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.
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.
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, solutionfor injection, multidose pen
18 million IU/pen
|1 full turn (5 clicks)||1.5|
|2 full turns (10 clicks)||3|
|3 full turns (15 clicks)||4.5|
|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
|1 full turn (5 clicks)||2.5|
|2 full turns (10 clicks)||5|
|3 full turns (15 clicks)||7.5|
|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 (millionIU) using IntronA, solution for
injection, multidose pen 60
|1 full turn (5 clicks)||5|
|2 full turns (10 clicks)||10|
|11 clicks12 clicks
|11 12 131 A|
|3 full turns (15 clicks)||14|
|4 full turns||19|
*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.