Gastron 2 mg & 1 mg/5 ml TABLETS, SYRUP

GASTRON is indicated for:

• The control of acute and chronic diarrhoea.
• The control of intestinal transit time in patients with ileostomies, colostomies and other intestinal resections.

GASTRON SYRUP is indicated for: Inhibition of peristalsis and slowing intestinal transit time in children below 6 years of age.

Posology

Adults

Acute Non-specific Diarrhoea

The usual initial dose of GASTRON TABLETS is two tablets (4 mg) followed by one tablet (2 mg) after each loose stool, up to a total of 8 tablets (16 mg) daily. Do not exceed the following maximum daily dosages.

WEIGHT IN KILOGRAMS (kg) MAXIMUM DAILY DOSE

• From 14 kg 2 tablets (4 mg)
• From 20 kg 3 tablets (6 mg)
• From 27 kg 4 tablets (8 mg)
• From 34 kg 5 tablets (10 mg)
• From 40 kg 6 tablets (12 mg)
• From 47 kg 7 tablets (14 mg)
• From 54 kg 8 tablets (16 mg)

Important: Stop GASTRON as soon as diarrhoea is under control. In acute diarrhoea, if clinical improvement is not observed within 48 hours, the administration of GASTRON should be discontinued, and patients should be advised to consult their doctor.

Chronic Non-specific Diarrhoea (consult your doctor)

With individually adjusted dosage it is usually possible to obtain a virtually normal bowel movement. The initial dosage is 2 to 4 tablets of GASTRON TABLETS daily in divided doses for adults. The initial dose should be adjusted until 1 to 2 solid stools per day are obtained. If constipation occurs, the dosage should be decreased.

Special populations

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, GASTRON should be used with caution in such patients because of reduced first pass metabolism.

Paediatric population

GASTRON TABLETS should not be administered to children under 5 years. Important: Stop GASTRON SYRUP as soon as diarrhoea is under control.

Acute Non-specific Diarrhoea

In acute diarrhoea, if clinical improvement is not observed within 48 hours, the administration of GASTRON SYRUP should be discontinued and patients should be advised to consult their doctor.

CHILDREN 2 TO 5 YEARS (13 kg to 20 kg body mass)

One medicine measure (5 ml) of GASTRON SYRUP three times a day for the first day, followed by one medicine measure (5 ml) per 10,0 kg body mass after each loose stool. The total daily dose should not exceed 3 medicines measures (15 ml).

CHILDREN 5 TO 8 YEARS (20 kg to 30 kg body mass)

One medicine measure (5 ml) of GASTRON SYRUP four times a day for the first day, followed by one medicine measure (5 ml) per 10,0 kg body mass after each loose stool. The total daily dose should not exceed 4 medicines measures (20 ml).

CHILDREN 8 TO 12 YEARS (over 30 kg)

Two medicine measures (10 ml) of GASTRON SYRUP three to four times a day, for the first day followed by one medicine measure (5 ml) per 10,0 kg body mass after each loose stool. The total daily dose should not exceed 8 medicine measures (40 ml).

Chronic non-specific diarrhoea

With individual adjusted dosage it is usually possible to obtain a virtually normal bowel movement. Starting dose is 1 medicine measure (5 ml) per 12, 5 kg body mass a day for children. The daily dose should be adjusted until 1 to 2 solid stools per day are obtained. This is usually achieved on a maintenance dose of half to 2 medicine measures (2,5 ml to 10 ml) daily. If constipation occurs, the dosage should be decreased.

Method of administration

For oral administration.

GASTRON is contraindicated in:

• Patients with hypersensitivity to loperamide hydrochloride or to any excipients in GASTRON (see section 6.1).
• Infants below 24 months of age.
• Primary therapy in patients with acute dysentery, which is characterised by blood in stools and high fever.
• Patients with acute ulcerative colitis.
• Patients with bacterial enterocolitis caused by invasive organisms including Salmonella, Shigella, and Campylobacter.
• Patients with pseudomembranous colitis associated with the use of broad spectrum antibiotics.
• Where constipation is present or in patients with inflammatory bowel disease.
• The treatment of acute infective diarrhoea.
• Hepatic dysfunction, as it may result in relative overdosing.
• Safety in pregnancy has not been established.
• GASTRON TABLETS should not be administered to children under 5 years.

In general, GASTRON should not be used when inhibition of peristalsis must be avoided due to the possible risk of significant sequelae including ileus, megacolon and toxic megacolon.

Treatment of diarrhoea with GASTRON is only symptomatic. Whenever an underlying aetiology can be determined, specific treatment should be given when appropriate (or when indicated).

Acute diarrhoea

In patients with diarrhoea, especially in infants, fluid and electrolyte depletion may occur. In such cases administration of appropriate fluid and electrolyte replacement (oral rehydration therapy (ORT)) is the most important measure.

Medical advice

Patients should be told not to continue medication if no response is obtained within 48 hours; medical advice should then be sought (see section 4.2).

Constipation, abdominal distension or subileus

Discontinue use immediately if constipation, abdominal distension or subileus develop (see section 4.2 and 4.3).

AIDS Patients

Patients with acquired immunodeficiency syndrome (AIDS) treated with loperamide, as contained in GASTRON, for diarrhoea should have therapy stopped at the earliest signs of abdominal distension. There have been reports of toxic megacolon in AIDS patients with infectious colitis from both viral and bacterial pathogens treated with loperamide, as in GASTRON.

Acute ulcerative colitis or pseudomembranous colitis

Do not use in patients with acute ulcerative colitis or pseudomembranous colitis associated with broad spectrum antibiotics (see section 4.3).

Cardiac events

Cardiac events including QT interval and QRS complex prolongation and torsades de pointes have been reported in association with overdose. Some cases had a fatal outcome (see section 4.9). Overdose can unmask existing Brugada syndrome. Patients should not exceed the recommended dose and/or the recommended duration of treatment.

Abuse and misuse

Abuse and misuse of loperamide, as an opioid substitute, have been described in individuals with opioid addiction (see section 4.9).

Excipients

GASTRON SYRUP contains parahydroxybenzoates which may cause allergic reactions (possibly delayed).

Quinidine or Ritonavir

Non-clinical data have shown that loperamide, as in GASTRON, is a P-glycoprotein substrate. In two separate studies, 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 with concomitant administration with quinidine, but not with ritonavir; there was evidence of respiratory suppression. 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.

Gemfibrozil and/or Itraconazole

The concomitant administration of loperamide (4 mg single dose) and itraconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 3 to 4-fold increase in loperamide plasma concentrations. In the same study a CYP2C8 inhibitor, gemfibrozil, increased loperamide by approximately 2-fold. The combination of itraconazole and gemfibrozil resulted in a 4-fold increase in peak plasma levels of loperamide and a 13-fold increase in total plasma exposure. These increases were not associated with CNS effects as measured by psychomotor tests (i.e., subjective drowsiness and the Digit Symbol Substitution Test).

Ketoconazole

The concomitant administration of loperamide, as in GASTRON (16 mg single dose) and ketoconazole, an inhibitor of CYP3A4 and P-glycoprotein, resulted in a 5-fold increase in loperamide plasma concentrations. This increase was not associated with increased pharmacodynamic effects as measured by pupillometry.

Desmopressin

Concomitant treatment with oral desmopressin resulted in a 3-fold increase of desmopressin plasma concentrations, presumably due to slower gastrointestinal motility.

Medicines with similar pharmacological properties and those that accelerate gastrointestinal transit

It is expected that medicines with similar pharmacological properties may potentiate loperamideu2019s effect and that medicines that accelerate gastrointestinal transit may decrease its effect.

Pregnancy

The safety of GASTRON in pregnancy has not been established (see section 4.3).

Breastfeeding

Small amounts of loperamide may appear in human breast milk. Therefore, GASTRON is not recommended during breastfeeding.

Fertility

There are no data available.

GASTRON has moderate influence on the ability to drive or operate machinery. Since adverse reactions such as loss of consciousness, depressed level of consciousness, tiredness, dizziness, and drowsiness have been reported in patients receiving GASTRON, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that GASTRON does not adversely affect their ability to do so (see section 4.8).

a) Summary of the safety profile

The most commonly reported adverse reactions in patients with acute diarrhoea were constipation, flatulence, headache and nausea. In patients with chronic diarrhoea, the most commonly reported adverse reactions were flatulence, constipation, nausea and dizziness.

b) Tabulated list of adverse reactions

System organ class Frequent Less frequent

• Immune system disorders Allergic reactions, hypersensitivity reactions including anaphylactic shock and anaphylactoid reactions
• Nervous system disorders Headache, dizziness Somnolence, drowsiness, abnormal coordination, depressed level of consciousness, hypertonia, loss of consciousness, stupor
• Eye disorders Miosis
• Gastrointestinal disorders Constipation, dry mouth, flatulence, abdominal cramp, colic, nausea, vomiting, meteorism, abdominal pain Abdominal discomfort, upper abdominal pain, abdominal distension, dyspepsia, ileus (including reversible paralytic ileus, at high doses), megacolon including toxic megacolon, glossodynia, increased risk of abdominal pain, including pancreatitis
• Skin and subcutaneous tissue disorders Skin rash, urticaria, pruritus, angioedema, and bullous eruptions, including Stevens-Johnson Syndrome, erythema multiforme and toxic epidermal necrolysis
• Renal and urinary disorders Urinary retention
• General disorders Fatigue

c) Description of selected adverse reactions

A number of the adverse events reported during the clinical investigations and post-marketing experience with loperamide as in GASTRON are also frequent symptoms of the underlying diarrheal syndrome (abdominal pain/discomfort, nausea, vomiting, dry mouth, tiredness, drowsiness, dizziness, constipation, and flatulence). These symptoms may be difficult to distinguish from undesirable medicine effects.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Aspen Pharmacare: E-mail: [email protected] Tel: 0800 118 088/ +27 (0)11 239-6200

Symptoms

Overdosage may result in constipation. Depression of the central nervous system may be seen in overdosage. Excessive inhibition of peristalsis with nausea and dryness of the mouth. In case of overdose (including relative overdose due to hepatic dysfunction), central nervous system depression (e.g. stupor, coordination abnormality, somnolence, miosis, muscular hypertonia and respiratory depression), urinary retention, constipation and paralytic ileus may occur. Children may be more sensitive to central nervous system depressant effects of loperamide than adults. Convulsions have been reported in children under the age of 2 years. In individuals who have intentionally ingested overdoses of loperamide HCl, QT interval and QRS complex prolongation and/or serious ventricular dysrhythmias, including Torsade de Pointes, have been observed (see section 4.4). Fatal cases have also been reported.

Abuse, misuse and/or overdose with excessively large doses of loperamide, may unmask Brugada syndrome.

Treatment

Treatment is symptomatic and supportive. Naloxone can be given as an antidote. Since the duration of action of IMODIUM is longer than that of naloxone (1 to 3 hours) repeated treatment with naloxone might be indicated. Therefore, the patient should be monitored closely for at least 48 hours in order to detect possible central nervous system depression.