Lafaxid-D Tablets

Each modified release uncoated bilayered

tablet contains :

Lafutidine 10 mg

(As immediate release)

Domperidone Maleate IP

equivalent to Domperidone 30 mg

(As prolonged release)

Excipients q.s.

Colour : Red Oxide of Iron

Gastroesophageal reflux disease (GERD).

Contraindications :

General

Hypersensitivity to the active substance or to any of the excipients.

Domperidone

• Prolactin-releasing pituitary tumour (prolactinoma).

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

• 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 or underlying cardiac disease such as congestive heart failure.

• Co-administration with QT-prolonging drugs.

• Co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects).

Dosage and Administration :

One tablet once or twice daily.

Overdosage

Domperidone

Symptoms

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, 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 within 2 hours of overdosage. ECG monitoring should be undertaken, because of the possibility of QT prolongation. Close medical supervision and supportive therapy is recommended. Anticholinergic, anti-parkinson drugs may be helpful in controlling extrapyramidal reactions.

Lafutidine

No data on overdosage with Lafutidine is available.

Adverse Effects :

Domperidone

As the hypophysis is outside the blood brain barrier, Domperidone may cause an increase in prolactin levels. In rare cases this hyperprolactinaemia may lead to neuro-endocrine side effects such as galactorrhoea, gynaecomastia and amenorrhoea. Extrapyramidal side effects are uncommon in adults. These side effects reverse spontaneously and completely as soon as treatment is stopped.

Lafutidine

Constipation, diarrhea, drug rash, nausea or vomiting and dizziness are the adverse reactions observed during clinical trials. Other adverse effects of unknown frequency include abnormal changes in liver function tests, elevation of serum uric acid levels and hypersensitivity reactions (itching, redness of the skin, skin rash).

Drug Interactions :

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. Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral Ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of Domperidone's CYP3A4 mediated first pass metabolism by these drugs.

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

• 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 and some macrolides.

Concomitant use of the following substances requires caution in use

Caution with bradycardia and hypokalaemia-inducing drugs, as well as with the following macrolides involved in QT-interval prolongation: azithromycin and roxithromycin (clarithromycin is contra-indicated as it is a potent CYP3A4 inhibitor).

Levodopa : Increase of plasma levels of levodopa (max 30-40%).

The above list of substances is representative and not exhaustive.

Opioids may antagonise the effects of Domperidone on gastric emptying.

Lafutidine

Not known

Pregnancy

There are no data about the use of Lafaxid D in pregnant patients

Domperidone

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. Such patients on prolonged therapy should be reviewed regularly

Cardiovascular effects

Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. Epidemiological studies showed that Domperidone was associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging drugs or CYP3A4 inhibitors. Treatment with Domperidone should be stopped if signs or symptoms occur that may be associated with cardiac arrhythmia, and the patients should consult their physician. Domperidone should be used at the lowest effective dose in adults and children.

Co-administration of Levodopa

Although no dosage adjustment of levodopa is deemed necessary, an increase of plasma levodopa concentration (max 30-40%) has been observed when Domperidone was taken concomitantly with levodopa.

Lafutidine

• Careful observation should be made for any changes in hematological, hepatic or renal parameters, and for changes in other factors.
• Since treatment with this product may mask the symptoms of gastric cancer, administration should be made after confirming the tumor is not malignant.

Store protected from light & moisture at a temperature not exceeding 30°C.

Keep out of reach of children.

A blister strip of 10 tablets.