IMODIUM^™ SYRUP

Loperamide hydrochloride 0.2 mg/ml

For a full list of excipients, see section 6.1

Syrup for oral administration.

A clear, red, slightly viscous fruit-flavoured oral solution.

Acute diarrhoea

Not recommended for children under 4 years of age.

Further investigation into the cause of the diarrhoea should be considered if there is no improvement within two days of starting treatment with Imodium.

Chronic Diarrhoea

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.

Imodium is contraindicated in:

• patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.

• children less than 4 years of age.

• 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.

In patients with diarrhoea, especially young children, fluid and electrolyte depletion may occur. Use of Imodium does not preclude the administration of appropriate fluid and electrolyte replacement therapy.

Since persistent diarrhoea can be an indicator of potentially more serious conditions, Imodium should not be used for prolonged periods until the underlying cause of the diarrhoea has been investigated.

Imodium must be used with caution when the hepatic function necessary for the drug's metabolism is defective (eg in cases 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.

Also for P use only.

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

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.

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.

Tiredness, dizziness, or drowsiness may occur when diarrhoea is treated with Imodium. Therefore, it is advisable to use caution when driving a car or operating machinery. See section 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.

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.

Pharmacotherapeutic Group: Antipropulsives; ATC code: A07DA03

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

The half-life of loperamide in man is 10.8 hours with a range of 914 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.

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

Glycerol

Sodium saccharin

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Cochineal Red A

Raspberry Flavour

Red Currant Flavour

Ethanol (96%)

Citric acid monohydrate

Purified water

Not applicable.

60 months.

None.

Amber glass bottle with either a pilfer-proof aluminium screw cap coated on the inside with PVC or a child resistant polypropylene screw cap lined inside with an LDPE insert and a 5 ml or 10 ml polypropylene measuring cup.

Imodium syrup may be presented in bottle sizes of 30, 40, 50, 90 and 100 mls.

(Not all pack sizes may be marketed.)

Not applicable.

Janssen-Cilag Ltd.

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

PL 0242/0040

Date of first authorisation: 03 December 1975

Date of renewal of authorisation: 20 December 1996

10 September 2008

Legal category POM/P