Imodium Capsules

1. Name Of The Medicinal Product

Imodium^® Capsules

2. Qualitative And Quantitative Composition

Loperamide hydrochloride 2 mg

Excipient: lactose

For a full list of excipients, see Section 6.1

3. Pharmaceutical Form

Capsule, hard.

Opaque green cap and grey body, hard gelatin capsule imprinted with 'Imodium' on cap and 'Janssen' on body containing white powder.

4. Clinical Particulars

4.1 Therapeutic Indications

POM

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 8 years. For the symptomatic treatment of chronic diarrhoea in adults.

P and GSL

For the symptomatic treatment of acute diarrhoea in adults and children aged 12 years and over.

For the symptomatic treatment of acute episodes of diarrhoea associated with Irritable Bowel Syndrome in adults aged 18 years and over following initial diagnosis by a doctor.

4.2 Posology And Method Of Administration

ACUTE DIARRHOEA

P and POM

Adults and children over 12:

Two capsules initially, followed by one capsule after each loose stool. The usual dose is 3-4 capsules a day. The total daily dose should not exceed 8 capsules.

POM

Children 4-8 years:

Use Syrup.

Children 9-12 years:

One capsule four times daily until diarrhoea is controlled (up to 5 days). This dose should not be exceeded.

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.

GSL

Adults and children over 12:

2 capsules initially followed by 1 capsule after every loose stool.

The maximum daily dose should not exceed 6 capsules.

CHRONIC DIARRHOEA (POM)

Adults:

Studies have shown that patients may need widely differing amounts of Imodium. The starting dose should be between two and four capsules per day in divided doses, depending on severity. If required, this dose can be adjusted according to result up to a maximum of eight capsules daily.

Having established the patient's daily maintenance dose, the capsules may be administered on a twice daily regimen. Tolerance has not been observed and therefore subsequent dosage adjustment should be unnecessary.

SYMPTOMATIC TREATMENT OF ACUTE EPISODES OF DIARRHOEA ASSOCIATED WITH IRRITABLE BOWEL SYNDROME IN ADULTS AGED 18 YEARS AND OVER

P

Two capsules to be taken initially. The usual dose is between 2 and 4 capsules per day in divided doses, depending on severity. If required, this dose can be adjusted according to result, up to a maximum of 8 capsules daily.

GSL

Two capsules to be taken initially, followed by 1 capsule after every loose stool, or as previously advised by your doctor. The maximum daily dose should not exceed 6 capsules.

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 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

The priority in acute diarrhoea is the prevention or reversal of fluid and electrolyte depletion. This is particularly important in young children and in frail and elderly patients with acute diarrhoea. 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.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine because it contains lactose.

Also for P and GSL use

In cases of acute diarrhoea, 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 previously 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 diarrhoea continue for more than two weeks or there is a need for continued treatment of more than two weeks.

Special Warnings to be included on the GSL leaflet

Only take Imodium to treat acute episodes of diarrhoea associated with Irritable Bowel Syndrome if your doctor has previously diagnosed IBS.

If any of the following apply, do not use the product without first consulting your doctor, even if you know you have IBS:

• If you are 40 years or over and it is some time since your last attack of IBS or the symptoms are different this time

• If you have recently passed blood from the bowel

• If you suffer from severe constipation

• If you are feeling sick or vomiting

• If you have lost your appetite or lost weight

• If you have difficulty or pain passing urine

• If you have a fever

• If you have recently travelled abroad

Consult your doctor if you develop new symptoms, or if your symptoms worsen, or your symptoms have not improved over 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.

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 pregnant or 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.

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

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose

Maize starch

Talc

Magnesium stearate

Capsule cap:

Titanium dioxide

Yellow ferric oxide

Indigotindisulphonate sodium

Gelatin

Capsule body:

Titanium dioxide

Black ferrous oxide

Indigotindisulphonate sodium

Erythrosin

Gelatin

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

Blister packs consisting of aluminium foil, hermetalu and polyvinyl chloride genotherm glass clear.

The blister strips are packed in cardboard cartons to contain 2, 6, 8, 12, 18 or 30 capsules (4, 28, 60 and 100 pack sizes not marketed).

OR

Tubs of capsules containing 250 capsules (500, 1000 and 10000 pack sizes not marketed).

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Janssen-Cilag Ltd.

50-100 Holmers Farm Way

High Wycombe

Buckinghamshire

HP12 4EG

UK

8. Marketing Authorisation Number(S)

PL 00242/0028

9. Date Of First Authorisation/Renewal Of The Authorisation

17 March 1975 / 18 June 2001

10. Date Of Revision Of The Text

22 September 2010