfer. Therefore, you must continue to take appropriate precautions to avoid giving the virus to others.

During your treatment, other infections linked to your weakened immunity (opportunistic infections) may arise. These will require specific and sometimes preventive treatment.

2. BEFORE YOU TAKE ZERIT

Do not take Zerit:

If you are allergic (hypersensitive) to stavudine or any of the other ingredients of Zerit. Contact your doctor or pharmacist for advice.

Take special care with Zerit:

Before treatment with Zerit, you should have told your doctor:

■  if you suffer from kidney disease or liver disease (such as hepatitis),

■  if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or hands), or

■  if you have suffered from pancreatitis (inflammation of the pancreas).

The class of medicines to which Zerit belongs (NRTIs) can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This condition usually does not occur until a few months after onset of treatment. This rare, but very serious side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver failure/renal failure or fatal hepatitis have been reported.

Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for severe and potentially fatal liver adverse events and may require blood tests for control of liver function.

If you develop one of the following, contact your doctor:

■  persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of peripheral neuropathy, an adverse effect on the nerves), muscular weakness or

■  abdominal pain, nausea or vomiting, or

■  rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as hepatitis, or lactic acidosis).

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor immediately.

Redistribution, accumulation, or loss of body fat may occur in patients receiving antiretroviral therapy. Some NRTIs, such as stavudine, have been associated with a loss of body fat (lipoatrophy). Contact your doctor if you notice changes in body fat.

Bone problems: some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Except for zidovudine, which interferes with the activity of stavudine, Zerit may be taken with many of the other medicines commonly used in patients with HIV infection. These include the protease inhibitors (such as nelfinavir) and NRTIs. Please tell your doctor if you are taking doxorubicin or ribavirin as undesirable interactions may occur.

Taking Zerit with food and drink:

For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour before a meal. If this is not possible, the capsules may also be taken with a light meal.

Pregnancy and breast-feeding:

Pregnancy

If you become pregnant, or are planning to become pregnant, you must contact your doctor to discuss the potential adverse effects and the benefits and risks of your antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in pregnant women who received stavudine in combination with other antiretroviral treatment.

If you have taken Zerit during your pregnancy, your doctor may request regular visits to monitor the development of your child. Such visits may include blood tests and other diagnostic tests.

In children whose mother took nucleoside and nucleotide analogues during pregnancy, the benefit from the reduced chance of being infected with HIV is greater than the risk of suffering from side effects.

Breast-feeding

Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not breast-feed under any circumstances in order to avoid transmission of HIV to the baby.

Driving and using machines:

It is unlikely that Zerit affects the ability to drive or operate machinery.

Important information about some of the ingredients of Zerit:

These capsules contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. HOW TO TAKE ZERIT

Always take Zerit exactly as your doctor has told you. You should check with your doctor if you are not sure. Your doctor has defined your daily dose based on your weight and individual characteristics.

Please follow these recommendations closely as they will give you the best chance to delay development of a resistance to the medicinal product. Do not change the dose on your own. Continue to take this medicine until your doctor tells you otherwise.

For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice daily (with approximately 12 hours between each dose).

To obtain optimal absorption, the capsules should be swallowed with a glass of water, preferentially at least one hour before a meal and on an empty stomach. If this is not possible, Zerit may also be taken with a light meal.

If you have problems swallowing capsules you should ask your doctor about the possibility of changing to the solution form of this medicine or you could carefully open the capsule and mix its contents with some food.

Use in Children

For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice daily (with approximately 12 hours between each dose).

Children older than 3 months, whose body weight is less than 30 kg, should receive 1 mg/kg twice daily.

If you take more Zerit than you should:

If you have taken too many capsules or if someone accidentally swallows some, there is no immediate danger. However, you should contact your doctor or the nearest hospital for advice.

If you forget to take Zerit:

If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not take a double dose to make up for a forgotten dose.

If you stop taking Zerit:

The decision to stop using Zerit should be discussed with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Zerit can cause side effects, although not everybody gets them.

When treating HIV infection, it is not always possible to differentiate between unwanted effects caused by Zerit, or those caused by any other medicines you may be taking at the same time, or by the complications of the infection. For this reason, it is important that you inform your doctor of any change in your health.

Therapy for HIV including stavudine often causes changes in body shape due to changes in fat distribution. These may include loss of fat from legs, arms and face (lipoatrophy), and development of fatty lumps on the back of the neck (“buffalo hump”). Loss of body fat has been shown to be not fully reversible after discontinuation of stavudine. It occurs more often with Zerit compared to other HIV medicines. Your doctor should monitor for clinical signs and symptoms of changes in your body shape. Tell your doctor if you notice any changes in your body shape or loss of fat from your legs, arms, and face. When these signs occur, consideration should be given to discontinuing ZERIT treatment.

The frequency of possible side effects listed below is defined using the following convention:

very common:	affects more than 1 user in 10
common:	affects 1 to less than 10 users in 100
uncommon:	affects 1 to less than 10 users in 1,000
rare:	affects 1 to less than 10 users in 10,000
very rare:	affects less than 1 user in 10,000
not known:	frequency cannot be estimated from the available data

Patients treated with Zerit have reported the following side effects: Common:

■  asymptomatic hyperlactatemia (build up of acid in your blood)

■  lipoatrophy or lipodystrophy syndrome (body changes due to fat redistribution, accumulation, or loss of body fat),

■  depression

■  peipheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral neuritis (numbness, weakness, tingling or pain in the arms and legs)

■  dizziness, abnormal dreams, headache

■  insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking,

■  diarrhoea, abdominal pain (stomach pain of discomfort),

■  nausea, dyspepsia (indigestion)

■  rash, pruritus (itching)

■  fatigue (extreme tiredness)

Uncommon:

■  lactic acidosis (build up of acid in your blood) in some cases involving motor weakness (weakness in your arms, legs or hands)

■  gynaecomastia (breast enlargement in men)

■  anorexia (loss of appetite), anxiety, emotional lability

■  pancreatitis (inflammation of the pancreas), vomiting

■  hepatitis, jaundice (yellow of the skin or eyes)

■  urticaria (itchy rash), arthralgia (joint pain)

■  myalgia (aching muscles), asthenia (unusual tiredness or weakness)

Frequency not known:

■  anemia, thrombocytopenia, neutropenia (blood disorders)

■  diabetes mellitis, hyperglycaemia (high sugar levels in the blood)

■  motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic acidosis syndrome

■  liver failure, hepatitis (infiamation of the liver) and hepatic steatosis (fat in the liver)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell you doctor or pharmacist.

5. HOW TO STORE ZERIT

Keep out of the reach and sight of children.

Store below 25 °C (aclar/alu blisters) Do not store above 30°C. (HDPE bottles) Store in the original package.

Do not use Zerit after the expiry date which is stated on the carton, the bottle label and/or the blister after EXP. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What Zerit contains

The active substance is stavudine

The other ingredients of the powder contained in the hard capsule are: lactose (120 mg, 180mg, or 240mg), magnesium stearate, microcrystalline cellulose and sodium starch glycolate.

The ingredients of the capsule shell are gelatine, iron oxide colorant (E172), silicon dioxide, sodium laurilsulphate and titanium dioxide colorant (El71).

The capsule shells are marked using edible black printing ink containing shellac, propylene glycol, purified water, potassium hydroxide and iron oxide (El72).

What Zerit looks like and content of the pack

Zerit 20 mg hard capsules are brown and marked with “BMS 1965″ on one side and “20″ on the other side.

Zerit 30 mg hard capsules are light and dark orange and marked with “BMS 1966″ on one side and “30″ on the other side.

Zerit 40 mg hard capsules are dark orange and marked with “BMS 1967″ on one side and “40″ on the other side.

Zerit 20 mg, 30 mg & 40 mg hard capsules are supplied in blister packs of 56 hard capsules or bottles of 60 hard capsules. To help protect the capsules from excessive moisture, the bottle includes a desiccant canister.

 

Vistide 75 mg/ml concentrate for solution for infusion

Cidofovir

1. What Vistide is and what it is used for

Vistide is used to treat an eye infection called CMV retinitis in patients with AIDS (Acquired Immunodeficiency Syndrome). Vistide will not cure CMV retinitis but may improve your condition by delaying progression of the disease.

The safety and efficacy of Vistide has not been demonstrated in diseases other than CMV retinitis in patients with AIDS.

Vistide must be administered by a healthcare professional (doctor or nurse) in a hospital setting.

What is CMV retinitis?

CMV retinitis is an eye infection caused by a virus named cytomegalovirus (CMV). CMV attacks the retina of the eye and may cause loss of vision, and eventually lead to blindness. Patients with AIDS are at high risk of developing CMV retinitis or other forms of CMV disease such as colitis (an inflammatory bowel disease). Treatment for CMV retinitis is necessary to reduce the potential for blindness.

Vistide is an antiviral medicine which blocks the replication of CMV by interfering with viral DNA production.

2. Before you use Vistide Do not use Vistide

•  If you are allergic (hypersensitive) to cidofovir or any of the other ingredients of Vistide.

•  If you have ever had kidney disease.

•  If you cannot take the medicine probenecid because of a serious allergy to probenecid or other sulfa-containing medicines (e.g. sulfamethoxazole).

If any of these apply to you, talk to your doctor. You are not to be given Vistide.

Take special care with Vistide

•  Kidney damage is the major side effect of Vistide treatment. To reduce the risk of kidney damage, you will receive intravenous fluids (normal saline) before each dose of Vistide and probenecid tablets before and after each dose of Vistide (see section 3 below for more information). Your doctor may also instruct you to drink plenty of fluids. Your doctor will monitor your kidney function before each dose of Vistide. Your treatment with Vistide may be stopped by your doctor if changes in kidney function occur.

•  Tell your doctor if you have diabetes mellitus. Vistide should be used with caution in diabetic patients due to the potential increased risk of developing low pressure in the eye (ocular hypotony).

•  During treatment with Vistide you should receive regular follow-up eye examinations for possible eye irritation, inflammation or swelling. If you get pain, redness or itching of the eye or changes in your vision, tell your doctor promptly.

•  Vistide caused reduced testes weight and low sperm count (hypospermia) in animals. Although not observed in human studies of Vistide, such changes may occur in humans and cause infertility. Men should practice barrier birth control methods during and for 3 months after treatment with Vistide.

•  Vistide is not used for the treatment of HIV infection. Vistide will not stop you passing HIV infection onto other people so you should continue to take precautions to avoid infecting others.

Use in children

Vistide has not been studied in children. Therefore, this medicine should not be used in children.

Using other medicines

•  Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription, as these may interact with Vistide or probenecid.

It is very important to tell your doctor if you are receiving other medicines that may damage your kidneys.

These include:

•  tenofovir containing medicines, used to treat HIV-1 infection and/or chronic hepatitis B infection

•  aminoglycosides, pentamidine or vancomycin (for bacterial infections)

•  amphotericin B (for fungal infection)

•  foscarnet (for viral infection)

•  adefovir (for HBV infection)

These medicines must be stopped at least 7 days before taking Vistide.

•  Probenecid may interact with other medicines commonly used in the treatment of AIDS and AIDS-related illnesses, such as zidovudine (AZT). If you are taking zidovudine, you should discuss with your doctor whether to temporarily stop taking zidovudine or decrease the dose of zidovudine by 50% on days when Vistide and probenecid are given.

•  The potential for interactions between Vistide and anti-HIV protease inhibitors has not been studied.

Using Vistide with food and drink

Food should be taken before you are given Vistide. Your doctor may instruct you to drink plenty of fluids before receiving Vistide.

Pregnancy and breast-feeding

•  You should not be given Vistide if you are pregnant. If you become pregnant while receiving this medication, you must inform your doctor immediately. Vistide has been shown to cause damage in unborn animals and should not be used during pregnancy unless the potential benefits justify the risks to the foetus. If you could get pregnant, you must use an effective method of contraception to stop you getting pregnant during treatment with Vistide and for 1 month afterwards.

•  You should not be given Vistide if you are breast-feeding. It is not known whether Vistide is passed on to the baby in human milk. Because many medicines are passed through to human milk, nursing mothers should stop Vistide or stop breast-feeding if they continue to receive Vistide.

•  In general, women with HIV should not breast-feed in order to avoid passing HIV to their infant through the milk.

Driving and using machines

Vistide may cause short-term side effects such as fatigue or weakness. If you drive or operate machinery, discuss this with your doctor to get their advice about stopping these activities based upon your disease and your tolerance of the medicine.

Important information about some of the ingredients of Vistide

This medicine contains 2.5 mmol (or 57 mg) sodium per vial which should be taken into consideration if you are on a controlled sodium diet.

3. How to use Vistide

Vistide is given by intravenous infusion (a drip into a vein). It must not be administered by other methods including intraocular injection (direct injection into the eye) or topically (on the skin). Vistide must be given by a doctor or nurse with appropriate experience in treating people with AIDS.

The doctor or nurse will transfer the appropriate dose of Vistide from the vial to an infusion bag containing 100 ml 0.9% (normal) saline solution. The entire volume of the bag will be infused into your vein at a constant rate over a period of 1 hour using a standard infusion pump. The recommended dose, frequency of use, or rate of infusion must not be exceeded. At the end of this leaflet, there is further information for healthcare professionals on how to administer Vistide.

To lower the risk of kidney damage, probenecid tablets and intravenous fluids (saline solution) must be given on the day of each Vistide infusion. (See sub-sections “How to take probenecid with Vistide” and “How IV fluids are given before Vistide” below.)

Dose in adults

The dose you will need is calculated based on your body weight.

Starting (induction) treatment

The recommended dose of Vistide in patients with normal kidney function is 5 mg per kg of body weight given once weekly for two consecutive weeks.

Maintenance treatment

Beginning two weeks after completion of induction treatment, the recommended maintenance dose of Vistide in patients with normal kidney function is 5 mg per kg of body weight given once every two weeks.

Dose adjustment

If you have kidney problems, Vistide may not be appropriate treatment for you. Samples of your urine and/or blood will be taken before each infusion of Vistide and used for testing kidney function. For patients with evidence of decreased kidney function, your Vistide dose may be interrupted or stopped depending on your individual case.

If you have accidentally been given more Vistide than prescribed for you, tell your doctor immediately.

How to take probenecid with Vistide

Probenecid tablets are given to lower the risk of kidney damage. You must take 3 doses of probenecid tablets orally on the same day as Vistide as shown in the following table:

Time	Dose
3 hours before start of Vistide infusion	2 g probenecid
2 hours after end of Vistide infusion	1 g probenecid
8 hours after end of Vistide infusion	1 g probenecid
Total	4 g probenecid

Probenecid is only taken on the same day that Vistide is given.

How IV fluids are given before Vistide

Normal saline is given to lower the risk of kidney damage. You should receive a total of one litre of 0.9% (normal) saline solution intravenously (as a drip into a vein) before each Vistide dose. The saline solution should be infused over a 1 hour period immediately before the Vistide infusion. If you can tolerate the additional fluid load, your doctor may administer a second litre of fluid. If administered, the second litre of saline should be given either at the start of the Vistide infusion or immediately afterwards, and infused over a 1 to 3 hour period. Your doctor may also tell you to drink plenty of fluids.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Vistide can cause side effects, although not everybody gets them.

These side effects usually disappear when treatment with Vistide is stopped. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist immediately.

The most common side effect observed with Vistide is damage to the kidneys.

Very common side effects

{These can affect more than 1 user in 10)

•  low white blood cell counts, headache, nausea, vomiting, protein in the urine, increase in blood creatinine (a measure of kidney function), hair loss, rash, weakness/fatigue and fever.

Common side effects

{These can affect 1 to 10 users in 100)

•  inflammation of the eye, reduced pressure in the eyes, difficult or laboured breathing, shortness of breath, diarrhoea and chills.

Any pain, redness or itching of the eye or changes in your vision should be promptly reported to your doctor so that your treatment can be reviewed.

Additional reactions reported from post-marketing experience include kidney failure, damage to kidney tubule cells, inflammation of the pancreas and hearing impairment.

Possible side effects of taking probenecid

Very common side effects possibly related to probenecid

{These can affect more than 1 user in 10)

•  nausea, vomiting, rash and fever.

Common side effects possibly related to probenecid

{These can affect 1 to 10 users in 100)

•  headache, weakness/fatigue, chills and allergic reactions.

To reduce the risk of nausea and/or vomiting associated with taking probenecid, you should eat food before each dose. Your doctor might instruct you to take other medicines such as anti-emetics (anti sickness medicines), antihistamines and/or paracetamol to decrease the side effects of probenecid.

Probenecid may also cause other side effects including loss of appetite, sore gums, flushing, hair loss, dizziness, reduced red blood cell count and increased frequency of passing water (urinating). Allergic reactions, with skin inflammation, itching, hives and, rarely, severe allergic reactions, and serious skin reaction have occurred. There have been reports of reduced white blood counts, liver toxicity, kidney toxicity and destruction of red blood cells. Reductions in blood cell and platelet counts have also occurred.

Therefore before giving you probenecid your doctor should consult the current prescribing information regarding the safety of probenecid. You should also read the probenecid package leaflet.

5. How to store Vistide

Keep out of the reach and sight of children.

Do not use Vistide after the expiry date which is stated on the label.

Do not store above 30°C. Do not refrigerate or freeze.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Vistide contains

The active substance of Vistide 75 mg/ml is cidofovir. Each ml contains 75 mg cidofovir anhydrous. Each vial contains 375 mg/5 ml cidofovir anhydrous.

The other ingredients are

•  Sodium hydroxide

•  Hydrochloric acid

• Water for injections

What Vistide looks like and contents of the pack

Vistide is supplied as a sterile concentrate for solution for infusion in clear, glass vials containing 375 mg of the active ingredient, anhydrous cidofovir, formulated in 5 ml water for injections at a concentration of 75 mg/ml. The formulation is pH-adjusted with sodium hydroxide (and hydrochloric acid if needed) and contains no preservatives.

The following information is intended for medical or healthcare professionals only:

Vistide vials should be inspected visually prior to use. If visible particles or discolouration are observed, the vial should not be used.

Adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration and disposal of Vistide. The preparation of Vistide diluted solution should be done in a laminar flow biological safety cabinet. Personnel preparing the solution should wear surgical gloves, safety glasses and a closed front surgical-type gown with knit cuffs. If Vistide contacts the skin, wash membranes and flush thoroughly with water.

The appropriate dose of Vistide should be transferred from the vial to an infusion bag containing 100 ml 0.9% (normal) saline solution. The entire volume of the bag should be infused into the patient’s vein at a constant rate over a period of 1 hour using a standard infusion pump. The recommended dose, frequency of use, or rate of infusion must not be exceeded.

The chemical stability of Vistide mixed in saline solution has been demonstrated in glass bottles, in infusion bags composed of either polyvinyl chloride (PVC) composition or ethylene/propylene copolymer, and in PVC based vented IV administration sets. Other types of IV set tubing and infusion bags have not been studied.

Compatibility of Vistide with Ringer’s Solution, Lactated Ringer’s Solution or bacteriostatic infusion fluids has not been evaluated.

From a microbiological point of view, the product must be used immediately.

Chemical and physical in-use stability has been demonstrated for up to 24 hours at 2 – 8°C when dilution is performed under controlled and validated aseptic conditions. Storage beyond 24 hours or freezing is not recommended. Refrigerated infusion bags should be allowed to warm to room temperature prior to use.

Vistide is supplied in single-use vials. Partially used vials must be discarded.

 

Tyverb 250 mg film-coated tablets

Lapatinib

1. WHAT TYVERB IS AND WHAT IT IS USED FOR

Tyverb is used to treat certain types of breast cancer (HER2-overexpressing) which have spread beyond the original tumour {advanced or metastatic breast cancer). It may slow or stop cancer cells from growing, or may kill them.

Tyverb is prescribed to be taken in combination with another anti-cancer medicine.

Tyverb is prescribed in combination with capecitabine, for patients who have had other treatment for advanced or metastatic breast cancer before.

Tyverb is prescribed in combination with an aromatase inhibitor, for patients with hormone sensitive metastatic breast cancer (breast cancer that is more likely to grow in the presence of hormones), who are not currently intended for chemotherapy.

Information about these medicines is described in separate patient information leaflets. Ask your doctor to give you information about these other medicines.

2. BEFORE YOU TAKE TYVERB

Do not take Tyverb

•     if you are allergic (hypersensitive) to lapatinib or any of the other ingredients of Tyverb.

Take special care with Tyverb

Your doctor will run tests to check that your heart is working properly before and during your treatment with Tyverb.

Tell your doctor if you have any heart problems before you take Tyverb.

Your doctor also needs to know before you take Tyverb:

•  if you have any liver problems.

•  if you have any kidney problems.

Your doctor will run tests to check that your liver is working properly before and during your treatment with Tyverb.

Tell your doctor if any of these apply to you.

Taking other medicines

Tell your doctor or pharmacist if you are taking, or have recently taken any other medicines.

This includes any medicines you bought without a prescription.

It is especially important to tell your doctor if you are taking, or have recently taken any of the following medicines. Some medicines may affect the way Tyverb works or Tyverb may affect how other medicines work. These medicines include some medicines in the following groups:

•  St John’s Wort – a herb extract used to treat depression

•  erythromycin, ketoconazole, itraconazole, posaconazole, voriconazole, rifabutin, rifampicin, telithromycin – medicines used to treat infections

•  cyclosporine – a medicine used to suppress the immune system for example after organ transplantations

•  ritonavir, saquinavir – medicines used to treat HIV

•  phenytoin, carbamazepine – medicines used to treat seizures

•  cisapride – a medicine used to treat certain digestive system problems

•  pimozide – a medicine used to treat certain mental health problems

•  quinidine, digoxin – medicines used to treat certain heart problems

•  repaglinide – a medicine used to treat diabetes

•  verapamil – a medicine used to treat high blood pressure or heart problems (angina)

•  nefazodone – a medicine used to treat depression

•  topotecan, paclitaxel, irinotecan, docetaxel – medicines used to treat certain types of cancer

•  rosuvastatin – a medicine used to treat high cholesterol

•  medicines that decrease stomach acidity – used to treat stomach ulcers or indigestion

Tell your doctor if you’re taking, or have recently taken, any of these.

Your doctor will review the medicines you are currently taking to make sure you are not taking something that can’t be taken with the Tyverb. Your doctor will advise you whether an alternative is available.

Taking Tyverb with food and drink

Take Tyverb either at least one hour before or at least one hour after food.

Tyverb is affected by food intake. It is important that you take your tablets at the same time in relation to food each day – for example, you could always take your tablet one hour before breakfast.

Don’t drink grapefruit juice while you are being treated with Tyverb.

Pregnancy and breast-feeding

The effect of Tyverb during pregnancy is not known. You should not use Tyverb if you are pregnant unless your doctor specifically recommends it.

•  If you are pregnant or planning to become pregnant tell your doctor.

•  Use a reliable method of contraception to avoid becoming pregnant while you’re taking Tyverb.

•  If you become pregnant during treatment with Tyverb, tell your doctor.

It is not known whether Tyverb passes into breast-milk. Do not breast-feed while taking Tyverb.

•  If you are breast-feeding or planning to breast-feed, tell your doctor.

Ask your doctor or pharmacist for advice before taking Tyverb if you are unsure. Driving and using machines

No studies have been performed on the effects of Tyverb on your ability to drive or use machines.

You are responsible to decide if you are able to drive a motor vehicle or perform other tasks that require increased concentration. Because of the possible side effects of Tyverb, your ability to drive or operate machinery could be affected.

Read all the information in this leaflet for guidance. Discuss with your doctor, nurse or pharmacist if you are unsure about anything.

3. HOW TO TAKE TYVERB

Always take Tyverb exactly as your doctor has told you. Check with your doctor or pharmacist if you’re not sure.

Your doctor will decide on the correct dose of Tyverb depending on the type of breast cancer being treated.

If you are prescribed Tyverb in combination with capecitabine, the usual dose is 5 Tyverb tablets a day, as a single dose.

If you are prescribed Tyverb in combination with an aromatase inhibitor, the usual dose is 6 Tyverb tablets a day, as a single dose.

Take the prescribed dose every day for as long as your doctor tells you to.

Your doctor will advise you about the dose of your other anti-cancer medicine, and how to take it.

Taking your tablets

•     Swallow the tablets whole with water, one after the other, at the same time each day.

•     Take Tyverb either at least one hour before or at least one hour after food. Take Tyverb at the same time in relation to food each day.

While you are taking Tyverb

•  Depending on your response to treatment, your doctor may recommend lowering your dose or temporarily stopping your treatment.

•  Your doctor will also carry out tests to check your heart and liver function before and during treatment with Tyverb.

If you take too much Tyverb

Contact a doctor or pharmacist immediately. If possible show them the pack.

If you forget to take Tyverb

Don’t take a double dose to make up for a missed dose. Just take the next dose at the scheduled time.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Tyverb can cause side effects, although not everybody gets them.

Severe allergic reaction

This rare side effect may affect up to 1 in 1000 people and develop rapidly. Symptoms may include:

•  skin rash (including itchy, bumpy rash)

•  unusual wheezing, or difficulty in breathing

•  swollen eyelids, lips or tongue

•  pains in muscles or joints

•  collapse or blackout.

Tell your doctor immediately if you get any of these symptoms. Don’t take any more tablets. Very common side effects

These may affect more than 1 in 10 people:

•  diarrhoea (which may make you dehydrated and lead to more severe complications)

Tell your doctor if you get diarrhoea.

•  rash, dry skin, itching

Tell your doctor if you get a skin rash.

Other very common side effects

•  loss of appetite

•  feeling sick (nausea)

•  being sick (vomiting)

•  tiredness, feeling weak

•  indigestion

•  constipation

•  sore mouth/mouth ulcers

•  stomach pain

•  trouble sleeping

•  back pain

•  pain in hands and feet

• joint or back pain

•  a skin reaction on the palms of the hands or soles of the feet (including tingling, numbness, pain, swelling or reddening)

•  cough, shortness of breath

•  headache

•  nose bleed

•  hot flush

•  unusual hair loss or thinning

Tell your doctor if any of these side effects get severe or troublesome. Common side effects

These may affect up to 1 in 10 people:

•  an effect on how your heart works

In most cases, the effect on your heart will not have any symptoms. If you do experience symptoms associated with this side effect, these are likely to include an irregular heartbeat and shortness of breath.

•  liver problems, which may cause itching, yellow eyes or skin {jaundice), or dark urine or pain or discomfort in the right upper area of the stomach.

Tell your doctor if you get any of these symptoms.

Other common side effects

•  nail disorders – such as a tender infection and swelling of the cuticles Tell your doctor or pharmacist if this side effect gets severe or troublesome. Uncommon side effects

These may affect up to 1 in 100 people:

•  treatment-induced lung inflammation, which may cause shortness of breath or cough Tell your doctor immediately if you get either of these symptoms.

Other uncommon side effects include:

•  blood tests results that show changes in liver function (usually mild and temporary)

Rare side effects

This may affect up to 1 in 1000 people:

•   severe allergic reactions

If you get other side effects

If you notice any side effects not listed in this leaflet: Tell your doctor or pharmacist.

Reducing the risk of diarrhoea and skin rash

Tyverb can cause severe diarrhoea

If you suffer from diarrhoea while taking Tyverb:

•     drink plenty of fluids (8 to 10 glasses a day), such as water, sports drinks or other clear liquids

•     eat low-fat, high protein foods instead of fatty or spicy foods

•     eat cooked vegetables instead of raw vegetables and remove the skin from fruits before eating

•     avoid milk and milk products (including ice cream)

•     avoid herbal supplements (some may cause diarrhoea).

Tell your doctor if your diarrhoea continues.

Tyverb can cause skin rash

Your doctor will check your skin before and during treatment. To care for sensitive skin:

•     wash with a soap-free cleanser

•     use fragrance free, hypoallergenic beauty products

•     use sunscreen (Sun Protection Factor [SPF] 30 or higher).

Tell your doctor if you get a skin rash.

5. HOW TO STORE TYVERB

Keep out of the reach and sight of children.

Do not use Tyverb after the expiry date which is stated on the blister and the carton.

Do not store above 30°C

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

• What Tyverb contains

The active substance in Tyverb is lapatinib. Each film-coated tablet contains lapatinib ditosylate monohydrate, equivalent to 250 mg lapatinib.

The other ingredients are:

Microcrystalline cellulose, povidone (K30), sodium starch glycolate (Type A), magnesium stearate, hypromellose, titanium dioxide (E171), macrogol 400, polysorbate 80, iron oxide yellow (E172), iron oxide red (El72).

• What Tyverb looks like and contents of the pack

Tyverb film-coated tablets are oval, biconvex, yellow film-coated, with ‘GS XJG’ marked on one side.

Each pack of Tyverb contains 70 or 84 tablets in aluminium foil blisters of 10 or 12 tablets each. Each foil has a perforation down the middle and can be divided into two blisters with 5 or 6 tablets in each, depending on the pack size. Always take the number of Tyverb tablets each day exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Tyverb is also available in multipacks containing 140 tablets that comprise 2 packs, each containing 70 tablets.

Not all pack sizes may be marketed.

 

Rifinah 150/100mg Tablets

Rifampicin, Isoniazid

1. What Rifinah 150/100 mgTablets are and what they are used for

Rifinah 150/100 mgTablets contain two different medicines called rifampicin and isoniazid. They both belong to a group of medicines called anti-tuberculous drugs. They work by killing the bacteria that cause tuberculosis. Rifinah 150/100 mgTablets are used to treat tuberculosis (also known as TB).

2. Before you take Rifinah 150/100 mg Tablets

Do not take Rifinah 150/100 mg Tablets if:

You are allergic (hypersensitive) to

-   rifampicin

-   isoniazid

-   any of the other ingredients of the Rifinah 150/100 mgTablets

Signs of an allergic reaction include: a rash, swallowing or breathing problems,

swelling of your lips, face, throat or tongue X You have yellowing of the skin and eyes (jaundice) X You are taking saquinavir or ritonavirforan HIV infection

Do not take if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Rifinah 150/100mgTablets.

Take special care with Rifinah 150/100 mgTablets Check with your doctor or pharmacist before taking this medicine if:

• You have liver problems
• You have any kidney problems and if you are having more than 600mg rifampicin per day
• You have diabetes. Your diabetes may become more difficult to control while taking this medicine
• You have epilepsy
• You have or have ever had mental health problems (such as depression or schizophrenia)
• You feel numb or weak in your arms and legs (peripheral neuropathy)
• You have an HIV infection
• You are underweight or malnourished
• You drink alcohol every day or you are an alcoholic
• You inject yourself with drugs
• You area black or Hispanic woman
• You have a rare blood problem called ‘porphyria’
• You doctor has told you that your body takes a long time to get rid of some drugs (you have a slow acetylator status)
• You wear contact lenses. Taking Rifinah 150/100 mgTablets may permanently stain soft contact lenses

The person taking this medicine is a child

You are aged 65 years or older

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Rifinah 150/100 mgTablets.

Blood Tests

Your doctor will need to check your blood before you take this medicine. This will help your doctor know if any changes happen to your blood after taking this medicine. If you are aged 35 years or older, you will also need to have monthly blood tests to check how your liver is working.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Rifinah 150/100 mgTablets can affect the way some other medicines work. Also some medicines can affect the way Rifinah 150/100 mgTablets work.

In particular, do not take this medicine, and tell your doctor, if you are taking:

Saquinavir or ritonavir used for HIV infection

The following medicines can make Rifinah 150/100 mgTablets work less well:

•  Antacids used for indigestion. Take Rifinah 150/100 mgTablets at least 1 hour before taking antacids

•   Other medicines used for TB such as P-aminosalicyclic acid (PAS) and cycloserine. PAS and Rifinah 150/100 mgTablets should be taken at least 8 hours apart

Tell your doctor if you are taking any of the following medicines:

Heart and blood medicines

•   Medicines for high blood pressure

•   Medicines for heart problems or to control your heartbeat

•   Medicines used to thin the blood such as warfarin

•   Medicines used to lower cholesterol

•  Water tablets (diuretics) such as eplerenone

Mental health, epilepsy and motor neurone medicines

•   Medicines for thought disorders known as ‘antipsychotics’ such as haloperidol

•   Medicines to calm or reduce anxiety (hypnotics, anxiolytics)

•   Medicines to help you sleep (barbiturates)

•   Medicines used for epilepsy such as phenytoin and carbamazepine

•  Some medicines used for depression such as amitriptyline and nortriptyline

•   Riluzole – used for motor neurone disease

Medicines for infections and the immune system

•  Some medicines used for an HIV infection such as stavudine and zalcitabine

•  Some medicines used for viral infections such as indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir and neviparine

•   Medicines used for fungal infections

•   Medicines used for bacterial infections (antibiotics)

•   Medicines used for lowering your immune system such as ciclosporin, sirolimusand tacrolimus

•   Praziquantel – used for tapeworm infections

•  Atovaquone – used for pneumonia

Hormone and cancer medicines

•  Some hormone medicines (estrogen, systemic hormones, progestogens) used for contraception or some types of cancer such as ethinyloestradiol, levonorgestrel or dydrogesterone

•  Some hormone medicines (anti-estrogens) used for breast cancer or endometriosis such as tamoxifen, toremifene and gestrinone

•  Some medicines used for cancer (cytotoxics) such as imatinib

•   Levothyroxine (thyroid hormone) used for thyroid problems

•   Irinotecan – used for cancer

Pain and inflammation medicines

•   Non-steroidal anti-inflammatory drugs (NSAIDS) such as etoricoxib, aspirin and indometacin

•   Medicines used for pain such as codeine, morphine, fentanyl or pethidine

•  Corticosteroids used for inflammation such as hydrocortisone, betamethasoneand prednisolone

•   Methadone – used for heroin withdrawal

Other medicines

•   Medicines used for diabetes

•   Medicines used to relax muscles before surgery (anaesthetics) such as halothane

•  Some medicines used for feeling sick or being sick such as ondansetron and aprepitant

•  Quinine-used for malaria

•  Theophylline – used for wheezing or difficulty in breathing

Taking Rifinah 150/100 mgTablets with food and drink

If Rifinah 150/100 mgTablets are taken with the food and drink listed below you may experience headache, sweating, flushing, fast, uneven or forceful heartbeat (palpitations), dizziness, feel lightheaded or faint (due to low blood pressure).

While taking Rifinah 150/100 mgTablets do not have:

•  Cheese

•  Skipjack tuna or other tropical fish

•   Red wine

Pregnancy and breast-feeding

Talk to your doctor before taking this medicine if you are pregnant, plan to get pregnant or think you are pregnant.

Rifinah 150/100 mgTablets may make the contraceptive “pill” work less well. This means you should change to a different type of contraception. Instead, you must use a reliable barrier method of contraception such as condoms or the “coil” while taking Rifinah 150/100 mgTablets. If you have any questions or are unsure about this talk to your doctor or pharmacist.

You should not breast-feed if you are taking Rifinah 150/100 mg Tablets.

This is because small amounts may pass into the mothers’ milk. If you are breast-feeding or planning to breast feed, talk to your doctor or pharmacist before taking any medicine.

Driving and using machines

You may feel dizzy or faint, have problems with vision or have other side effects that could affect your ability to drive while taking this medicine. If this happens, do not drive or use any tools or machines.

Important information about some of the ingredients of Rifinah 150/100mg Tablets contain:

•    Sucrose:  If you have been told by your doctor that you cannot tolerate some sugars, talk to your doctor before taking Rifinah 150/100 mgTablets

•    Sodium: These tablets contain less than 1 mmol sodium (23 mg) per daily dose and are essentially ‘sodium-free’.

3. How to take Rifinah 150/100 mgTablets

Always take Rifinah 150/100 mgTablets exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Keep taking this medicine

•    You must take the tablets every day for the whole time the doctor has told you to take them

•    Do not stop and start taking the tablets. This may increase the risk of side effects and your TB will not be treated properly

How to take the tablets

•    Take this medicine by mouth

•    Swallow the tablets whole, with a drink of water

•    Take at least 30 minutes before a meal or 2 hours after a meal. They are best taken at least 30 minutes before breakfast

•    Take all your tablets together each day, as a single dose

•    Do not give this medicine to children

•    If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor

Your doctor may ask you to take Vitamin B₆ during treatment with Rifinah 150/100 mgTablets, especially if you are malnourished, elderly or a diabetic.

How much to take

The usual dose is:

Adults and the Elderly weighing less than 50kg

•  3 tablets each day

•   If you are elderly, your doctor may monitor your treatment more closely

Adults and the Elderly weighing more than 50kg

•   Rifinah 300/150mg Tablets are usually prescribed

Children

This medicine is not recommended for use in children.

If you take more Rifinah 150/100 mgTablets than you should

If you take more Rifinah 150/100 mgTablets than you should, tell a doctor or go to a hospital casualty department straight away. Take the medicine pack with you. This is so the doctor knows what you have taken.

You may feel sick (nausea), be sick (vomiting), have stomach pain, itching or a headache. You may also feel tired, sleepy, dizzy, light-headed, have blurred or strange visions (hallucinations) and faint or feel faint. Other signs of taking too much includes swelling of the face, eyes or eyelids, slurring of speech, difficulty breathing, fast heartbeat, uneven heartbeats, fits and heart attack.

If you forget to take Rifinah 150/100 mgTablets

If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose. Do not take a double dose to make up for the forgotten tablets.

Tests

Taking Rifinah 150/100 mgTablets may affect the results of some blood tests. In particular, tests for folate, vitamin B₁₂ and liver function. If you are going to have a blood test, it is important to tell your doctor that you are taking Rifinah 150/100 mgTablets.

4. Possible side effects

Like all medicines, Rifinah 150/100 mgTablets can cause side effects, although not everybody gets them.

Stop taking and go to a hospital straight away if you notice any of the following serious side effects:

•    You have an allergic reaction. The signs may include: a rash, swallowing or breathing problems, wheezing, swelling of your lips, face, throat or tongue

•    You have a fever and yellowing of the skin or whites of the eyes, feel tired, weak or generally unwell, loss of appetite (anorexia), feeling sick (nausea), being sick (vomiting). These may be early signs of liver problems

•    You get blistering, peeling, bleeding, scaling or fluid filled patches on any part of your skin. This includes your lips, eyes, mouth, nose, genitals, hands or feet. You may have a serious skin problem

•    You bruise more easily than usual. Or you may have a painful rash of dark red spots under the skin which do not go away when you press on them (purpura). This could be because of a serious blood problem

•    You have chills, tiredness, unusually pale skin colour, shortness of breath, fast heartbeat or dark coloured urine. This could be signs of a serious type of anaemia

•    You have blood in your urine or an increase or decrease in amount of urine you produce. You may also get swelling, especially of the legs, ankles or feet. This may be caused by serious kidney problems

•    You have a sudden severe headache. This could be a sign of bleeding in the brain

•    Shortness of breath and wheezing

•    You get confused, sleepy, cold clammy skin, shallow or difficult breathing, a racing heartbeat or your skin is paler than normal. These could be signs of shock

•    You get more infections more easily than normal. Signs include fever, sore throat or mouth ulcers. This could be because you have a low number of white blood cells

•    You have bleeding from your nose, ear, gums, throat, skin or stomach. Signs may include a feeling of tenderness and swelling in your stomach, purple spots on your skin and black or tar-like stools

Talk to your doctor straight away if you notice any of the following serious side effects:

•    Mental problems with unusual thoughts and strange visions (hallucinations)

•    Severe watery diarrhoea that will not stop and you are feeling weak and have a fever. This may be something called ‘Pseudomembranous colitis’

•    Severe stomach pain which may reach through to your back. This could be a sign of pancreatitis

•    Your fits get worse or you start to have fits

•    Flu-like symptoms including chills, fever, headache, dizziness and bone pains

Tell your doctor as soon as possible if you have any of the following side effects:

•    Water retention (oedema) which may cause swollen face, stomach, arms or legs

•    Muscle weakness or pain or loss of muscle reflexes

•    Dizziness, feel lightheaded and faint especially when you stand or sit up quickly (due to low blood pressure)

•    Swollen fingers, toes or ankles

•    Hair loss

•    Balance problems with dizziness (vertigo)

•    Being unable to concentrate, feeling nervous, irritable or depressed

•    Feeling very tired and weak or difficulty sleeping (insomnia)

•    Unusual skin sensations such as feeling numb, tingling, pricking, burning or creeping on the skin (paraesthesia)

•    Short-term memory loss, anxiety, being less alert or responsive

•    Blurred or distorted eyesight

•    Wasting of muscles or other body tissues

•    Weight loss, night sweats and fever. These could be signs of a blood condition called eosinophilia

•    Feeling sick or being sick

Tell your doctor or pharmacist if any of the following side effects get serious or lasts longer than a few days:

•    Skin flushing or itching

•    Irregular periods

•    Constipation, diarrhoea, stomach discomfort or dry mouth

•    Headache

•    Loss of a p petite (a n o rexia)

•    Breast enlargement in men

•    Increased thirst, going to the toilet more often and feeling tired. Your blood sugar may be high

•    Acne

Other side effects you should discuss with your doctor if you are concerned about them

•    You notice an orange or reddish colour in your urine, sweat, phlegm (sputum), saliva or tears. This is quite common and you need not worry. However, the red colour may permanently stain soft contact lenses. The red colour in tears may last for some time after you have stopped having Rifinah 150/100 mgTablets.

Blood tests

•    A blood test may show changes in the way the liver is working

5. How to store Rifinah 150/100 mgTablets

Keep this medicine in a safe place where children cannot see or reach it.

Do not use Rifinah 150/100 mgTablets after the expiry date which is stated on the carton and blister packs. The expiry date refers to the last day of that month.

Store below 25°C

Medicines should not be disposed of via waterwaste or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Further information

What Rifinah 150/100 mgTablets contain:

•    Each tablet contains 150mg of rifampicin and 100mg of isoniazid. These are the active ingredients

•    The other ingredients are sodium lauryl sulphate, calcium stearate, sodium carboxymethyl cellulose, magnesium stearate, microcrystalline cellulose, acacia, gelatine, kaolin, magnesium carbonate light, talc, titanium dioxide (E171), colloidal silicon dioxide, polyvinylpyrollidone K30, sucrose, carnauba wax, colophony, white beeswax, hard paraffin, Erythrosine (E127)

What Rifinah 150/100 mgTablets look like and contents of the pack

The tablets are cyclamen, smooth, shiny, round, curved and sugar coated. Each pack contains 84 tablets.

 

Modigraf 0.2 mg, granules for oral suspension Modlgraf 1 mg, granules for oral suspension

Tacrolimus

1. WHAT MODIGRAF IS AND WHAT IT IS USED FOR

Modigraf is an immunosuppressant. Following your organ transplant (e.g. liver, kidney, heart), your body’s immune system will try to reject the new organ. Modigraf is used to control your body’s immune response enabling your body to accept the transplanted organ.

You may also be given Modigraf for an ongoing rejection of your transplanted liver, kidney, heart or other organ or if any previous treatment you were taking was unable to control this immune response after your transplantation.

2.  BEFORE YOU TAKE MODIGRAF

Do not take Modigraf

• If you are allergic (hypersensitive) to tacrolimus or any of the other ingredients of Modigraf.
• If you are allergic (hypersensitive) to sirolimus (another substance used to prevent rejection of your transplanted organ) or to any macrolide antibiotic (e.g. erythromycin, clarithromycin, josamycin).

Take special care with Modigraf

Tell your doctor if any of the following apply to you:

• if you are taking any medicines mentioned below under ‘Using other medicines’.
• if you have or have had liver problems.
• if you have diarrhoea for more than one day.
• if you need to receive any vaccinations. Your doctor may need to adjust your dose of Modigraf.

You should keep in regular contact with your doctor. From time to time, your doctor may need to do blood, urine, heart, eye tests, to set the right dose of Modigraf.

You should limit your exposure to the sun and UV (ultraviolet) light whilst taking Modigraf.

This is because immunosuppressants could increase the risk of skin cancer. Wear appropriate protective clothing and use a sunscreen with a high sun protection factor.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal preparations.

It is not recommended that Modigraf is taken with ciclosporin. Modigraf blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking Modigraf, which may require an increase or decrease in Modigraf dose. In particular, you should tell your doctor if you are taking or have recently taken medicines like:

• antifungal medicines and antibiotics, particularly so-called macrolide antibiotics, used to treat infections e.g.
• ketoconazole, fluconazole, itraconazole, voriconazole, clotrimazole, erythromycin, clarithromycin, josamycin, and
• rifampicin
• HIV protease inhibitors (e.g. ritonavir), used to treat HIV infection
• medicines for stomach ulcer and acid reflux (e.g. omeprazol, lansoprazol or cimetidine)
• anti-emetics, used to treat nausea and vomiting (e.g. metoclopramide)
• cisapride or the antacid magnesium-aluminium-hydroxide, used to treat heartburn the contraceptive pill, hormone treatments with ethinylestradiol, or hormone treatments with danazol
• medicines used to treat high blood pressure or heart problems (e.g. nifedipine, nicardipine, diltiazem and verapamil)
• medicines known as “statins” used to treat elevated cholesterol and triglycerides
• phenytoin or phenobarbital, used to treat epilepsy
• the corticosteroids prednisolone and methylprednisolone, belonging to the class of corticosteroids used to treat
• inflammations or suppress the immune system (e.g. in transplant rejection)
• nefazodone, used to treat depression
• Herbal preparations containing St. John’s Wort (Hypericum perforatum)

Tell your doctor if you are taking or need to take ibuprofen, amphotericin B or antivirals (e.g. aciclovir). These may worsen kidney or nervous system problems when taken together with Modigraf.

Your doctor also needs to know if you are taking potassium supplements or certain diuretics used for heart failure, hypertension and kidney disease, (e.g. amiloride, triamterene, or spironolactone), non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen) used for fever, inflammation and pain, anticoagulants (blood thinners), or oral medicines for diabetes, while you take Modigraf.

If you need to have any vaccinations, please tell your doctor before.

Taking Modigraf with food and drink

Take Modigraf on an empty stomach or 2 to 3 hours after a meal. Wait at least 1 hour until the next meal. Avoid grapefruit (also as juice) while on treatment with Modigraf, since it can affect its levels.

Pregnancy and breast-feeding

If you are, think you might be or are planning to become pregnant, ask your doctor for advice before using Modigraf. Modigraf passes into breast milk. Therefore, you should not breast-feed whilst using Modigraf.

Driving and using machines

Do not drive or use any tools or machines if you feel dizzy or sleepy, or have problems seeing clearly after taking Modigraf. These effects are more frequent if you also drink alcohol.

Important Information about some of the Ingredients of Modigraf

Modigraf contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. HOW TO TAKE MODIGRAF

Always take Modigraf exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Make sure that you receive the same tacrolimus medicine every time you collect your prescription, unless your transplant specialist has agreed to change to a different tacrolimus medicine.

This medicine should be taken twice a day. If the appearance of this medicine is not the same as usual, or if dosage instructions have changed, speak to your doctor or pharmacist as soon as possible to make sure that you have the right medicine.

The starting dose to prevent the rejection of your transplanted organ will be determined by your doctor calculated according to your body weight. Initial doses just after transplantation will generally be in the range of 0.075 – 0.30 mg per kg body weight per day depending on the transplanted organ.

Your dose depends on your general condition and on which other immunosuppressive medication you are taking.

Following the initiation of your treatment with Modigraf, frequent blood tests will be taken by your doctor to define the correct dose and to adjust the dose from time to time. Your doctor will usually reduce your Modigraf dose once your condition has stabilised. Your doctor will tell you exactly how many sachets to take.

You will need to take Modigraf every day as long as you need immunosuppression to prevent rejection of your transplanted organ. You should keep in regular contact with your doctor.

Modigraf is taken orally twice daily, usually in the morning and evening. See also “Taking Modigraf with food and drink”.

How to prepare the Modigraf sachets for use?

Your doctor will advise you on the number of sachets that you need to open and the volume of water that is required to make a suspension. For accurate measuring the volume of water you can use a syringe or graduated cylinder.

Carefully open the prescribed number of sachets, e.g. with a pair of scissors.

Pour the prescribed volume of water (at room temperature) into a glass or cup, up to a maximum of 50 ml. Place the cup with water on a stable surface. Do not use cups or spoons that are made of PVC (polyvinylchloride) to take Modigraf because the active substance in Modigraf may stick to PVC.

Open the sachet at the point indicated with an arrow. Hold the opened sachet between thumb and index finger above the cup with the open side of the sachet facing downwards. Gently tap on the closed end of the sachet and pour the contents of each sachet into the glass or cup containing the water. Do not use any utensils or liquids to empty the sachet. If you follow  these instructions, you will get the right amount of granules from the sachet. It is normal that some granules stay behind; the sachet was designed that way.

Stir, or swirl gently until the granules have been suspended completely. The suspension can be drawn up with a syringe or swallowed directly by the patient. The liquid has a sweet taste. Rinse the glass or cup once with the same amount of water and drink this, too. The liquid should be drunk immediately after preparation.

If you take more Modigraf than you should

If you have accidentally taken too much Modigraf, contact your doctor or nearest hospital emergency department immediately.

If you forget to take Modigraf

Do not take a double dose to make up for forgotten individual doses.

If you have forgotten to take your Modigraf, wait until it is time for the next dose, and then continue as before.

If you stop taking Modigraf

Stopping your treatment with Modigraf may increase the risk of rejection of your transplanted organ. Do not stop your treatment unless your doctor tells you to do so.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Modigraf can cause side effects, although not everybody gets them.

Modigraf reduces your body’s defence mechanism (immune system), which will not be as good at fighting infections. Therefore, you may be more prone to infections while you are taking Modigraf.

Severe effects may occur, including allergic and anaphylactic reactions (a very serious type of allergic reaction with fainting and difficulty breathing, which needs immediate medical attention). Benign and malignant tumours have been reported following Modigraf treatment.

Possible side effects are listed according to the following categories: very common: affects more than 1 user in 10 common: affects 1 to 10 users in 100 uncommon: affects 1 to 10 users in 1,000 rare: affects 1 to 10 users in 10,000 very rare: affects less than 1 user in 10,000 not known: frequency cannot be estimated from the available data.

Very common side effects:

• Increased blood sugar, diabetes mellitus, increased potassium in the blood
• Difficulty in sleeping
• Trembling, headache
• Increased blood pressure
• Liver function tests abnormal
• Diarrhoea, nausea
• Kidney problems

Common side effects:

• Reduction in blood cell counts (platelets, red or white blood cells). increase in white blood cell counts, changes in red blood cell counts (seen in blood tests)
• Reduced magnesium, phosphate, potassium, calcium or sodium in the blood, fluid overload, increased uric acid or lipids in the blood, decreased appetite, increased acidity of the blood, other changes in the blood salts (seen in blood tests)
• Anxiety symptoms, confusion and disorientation, depression, mood changes, nightmare, hallucination, mental disorders
• Fits, disturbances in consciousness, tingling and numbness (sometimes painful) in the hands and feet, dizziness. impaired writing ability, nervous system disorders
• Blurred vision, increased sensitivity to light, eye disorders
• Ringing sound in your ears
• Reduced blood flow in the heart vessels, faster heartbeat
• Bleeding, partial or complete blocking of blood vessels, reduced blood pressure
• Shortness in breath, changes in the lung tissue, collection of liquid around the lung, inflammation of the throat, cough.
• flu-like symptoms
• Stomach problems such as inflammation or ulcer causing abdominal pain or diarrhoea, bleeding in the stomach.
• inflammation or ulcer in the mouth, collection of fluid in the belly, vomiting, abdominal pain, indigestion, constipation.
• passing wind, bloating, loose stools
• Bile duct disorders, yellowing of the skin due to liver problems, liver tissue damage and inflammation of the liver
• Itching, rash, hair loss, acne, increased sweating
• Pain in joints, limbs or back, muscle cramps
• Insufficient function of the kidneys, reduced production of urine, impaired or painful urination
• General weakness, fever, collection of fluid in your body, pain and discomfort, increase of the enzyme alkaline
• phosphatase in your blood, weight gain, feeling of temperature disturbed Insufficient function of your transplanted organ

Uncommon side effects:

• Changes in blood clotting, reduction in the number of all types of blood cells (seen in blood tests)
• Dehydration, inability to urinate
• Abnormal blood test results: reduced protein or sugar, increased phosphate, increase of the enzyme lactate
• dehydrogenase
• Coma, bleeding in the brain, stroke, paralysis, brain disorder, speech and language abnormalities, memory problems
• Clouding of the eye lens, impaired hearing
• Irregular heartbeat, stop of heartbeat, reduced performance of your heart, disorder of the heart muscle, enlargement
• of the heart muscle, stronger heartbeat, abnormal ECG, heart rate and pulse abnormal
• Blood clot in a vein of a limb, shock
• Difficulties in breathing, respiratory tract disorders, asthma
• Obstruction of the gut, increased blood level of the enzyme amylase, reflux of stomach content in your throat, delayed
• emptying of the stomach
• Inflammation of the skin, burning sensation in the sunlight
• Joint disorders
• Painful menstruation and abnormal menstrual bleeding
• Failure of some organs, flu-like illness, increased sensitivity to heat and cold, feeling of pressure on your chest, jittery or abnormal feeling, weight loss

Rare side effects:

• Small bleedings in your skin due to blood clots
• Increased muscle stiffness
• Blindness, deafness
• Collection of fluid around the heart
• Acute breathlessness
• Cyst formation in your pancreas
• Problems with blood flow in the liver
• Serious illness with blistering of skin, mouth, eyes and genitals; increased hairiness
• Thirst, fall, feeling of tightness in your chest, decreased mobility, ulcer

Very rare side effects:

• Muscular weakness
• Abnormal heart scan
• Liver failure
• Painful urination with blood in the urine Increase of fat tissue

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. HOW TO STORE MODIGRAF

Keep out of the reach and sight of children.

Do not use Modigraf after the expiry date which is stated on the carton and sachet after EXP The expiry date refers to the last day of that month.

This medicinal product does not require any special temperature storage conditions.

After preparation, the suspension should be taken immediately.

Medicines should not be disposed of via wastewater or household waste. Askyour pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What Modigraf contains

The active substance is tacrolimus.

Each sachet of Modigraf 0.2 mg granules contains 0.2 mg of tacrolimus (as monohydrate).

Each sachet of Modigraf 1 mg granules contains 1 mg of tacrolimus (as monohydrate).

The other ingredients are: lactose monohydrate, hypromellose (E464) and croscarmellose sodium (E468).

What Modigraf looks like and contents of the pack

Modigraf granules for oral suspension are white granules supplied in sachets. Packs containing 50 sachets are available.

 

Leustat injection

Cladribine

1. What Leustat is and what it is used for

Leustat contains a medicine called cladribine. This belongs to a group of medicines used to treat cancer (called ‘cytotoxic drugs’).

Leustat is for:

• An illness caused by the abnormal growth of white blood cells. This is called ‘hairy cell leukaemia’

• An illness caused by the abnormal growth of a type of white blood cell called ‘lymphocytes’. This illness is called ‘B-cell chronic lymphocytic leukaemia’. In this case, Leustat is used when the first treatment (called an ‘alkylating agent’) has not worked or has stopped working

Leustat works by killing abnormal white blood cells.

2. Before you are given Leustat

Do not have Leustat if:

•  You are allergic to anything in Leustat.

Take special care

Talk to your doctor before you are given Leustat if:

• You are suffering from any infection or fever

• You have ever had kidney or liver problems

• You have ever had bone marrow or blood problems

You may still be able to have Leustat, but you should discuss this with your doctor first.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines that you buy without a prescription or herbal medicines. In particular tell your doctor if you are already taking or are to be given:

• A live vaccine while being treated with Leustat

• Medicines to treat viral infections including HIV (such as didanosine, tenofovir, adefovir)

Blood tests

• Your doctor will arrange regular blood tests before and during your treatment. The blood tests check that your liver and kidneys are working properly. They also check how the Leustat treatment is working

• If you visit another hospital or your family doctor for a blood test, tell them that you have been given Leustat. This is because Leustat may affect the result of blood tests

Pregnancy and breast-feeding

Do not use this medicine if you are pregnant, think you may be pregnant or might become pregnant. This is because it may affect the baby.

You must not breast-feed while you are being treated with Leustat, or for 6 months after your treatment ends.

Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breast-feeding.

Family planning

Men should not father a child until at least 6 months after the last dose of Leustat.

Driving or using machines

Your illness and its treatment may affect you being able to drive. Do not drive or use any tools or machines without discussing this with your doctor first.

Important information about an ingredient of Leustat

If you need to control your salt intake (controlled sodium diet) be aware that:

• Each Leustat vial contains 1.55 mmol sodium (35.4 mg)

• The contents of the vial are diluted in a salt solution (called ‘saline’) before

being given to you. This salt solution also contains sodium

3. How Leustat is used

Leustat is put in a drip and given slowly into a vein. It is normally diluted in a salt solution (called ‘saline’). A doctor experienced at using this type of medicine will give it to you. Check with your doctor or nurse if you are not sure about anything.

Adults and the elderly

The dose of Leustat is based on your body weight in kilograms.

For abnormal growth of hairy white blood cells:

•The usual dose is 0.09 mg per kilogram each day

• The dose is given over 24 hours every day for 7 days, without a break

For abnormal growth of lymphocyte white blood cells:

• The usual dose is 0.12 mg per kilogram each day

• The dose is given every day for 5 days

• Each dose is normally given over 2 hours

• The 5 day course is repeated every 28 days

• You can receive a maximum of 6 of these courses

Children

Leustat has not been fully tested for use in children.

If you have too much Leustat

Tell your doctor or nurse straight away if you think you have been given too much Leustat.

4. Possible side effects

Like all medicines, Leustat can cause side effects, although not everybody gets them. Some side effects may be the same as symptoms of the illness. Your doctor may decide to delay or stop using Leustat if you get side effects.

Tell your doctor or nurse straight away if you notice any of the following serious side effects. You may need urgent medical treatment.

• The sudden appearance of rash, itching, hives (also known as nettle rash or urticaria), swollen face or lips, or shortness of breath. These may be signs of an allergic reaction.

• Fever and chills (affects more than 1 in 10 people). These may be the first signs that you have an infection. The infection may happen because of a fall in the number of white blood cells (neutropenia). Some infections are more common than others. Infection can happen anywhere in your body including:

• Your chest (cough, shortness of breath or difficulty breathing, noisy breathing, pneumonia)

• Your urinary system (pain or discomfort on passing water)

• Your skin (bacterial, fungal or viral infections that may leave the skin tender, hot or red)

• Your mouth (a fungal infection called thrush)

• Your gut (infection or inflammation of the intestines)

• Your blood (septicaemia)

• Easier bruising and bleeding under the skin (thrombocytopenia) or red or purple spots under the skin (petechiae). This can be caused by a fall in the number of small blood cells called platelets (affects more than 1 in 10 people) or problems with blood clotting.

• Feeling weak or breathless. This can be caused by a fall in the number of red blood cells (anaemia). The anaemia may be severe (affects more than 1 in 10 people)

• Build-up of fluid under the skin called oedema (affects more than 1 in 10 people)

• Swelling and clotting in a vein called phlebitis (affects less than 1 in 10 people)

• Stevens-Johnson syndrome (a serious illness with blistering of the skin, mouth, eyes and genitals) (affects less than 1 in 100 people)

• Tumour lysis syndrome (a serious condition resulting from breakdown of tumour cells. This can lead to heart and kidney problems, weakness and fits) (affects less than 1 in 100 people)

Tell your doctor or nurse at your next appointment if you notice any of the following side effects:

Very common (affects more than 1 in 10 people)

• Feeling dizzy or tired

• Headache

• Rash, sweating

• Feeling sick (nausea), being sick (vomiting)

• Redness, swelling or pain where the injection was given

Common (affects less than 1 in 10 people)

• Faster heart beat

• Stomach pain or wind (flatulence)

• Having less appetite

• Constipation or diarrhoea

• Joint pain, muscle pains or weakness

• Generalised pain

• Anxiety or difficulty sleeping (insomnia)

• Itching (pruritus)

• Conjunctivitis

• Generally feeing unwell

Uncommon (affects less than 1 in 100 people)

• A problem that affects the body being able to produce white blood cells, red blood cells and small blood cells (platelets). The effects may need further treatment

• An increase in a particular type of white blood cell (eosinophil)

• A decrease in the ability of your kidneys being able to get rid of waste products from the blood, and a decrease in urine production

• Serious nerve damage. The effects include partial or complete paralysis and may be permanent

• An increase in liver enzymes (shown in blood tests)

• Confusion, reduced consciousness, co-ordination problems (ataxia)

If any of the side effects gets serious, or if you notice any other side effects not listed in this leaflet, please tell your doctor or nurse.

5. How Leustat is stored

The vials are stored unopened in a hospital refrigerator where children can’t see or reach them. Vials should be protected from light.

Do not use Leustat after the expiry date stated on the label. The expiry date refers to the last day of that month.

Do not use Leustat if:

• The seal is broken or a dose has already been taken from the vial

• The liquid is coloured or you can see particles floating in it

• It has been diluted and refrigerated for more than 8 hours

• It has been diluted with a solution of 5% dextrose

6. Further information

The active substance in Leustat is cladribine (1 mg/ml).

The other ingredients are sodium chloride, phosphoric acid, dibasic sodium phosphate heptahydrate and water for injection.

What Leustat looks like and contents of the pack

Leustat is supplied in a clear glass vial containing 10 ml of a clear, colourless liquid.

 

IntronA 18 million IU, 30 million IU and 60 million IU solution for injection in multidose pen

1. WHAT INTRONA IS AND WHAT IT IS USED FOR

IntronA (interferon alfa-2b) modifies the response of the body’s immune system to help fight infections and severe diseases.

IntronA is used in adult patients to treat certain disorders that affect the blood, bone marrow, lymph glands, or skin and may extend into the body. Included are hairy cell leukaemia, chronic myelogenous leukaemia, multiple myeloma, follicular lymphoma, carcinoid tumour, and malignant melanoma.

IntronA is also used in adult patients for the treatment of chronic hepatitis B or C, which are viral infections of the liver.

IntronA is used in combination with ribavirin in children 3 years of age and older and adolescents who have previously untreated chronic hepatitis C.

2.  BEFORE YOU USE INTRONA

Do not use IntronA

- if you are allergic (hypersensitive) to interferon or any of the other ingredients of IntronA.

- if you have severe heart disease.

- if you have poor kidney or liver function.

- if you have advanced decompensated (uncontrolled) liver disease.

- if you have hepatitis and have been treated recently with medicines that suppress the immune system (other than short-term treatment with cortisone-type medicine).

- if you have a history of seizures (convulsions).

- if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that suppresses your immune system (your immune system helps protect you from infection).

- if you have thyroid disease that is not well controlled.

Children and adolescents:

- if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide.

Take special care with IntronA

- if you are pregnant or planning to become pregnant (see section “Pregnancy and breastfeeding”).

- if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and adolescents with existence of or history of severe psychiatric conditions is contraindicated.

- if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, dejection, etc.) while on treatment with IntronA.

- if you have psoriasis, it may get worse during treatment with IntronA.

- when receiving IntronA, you may temporarily have a greater risk of getting an infection. Check with your doctor if you think you are getting an infection.

- if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any difficulty in breathing, tell your doctor.

- if you notice unusual bleeding or bruising check with your doctor immediately.

- if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) while on this medicine seek medical help immediately.

- if you are also being treated for HIV (see section “Using other medicines”).

- if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk of rejection. Be sure to discuss this with your doctor.

Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving IntronA and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and membranes of the mouth during long-term treatment with the combination of IntronA with ribavirin. You should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly afterwards.

Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems,

diabetes, or high or low blood pressure.

Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; unconsciousness; thoughts of suicide or attempted suicide.

Be sure to tell your doctor if you are taking the Chinese herbal medicine Shosaikoto.

Using other medicines

IntronA will add to the effects of substances that slow down your nervous system, possibly causing drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking sleeping pills, sedatives or strong pain medicines.

Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medicines you are taking, or have taken recently, even those not prescribed, as the dose of some medicines may have to be adjusted while you are treated with IntronA. Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the addition of IntronA and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient Leaflet also). Additionally, patients treated with IntronA and ribavirin combination therapy and zidovudine could be at increased risk of developing anaemia (low number of red blood cells).

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

• Using IntronA with food and drink

While being treated with IntronA, your doctor may want you to drink extra fluids to help prevent low blood pressure.

• Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, interferons have sometimes caused miscarriage. The effect on human pregnancy is not known. If you are prescribed IntronA in combination with ribavirin, ribavirin can be very damaging to an unborn baby, thus both female and male patients must take special precautions in their sexual activity if there is any chance for pregnancy to occur:

—   if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, each month during treatment, and for the 4 months after treatment is

stopped. You and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping treatment. This can be discussed with your doctor.

—   if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 7 months after stopping treatment. This can be discussed with your doctor.

It is not known whether this medicine is present in human milk. Therefore, do not breast-feed an infant if you are taking IntronA. In combination therapy with ribavirin, take notice of the respective informing texts of ribavirin containing medicinal products.

Driving and using machines

Do not drive or use machines if you become drowsy, tired, or confused from using this medicine.

Important information about some of the ingredients of IntronA

This medicinal product contains less than 1 mmol sodium (23 mg) per 1.2 ml, i.e., essentially “sodium-free”.

3. HOW TO USE INTRONA

Your doctor has prescribed IntronA specifically for you and your current condition; do not share this medicine with anyone else.

Your doctor has determined the exact dosage for administration of IntronA according to your individual needs. The dosage will vary according to the disease being treated.

The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks.

The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks.

The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks.

If you are injecting IntronA yourself, please be sure that the dose that has been prescribed for you is clearly provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best given every other day.

The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may change your dose based on your specific needs:

Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin).

Chronic hepatitis C: Adults – 3 million IU 3 times a week (every other day) injected subcutaneously (under the skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents – 3 million IU/m2 3 times a week (every other day) injected subcutaneously (under the skin) in combination with ribavirin (Please also see ribavirin package leaflet).

Hairy Cell Leukaemia: 2 million lU/rm, 3 times a week (every other day) injected subcutaneously (under the skin).

Chronic Myelogenous Leukaemia: 4-5 million IU/m2 daily injected subcutaneously (under the skin).

Multiple myeloma: 3 million IU/m2, 3 times a week (every other day) injected subcutaneously (under the skin).

Follicular lymphoma: Adjunctively with chemotherapy, 5 million IU 3 times a week (every other day) injected subcutaneously (under the skin).

Carcinoid tumour: 5 million IU, 3 times a week (every other day) injected subcutaneously (under the skin).

Malignant melanoma, induction therapy: 20 million IU/m2, intravenously, given daily for 5 days a week for a 4 week period.

Maintenance treatment: 10 million IU/m2, 3 times a week (every other day) injected subcutaneously (under the skin).

Your doctor may prescribe a different dose of IntronA alone or in combination with other medicines (e.g., cytarabine, ribavirin). If you are prescribed IntronA in combination with another medicine, please refer also to the Package Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and regimen according to your needs. If you have the impression that the effect of IntronA is too strong or too weak, talk to your doctor or pharmacist.

Subcutaneous use:

IntronA is usually intended for subcutaneous use. This means that IntronA is injected with a short needle into the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this leaflet (see section “HOW TO SELF INJECT INTRONA” at the end of the leaflet).

One dose of IntronA is given on each scheduled day. IntronA is given either daily (5 or 7 times a week), or three times a week, every other day, for example on Monday, Wednesday, and Friday. Interferons may cause unusual tiredness; if you are injecting this medicine yourself, or giving it to a child, use it at bedtime.

Use IntronA exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take IntronA for as long as prescribed.

If you use more IntronA than you should

Contact your doctor or healthcare professional as soon as possible.

• If you forget to take IntronA

If you are self-administering treatment, or if you are the caregiver of a child taking IntronA in combination with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do not take a double dose to make up for a forgotten dose. If you are scheduled to inject this medicine every day, and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact your doctor or pharmacist if needed.

4. POSSIBLE SIDE EFFECTS

Like all medicines, IntronA can cause side effects, although not everybody gets them. Although not all of these side effects may occur, they may need medical attention if they do.

Psychiatric and central nervous system:

Some people get depressed when taking IntronA alone or in combination treatment with ribavirin, and in some cases people had thoughts about threatening the life of others, suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have actually committed suicide. Be sure to seek emergency care if you notice that

you are becoming depressed or have suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend to help you stay alert to signs of depression or changes in your behaviour.

Children and adolescents are particularly prone to develop depression when being treated with IntronA and ribavirin. Immediately contact the doctor or seek emergency treatment if they display any unusual behavioural symptoms, feel depressed, or feel they want to harm themselves or others.

Growth and development (children and adolescents):

During the one year of treatment with IntronA in combination with ribavirin, some children and adolescents did not grow or gain weight as much as expected. Some children did not reach their projected height within 1-5 years after completing treatment.

If any of the following side effects happen, stop taking IntronA and tell your doctor immediately or go to

the casualty department at your nearest hospital:

-swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing; hives; fainting. These are all very serious side effects. If you have them, you may have had a serious allergic reaction to IntronA. You may need urgent medical attention or hospitalisation. These very serious side effects are very rare.

Check with your doctor immediately if any of the following side effects occur: – chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure (convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane.

These may signal serious side effects that may need urgent medical attention. Your doctor will test your blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. Moderate and usually reversible reduction in all three bloodelements-white blood cells, red blood cells and platelets, has been reported.

At the beginning of treatment with IntronA, you may experience a flu-like reaction, with fever, fatigue, headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if you develop these symptoms.

Possible side effects listed below are grouped by frequency of occurrence:

Very common (affects more than 1 user in 10)

Common (affects 1 to 10 users in 100)

Uncommon (affects 1 to 10 users in 1,000)

Rare (affects 1 to 10 users in 10,000)

Very rare (affects less than 1 user in 10,000)

Not known (frequency cannot be estimated from the available data)

The following side effects have been reported:

Very commonly reported side effects:

pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing (sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some children have had a decrease in their rate of growth (height and weight).

Commonly reported side effects:

thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, problem with skin or nails, psoriasis (new or worsened), increased sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.

Uncommonly reported side effects:

bacterial infection and feeling of pins and needles.

Rarely reported side effects: pneumonia.

Very rarely reported side effects:

low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage, bleeding gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or reduced the production of red blood cells, has been reported. This causes severe anaemia, symptoms of which would include unusual tiredness and a lack of energy.

Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and swelling, skin lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check with your doctor immediately if you have any of these symptoms.

Not known side effects:

Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.

Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord), thoughts about threatening the life of others, mania (excessive or unreasonable enthusiasm), bipolar disorders (mood disorders characterized by alternating episodes of sadness and excitement) , congestive heart failure and pericardial effusion (a fluid collection that develops between the pericardium (the lining of the heart) and the heart itself) have been reported with IntronA use.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. HOW TO STORE INTRONA

Keep out of the reach and sight of children.

Do not use IntronA after the expiry date which is stated on the package.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Each pen is intended for a maximum four-week use period and must then be discarded. A maximum of 48 hours (two days) of exposure to 25°C is permitted over the four-week period to cover accidental delays in returning the pen to the refrigerator.

Do not use IntronA if you notice changes in the appearance of IntronA.

Depending upon your dose, you may have extra needles and swabs left in the pack. Please discard these appropriately and safely.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What IntronA contains

- The active substance is recombinant interferon alfa-2b. Each pen contains 18 million IU, 30 million IU or 60 million IU.

- The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections.

What IntronA looks like and contents of the pack

IntronA is presented as a solution for injection in a multidose pen. The clear and colourless solution is contained in a glass cartridge.

IntronA is available in three different pack sizes:

- Pack of 1 pen, 12 injection needles and 12 cleansing swabs

- Pack of 2 pens, 24 injection needles and 24 cleansing swabs

- Pack of 8 pens, 96 injection needles and 96 cleansing swabs Not all pack sizes may be marketed.

HOW TO SELF INJECT INTRONA

The following instructions explain how to inject IntronA yourself. Please read the instructions carefully and follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject IntronA. Do not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-injection.

Preparation

Collect necessary items before you begin:

-the IntronA multidose pen;

- a needle for subcutaneous injection (provided in the packaging);

- a cleansing swab (provided in the packaging).

Wash your hands carefully. Use the injection needles provided in the packaging only for IntronA. Use a new injection needle for each dose. Be sure the solution is at room temperature (up to 25°C) at the time of injection.

Diagrams A and B show you all the different parts of the pen and the injection needle. The most important parts to note are as follows:

- The push button scale tells you what dose has been set.

-The colour coding strip (brown, blue or pink) and the push button are at the bottom of the pen as it is held cap up.

- The pen can only be fully capped when the triangle on the cap scale is aligned with the dosage indicator on the barrel.

Measuring the dose of IntronA

Take the pen out of the refrigerator about one-half hour before administering the dose so that the solution in the pen is at room temperature when it is injected.

When you are ready to give your injection prepare your pen as follows:

Check that IntronA solution for injection is clear and colourless in appearance prior to use. If it does not have a clear uniform appearance or if it contains any particles, do not use.

Pull off the cap of the pen and disinfect the rubber membrane  with one cleansing swab.

needle is revealed once the protective tab is removed.

Gently push the injection needle onto the pen. (Notice that the rear portion of the injection needle will pierce through the rubber membrane that you disinfected previously). Now screw the injection needle onto the pen securely by turning it in a clockwise direction.

First, pull off the outer injection needle cap. Then, pull off the inner injection needle cap carefully, bearing in mind that the injection needle will now be exposed. Keep the outer injection needle cap for later use.

The pen is now ready to use. Since a small amount of air may collect in the injection needle and reservoir during storage, the next step is to remove any air bubbles. This is called performing the Air-Shot.

Hold the pen with the injection needle point upwards.

Tap the reservoir with your finger so that any air bubbles rise to the top of the reservoir, just below the injection needle.

Hold the pen by the barrel and turn the reservoir in the direction as indicated by the arrow (clockwise) until you feel it click.

Keeping the pen pointing upwards, press the push button up fully and see if a drop of solution appears at the injection needle tip.

If no drop appears, use a different pen, and return the faulty pen to your provider.

Note: some air may remain in the pen, but this is not important as you have removed the air from the injection needle and the dose will be accurate.

Replace the pen cap with the ‘triangle’ opposite the dosage indicator as seen in Diagram L.

The pen is now ready to set the dose. For the next step hold the pen in the middle of the barrel. This will allow the push button to move freely, ensuring that the correct dose is set. To set the required dose, hold the pen horizontally by the barrel with one hand. With the other hand, turn the cap in a clockwise direction indicated by the arrow in Diagram M. You will observe the push button rising, indicating the dose set. To set the correct dose, turn the cap as many times as indicated as follows:

Number of “turns” and “clicks”	Corresponding doses (million IU) using IntronA, solution for injection, multidose pen 18 million IU/pen
1 full turn (5 clicks)	1.5
6 clicks	1.8
7 clicks	2.1
8 clicks	2.4
9 clicks	2.7
2 full turns (10 clicks)	3
11 clicks	3.3
12 clicks	3.6
13 clicks	3.9
14 clicks	4.2
3 full turns (15 clicks)	4.5
16 clicks	4.8
17 clicks	5.1
18 clicks	5.4
19 clicks	5.7
4 full turns (20 clicks)*	6

*4 full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 18 million IU in doses ranging from 1.5 to 6 million IU. The pen will deliver a maximum of 12 doses of 1.5 million IU over a period not to exceed 4 weeks.

Number of “turns” and “clicks”	Corresponding doses (million IU) using IntronA, solution for injection, multidose pen 30 million IU/pen:
1 full turn (5 clicks)	2.5
6 clicks	3
7 clicks	3.5
8 clicks	4
9 clicks	4.5
2 full turns (10 clicks)	5
11 clicks	5.5
12 clicks	6
13 clicks	6.5
14 clicks	7
3 full turns (15 clicks)	7.5
16 clicks	8
17 clicks	8.5
18 clicks	9
19 clicks	9.5
4 full turns (20 clicks)*	10

* 4 full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 30 million IU in doses ranging from 2.5 to 10 million IU. The pen will deliver a maximum of 12 doses of 2.5 million IU over a period not to exceed 4 weeks.

Number of “turns” and “clicks”	Corresponding doses (million IU) using IntronA, solution for injection, multidose pen 60 million IU/pen:
1 full turn (5 clicks)	5
6 clicks	6
7 clicks	7
8 clicks	8
9 clicks	9
2 full turns (10 clicks)	10
11 clicks 12 clicks 13 clicks 14 clicks	11 12 13 1   A
3 full turns (15 clicks)	14
16 clicks	15
17 clicks	16
18 clicks	17
19 clicks	18
4 full turns	19
(20 clicks)*	20

*4 full turns correspond to the maximum dose to be administered in one injection. The pen is designed to deliver its contents of 60 million IU in doses ranging from 5 to 20 million IU. The pen will deliver a maximum of 12 doses of 5 million IU over a period not to exceed 4 weeks.

The push button scale will show you the dose set (see Diagram N below). For doses corresponding to full turns, the scale should line up with the correct dose marking. For doses corresponding to clicks intermediate between full turns, the scale should line up between the two appropriate full-turn dose markings. At that point check that you have the correct dose.

After each complete turn make sure that the triangle is opposite the dosage indicator (see Diagram O). If you have set a wrong dose, simply turn the cap back (anti-clockwise) as far as you can until the push button is fully home and start again. Once the correct dose is set you are ready to give the injection.

Injecting the solution

Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of the arm for injection. Change your injection site each time.

Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. With one hand, pinch a fold of loose skin. With your other hand, pick up the pen and hold it as you would a pencil. Insert the needle into the pinched skin at an angle of approximately 45°. Then press the push button down fully.

Keeping the push button down, leave the injection needle in place for a few seconds to allow the solution to distribute under the skin, then remove.

Carefully replace the outer injection needle cap.

Completely unscrew the injection needle assembly using an anti-clockwise turning motion as shown in Diagram R. Then carefully lift it off the pen and discard the capped injection needle.

Replace the pen cap with the triangle once again opposite the dosage indicator as shown in Diagram T. Then return the pen to the refrigerator.

 

 

IntronA 10 million IU/ml solution for injection or infusion

Interferon alfa-2b

1. WHAT INTRONA IS AND WHAT IT IS USED FOR

IntronA (interferon alfa-2b) modifies the response of the body’s immune system to help fight infections and severe diseases.

IntronA is used in adult patients to treat certain disorders that affect the blood, bone marrow, lymph glands, or skin and may extend into the body. Included are hairy cell leukaemia, chronic myelogenous leukaemia, multiple myeloma, follicular lymphoma, carcinoid tumour, and malignant melanoma.

IntronA is also used in adult patients for the treatment of chronic hepatitis B or C, which are viral infections of the liver.

IntronA is used in combination with ribavirin in children 3 years of age and older and adolescents who have previously untreated chronic hepatitis C.

2. BEFORE YOU USE INTRONA

Do not use IntronA

• if you are allergic (hypersensitive) to interferon or any of the other ingredients of IntronA.
• if you have severe heart disease.
• if you have poor kidney or liver function.
• if you have advanced decompensated (uncontrolled) liver disease.
• if you have hepatitis and have been treated recently with medicines that suppress the immune system (other than short-term treatment with cortisone-type medicine).
• if you have a history of seizures (convulsions).
• if you have a history of autoimmune disease, or have had an organ transplant and are taking medicine that suppresses your immune system (your immune system helps protect you from infection).
• if you have thyroid disease that is not well controlled. Children and adolescents:
• if you have had serious nervous or mental problems, such as severe depression or thoughts of suicide.

Take special care with IntronA

• if you are pregnant or planning to become pregnant.
• if you have had a severe nervous or mental disorder. The use of interferon alfa-2b in children and adolescents with existence of or history of severe psychiatric conditions is contraindicated.
• if you have ever had depression or develop symptoms associated with depression (e.g. feelings of sadness, dejection, etc.) while on treatment with IntronA.
• if you have psoriasis, it may get worse during treatment with IntronA. When receiving IntronA, you may temporarily have a greater risk of getting an infection. Check with your doctor if you think you are getting an infection.
• if you develop symptoms associated with a cold or other respiratory infection, such as fever, cough, or any difficulty in breathing, tell your doctor.
• if you notice unusual bleeding or bruising check with your doctor immediately, if you develop symptoms of a severe allergic reaction (such as difficulty in breathing, wheezing, or hives) while on this medicine seek medical help immediately, if you are also being treated for HIV, if you have received an organ transplant, either kidney or liver, interferon treatment may increase the risk of rejection. Be sure to discuss this with your doctor.

Dental and gum disorders, which may lead to loss of teeth, have been reported in patients receiving IntronA and ribavirin combination therapy. In addition, dry mouth could have a damaging effect on teeth and membranes of the mouth during long-term treatment with the combination of IntronA with ribavirin. You should brush your teeth thoroughly twice daily and have regular dental examinations. In addition some patients may experience vomiting. If you have this reaction, be sure to rinse your mouth thoroughly afterwards.

Tell your doctor if you have ever had a heart attack or a heart problem; if you have a history of breathing irregularities or pneumonia, problems with blood clotting, liver condition, thyroid problems, diabetes, or high or low blood pressure.

Tell your doctor if you have ever been treated for depression or any other psychiatric disorder; confusion; unconsciousness; thoughts of suicide or attempted suicide.

Be sure to tell your doctor if you are taking the Chinese herbal medicine Shosaikoto.

• Using other medicines

IntronA will add to the effects of substances that slow down your nervous system, possibly causing drowsiness. Therefore, check with your doctor or pharmacist about drinking alcoholic beverages, or taking sleeping pills, sedatives or strong pain medicines.

Tell your doctor if you are taking theophylline or aminophylline for asthma, and about all other medicines you are taking, or have taken recently, even those not prescribed, as the dose of some medicines may have to be adjusted while you are treated with IntronA.

Patients who also have HIV infection: Lactic acidosis and worsening liver function are side effects associated with Highly Active Anti-Retroviral Therapy (HAART), an HIV treatment. If you are receiving HAART, the addition of IntronA and ribavirin may increase your risk of lactic acidosis and of liver failure. Your doctor will monitor you for signs and symptoms of these conditions (Please be sure to read the ribavirin Patient Leaflet also). Additionally, patients treated with IntronA and ribavirin combination therapy and zidovudine could be at increased risk of developing anaemia (low number of red blood cells).

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

• Using IntronA with food and drink

While being treated with IntronA, your doctor may want you to drink extra fluids to help prevent low blood pressure.

• Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine. In studies in pregnant animals, interferons have sometimes caused miscarriage. The effect on human pregnancy is not known.

If you are prescribed IntronA in combination with ribavirin, ribavirin can be very damaging to an unborn baby, thus both female and male patients must take special precautions in their sexual activity if there is any chance for pregnancy to occur:

- if you are a girl or a woman of childbearing age, you must have a negative pregnancy test before treatment, each month during treatment, and for the 4 months after treatment is stopped. You and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 4 months after stopping treatment. This can be discussed with your doctor.

- if you are a man who is taking ribavirin, do not have sex with a pregnant woman unless you use a condom. This will lessen the chance for ribavirin to be left in the woman’s body. If your female partner is not pregnant now but is of childbearing age, she must be tested for pregnancy each month during treatment and for the 7 months after treatment has stopped. This can be discussed with your doctor. If you are a male patient, you and your partner must each use an effective contraceptive during the time you are taking ribavirin and for 7 months after stopping treatment. This can be discussed with your doctor.

It is not known whether this medicine is present in human milk. Therefore, do not breast-feed an infant if you are taking IntronA. In combination therapy with ribavirin, take notice of the respective informing texts of ribavirin containing medicinal products.

• Driving and using machines

Do not drive or use machines if you become drowsy, tired, or confused from using this medicine.

Important information about some of the ingredients of IntronA

This medicinal product contains less than 1 mmol sodium (23 mg) per 1 ml, i.e., essentially “sodium-free”.

3. HOW TO USE INTRONA

Your doctor has prescribed IntronA specifically for you and your current condition; do not share this medicine with anyone else.

Your doctor has determined the exact dosage for administration of IntronA according to your individual needs. The dosage will vary according to the disease being treated.

If you are injecting IntronA yourself, please be sure that the dose that has been prescribed for you is clearly provided with the package of medicine you receive. Dosages that are to be administered 3 times a week are best given every other day.

The usual starting dose for each condition follows; however, individual doses may vary, and the doctor may change your dose based on your specific needs:

Chronic hepatitis B: 5 to 10 million IU 3 times a week (every other day) injected subcutaneously (under the skin).

Chronic hepatitis C: Adults – 3 million IU 3 times a week (every other day) injected subcutaneously (under the skin) in combination with ribavirin or alone. Children 3 years of age and older and adolescents – 3 million IU/m² 3 times a week (every other day) injected subcutaneously (under the skin) in combination with ribavirin (Please also see ribavirin package leaflet).

Hairy Cell Leukaemia: 2 million IU/m², 3 times a week (every other day) injected subcutaneously (under the skin).

Chronic Myelogenous Leukaemia: 4-5 million IU/m² daily injected subcutaneously (under the skin).

Multiple myeloma: 3 million IU/m², 3 times a week (every other day) injected subcutaneously (under the skin).

Follicular lymphoma: Adjunctively with chemotherapy, 5 million IU 3 times a week (every other day) injected subcutaneously (under the skin).

Carcinoid tumour: 5 million IU, 3 times a week (every other day) injected subcutaneously (under the skin).

Malignant melanoma, induction therapy: 20 million IU/m², intravenously, given daily for 5 days a week for a 4 week period. Maintenance treatment: 10 million IU/m², 3 times a week (every other day) injected subcutaneously (under the skin).

Your doctor may prescribe a different dose of IntronA alone or in combination with other medicines (e.g., cytarabine, ribavirin). If you are prescribed IntronA in combination with another medicine, please refer also to the Package Leaflet of the medicine to be used in combination. Your doctor will determine the exact dosage schedule and regimen according to your needs. If you have the impression that the effect of IntronA is too strong or too weak, talk to your doctor or pharmacist.

• Subcutaneous use:

IntronA is usually intended for subcutaneous use. This means that IntronA is injected with a short needle into the fatty tissue just under the skin. If you are injecting this medicine yourself, you will be instructed how to prepare and give the injection. Detailed instructions for subcutaneous administration are provided with this post.

• Intravenous infusion:

The infusion must be prepared immediately prior to use. Any size vial may be used to measure the required dose; however, final concentration of interferon in sodium chloride solution must be not less than 0.3 million IU/ml. The appropriate dose of IntronA is withdrawn from the vial(s), added to 50 ml of 9 mg/ml (0.9 %) sodium chloride solution for injection in a PVC bag or glass bottle for intravenous use and administered over 20 minutes.

No other medicinal product can be infused concomitantly with IntronA.

One dose of IntronA is given on each scheduled day. IntronA is given either daily (5 or 7 times a week), or three times a week, every other day, for example on Monday, Wednesday, and Friday.

Interferons may cause unusual tiredness; if you are injecting this medicine yourself, or giving it to a child, use it at bedtime.

Use IntronA exactly as prescribed by your doctor. Do not exceed the recommended dosage, and take IntronA for as long as prescribed.

• If you use more IntronA than you should

Contact your doctor or healthcare professional as soon as possible.

• If you forget to take IntronA

If you are self-administering treatment, or if you are the caregiver of a child taking IntronA in combination with ribavirin, inject the recommended dose as soon as you remember and continue treatment as usual. Do not take a double dose to make up for a forgotten dose. If you are scheduled to inject this medicine every day, and you accidentally missed a full day’s dose, continue treatment at the usual dose the following day. Contact your doctor or pharmacist if needed.

4. POSSIBLE SIDE EFFECTS

Like all medicines, IntronA can cause side effects, although not everybody gets them. Although not all of these side effects may occur, they may need medical attention if they do.

Psychiatric and central nervous system:

Some people get depressed when taking IntronA alone or in combination treatment with ribavirin, and in some cases people had thoughts about threatening the life of others, suicidal thoughts or aggressive behaviour (sometimes directed against others). Some patients have actually committed suicide. Be sure to seek emergency care if you notice that you are becoming depressed or have suicidal thoughts or change in your behaviour. You may want to consider asking a family member or close friend to help you stay alert to signs of depression or changes in your behaviour.

Children and adolescents are particularly prone to develop depression when being treated with IntronA and ribavirin. Immediately contact the doctor or seek emergency treatment if they display any unusual behavioural symptoms, feel depressed, or feel they want to harm themselves or others.

Growth and development (children and adolescents):

During the one year of treatment with IntronA in combination with ribavirin, some children and adolescents did not grow or gain weight as much as expected. Some children did not reach their projected height within 1-5 years after completing treatment.

If any of the following side effects happen, stop taking IntronA and tell your doctor immediately or go to the casualty department at your nearest hospital:

swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing; hives; fainting. These are all very serious side effects. If you have them, you may have had a serious allergic reaction to IntronA. You may need urgent medical attention or hospitalisation. These very serious side effects are very rare.

Check with your doctor immediately if any of the following side effects occur:

chest pain or persistent and severe cough; irregular or rapid heartbeat; shortness of breath, confusion, difficulty remaining alert, numbness or tingling sensation or pain in hands or feet; seizure (convulsions); trouble sleeping, thinking or concentrating; altered mental state; suicidal thoughts, suicide attempt, changed behaviour or aggressive behaviour (sometimes directed against others), hallucinations; severe stomach pain; black or tar like stools; blood in stool or urine, severe nosebleed; waxy pallor, high sugar level in blood, fever or chills beginning after a few weeks of treatment, lower back or side pain, difficult urination, problems with your eyes or your eyesight or hearing, loss of hearing, severe or painful reddening or sores on your skin or mucous membrane. These may signal serious side effects that may need urgent medical attention. Your doctor will test your blood to ensure that your white blood cell (cells that fight infection) and red blood cell (cells that carry iron and oxygen) counts, platelets (blood clotting cells) and other laboratory values are at acceptable levels. Moderate and usually reversible reduction in all three blood elements-white blood cells, red blood cells and platelets, has been reported.

At the beginning of treatment with IntronA, you may experience a flu-like reaction, with fever, fatigue, headache, muscle ache, joint pain and chills/rigors. Your doctor may recommend that you take paracetamol if you develop these symptoms.

Possible side effects listed below are grouped by frequency of occurrence:

Very common      (affects more than 1 user in 10)

Common   (affects 1 to 10 users in 100)

Uncommon   (affects 1 to 10 users in 1,000)

Rare      (affects 1 to 10 users in 10,000)

Very rare      (affects less than 1 user in 10,000)

Not known    (frequency cannot be estimated from the available data)

The following side effects have been reported:

Very commonly reported side effects:

pain, swelling and redness or skin damage at site of injection, hair loss, dizziness, changes in appetite, stomach or abdominal pains, diarrhoea, nausea (feeling sick), viral infection, depression, emotional lability, insomnia, anxiety, sore throat and painful swallowing, fatigue, chills/rigors, fever, flu-like reaction, feeling of general discomfort, headaches, weight loss, vomiting, irritability, weakness, mood swings, coughing (sometimes severe), shortness of breath, itching, dry skin, rash, sudden and severe muscle pain, joint pain, musculoskeletal pain, changes in laboratory blood values including decreased white blood cell count. Some children have had a decrease in their rate of growth (height and weight).

Commonly reported side effects:

thirst, dehydration, high blood pressure, migraines, swollen glands, flushing, menstrual problems, decreased sexual drive, vaginal problem, breast pain, pain in testicle, problems with thyroid gland, red gums, dry mouth, red or sore mouth or tongue, tooth ache or tooth disorder, herpes simplex (fever blisters), taste change, upset stomach, dyspepsia (heartburn), constipation, enlargement of liver (liver problems, sometimes severe), loose stools, bedwetting in children, inflammation of the sinuses, bronchitis, eye pain, problem with your tear ducts, conjunctivitis (“pink eye”), agitation, sleepiness, sleepwalking, problem with behaviour, nervousness, stuffy or runny nose, sneezing, rapid breathing, pale or reddened skin, bruising, problem with skin or nails, psoriasis (new or worsened), increased sweating, increased need to pass urine, fine shaking movements, decreased sensitivity to touch, arthritis.

Uncommonly reported side effects:

bacterial infection and feeling of pins and needles.

Rarely reported side effects: pneumonia.

Very rarely reported side effects:

• low blood pressure, puffy face, diabetes, leg cramps, back pain, kidney problems, nerve damage,
• bleeding gums, aplastic anaemia. Pure red cell aplasia, a condition where the body stopped or
• reduced the production of red blood cells, has been reported. This causes severe anaemia,
• symptoms of which would include unusual tiredness and a lack of energy.

Very rarely sarcoidosis, (a disease characterised by persistent fever, weight loss, joint pain and

swelling, skin lesions and swollen glands) has been reported. Loss of consciousness has occurred very rarely, mostly in elderly patients treated at high doses. Cases of stroke (cerebrovascular events) have been reported. Check with your doctor immediately if you have any of these symptoms.

Not known side effects:

Periodontal (affecting gums) and dental disorders, altered mental status, loss of consciousness, acute hypersensitivity reactions including urticaria (hives), angioedema (swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing), bronchoconstriction and anaphylaxis (a severe, whole-body allergic reaction) have been reported, but their frequency is unknown.

Additionally, Vogt-Koyanagi-Harada syndrome (an autoimmune inflammatory disorder affecting the eyes, skin and the membranes of the ears, brain and spinal cord), thoughts about threatening the life of others, mania (excessive or unreasonable enthusiasm), bipolar disorders (mood disorders characterized by alternating episodes of sadness and excitement), congestive heart failure and pericardial effusion (a fluid collection that develops between the pericardium (the lining of the heart) and the heart itself) have been reported with IntronA use.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. HOW TO STORE INTRONA

Keep out of the reach and sight of children.

Do not use IntronA after the expiry date which is stated on the package.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

For short term travelling, the solution can be kept out of the refrigerator at or below 25 °C for a period up to seven days before use. IntronA can be put back in the refrigerator at any time during this seven-day period. If the medicine is not used during the seven-day period, it should be discarded.

Do not use IntronA if you notice changes in the appearance of IntronA.

Any unused medicine must be discarded after withdrawal of the dose.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

• What IntronA contains

The active substance is recombinant interferon alfa-2b. Each vial contains 10 million IU in 1 ml of solution.

The other ingredients are disodium phosphate anhydrous, sodium dihydrogen phosphate monohydrate, edetate disodium, sodium chloride, m-cresol, polysorbate 80 and water for injections.

• What IntronA looks like and contents of the pack

IntronA is presented as a solution for injection or infusion.

HOW TO SELF INJECT INTRONA

The following instructions explain how to inject IntronA yourself. Please read the instructions carefully and follow them step by step. Your doctor or his/her assistant will instruct you how to self-inject IntronA. Do not attempt to inject yourself unless you are sure you understand the procedure and requirement of self-injection.

Preparation

Collect necessary items before you begin:

a vial of IntronA solution for injection;

a 2 ml syringe;

a needle for the subcutaneous injection (for example 0.4 x 13 mm [27 gauge 0.5 inch]);

a cleansing swab (provided in the packaging). Wash your hands carefully.

Measuring the dose of IntronA

Remove the cap from the vial. Clean the rubber stopper on the top of the vial containing the

IntronA solution with a cleansing swab.

Remove the syringe from the wrapping. Do not touch the tip of the syringe. Take the needle and place it firmly onto the tip of the syringe.

Remove the needle guard without touching the needle, and fill the syringe with air by pulling the plunger to the level that represents your dose as prescribed by your doctor.

Hold the IntronA vial upright without touching the cleaned top of the vial with your hands.

Insert the needle into the vial containing the IntronA solution and inject air into the vial.

Turn the vial and the syringe upside down in one hand. Be sure the tip of needle is in the IntronA solution. Your other hand will be free to move the plunger. Pull back on the plunger slowly to draw the correct dose as prescribed by your doctor into the syringe.

Remove the needle from the vial and check for air bubbles in the syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle pointing up, until the bubbles disappear. Push up the plunger slowly back to the correct dose. Replace the needle guard and place the syringe with the needle on a flat surface.

Be sure the solution is at room temperature up to 25 °C. If the solution is cold, warm the syringe between your palms. Examine the solution prior to administration: it should be clear and colourless. Do not use if discolouration or particulate matter is present. You are now ready to inject the dose.

Injecting the solution

Select the injection site. The best sites for injection are tissues with a layer of fat between skin and muscle: thigh, outer surface of the upper arm (you may need the assistance of another person to use this site), abdomen (except the navel or waistline). If you are exceptionally thin, use only the thigh or outer surface of the arm for injection.

Change your injection site each time.

Cleanse and disinfect the skin where the injection is to be made. Wait for the area to dry. Remove the needle guard. With one hand, pinch a fold of loose skin. With your other hand hold the syringe as you would a pencil. Insert the needle into the pinched skin at an angle of 45° to 90°. Inject the solution by pushing the plunger all the way down gently. Pull the needle straight out of the skin. Press the injection site with a small bandage or sterile gauze if necessary for several seconds. Do not massage the injection site. If there is bleeding, cover with an adhesive bandage.

The vial and injection materials intended for single use must be discarded. Dispose of the syringe and needle safely in a closed container.

 

Exjade 125 mg dispersible tablets

Exjade 250 mg dispersible tablets

Exjade 500 mg dispersible tablets

Deferasirox

1. What Exjade is and what it is used for

• What Exjade is

Exjade contains an active substance called deferasirox. It is an iron chelator which is a medicine used to remove the excess iron from the body (also called iron overload).

• What Exjade is used for

Exjade is used to treat iron overload caused by blood transfusions.

Repeated blood transfusions may be necessary in patients with various types of anaemia (for example thalassaemia, sickle cell disease or myelodysplastic syndromes). However, repeated blood transfusions can cause a build-up of excess iron. This is because blood contains iron and your body does not have a natural way to remove the excess iron you get with your blood transfusions. Over time, the excess iron can damage important organs such as the liver and heart. Medicines called iron chelators are used to remove the excess iron and reduce the risk of it causing organ damage.

Exjade is used to treat chronic iron overload caused by frequent blood transfusions in patients with beta thalassaemia major aged 6 years and older.

Exjade is also used when deferoxamine therapy is contraindicated or inadequate in patients with beta thalassaemia major with iron overload caused by infrequent blood transfusions, in patients with other types of anaemias, and in children aged 2 to 5 years.

• How Exjade works

Exjade traps and removes excess iron which is then excreted mainly in the stools.

• Monitoring your Exjade treatment

You will have regular blood and urine tests during treatment. These will monitor the amount of iron in your body (blood level offerritin) to see how well Exjade is working. The tests will also monitor your kidney function (blood level of creatinine, presence of protein in the urine) and liver function (blood level of transaminases). Your doctor will take these tests into consideration when deciding on the dose of Exjade most suitable for you.

You will get a booklet from your doctor which will help you to track your response to Exjade. Your doctor will write your blood tests in this booklet at each visit. Keep the booklet safe and bring it with you each time you visit your doctor.

Your eyesight and hearing will be tested each year during treatment as a precautionary measure.

If you have any questions about how Exjade works or why this medicine has been prescribed for you, ask your doctor.

2. Before you take Exjade

Follow all the doctor’s instructions carefully. They may differ from the general information in this leaflet.

Do not take Exjade

if you are allergic (hypersensitive) to deferasirox or any of the other ingredients of Exjade .

If this applies to you, tell your doctor before taking Exjade. If you think you may be allergic, ask your doctor for advice.

if you have kidney disease.

if you are currently taking another iron chelator medication.

Exjade is not recommended

if you are at an advanced stage of myelodysplastic syndrome (MDS) or have advanced cancer.

Take special care with Exjade

• if you have a liver problem.

• if you have a cardiac problem due to iron overload.

• if you notice a marked decrease in your urine output (sign of kidney problem).

• if you develop a severe rash, or difficulty breathing and dizziness or swelling mainly of the face and throat (signs of severe allergic reaction).

• if you develop a rash, reddening of the skin, blistering of lips, eyes or mouth, skin peeling, sore throat (signs of severe skin reaction).

• if you experience a combination of drowsiness, upper right abdominal pain, yellowing or increased yellowing of your skin or eyes and dark urine (signs of liver problems).

• if you vomit blood and/or have black stools.

• if you experience frequent abdominal pain, particularly after eating or taking Exjade.

• if you experience frequent heartburn.

• if you are taking or have recently taken certain painkillers, anti-inflammatory medicines or oral bisphosphonates.

• if you are taking or have recently taken anticoagulant medication.

• if you have a low level of platelets in your blood test.

If any of these apply to you, tell your doctor straight away.

Taking other medicines

Antacids (medicines used to treat heartburn) containing aluminium should not be taken at the same time of day as Exjade.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This includes in particular:

1. ciclosporin (used to prevent the body rejecting a transplanted organ or for other conditions, such as
2. rheumatoid arthritis or atopic dermatitis),
3. simvastatin (used to lower cholesterol),
4. certain painkillers or anti-inflammatory medicines (e.g. aspirin, ibuprofen, corticosteroids),
5. oral bisphosphonates (used to treat osteoporosis),
6. anticoagulant medicines (used to prevent or treat blood clotting),
7. hormonal contraceptive agents (birth control medicines),
8. bepridil, ergotamine,
9. repaglinide (used to treat diabetes),
10. rifampicin (used to treat tuberculosis),
11. phenytoin, phenobarbital, carbamazepine (used to treat epilepsy),
12. ritonavir (used in the treatment of HIV infection),
13. paclitaxel (used in cancer treatment),
14. theophylline (used to treat respiratory diseases such as asthma),
15. clozapine (used to treat psychiatric disorders such as schizophrenia),
16. tizanidine (used as a muscle relaxant).

Additional tests may be required to monitor the blood levels of some of these medicines.

Older people (age 65 years and over)

Exjade can be used by people aged 65 years and over at the same dose as for other adults. Elderly patients may experience more side effects than younger patients. They should be monitored closely by their doctor for side effects that may require a dose adjustment.

Children and adolescents (age 2 years to 17 years)

Exjade can be used in adolescents and children aged 2 years and over. As the patient grows the doctor will adjust the dose.

• Pregnancy and breast-feeding

Exjade is not recommended during pregnancy unless clearly necessary. If you are pregnant or think that you may be, tell your doctor who will discuss with you whether you can take Exjade during your pregnancy.

Breast-feeding is not recommended during treatment with Exjade. Tell your doctor if you are breastfeeding.

Ask your doctor or pharmacist for advice before taking any medicine.

• Driving and using machines

If you feel dizzy after taking Exjade, do not drive or operate any tools or machines until you are feeling normal again.

Important information about some of the ingredients of Exjade

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Exjade

Always take Exjade exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

How much Exjade to take

The dose of Exjade is related to body weight for all patients. Your doctor will calculate the dose you need and tell you how many tablets to take each day.

•   The usual daily dose at the start of the treatment is 20 mg per kilogram body weight. A higher or lower starting dose may be recommended by your doctor based on your individual treatment needs.

•   Depending on how you respond to treatment, your doctor may later adjust your treatment to a higher or lower dose.

•   The maximum recommended daily dose is 40 mg per kilogram body weight.

When to take Exjade

•   Take Exjade once a day, every day, at about the same time each day.

•   Take the tablets on an empty stomach.

•   Then wait at least 30 minutes before eating any food.

Taking Exjade at the same time each day will help you remember when to take your tablets.

How long to take Exjade

Continue taking Exjade every day for as long as your doctor tells you. This is a long-term treatment, possibly lasting for months or years. Your doctor will regularly monitor your condition to check that the treatment is having the desired effect (see also section 1: “Monitoring your Exjade treatment”).

If you have questions about how long to take Exjade, talk to your doctor.

• If you take more Exjade than you should

If you have taken too much Exjade, or if someone else accidentally takes your tablets, contact your doctor or hospital for advice straight away. Show them the pack of tablets. Medical treatment may be necessary.

• If you forget to take Exjade

If you miss a dose, take it as soon as you remember on that day. Take your next dose as scheduled. Do not take a double dose on the next day to make up for the forgotten tablet(s).

• If you stop taking Exjade

Do not stop taking Exjade unless your doctor tells you to. If you stop taking it, the excess iron will no longer be removed from your body.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Exjade can cause side effects, although not everybody gets them. Most of the side effects are mild to moderate and will generally disappear after a few days to a few weeks of treatment.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Some side effects could be serious and need immediate medical attention.

These side effects are uncommon or rare.

•   If you get a severe rash, or difficulty breathing and dizziness or swelling mainly of the face and throat (signs of severe allergic reaction),

•   If you notice a marked decrease in your urine output (sign of kidney problem),

•   If you experience a combination of drowsiness, upper right abdominal pain, yellowing or increased yellowing of your skin or eyes and dark urine (signs of liver problems),

•   If you vomit blood and/or have black stools,

•   If you experience frequent abdominal pain, particularly after eating or taking Exjade,

•   If you experience frequent heartburn,

•   If you experience partial loss of vision, tell your doctor straight away.

Some side effects could become serious.

These side effects are uncommon, that is they may affect less than 1 in every 100 patients.

•   If you get blurred or cloudy eyesight,

•   If you get reduced hearing, tell your doctor as soon as possible.

Some side effects are very common.

These side effects may affect more than 1 in every 10patients.

•   Disturbance in renal function tests.

Some side effects are common.

These side effects may affect between 1 and 10 in every 100patients.

•   Gastrointestinal disorders, such as nausea, vomiting, diarrhoea, pain in the abdomen, bloating, constipation, indigestion

•   Rash

•   Headache

If any of these affects you severely, tell your doctor.

Other side effects are uncommon.

These side effects may affect less than 1 in every 100 patients.

•   Dizziness

•   Fever

•   Sore throat

•   Swelling of arms or legs

•   Change in the colour of the skin

•   Anxiety

•   Sleep disorder

•   Tiredness

If any of these affects you severely, tell your doctor.

Frequency not known (cannot be estimated from the available data).

•   A decrease in the number of cells involved in blood clotting (thrombocytopenia), or in all kinds of blood cells (pancytopenia)

•   Hair loss

•   Rash, reddening of the skin, blistering of lips, eyes or mouth, skin peeling, sore throat (signs of severe skin reaction)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5.  How to store Exjade

•   Keep out of the reach and sight of children.

•   Do not use Exjade after the expiry date which is stated on the blister and the carton. The expiry date refers to the last day of that month.

•   Store in the original package in order to protect from moisture.

•   Do not use any pack that is damaged or shows signs of tampering.

6.  Further information

What Exjade contains

The active substance is deferasirox.

Each tablet of Exjade 125 mg contains 125 mg deferasirox.

Each tablet of Exjade 250 mg contains 250 mg deferasirox.

Each tablet of Exjade 500 mg contains 500 mg deferasirox.

The other ingredients are lactose monohydrate, crospovidone type A, povidone, sodium lauryl sulphate,

microcrystalline cellulose, colloidal anhydrous silica and magnesium stearate.

What Exjade looks like and contents of the pack

Exjade is supplied as dispersible tablets. The tablets are off-white, round and flat. Each tablet contains

125 mg, 250 mg or 500 mg deferasirox:

•   Exjade 125 mg tablets are stamped on each tablet with “J 125″.

•   Exjade 250 mg tabletsare stamped on each tablet with “J 250″.

•   Exjade 500 mg tablets are stamped on each tablet with “J 500″.

Each blister pack contains 28, 84 or 252 dispersible tablets. Not all pack sizes or strengths may be available in your country.