Imodium (Loperamide)

What Is Imodium (Loperamide)?

This pack contains capsules and sachets. The capsules contain loperamide, which belongs to a group of medicines called anti-diarrhoeals. It acts to relieve the symptoms of sudden, short-term diarrhea (acute diarrhea). It works by making the stools more solid and less frequent.

The sachets contain glucose and various salts, which belong to a group of medicines called oral electrolytes. These act to replace fluids and salts lost when you have diarrhea.

This medicine can relieve acute diarrhea and replace lost fluids and salts in adults and children 12 years and over.

Ingredients

Each capsule contains Loperamide Hydrochloride 2 mg, and each sachet contains Citric Acid Anhydrous 0.128 g, glucose Monohydrate 3.58 g, Potassium Chloride 0.3 g, Sodium Chloride 0.47 g, Sodium Citrate 0.39 g, which are the active ingredients.

As well as the active ingredients, the capsules contain lactose monohydrate, maize starch, talc, and magnesium stearate. The capsule shell contains gelatin, quinoline yellow (E104), erythrosine (E127), patent blue (E131), and titanium dioxide (E171). The sachets also contain aspartame (E951, a source of phenylalanine), colloidal silicon dioxide, and blackcurrant flavorings.

The pack contains six blue and grey colored capsules and six sachets containing white, free-flowing powder.

Pharmacokinetics

About 40% of a dose of loperamide is reported to be absorbed from the gastrointestinal tract to undergo first-pass metabolism in the liver and excretion in the feces via the bile; as an inactive conjugate, there is slight urinary excretion. The little intact drug reaches the systemic circulation. The elimination half-life is reported to be about 10 hours.

Metabolism

Loperamide is metabolized to desmethyl loperamide through N-demethylation. An in-vitro study established that this occurs mainly via cytochrome P450 isoenzymes CYP2C8 and CYP3A4; CYP2B6 and CYP2D6 also play a role. Loperamide is also a substrate of P-glycoprotein.

Before You Take This Medicine

This medicine can be taken by adults and children aged 12 years and over. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.

Do Not Take Loperamide

• If you are allergic to any of the ingredients.
• If you have phenylketonuria (this medicine contains aspartame, a source of phenylalanine).
• If you have a swollen stomach, inflammation of the bowel, paralysis of the bowel muscles, pseudomembranous colitis.
• If you have any condition which may cause constipation or where constipation should be avoided.
• If you are intolerant to some sugars unless your doctor tells you to (this medicine contains glucose and lactose).
• If you are under 12 years of age.
• If you are pregnant.

Talk to Your Pharmacist or Doctor

• If you have kidney or severe liver problems.
• If you are producing little or no urine.
• If you have persistent diarrhea or are sick.
• If you are unable to drink or keep fluids down.
• If you are on a low salt (sodium) diet (each sachet contains 276 mg of sodium, which may be harmful to you).
• If you are on a low-potassium diet (each sachet contains 157 mg of potassium, which may harm you).
• If you are breastfeeding.

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 or pharmacist if you are taking any of the following:

• ritonavir (used to treat HIV)
• quinidine (used to treat abnormal heart rhythms or malaria)
• oral desmopressin (used to treat excessive urination).

Pregnancy and Breastfeeding

Tell your doctor before taking Imodium capsules if you are pregnant, think you may be pregnant, or might become pregnant.

Do not take this medicine if you are breastfeeding, as small amounts may get into your milk. Talk to your doctor about a suitable treatment.

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

Driving or Using Machines

This medicine may make you feel dizzy, tired, or sleepy. You may also lose consciousness and feel faint or less alert. If affected, do not drive or operate machinery.

Other Important Information

Diarrhea is a common symptom of several serious stomach and bowel conditions. Talk to your doctor if your diarrhea continues for more than 24 hours or keeps returning.

Uses and Administration

Loperamide is a synthetic derivative of pethidine that inhibits gut motility and may also reduce gastrointestinal secretions. It is given orally as an antidiarrhoeal drug as an adjunct in managing acute and chronic diarrheas. It may also be used to manage colostomies or ileostomies to reduce the discharge volume.

In acute diarrhea, the usual initial dose for adults is loperamide hydrochloride 4 mg, followed by 2 mg after each loose stool to a maximum of 16 mg daily; the usual daily dose is 6 to 8 mg. In the UK, it is not licensed for children under four. Suggested doses for older children are the following:

• 4 to 8 years, 1 mg three or four times daily for up to 3 days;
• 9 to 12 years, 2 mg four times daily for up to 5 days.

In the USA, loperamide is not recommended for children under the age of 2 years, and an initial dose of 1 mg three times daily is suggested for children aged 2 to 5 years. 

In chronic diarrhea, the usual initial dose for adults is 4 to 8 mg daily in divided doses; subsequently adjusted as necessary, doses of 16 mg daily should not be exceeded. Further use is unlikely to benefit if no improvement has been seen after treatment with 16 mg daily for at least ten days. Although not licensed for use in children with chronic diarrhea, in the UK, the BNFC allows for the following oral doses of loperamide hydrochloride:

• 1 month to 1 year: 100 to 200 micrograms/kg twice daily, given 30 minutes before feeds up to a maximum of 2 mg/kg daily in divided doses may be required
• 1 to 12 years: 100 to 200 micrograms/kg (maximum dose 2mg) three to four times daily up to 1.25 mg/kg daily in divided doses may be required, to a maximum of 16 mg daily
• 12 to 18 years: 2 to 4 mg two to four times daily, to a maximum of 16 mg daily

Loperamide is also given as the prodrug, loperamide oxide, which is converted to loperamide in the gastrointestinal tract. It has been given for acute diarrhea in doses of 2 to 4 mg initially, followed by 1 mg after each loose stool, to a maximum of 8 mg daily.

Diarrhea

The mainstay of treatment for acute diarrhea is rehydration therapy. Antidiarrhoeals may have a role in symptomatic relief in adults with acute diarrhea, and loperamide is often chosen in such circumstances, but WHO does not recommend using any antidiarrhoeal drug in children with diarrhea. Similarly, in the UK, the BNFC considers that antimotility drugs are not recommended for acute diarrhea in children under 12. There have been problems regarding using antidiarrhoeals, such as loperamide, in young children in developing countries.

Manufacturers have considered that a lower age limit is acceptable in those countries than is recommended in the UK or USA, even though a lower limit is not always observed in practice, and there have been reports of severe toxicity in very young children. In response to such reports, the manufacturers withdrew concentrated drops of loperamide worldwide and syrup from countries where the WHO had a program to control diarrhoeal diseases, but tablets and capsules remain available. In some countries, the use of antidiarrhoeals is now restricted by law.

In the UK, NICE states that loperamide is the antidiarrhoeal of first choice in adults with fecal incontinence; it can be used long-term in doses from 500 micrograms to 16 mg daily as needed. Loperamide should be started at a very low dose, which can be increased and adjusted in response to stool consistency. It should not be given to those with hard or infrequent stools, acute diarrhea of unknown cause, or acute ulcerative colitis. Patients who cannot tolerate loperamide may be offered codeine phosphate or co-phe-notrope.

How to Take This Medicine

Check the foil is not broken before use. If it is, do not take that capsule. Check the sachet is not broken before use. If it is, do not take the sachet. How to prepare the medicine:

1. Mix the contents of each sachet with 200 ml (seven fluid ounces) of fresh drinking water.
2. When fresh drinking water is unavailable, use freshly boiled and cooled water.
3. Prepare the sachet only as needed and drink within one hour once made up. If required, the refrigerated solution may be kept for 24 hours.
4. Only use water to make up the contents of the sachet. Ensure you use the right amount of water (i.e., 200 ml for one sachet and 400 ml for two sachets). This ensures the salts and water can be absorbed into the body correctly.

Drink the solution.

Age	How many to take	How often to take them
Adults and children of 12 years and over	Capsule: Two capsules after the first loose bowel movement. After that, one capsule only. Sachet: One or two, dissolved in water.	After each loose bowel movement. Don’t take more than 6 capsules in 24 hours. Don’t take more than 16 sachets in 24 hours.

 Swallow the capsule whole with water.

• Do not give to children under 12 years.
• Do not take more than the amount recommended above.
• Do not take this medicine for more than 24 hours.

Talk to your doctor if your diarrhea does not go away within 24 hours.

! If you take too many capsules or sachets, talk to a doctor immediately. Take your medicine and this leaflet with you.

Adverse Effects and Treatment

Abdominal pain or bloating, nausea, constipation, dry mouth, dizziness, fatigue, and hypersensitivity reactions, including skin rashes, have been reported. Loperamide has been associated with paralytic ileus, particularly in infants and young children, and deaths have been reported. Depression of the CNS, to which children or those with hepatic impairment may be more sensitive, may also be seen in overdosage, constipation, and urinary retention. Naloxone hydrochloride has been recommended for the treatment of severe overdosage.

Toxicity

Toxic megacolon has been reported after the use of loperamide. Severe effects reported in young children have included loss of consciousness and delirium. Several cases of paralytic ileus have also occurred in children, some of which were fatal.

Precautions

Loperamide should not be used when inhibition of peristalsis is to be avoided, particularly where ileus or constipation occurs, and should be avoided in patients with abdominal distension, acute inflammatory bowel disease, or antibiotic-associated colitis. Loperamide should not be used alone in patients with dysentery. Loperamide should be used cautiously in patients with hepatic impairment because of its considerable first-pass metabolism in the liver. It should also be used cautiously in young children because of greater response variability in this age group. It is not recommended for use in infants.

Breastfeeding

Loperamide is distributed into breast milk in small amounts. The American Academy of Pediatrics states that there have been no reports of any clinical effect on the infant associated with the use of loperamide by breastfeeding mothers. Therefore, it may be considered to be compatible with breastfeeding.

Interactions

Loperamide may increase the gastrointestinal absorption of desmopressin.

Antifungals

A pharmacokinetic study in 12 healthy subjects found that itraconazole significantly increased peak plasma concentrations and area under the concentration-time curve of loperamide and also prolonged the half-life of loperamide. Itraconazole also inhibited the metabolism of loperamide to N-desmethyl loperamide, suggesting that the metabolism of loperamide in humans concurs with in-vitro data. The use of itraconazole with gemfibrozil synergistically increased exposure to loperamide.

Antivirals

In a single-dose study, oral ritonavir significantly increased the bioavailability of loperamide, possibly through inhibition of the cytochrome P450 isoenzyme CYP3A4, and not necessarily as initially supposed through P-glycoprotein inhibition. No serious adverse effects occurred. Licensed information for one UK preparation of loperamide (Imodium; Janssen-Cilag, UK) states that the clinical relevance of the pharmacokinetic interaction with P-glycoprotein inhibitors such as ritonavir is unknown.

Cardiovascular Drugs

A pharmacokinetic study in 12 healthy subjects found that gemfibrozil significantly increased peak plasma concentrations and area under the concentration-time curve of loperamide and also prolonged the half-life of loperamide. Gemfibrozil also inhibited the metabolism of loperamide to N-des-methyl loperamide, suggesting that the metabolism of loperamide in humans concurs with in-vitro data. The use of gemfibrozil with itraconazole synergistically increased exposure to loperamide.

Co-trimoxazole

Using co-trimoxazole increases loperamide’s bioavailability, apparently by inhibiting its first-pass metabolism.

Quinidine

A small study found that giving quinidine with loperamide caused respiratory depression in 8 healthy subjects; when given a placebo, loperamide produced no respiratory depression. The authors supposed that inhibition of P-glycoprotein by quinidine had increased the entry of loperamide into the CNS.

Further Information

The active substance in Imodium capsules is loperamide hydrochloride. Each Imodium capsule contains 2 mg of loperamide hydrochloride.

The other ingredients are lactose, maize starch, talc, and magnesium stearate. The capsule is made up of titanium dioxide (E171), iron oxides (E172), indigo carmine (E132), erythrosine (E127), and gelatin.

What Imodium Capsules Look Like and Contents of the Pack

Imodium capsules are green/grey capsules marked ‘Imodium‘ and ‘JANSSEN.’ They are available in blister packs of 30 capsules or tubs of 250 capsules (for the pharmacist).

Drug Approvals

(British Approved Name Modified, US Adopted Name, rINN)

Synonyms: Loperamid hydrochlorid; Loperamid-hidroklorid; Loperamida, hidrocloruro de; Loperamidhydroklorid; Loperamidi Hydrochloridum; Loperamidihydrokloridi; Loperamido hidrochloridas; R-18553

BAN: Loperamide Hydrochloride [BANM]

USAN: Loperamide Hydrochloride

INN: Loperamide Hydrochloride [rINNM (en)]

INN: Hidrocloruro de loperamida [rINNM (es)]

INN: Lopéramide, Chlorhydrate de [rINNM (fr)]

INN: Loperamidi Hydrochloridum [rINNM (la)]

INN: Лоперамида Гидрохлорид [rINNM (ru)]

Chemical name: 4-(4-p-Chlorophenyl-4-hydroxypiperidino)-NN-dimethyl-2,2-diphenylbutyramide hydrochloride

Molecular formula: C29H33ClN2O2,HCl =513.5

CAS: 53179-11-6 (loperamide); 34552-83-5 (loperamide hydrochloride)

ATC code: A07DA03

Read code: y01Qd

Pharmacopoeias. In China, Europe, International, and the US.

European Pharmacopoeia, 6th ed. (Loperamide Hydrochloride). A white or almost white powder. It exhibits polymorphism. Slightly soluble in water, freely soluble in alcohol, and methyl alcohol. Protect from light.

The United States Pharmacopeia 31, 2008 (Loperamide Hydrochloride). A white to slightly yellow powder. Slightly soluble in water and dilute acids freely soluble in chloroform and in methyl alcohol very slightly soluble in isopropyl alcohol.

Loperamide Oxide

Drug Approvals

(British Approved Name, rINN)

Synonyms: Loperamid oxid; Loperamida, óxido de; Loperamidi Oxidum; Loperamidioksidi; Loperamido oksidas; Loperamidoxid; R-58425

BAN: Loperamide Oxide

INN: Loperamide Oxide [rINN (en)]

INN: Óxido de loperamida [rINN (es)]

INN: Lopéramide Oxyde [rINN (fr)]

INN: Loperamidum Oxidum [rINN (la)]

INN: Лоперамида Оксид [rINN (ru)]

Molecular formula: C29H33ClN2O3 =493.0

CAS: 106900-12-3

ATC code: A07DA05

Pharmacopoeias. Europe includes the monohydrate.

European Pharmacopoeia, 6th ed. (Loperamide Oxide Monohydrate Loperamidi Oxidum Monohydricum). A white or almost white, slightly hygroscopic powder. Practically insoluble in water, freely soluble in alcohol, and dichloromethane. Store in airtight containers. Protect from light.