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Loperamide 2 Mg Tablets

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Document: spc-doc_PL 40378-0127 change

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Loperamide 2 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2 mg Loperamide hydrochloride.

Excipients:

Lactose monohydrate. Each tablet contains 100 mg lactose monohydrate (see section 4.4).

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Tablet

Light green coloured capsule shaped, biconvex uncoated tablets with ‘2’ debossed on one side and score line on other side.

The score line only to facilitate breaking for ease of swallowing and not to divide into equal doses.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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

Adults and children over 12 years

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

Symptomatic treatment of acute episodes of diarrhoea associated with Irritable Bowel Syndrome already diagnosed bv a doctor Adults aged 18 years and over

Two tablets to be taken initially. The usual dose is between 2 and 4 tablets per day in divided doses, depending on severity. If required, this dose can be adjusted according to result, up to a maximum of 8 tablets 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, Loperamide should be used with caution in such patients because of reduced first pass metabolism (see section 4.4).

Paediatric population

Other pharmaceutical forms/strengths (e.g. syrup) are available for children aged 4 years and over.

Method of administration Oral use.

4.3 Contraindications

Loperamide 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.

Loperamide 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 Loperamide does not preclude the administration of appropriate fluid and electrolyte replacement therapy.

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

Loperamide 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 Loperamide 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.

In cases of acute diarrhoea, if symptoms persist for more than 24 hours, consult your doctor.

If you are taking Loperamide 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.

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 Fertility, pregnancy and lactation

Fertility

There is no relevant data to demonstrate the effect of Loperamide on human fertility.

Pregnancy

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 Loperamide in pregnancy.

Lactation

Small amounts of loperamide may appear in human breast milk. Therefore, Loperamide 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 Loperamide. Therefore, it is advisable to use caution when driving a car or operating machinery (see section 4.8).

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. For clinical trials, the frequency is defined as follows: very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000), including isolated reports.

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

Frequency

Organ system

Very rare (<1/10,000), not known (cannot be estimated from the available data)

Immune system disorders

Isolated occurrences of allergic reactions, severe hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions

Psychiatric disorders

Drowsiness

Nervous system disorders

Loss of consciousness, depressed level of consciousness, dizziness

Gastrointestinal disorders

Abdominal pain, ileus, abdominal distension, nausea, constipation, vomiting, megacolon including toxic megacolon, flatulence and dyspepsia

Skin and subcutaneous tissue disorders

Rash, urticaria and pruritis

Isolated occurrences of angioedema, and bullous eruptions

including Stevens-Johnson Syndrome, erythema multiforme, and toxic epidermal necrolysis

Renal and urinary disorder

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

Maize starch Lactose monohydrate Povidone (K-30)

Brilliant Blue FCF (E133)

Quinoline Yellow (E104)

Magnesium stearate Talc

Colloidal anhydrous silica Sodium starch glycolate (Type A)

Purified water

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

6.4


Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

6.5 Nature and contents of container

Clear PVC/PVdC film / Aluminium blister strips. The blister strips are packed in cartons to contain 8, 12 or 18 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Not applicable

7    MARKETING AUTHORISATION HOLDER

APTIL Pharma Limited

9th Floor, CP House 97 - 107 Uxbridge Road Ealing, London W5 5TL

8    MARKETING AUTHORISATION NUMBER(S)

PL 40378/0127

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

21/11/2012

10 DATE OF REVISION OF THE TEXT

21/11/2012