Imodium Syrup

1. Name Of The Medicinal Product

IMODIUM™ SYRUP

2. Qualitative And Quantitative Composition

Loperamide hydrochloride 0.2 mg/ml

Excipients:

Methyl parahydroxybenzoate (E218) Propyl parahydroxybenzoate (E216) Ethanol

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Syrup for oral administration.

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

4. Clinical Particulars

4.1 Therapeutic Indications

P Classification:	For the symptomatic treatment of acute diarrhoea in adults and children aged 12 years and over.
POM Classification:	For the symptomatic treatment of acute diarrhoea of any aetiology including acute exacerbations of chronic diarrhoea for periods of up to 5 days in adults and children over 4 years. For the symptomatic treatment of chronic diarrhoea in adults.

4.2 Posology And Method Of Administration

Acute diarrhoea

Adults:	Four 5 ml spoonfuls initially, followed by two 5 ml spoonfuls after each loose stool. The total daily dose should not exceed sixteen spoonfuls.
Children:	The following doses should not be exceeded.
Children over 8 years:	Two 5 ml spoonfuls four times daily with the duration limited to 5 days.
Children 4 - 8 years:	One 5 ml spoonful three or four times daily with the duration limited to 3 days.

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

Adults:

Patients may need widely differing amounts of Imodium. The starting dose should be between four and eight 5 ml spoonfuls per day in divided doses, depending on severity. If required this dose can be adjusted up to a maximum of sixteen 5 ml spoonfuls daily. Having established the patient's daily maintenance dose, Imodium may be administered on a twice daily regimen. Tolerance has not been observed and therefore subsequent dosage adjustment should be unnecessary.

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 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.

4.4 Special Warnings And Precautions For Use

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.

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.

The results of one published pharmacokinetic study suggested that the concomitant administration of loperamide with oral desmopressin may result in a 3-fold increase of desmopressin plasma concentrations, although no clinical effects were reported.

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

Loss of consciousness, depressed level of consciousness, 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.

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:

Immune system disorders

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

Psychiatric disorders

Very rare: drowsiness

Nervous system disorders

Very rare: Loss of consciousness, depressed level of consciousness, dizziness

Gastrointestinal disorders

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

Skin and subcutaneous tissue disorders

Very rare: rash, urticaria and pruritus.

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

Renal and urinary disorders

Very rare: isolated reports of urinary retention.

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

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.

5.2 Pharmacokinetic Properties

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

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Glycerol

Sodium saccharin

Methyl parahydroxybenzoate (E218)

Propyl parahydroxybenzoate (E216)

Cochineal Red A

Raspberry Flavour

Red Currant Flavour

Ethanol (96%)

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

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.)

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

Administrative Data

7. Marketing Authorisation Holder

Janssen-Cilag Ltd.

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

8. Marketing Authorisation Number(S)

PL 0242/0040

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 03 December 1975

Date of renewal of authorisation: 20 December 1996

10. Date Of Revision Of The Text

22 September 2010

LEGAL CATEGORY

POM/P.