Imodium Instants: For the symptomatic treatment of acute diarrhoea in adults and children aged 12 years and over

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

Posology and method of administration
Acute diarrhoea:

Adults, the elderly, and children 12 years and over:

Two tablets initially followed by 1 tablet after every loose stool.  The maximum daily dose should not exceed 6 tablets.


Symptomatic treatment of acute episodes of diarrhoea associated with irritable bowel syndrome

Adults aged 18 years and over:

Two tablets initially, followed by 1 tablet after every loose stool, or as previously advised by your doctor.  The maximum daily dose should not exceed 6 tablets.


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 Instants 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.  Allow the tablet to disintegrate on the tongue and swallow the medication

Contraindications
Imodium Instants are contraindicated in patients with a known hypersensitivity to loperamide hydrochloride or to any of the excipients.

Imodium Instants should not be used in children less than 12 years of age.

Imodium Instants must not be used 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 Instants should not be used alone in acute dysentery, which is characterised by blood in stools and elevated body temperatures.

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 Instants 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 Instants must be used with caution when the hepatic function necessary for the drug's metabolism is defective (e.g.  in cases of severe hepatic disturbance), as this might result in a relative overdose leading to CNS toxicity.

Patients with AIDS treated with Imodium Instants 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.

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

If you are taking Imodium Instants 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 leaflet:

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

If any of the following now 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, if your symptoms worsen, or your symptoms have not improved over two weeks.


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

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 loperamide in pregnancy.

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 should therefore be advised to consult their doctor for appropriate treatment.



Go to top of the page4.7 Effects on ability to drive and use machines
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 Undesirable effects.



Go to top of the page4.8 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 experiences have also been reported, and within each system organ class, are ranked by frequency, using the following convention: Very common (>1/10), Common (>1/100, < 1/10), Uncommon (> 1/ 1,000, < 1/100), Rare (>1/10,000, < 1/1,000), Very rare (<1/10,000), including isolated reports.

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.

Immune system disorders

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

Gastrointestinal disorders

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

Renal and urinary disorders

Very rare: isolated reports of urinary retention.

Psychiatric system disorders:

Very rare: drowsiness

Nervous system disorders

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



Go to top of the page4.9 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.



Go to top of the page5.  PHARMACOLOGICAL PROPERTIES
ATC Code: A07DA



Go to top of the page5.1 Pharmacodynamic properties
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 anti-diarrhoeal drugs confirmed this exceptionally rapid onset of action of loperamide.



Go to top of the page5.2 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.