The Cathay Drug Co., Inc.
Each film-coated tablet contains:
Ondansetron Hydrochloride Dihydrate, USP
eq. Ondansetron ………. …………8 mg
A white to off white coloured, round biconvex, both side plain film-coated tablets.
Mechanism of Action
Ondansetron is a potent, highly selective 5-HT3 receptor antagonist.
Its precise antiemetic and antinauseal mechanism of action is not known. Chemotherapeutic agents and radiotherapy may cause release of 5-HT3 in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5-HT3 in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of Ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of receptors on neurons located both in the peripheral and central nervous system.
The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.
Ondansetron does not alter plasma prolactin concentrations.
The role of Ondansetron in opiate-induced emesis is not yet established.
Peak plasma concentrations of Ondansetron occur about 1.5 hours after an oral dose of 8 mg, and about 6 hours after a rectal dose. The absolute bioavailability may be somewhat higher (65%) and clearance lower, presumably due to reduced hepatic first-pass metabolism.
Ondansetron is extensively distributed in the body; about 70 to 75% of the drug is protein bound.
It is metabolized in the liver through multiple enzymatic pathways; Ondansetron is a substrate for cytochrome P450 isoenzymes, primarily CYP3A4, but also CYP1A2 and CYP2D6. Less than 5% of a dose is excreted unchanged in the urine.
Ondansetron is a 5-HT3 antagonist with antiemetic activity. It is used in the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. It is also used for the prevention and treatment of post-operative nausea and vomiting.
DOSAGE AND ADMINISTRATION
8 mg can be given by mouth up to 2 hours before treatment followed by 8 mg to 12 hours later.
To protect against delayed emesis, these regimens are followed by Ondansetron 8 mg by mouth twice daily for up to 5 days after the end of a course of chemotherapy.
Or as prescribed by the physician.
For children aged 4 to 11 years a dose of 4 mg can be given 30 minutes before start of chemotherapy, with subsequent 4 mg doses given 4 and 8 hours thereafter. A dose of 4 mg three times daily by mouth may be given for 1 to 2 days after the end of chemotherapy.
PREVENTION AND TREATMENT OF POST-OPERATIVE NAUSEA AND VOMITING
Adults: 16 mg orally an hour before anaesthesia or 8 mg orally an hour before anaesthesia followed by 2 further doses of 8 mg at 8-hour intervals.
PATIENTS WITH RENAL/HEPATIC IMPAIRMENT
Patients with renal impairment: A total dose should not exceed 8 mg.
The concomitant use of apomorphine with Ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Ondansetron.
ADVERSE DRUG REACTIONS
Ondansetron may cause headache, a sensation of flushing or warmth, hiccups, and constipation. A transient rise in liver enzymes has occasionally occurred.
There have been rare reports of immediate hypersensitivity reactions, including anaphylaxis, chest pain, hypotension, tachycardia, and bradycardia have been reported rarely.
Ondansetron should be used with care in patients with signs of subacute intestinal obstruction or ileus. Ondansetron should be given in reduced doses to patients with moderate to severe hepatic impairment.
There is no evidence that Ondansetron either induces or inhibits the metabolism of other medical products commonly co-administered with it. Specific studies have shown that Ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lignocaine, propofol and thiopental. Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising Ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall Ondansetron clearance or dose requirement.
Caution should be exercised when Ondansetron is co-administered with drugs that prolong the QT interval and/or cause electrolyte abnormalities.
Use of Ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of Ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias.
Serotonergic Drugs (e.g. SSRIs and SNRIs)
There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of Ondansetron and other serotonergic drugs (including SSRIs and SNRIs).
Based on reports of profound hypotension and loss of consciousness when Ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.
Phenytoin, Carbamazepine and Rifampicin
In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and Ondansetron blood concentrations were decreased.
Data from small studies indicate that Ondansetron may reduce the analgesic effect of tramadol.
FERTILITY, PREGNANCY AND LACTATION
The safety of Ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or foetus, the course of gestation pre-and post-natal development. However as animal studies are not always predictive of human response the use of Ondansetron in pregnancy is not recommended.
Tests have shown that Ondansetron passes into the milk of lactating animals. It is therefore, recommended that mothers receiving Ondansetron should not breastfeed their babies.
There is no information on the effects of Ondansetron on human fertility.
OVERDOSE AND TREATMENT
Manifestations that have been reported include severe constipation, visual disturbances, hypotension and a vasovagal episode with transient second degree AV block. In case of suspected overdose, symptomatic and supportive therapy should be given as appropriate, as there is no specific antidote for Ondansetron.
Foods, Drugs, Devices, and Cosmetics Act prohibits dispensing without prescription.
Store at temperatures not exceeding 30°C. Protect from light.
KEEP ALL MEDICINES OUT OF REACH OF CHILDREN.
Alu/PVC Blister pack x 10’s (Box of 10’s)
Marketing Authorization Holder
THE CATHAY DRUG CO., INC.
2/F Vernida I Condominium
120 Amorsolo St., Legaspi Village
Makati, Metro Manila
STALLION LABORATORIES PVT. LTD.
C-1B, 305/2 & 3, G.I.D.C. Kerala, Bavla-382 220
Dist: Ahmedabad, Gujarat, India
ENDURANCE HEALTHCARE PVT. LTD.
823, Devpath, B/H Lal Bungalow, Ellisbridge
Ahmedabad-380 006, India
AMBICA INTERNATIONAL CORPORATION
No. 9 Amsterdam Extension, Merville Park Subd.
Parañaque, Metro Manila
DATE OF REVISION: September 21, 2021