APR ONDANICE MD

INFORMATION FOR THE USER

Ondansetron 2mg/5ml Syrup

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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.

COMPOSITION:
Each 5ml of syrup contains:
Ondansetron – 2mg

For Oral use only.

DESCRIPTION:
Ondansetron belongs to a class of drugs known as anti-emetics. It is used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy or surgery. It is also useful in gastroenteritis.

PHARMACOLOGICAL ACTION:
Ondansetron is a potent, highly selective 5-HT3 receptor-antagonist. Chemotherapeutic agents & radiotherapy may cause release of 5-HT in small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. It blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5-HT in the area postrema located on the floor of the 4th ventricle & this may also promote emesis through a central mechanism. The effect in the management of nausea & vomiting is due to antagonism of 5-HT3 receptors on neurons located both in the peripheral & central nervous system. The mechanisms of action in post-operative nausea & vomiting are not known but there may be common pathways with cytotoxic induced nausea & vomiting. It does not alter plasma prolactin concentrations.
CLINICAL PHARMACOKINETICS:
Following oral administration ondansetron is passively & completely absorbed from the GI tract & undergoes first pass metabolism (bioavailability~60%). Peak plasma concentrations of about 30 ng/ml are attained approx. 1.5 hours after an 8mg dose. For doses above 8mg the increase in systemic exposure with dose is greater than proportional; this may reflect some reduction in first pass metabolism at higher oral doses. Bioavailability following oral administration is slightly enhanced by the presence of food but unaffected by antacids. Studies in healthy elderly volunteers have shown slight, but clinically insignificant, age-related increases in both oral bioavailability (65%) & half-life (5 hours). Gender differences were shown in the disposition. The extent & rate of absorption is greater in women than men. Slower clearance in women, a smaller apparent volume of distribution (adjusted for weight) & higher absolute bioavailability resulted in higher plasma levels. These higher plasma levels may in part be explained by differences in body weight between men & women. The disposition following oral dosing is similar with a terminal half life of about 3 hours & steady state volume of distribution of about 140L. Equivalent systemic exposure is achieved after IM & IV administration. The protein binding is 70-76%. A direct effect of plasma concentration & anti-emetic effect has not been established. It is cleared from the systemic circulation predominantly by hepatic metabolism through multiple enzymatic pathways. Less than 5% of the absorbed dose is excreted unchanged in the urine. The absence of the enzyme CYP2D6 has no effect on pharmacokinetics. The pharmacokinetic properties are unchanged on repeat dosing. In patients with renal impairment (creatinine clearance 15-60 ml/min) both systemic clearance & volume of distribution are reduced following IV administration resulting in a slight but clinically insignificant increase in elimination half-life (5.4h). A study in patients with severe renal impairment who required regular haemodialysis showed pharmacokinetics to be essentially unchanged. Following oral, IV or IM dosing in patients with severe hepatic impairment systemic clearance is markedly reduced with prolonged elimination half-lives (15-32 h) & an oral bioavailability approaching 100% due to reduced pre-systemic metabolism.

INDICATIONS:
Ondansetron is indicated for:
Management of nausea & vomiting induced by cytotoxic chemotherapy & radiotherapy.
For the prevention & treatment of post-operative nausea and vomiting (PONV).

CONTRAINDICATIONS:
Ondansetron tablets are contraindicated in the following cases:
Hypersensitivity to ondansetron or to any of the excipients.
Hypersensitivity to other selective 5-HT3 receptor antagonists (e.g. granisetron, dolasetron).
Concomitant use with apomorphine.

WARNINGS AND PRECAUTIONS:
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.
Prolongs the QT interval in a dose-dependent manner. Avoid in patients with congenital long QT syndrome. Should be administered with caution to patients who have/may develop prolongation of QTc, including patients with electrolyte abnormalities, congestive heart failure etc. 
Hypokalemia & hypomagnesemia should be corrected prior to administration. 
Known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.
In adenotonsillar surgery prevention of nausea & vomiting it may mask occult bleeding.
Caution should be exercised if ondansetron is co-administered with anaesthetics to patients with arrhythmias/cardiac conduction disorders or to patients who are being treated with antiarrhythmic agents or beta-blockers.
Very rarely & predominantly with IV ondansetron, transient ECG changes including QT interval prolongation have been reported. Caution is advised if patients have received cardiotoxic agents & in patients with a history of prolonged QT syndrome.
Respiratory events should be treated symptomatically & clinicians should pay particular attention to them as precursors of hypersensitivity reactions.

ADVERSE EFFECTS:
Common side effects associated with ondansetron are:
Headache
Sensation of warmth/flushing
Constipation
Hypotension
Hiccups

DRUG INTERACTIONS:
There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability & neuromuscular abnormalities) following the concomitant use of ondansetron and other serotonergic drugs (including SSRIs & SNRIs).
Apomorphine: Based on reports of profound hypotension & loss of consciousness when administered with apomorphine, concomitant use with apomorphine is contraindicated.
Phenytoin, Carbamazepine & Rifampicin: The clearance of ondansetron was increased & ondansetron blood concentrations were decreased.
Tramadol: May reduce the analgesic effect of tramadol.
Concomitant use of ondansetron with cardiotoxic drugs (eg. doxorubicin, daunorubicin or trastuzimab), antibiotics (eg. erythromycin or ketoconazole), antiarrhythmics (eg. amiodarone) & beta blockers (eg. atenolol or timolol) may increase the risk of arrhythmias.

DOSAGE:
The route of administration and dose of ondansetron should be flexible in the range of 8-32 mg a day and selected.

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.

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

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Last revised on May 2019.