BOSMOTI

DOSAGE

This medicine should be used at the lowest effective dose for the shortest duration necessary to control nausea and vomiting.

It is recommended to take this drug before meals. If taken after meals, absorption of domperidone is somewhat delayed.

Patients should try to take each dose at the scheduled time. If a scheduled dose is missed, the missed dose should be omitted and the usual dosing schedule resumed. The dose should not be doubled to make up for a missed dose.

Usually, the maximum treatment duration should not exceed one week.

Adults and adolescents (12 years of age and older and weighing 35 kg or more):

1 to 2 sachets (each sachet contains 5 mg of domperidone) up to three times per day with a maximum daily dose of 6 sachets per day.

Neonates, infants, children (less than 12 years of age) and adolescents weighing less than 35 kg:

This medicine is not recommended for neonates, infants, children less than 12 years old and adolescents weighing less than 35 kg because dosing exactly is not guaranteed.

Oral domperidone should be taken before meals. If taken after meals absorption of the drug is somewhat delayed.

Hepatic Impairment:

Domperidone is contraindicated in moderate or severe hepatic impairment. Dose modification in mild hepatic impairment is however not needed.

Renal Impairment:

Since the elimination half-life of domperidone is prolonged in severe renal impairment, on repeated administration, the dosing frequency of domperidone should be reduced to once or twice daily depending on the severity of the impairment, and the dose may need to be reduced. Such patients on prolonged therapy should be reviewed regularly.

ADMINISTRATION

Disperse the powder in about 10 ml of water. Drink this suspension with empty stomach. It is recommended to administrate this drug 15 – 30 minutes before meals.

CONTRAINDICATIONS

• Hypersensitivity to any component;
• Pituitary tumor prolactin (prolactinoma);
• When the stimulation of gastric motility could be harmful, for example in patients with gastrointestinal bleeding, mechanical obstruction or perforation;
• In patients with moderate or severe hepatic impairment;
• In patients with known prolongation of cardiac conduction intervals, particularly QTc interval, patients with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure;
• Coadministration with drugs that prolong the QT interval;
• Coadministration with potent CYP3A4 inhibitors (whatever their lengthening effects of the QT interval).

WARNINGS AND PRECAUTIONS

Renal impairment

The elimination half-life of domperidone is prolonged in severe renal impairment. For repeated administration, the dosing frequency of domperidone should be reduced to once or twice daily depending on the severity of the impairment. The dose may also need to be reduced.

Cardiovascular effects

Epidemiological studies have shown that the use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. The risk may be higher in patients older than 60 years or those treated with daily doses above 30 mg. Domperidone should be used at the lowest effective dose for adults and children.

It is recommended to use domperidone cautiously and other drugs that prolong the QTc interval in patients with prolongation of cardiac conduction intervals, particularly QTc, and patients with significant electrolyte disturbances or heart disease underlying such as congestive heart failure.

INTERACTIONS

Domperidone

Antacids or antisecretory agents should not be taken simultaneously with oral formulations of domperidone as they lower the oral bioavailability of domperidone. Domperidone should be taken before meals and antacids or antisecretory agents after meals.

Concomitant administration of anticholinergic drugs may antagonise the anti-dyspeptic effects of domperidone.

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

Increased risk of occurrence of QT-interval prolongation, due to pharmacodynamic and/or pharmacokinetic interactions.

Association contraindicated

QTc prolonging medicinal products:

+  Anti-arrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine);

+  Anti-arrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol);

+  Certain anti-psychotics (e.g., haloperidol, pimozide, sertindole);

+  Certain anti-depressants (e.g., citalopram, escitalopram);

+  Certain antibiotics (e.g. , erythromycin, levofloxacin, moxifloxacin, spiramycin);

+  Certain antifungal agents (e.g., pentamidine);

+  Certain antimalarial agents (in particular halofantrine, lumefantrine);

+  Certain gastro-intestinal medicines (e.g., cisapride, dolasetron, prucalopride);

+  Certain antihistaminics (e.g., mequitazine, mizolastine);

+  Certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine);

+  Certain other medicines (e.g., bepridil, diphemanil, methadone).

Potent CYP3A4 inhibitors:

+  Protease inhibitors;

+  Systemic azole antifungals;

+  Some macrolides (erythromycin, clarithromycin, telithromycin). 

Association not recommended:

Moderate CYP3A4 inhibitors: diltiazem, verapamil and some macrolides. 

Combinations require caution in use:

The caution with drugs that induce bradycardia, hypokalemia and with the following macrolides, that prolong the QT interval: azithromycin and roxithromycin.

The list of substances mentioned above is representative and not exhaustive.

Simeticone

Levothyroxine may bind to simeticone. Absorption of levothyroxine may be impaired if simeticone is given concurrently. These two drugs should be given separately at least 4 hours.

PREGNANCY AND LACTATION

Pregnancy

There are few post-marketing data on the use of domperidone in pregnant women. A study in rats showed a toxic effect on reproduction at high doses toxic to the mother. The potential risk for humans is unknown. Therefore, this drug should only be used during pregnancy only if the expected therapeutic benefit justifies.

Breast-feeding

Domperidone is excreted in human milk and breast-fed infants receive less than 0.1 % of the maternal weight-adjusted dose. Occurrence of adverse effects, in particular cardiac effects cannot be excluded after exposure via breast milk. A decision should be made whether to discontinue breast-feeding or to discontinue/abstain from domperidone therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Caution should be exercised in case of QTc prolongation risk factors in breast-fed infants.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

This drug has no or negligible influence on the ability to drive and use machines.

UNDESIRABLE EFFECTS

Simeticone: None stated.

Domperidon

Frequency categories are defined according to the following convention: 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), not known (cannot be estimated from the available data).

OVERDOSE AND TREATMENT

Related to domperidone

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

Treatment: There is no specific antidote to domperidone, but in the event of overdose, standard symptomatic treatment should be given immediately. Gastric lavage as well as the administration of activated charcoal, may be useful. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation. Close medical supervision and supportive therapy is recommended.

Anticholinergic, anti-parkinson drugs may be helpful in controlling the extrapyramidal reactions.

Related to simeticone

No cases of overdose have been reported. Theoretically, constipation may occur. Treat with fluids and keep under observation.

STORAGE CONDITION

In a dry place, below 30°C, protect from light.

SHELF-LIFE

36 months from the manufacturing date. Do not use after the expiry date.