Imodium Liquid

1. Name Of The Medicinal Product

Imodium™ Liquid

2. Qualitative And Quantitative Composition

Loperamide hydrochloride Ph Eur 1 mg per 5 ml.

3. Pharmaceutical Form

Oral liquid.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of acute diarrhoea.

For the symptomatic treatment of acute episodes of diarrhoea associated with irritable bowel syndrome in adults following initial diagnosis by a doctor.

4.2 Posology And Method Of Administration

For adults and children 12 years and over:

4 mg initially (20 ml) and then 2 mg (10 ml) after each loose stool.

Symptomatic treatment of acute episodes of diarrhoea associated with irritable bowel syndrome in adults:

Two 10 ml doses to be taken initially. The usual dose is between 4 mg (20 ml) and 8 mg (40 ml) per day in divided doses, depending on severity. If required, this dose can be adjusted according to result up to a maximum of 16 mg (80 ml) daily.

Use in Elderly:

No dose adjustment is required for the elderly.

Renal impairment

No dose adjustment is required for patients with renal impairment.

Hepatic impairment

Although no pharmacokinetic data are available in patients with hepatic impairment, Imodium should be used with caution in such patients because of reduced first pass metabolism. (see 4.4 Special warnings and special precautions for use).

Method of administration: Oral use.

4.3 Contraindications

Imodium Liquid is contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.

Imodium Liquid should not be used in children less than 4 years of age.

Imodium Liquid must not be used when inhibition of peristalsis is to be avoided due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon, in particular:

- when ileus or constipation are present or when abdominal distension develops, particularly in severely dehydrated children,

- in patients with acute ulcerative colitis,

- in patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter,

- in patients with pseudomembranous colitis associated with the use of broad-spectrum antibiotics.

Imodium should not be used alone in acute dysentery, which is characterised by blood in stools and elevated body temperatures.

4.4 Special Warnings And Precautions For Use

Loperamide is for the symptomatic relief of acute diarrhoea only and is not a suitable substitute for rehydration therapy.

Loperamide must be used with caution when the hepatic function necessary for the drug's metabolism is defective (eg in the case of severe hepatic disturbance), as this might result in a relative overdose leading to CNS toxicity.

Patients with AIDS treated with Imodium for diarrhoea should have therapy stopped at the earliest signs of abdominal distension. There have been isolated reports of toxic megacolon in AIDS patients with infectious colitis from both viral and bacterial pathogens treated with loperamide hydrochloride.

If symptoms persist for more than 24 hours, consult your doctor.

If you are taking Imodium to control episodes of diarrhoea associated with Irritable Bowel Syndrome diagnosed by your doctor, you should return to him/her if the pattern of your symptoms changes. You should also return to your doctor if your episodes of acute symptoms continue for more than two weeks or there is a need for continuous treatment of more than two weeks.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Non-clinical data have shown that loperamide is a P-glycoprotein substrate. Concomitant administration of loperamide (16 mg single dose) with quinidine, or ritonavir, which are both P-glycoprotein inhibitors, resulted in a 2 to 3-fold increase in loperamide plasma levels. The clinical relevance of this pharmacokinetic interaction with P-glycoprotein inhibitors, when loperamide is given at recommended dosages (2 mg, up to 16 mg maximum daily dose), is unknown.

4.6 Pregnancy And Lactation

Safety in human pregnancy has not been established although studies in animals have not demonstrated any teratogenic effects. As with other drugs it is not advisable to administer Imodium in pregnancy.

Small amounts of loperamide may appear in human breast milk. Therefore, Imodium is not recommended during breast-feeding.

Women who are breast feeding infants should therefore be advised to consult their doctor for appropriate treatment.

4.7 Effects On Ability To Drive And Use Machines

Tiredness, dizziness, or drowsiness may occur when diarrhoeal syndromes are treated with Imodium. Therefore, it is advisable to use caution when driving a car or operating machinery. See section 4.8 Undesirable effects.

4.8 Undesirable Effects

In clinical trials, constipation and dizziness have been reported with greater frequency in loperamide hydrochloride treated patients than placebo treated patients.

The following adverse events have also been reported with use of loperamide hydrochloride:

Skin and Appendages

Very rare: rash, urticaria and pruritus.

Isolated occurrences of angioedema, and bullous eruptions including Stevens-Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis.

Body as a whole, general

Very rare: isolated occurrences of allergic reactions and in some cases severe hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions.

Gastrointestinal System Disorders

Very rare: abdominal pain, ileus, abdominal distension, nausea, constipation, vomiting, megacolon including toxic megacolon, flatulence, and dyspepsia.

Genitourinary

Very rare: isolated reports of urinary retention.

Psychiatric

Very rare: drowsiness

Central and Peripheral Nervous System

Very rare: dizziness

A number of the adverse events reported during the clinical investigations and post-marketing experience with loperamide are frequent symptoms of the underlying diarrhoeal syndrome (abdominal pain/discomfort, nausea, vomiting, dry mouth, tiredness, drowsiness, dizziness, constipation, and flatulence). These symptoms are often difficult to distinguish from undesirable drug effects.

4.9 Overdose

In case of overdose the following effects may be observed: constipation, urinary retention, ileus and neurological symptoms (miosis, muscular hypertonia, somnolence and bradypnoea). If intoxication is suspected, naloxone may be given as an antidote. Since the duration of action of loperamide is longer than that of naloxone, the patient should be kept under constant observation for at least 48 hours in order to detect any possible depression of the central nervous system. Children, and patients with hepatic dysfunction, may be more sensitive to CNS effects. Gastric lavage, or induced emesis and/or enema or laxatives may be recommended.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Loperamide binds to the opiate receptor in the gut wall, reducing the propulsive peristalsis and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter.

In a double blind randomised clinical trial in 56 patients with acute diarrhoea receiving loperamide, onset of anti-diarrhoeal action was observed within one hour following a single 4 mg dose.

Clinical comparisons with other antidiarrhoeal drugs confirmed this exceptionally rapid onset of action of loperamide.

5.2 Pharmacokinetic Properties

The half-life of loperamide in man is 10.8 hours with a range of 9-14 hours.

Studies on distribution in rats show high affinity for the gut wall with preference for binding to the receptors in the longitudinal muscle layer.

Loperamide is well absorbed from the gut, but is almost completely extracted and metabolised by the liver where it is conjugated and excreted via the bile.

Due to its high affinity for the gut wall and its high first pass metabolism, very little loperamide reaches the systemic circulation.

5.3 Preclinical Safety Data

Not applicable.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Glycerol

Sodium saccharin

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

Cochineal red A

Raspberry flavour

Redcurrant flavour

Alcohol

Citric acid monohydrate

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

60 months.

6.4 Special Precautions For Storage

None.

6.5 Nature And Contents Of Container

30, 40, 50, 90 and 100 ml glass bottles with child-resistant polypropylene caps, lined inside with an LDPE insert.

A 5 ml or 10 ml polypropylene measuring cup is supplied.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Janssen-Cilag Ltd

Saunderton

High Wycombe

Buckinghamshire

HP14 4HJ

Distributor

Johnson & Johnson _° MSD

Consumer Pharmaceuticals

Enterprise House

Station Road

Loudwater

Buckinghamshire

HP10 9UF

8. Marketing Authorisation Number(S)

0242/0115

9. Date Of First Authorisation/Renewal Of The Authorisation

31 July 1997

10. Date Of Revision Of The Text

6 July 2004

Legal category P.