MOTILIUM Oral suspension

Therapeutic indications:

1. The dyspeptic symptom complex that is often associated with delayed gastric emptying, gastro-oesophageal reflux and oesophagitis:

- epigastric sense of fullness, early satiety, feeling of abdominal distension, upper abdominal pain,

- bloating, eructation, flatulence,

- nausea and vomiting,

- heartburn with or without regurgitations of gastric contents in the mouth.

2. Nausea and vomiting of functional, organic, infectious or dietary origin.

3. Nausea and vomiting induced by:

- radiotherapy or drug therapy

- dopamine agonists (such as L-dopa and bromocriptine) used in the treatment of Parkinson’s disease.

Posology and method of administration

It is recommended to take oral MOTILIUM before meals. If taken after meals, absorption of the drug is somewhat delayed.

- Adults and adolescents ≥ 12 years of age and weighing ≥ 35kg and children weighing ≥ 35kg

Oral suspension (1mg/ml oral suspension).

- Infants and children < 12 years of age and weighing < 35kg and adults and adolescents weighing < 35kg

The dose of MOTILIUM should be the lowest effective dose. The total daily is dependent on weight. Since metabolic functions and the blood brain barrier are not fully developed in the first months of life, the risk of neurological side effects is higher in young children (see side effects). Overdosing may cause nervous system disorders in children. The dose should be determined accurately and not exceed the recommended maximum individual and daily dose in neonates, infant, toddlers and small children. The initial duration of treatment is up to four weeks. If treatment, exceeds four weeks, patients should be reevaluated and the need for continued treatment reassessed.

Oral suspension (1mg/ml)

0.25-0.5mg/kg three to four times per day, with a maximum daily dose of 80mg (2.4mg/kg but no more than 80ml)

- Use in renal insufficiency

Since the elimination half life of domperidone is prolonged in severe renal impairment, on repeated administration 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 on prolonged therapy should be reviewed regularly (see Pharmacokinetic Properties).

MOTILIUM is contraindicated in the following situations:

- Known hypersensitivity to domperidone or any of the excipients.

- Prolectin-releasing pituitary tumour (prolactinoma).

- Co-administration with oral ketoconazole, erythromycin, or other potent CYP3A4 inhibitors which prolong the QTc interval such as fluconazole, voriconazole, clarithromycin, amiodarone, and telithromycin (see 4.5 interaction with other medical products and other forms of interaction).

- 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 or severe hepatic impairment (see 5.2 Pharmacokinetic Properties)

+Psychiatric disorders

- Depression

- Anxiety

- libido decreased/loss of libido

+Nervous system disorders

- headache

- somnolence

- Akathisia

+Gastrointestinal disorders

- diarrhea

+Skin and subcutaneous tissue disorders

- Rash

- Pruritus

+Repreductive system and breast disorders

- breast enlargement/Gynaecomastia

- breast tenderness

- Galactorrhoea

- Amenorrhoea

- Breast pain

- Menstruation irregular

- Lactation disorder

+General disorders and administration site conditions

- asthenia

+Others

- Hypersensitivity, urticaria, breast discharge, breast swelling

Antacids or antisecretory agents should not be given simultaneously with oral formulations of MOTILIUM as they lower the oral bioavailability of domperidone (see also 4.4 special warnings and special precautions for use).

Concomitant administration of anticholinergic drugs may antagonize the anti-dyspeptic effect of MOTILIUM.

The main metabolic pathway of domperidone is through CYP3A4. In vitro and human data show that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone.

Examples of potent CYP3A4 inhibitors include:

- Azole antifungals, such as fluconazole*, itraconazole, ketoconazole*, and voriconazole*,

- Macrolide antibiotics, such as clarithromycin* and erythromycin*,

- HIV protease inhibitors, such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir.

- Calcium antagonists, such as diltiazem, verapamil,

- Amiodarone*

- Aprepitant

- Nefazodone

- Telithromycin*

(* also prolong the QTc interval, see 4.3 contraindications)

Use during pregnancy:

There are limited post-marketing data on the use of domperidone in pregnant women. A study in rats has shown reproductive toxicity at a high, maternally toxic dose. The potential risk for humans is unknown. Therefore, MOTILIUM should only be used during pregnancy when justified by the anticipated therapeutic benefit.

Use during lactation:

The drug is excreted in breast milk of lactating rats (mostly as metabolites, peak concentration of 40 and 800 mg/ml after oral and IV administration of 2.5 mg/kg, respectively. Domperidone concentrations in breast milk of lactating women are 10 to 50% of the corresponding plasma concentrations and expected not to exceed 10mg/ml. The total amount of domperidone excreted in human breast milk is expected to be less than 7µg per day at the highest recommended dosing regimen. It is not known whether this is harmful to the newborn. Therefore, breast-feeding is not recommended for mothers who are taking MOTILIUM.

Cardiac effects

MOTILIUM should be used with caution in older patients or those with current or a history of cardiac disease. Some epidemiological studies have shown domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death (see side effects). These studies suggest 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.

Antacids or antisecretory agents should not be taken simultaneously with oral formulations of MOTILIUM as they lower the oral bioavailability of MOTILIUM (see interactions with other Medical products and other forms of interaction). When used concomitantly, MOTILIUM should be taken before meals and actacids or antisecretory agents after meals

The oral suspension contains sorbitol and may be unsuitable for patients with sorbitol intolerance.