Loperamide 2 Mg Tablets
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 is 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 of any aetiology including acute exacerbations of chronic diarrhoea for periods of up to 5 days in adults and children 9 years and over. For the symptomatic treatment of chronic diarrhoea in adults.
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.
Children 9 to 12 years
One tablet four times daily until diarrhoea is controlled (up to 5 days). This dose should not be exceeded.
Further investigation into the cause of the diarrhoea should be considered if there is no improvement within two days of starting treatment with Loperamide.
Chronic diarrhoea Adults
Studies have shown that patients may need widely differing amounts of Loperamide. The starting dose should be between two and four tablets per day in divided doses, depending on severity. If required, this dose can be adjusted according to result up to a maximum of eight tablets daily.
Having established the patient's daily maintenance dose, the tablets 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, 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.
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.
|
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 |
The following adverse events have been reported with use of loperamide hydrochloride:_
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 12 or 30 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 40378/0126
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
21/11/2012
10 DATE OF REVISION OF THE TEXT
21/11/2012