APR DOMIREST

INFORMATION FOR THE USER

Domperidone 10mg Tablets

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

1. COMPOSITION:
Each tablet contains:
Domperidone – 10mg

For oral use only.

2. DESCRIPTION:
Domperidone is a drug that is useful as an antiemetic and a gastro prokinetic agent. It falls under the category of dopamine D2 receptor antagonist

3. PHARMACOLOGICAL ACTION:
Domperidone is a dopamine antagonist with anti-emetic properties. It does not readily cross the blood brain barrier. Extrapyramidal side effects are very rare, but it promotes the release of prolactin from the pituitary. Its anti-emetic effect may be due to a combination of peripheral (gastrokinetic) effects & antagonism of dopamine receptors in the chemoreceptor trigger zone which lies outside the blood-brain barrier in the area postrema. Studies together with the low concentrations found in the brain indicate a predominantly peripheral effect on dopamine receptors. It increases lower oesophageal pressure, improves antroduodenal motility & accelerates gastric emptying. There is no effect on gastric secretion.

4. CLINICAL PHARMACOKINETICS:
Domperidone is rapidly absorbed after oral administration with peak plasma concentrations occurring at approximately 1 hr after dosing. The Cmax& AUC values increased proportionally with dose in the 10mg- 20mg range. A 2-3 fold accumulation of AUC was observed with repeated 4 times daily (every 5 hr) dosing for 4 days. The low absolute bioavailability (approx. 15%) is due to an extensive first-pass metabolism in gut wall & liver. Although bioavailability is enhanced when taken after a meal patients with GI complaints should take domperidone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption. Bioavailability is decreased by prior concomitant administration of cimetidine & sodium bicarbonate. The time of peak absorption is slightly delayed & the AUC somewhat increased when taken after a meal. It does not appear to accumulate/induce its own metabolism; a peak plasma level after 90 minutes of 21ng/ml after 2 weeks. It is 91-93% bound to plasma proteins. Studies have shown wide tissue distribution, but low brain concentration. It undergoes rapid & extensive hepatic metabolism by hydroxylation & N-dealkylation. Urinary & faecal excretions amount to 31 & 66%. The proportion of the drug excreted unchanged is small (10% of faecal excretion & approx. 1% of urinary excretion). Plasma half life is 7-9 hours but is prolonged in patients with severe renal insufficiency.
5. INDICATIONS:
Domperidone is indicated for the relief of the symptoms of nausea & vomiting.

6. CONTRAINDICATIONS:
Domperidone is contraindicated in the following situations:
• In patients with moderate or severe hepatic impairment.
• In patients who have known existing prolongation of cardiac conduction intervals, particularly QTc patients with significant electrolyte disturbances/underlying cardiac diseases such as congestive heart failure.
• Co-administration with QT-prolonging drugs, at the exception of apomorphine.
• Co-administration with potent CY3A4 inhibitors (regardless of their QT prolonging effects).
• Known hypersensitivity to domperidone or any of the excipients.
• Prolactin-releasing pituitary tumour (prolactinoma).
• Renal impairment and hepatic impairment

Should not be used when stimulation of gastric motility could be harmful: gastro-intestinal haemorrhage, mechanical obstruction or perforation.

7. WARNINGS AND PRECAUTIONS:
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in infants: Since metabolic functions & 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. Overdosing may cause extrapyramidal symptoms in children, but other causes should be taken into consideration.
Renal Impairment: Elimination half-life is prolonged in severe renal impairment.
Cardiovascular effects: Has been associated with prolongation of the QT interval on the electrocardiogram.
Use with apomorphine: Domperidone is contra-indicated with QT prolonging drugs including apomorphine, unless the benefit of the co-administration with apomorphine outweighs the risks.

8. ADVERSE EFFECTS:
The common adverse effects associated with treatment with Domperidone include:
– Dry mouth
– Anxiety
– Headache
– Gallactorrhoea
– Breast pain and tenderness
– Asthenia

9. DRUG INTERACTIONS:
Concomitant use of the following substances is contraindicated:
• anti-arrhythmics class IA (e.g. disopyramide, hydroquinidine, quinidine)
• anti-arrhythmics 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. 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)
• apomorphine, unless the benefit of the co-administration outweighs the risks, and only if the recommended precautions for co-administration are strictly fulfilled. Please refer to the apomorphine SmPC.
Potent CYP3A4 inhibitors (regardless of their QT prolonging effects), i.e :
• protease inhibitors
• systemic azole antifungals
• some macrolides (erythromycin, clarithromycin and telithromycin)
Concomitant use of the following substances is not recommended
Moderate CYP3A4 inhibitors i.e. diltiazem, verapamil & some macrolides.
Concomitant use of the following substances requires caution in use
Caution with bradycardia & hypokalaemia-inducing drugs as well as with the following macrolides involved in QT-interval prolongation: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent CYP3A4 inhibitor).
Ketoconazole or oral erythromycin: marked inhibition of domperidone’s CYP3A4 mediated first pass metabolism by these drugs.
10. DOSAGE:
One 10mg tablet up to three times per day with maximum dose of 30 mg per day.

11. ADMINISTRATION:
The tablets need to be swallowed with a glass of liquid. Do not crush or break the tablet as it will destroy the film coating.

12. STORAGE:
Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

13. MANUFACTURED BY:

14. MARKETED BY:

Last revised on May 2019.