Motilium 10 mg FC tablets.

MOTILIUM tablets are indicated in adults and adolescents over 12 years of age and weighing over 35 kg for:

• Short-term management (not exceeding 7 days) of delayed gastric emptying of functional origin with gastro-oesophageal reflux and/or dyspepsia.
• Short term management (not exceeding 7 days) for control of nausea and vomiting of central or local origin.
• As an anti-emetic in patients receiving cytostatic and radiation therapy for up to 4 weeks.
• Facilitation of radiological examination of the upper gastro-intestinal tract administered at the time before the examination as directed by the radiologist.

Posology

Adults and adolescents > 12 years of age and > 35 kg

It is recommended to take oral MOTILIUM 15 u2013 30 minutes before meals. If taken after meals, absorption of the medicine is somewhat delayed. The dose of MOTILIUM film coated tablets should be the lowest effective dose for the individual situation (typically 30 mg/day) with a maximum daily oral dose of 30 mg. If the conditions mentioned under indications are not resolved within the time frames indicated, patients should be re-evaluated and the need for continued treatment be assessed.

Formulation (domperidone per unit)

Dosage Maximum dose per day

Film-coated tablets (10 mg/tablet) 1 tablet three times per day 30 mg (3x10 mg tablet).

Paediatrics

The efficacy of domperidone was not demonstrated in children less than or equal to 12 years of age (see section 5.1). The safety of MOTILIUM in adolescents weighing u2264 35 kg has not been established.

Special populations

Renal impairment

Since the elimination half-life of domperidone is prolonged in severe renal impairment (serum creatinine > 6 mg/100 mL, i.e. > 0,6 mmol/L), the dosing frequency of MOTILIUM should be reduced to once or twice daily, depending on the severity of the impairment, and the dose may need to be reduced. Patients with severe renal impairment should be reviewed regularly.

Hepatic impairment

MOTILIUM is contraindicated for patients with moderate (Child-Pugh 7 to 9) or severe (Child-Pugh > 9) hepatic impairment (see section 4.3). Dose adjustment is not required for patients with mild (Child-Pugh 5 to 6) hepatic impairment (see section 5.2, Pharmacokinetic properties).

MOTILIUM is contraindicated in the following situations:

• Known hypersensitivity to domperidone or any of its excipients.
• Prolactin-releasing pituitary tumour (prolactinoma).
• Co-administration with other potent CYP3A4 inhibitors which have been shown to cause QT interval prolongation such as fluconazole, itraconazole, ketoconazole, voriconazole, posaconazole, clarithromycin, erythromycin, azithromycin, roxithromycin, amiodarone, telithromycin, amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir and quinolones (see sections 4.4 and 4.5).
• Co-administration with medicines known to induce Torsades de Pointes and/or prolong the QT interval e.g. cisapride, class 1A antidysrythmics.
• Hypokalaemia, hypomagnesaemia
• Bradycardia or heart block
• Pre-existing cardiac disease
• Known congenital long QT interval or family history thereof.
• Whenever stimulation of gastric motility might be dangerous, e.g. in the presence of gastro-intestinal haemorrhage, mechanical obstruction or perforation.
• In patients with moderate (child pugh score 7 u2013 9) or severe (child pugh score > 9) hepatic impairment (see section 5.2).

MOTILIUM film coated tablets are unsuitable for use in children weighing less than 35 kg.

Cardiac effects

Epidemiological studies have shown that MOTILIUM is associated with an increased risk of serious ventricular dysrhythmias or sudden cardiac death (see section 4.8). These studies suggested that this increased risk may be higher in patients older than 60 years of age or in patients taking oral doses greater than 30 mg per day. Therefore, MOTILIUM should be used with caution in older patients.

Medicine interaction potential

The main metabolic pathway of domperidone is through CYP3A4. In vitro and human data show that the concomitant use of medicines that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Co-administration of MOTILIUM with potent CYP3A4 inhibitors which have been shown to cause QT interval prolongation is contraindicated (see section 4.3). Caution should be exercised when MOTILIUM is co-administered with potent CYP3A4 inhibitors which have not been shown to cause QT interval prolongation and patients should be monitored closely for signs and symptoms of adverse reactions (see section 4.8). Caution should be exercised when MOTILIUM is co-administered with medicines which have been shown to cause QT interval prolongation and patients should be monitored closely for signs or symptoms of cardiovascular adverse reactions (see section 4.8). Examples include:

• Anti-dysrhythmias class IA (e.g. disopyramide, quinidine)
• Anti-dysrhythmias class III (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol)
• Certain antipsychotics (e.g. haloperidol, pimozide, sertindole)
• Certain antidepressants (e.g. citalopram, escitalopram)
• Certain antibiotics (e.g. levofloxacin, moxifloxacin and quinolones)
• Certain antifungal medicines (e.g. pentamidine)
• Certain antimalarial medicines (e.g. halofantrine)
• Certain gastro-intestinal medicines (e.g. dolasetron)
• Certain medicines in cancer (e.g. toremifene, vandetanib)
• Certain other medicines (e.g. bepridil, methadone)

The above list is representative and not exhaustive.

Domperidone base

Antacids and anti-secretory medicines should not be taken simultaneously with oral formulations of MOTILIUM as they lower the oral bioavailability of MOTILIUM. When used concomitantly, MOTILIUM should be taken before meals and antacids or anti-secretory medicines after meals.

Excipients

MOTILIUM film coated tablets contain lactose. Patients with rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take MOTILIUM. MOTILIUM film coated tablets contains lactose, which may have an effect on the glycaemic control of patients with diabetes mellitus.

The main metabolic pathway of domperidone is through CYP3A4. In vitro and human data show that the concomitant use of medicines that significantly inhibit this enzyme may result in increased plasma levels of domperidone. When MOTILIUM was co-administered with potent CYP3A4 inhibitors which have been shown to cause QT interval prolongation, clinically relevant changes in QT intervals were observed. Therefore, co-administration of MOTILIUM with certain medicines is contraindicated (see section 4.3). Caution should be exercised when MOTILIUM is co-administered with potent CYP3A4 inhibitors which have not been shown to cause QT interval prolongation or medicines which have been shown to cause QT interval prolongation (see section 4.4). Concomitant administration of anti-cholinergic medicines (e.g. dextromethorphan, diphenhydramine) may antagonise the anti-dyspeptic effects of MOTILIUM.

Since MOTILIUM has gastro-kinetic effects, it could influence the absorption of concomitant orally administered medicines, particularly those with sustained release or enteric coated formulations. However, in patients already stabilised on digoxin or paracetamol, concomitant administration of MOTILIUM did not influence the blood levels of these medicines. MOTILIUM may also be given with:

• Neuroleptics, the action of which it does not potentiate.
• Dopaminergic agonists (bromocriptine, L-dopa), whose unwanted peripheral effects such as digestive disorders, nausea and vomiting it suppresses without counteracting their central properties.

Reduced gastric acidity impairs the absorption of MOTILIUM. Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. As MOTILIUM interferes with serum prolactin levels, it may interfere with other hypoprolactinaemic agents and with some diagnostic tests.

The safety of use during pregnancy and lactation has not been established. Domperidone is excreted in human breast milk therefore women on treatment with MOTILIUM should not breastfeed their babies.

Dizziness and somnolence have been observed following use of MOTILIUM (see section 4.8). Therefore, patients should be advised not to drive or use machinery or engage in other activities requiring mental alertness and coordination until they have established how MOTILIUM affects them.

Clinical Trial Data

The adverse drug reactions are ranked by frequency, using the following convention: Very common (u22651/10); common (u22651/100, <1/10); uncommon (u22651/1 000, < 1/100); rare (u22651/10 000, < 1/1 000); very rare (< 1/10 000), including isolated reports.

Psychiatric disorders

Common: Depression, anxiety, libido decreased/loss of libido.

Nervous system disorders

Common: Headache, somnolence, akathisia.

Gastro-intestinal disorders

Common: Diarrhoea.

Immune system disorders

Uncommon: Hypersensitivity.

Skin and subcutaneous tissue disorders

Common: Rash, pruritus.

Uncommon: Urticaria.

Reproductive system and breast disorders

Common: Breast enlargement/ gynaecomastia, breast tenderness, galactorrhoea, amenorrhoea, breast pain, menstruation irregular, lactation disorder.

Uncommon: Breast discharge, breast swelling.

General disorders and Administration site conditions

Common: Asthenia. Dry mouth has also been reported.

Postmarketing data

In addition to the adverse effects reported during clinical studies and listed above, the following adverse drug reactions have been reported postmarketing:

Immune System Disorders

Anaphylactic reaction (including anaphylactic shock).

Psychiatric Disorders

Agitation, nervousness.

Nervous System Disorders

Dizziness, extrapyramidal disorder, convulsion.

Cardiac Disorders

Sudden cardiac death, serious ventricular dysrhythmias (see section 4.4).

Skin and Subcutaneous Tissue Disorders

Angioedema.

Renal and Urinary Disorders

Urinary retention.

Investigations

Abnormal liver function test, increased blood prolactin.

Paediatric population

Although not approved for paediatric use, inappropriate/inadvertent ingestion in children resulted in extrapyramidal disorders and central nervous system related effects of convulsions, agitation and somnolence. See overdose.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the : 6.04 Adverse Drug Reactions Reporting Form, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Symptoms and signs

Overdose has been reported primarily in infants and children. Symptoms of overdosage may include agitation, altered consciousness, convulsion, disorientation, somnolence and extrapyramidal reactions.

Treatment

There is no specific antidote to domperidone. Symptomatic and supportive therapy is indicated. Close medical supervision and supportive therapy is recommended. Anticholinergic or anti-Parkinson medicines may be helpful in controlling the extrapyramidal reactions.

It is advisable to contact a poison control centre without delay to obtain the latest recommendations for the management of an overdose.