ondansetron HCl 4 MG Oral Tablet
WARNINGS
Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT 3 receptor antagonists.
ECG changes including QT interval prolongation has been seen in patients receiving ondansetron.
In addition, post-marketing cases of Torsade de Pointes have been reported in patients using ondansetron.
Avoid ondansetron hydrochloride in patients with congenital long QT syndrome.
ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation.
DRUG INTERACTIONS
Drug Interactions Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver (see CLINICAL PHARMACOLOGY, Pharmacokinetics ).
Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of ondansetron.
On the basis of available data, no dosage adjustment is recommended for patients on these drugs.
Apomorphine Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, concomitant use of apomorphine with ondansetron is contraindicated (see CONTRAINDICATIONS ).
Phenytoin, Carbamazepine, and Rifampicin In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased.
However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.
1, 3 Tramadol Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small studies indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.
4, 5 Chemotherapy Tumor response to chemotherapy in the P-388 mouse leukemia model is not affected by ondansetron.
In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.
In a crossover study in 76 pediatric patients, I.V.
ondansetron did not increase blood levels of high-dose methotrexate.
OVERDOSAGE
There is no specific antidote for ondansetron overdose.
Patients should be managed with appropriate supportive therapy.
Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events.
These doses are more than 10 times the recommended daily dose.
In addition to the adverse events listed above, the following events have been described in the setting of ondansetron overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes’ duration plus severe constipation occurred in 1 patient that was administered 72 mg of ondansetron intravenously as a single dose.
Hypotension (and faintness) occurred in a patient that took 48 mg of ondansetron tablets.
Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed.
In all instances, the events resolved completely.
DESCRIPTION
The active ingredient in ondansetron tablets is ondansetron hydrochloride (HCl) as the dihydrate, the racemic form of ondansetron and a selective blocking agent of the serotonin 5-HT 3 receptor type.
Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one, monohydrochloride, dihydrate.
It has the following structural formula: The molecular formula is C 18 H 19 N 3 O•HCl•2H 2 O, representing a molecular weight of 365.9.
Ondansetron HCl dihydrate is a white to off-white powder that is soluble in water and normal saline.
Each 4 mg ondansetron tablet, USP for oral administration contains ondansetron hydrochloride dihydrate equivalent to 4 mg of ondansetron.
Each 8 mg ondansetron tablet, USP for oral administration contains ondansetron hydrochloride dihydrate equivalent to 8 mg of ondansetron.
Each tablet also contains the inactive ingredients croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch, titanium dioxide, triacetin, and iron oxide yellow (8 mg tablet only).
This product meets USP Dissolution Test 3.
chemical structure
HOW SUPPLIED
Product: 50090-1600 NDC: 50090-1600-0 10 TABLET, FILM COATED in a BOTTLE NDC: 50090-1600-2 20 TABLET, FILM COATED in a BOTTLE NDC: 50090-1600-4 3 TABLET, FILM COATED in a BOTTLE
GERIATRIC USE
Geriatric Use Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign-controlled clinical trials, for which there were subgroup analyses, 938 were 65 years of age and over.
No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Dosage adjustment is not needed in patients over the age of 65 (see CLINICAL PHARMACOLOGY ).
INDICATIONS AND USAGE
INDICATIONS & USAGE Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥ 50 mg/m 2 .
Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.
Prevention of postoperative nausea and/or vomiting.
As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.
In patients where nausea and/or vomiting must be avoided postoperatively, ondansetron tablets are recommended even where the incidence of postoperative nausea and/or vomiting is low.
PEDIATRIC USE
Pediatric Use Little information is available about dosage in pediatric patients 4 years of age or younger (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION sections for use in pediatric patients 4 to 18 years of age).
PREGNANCY
Pregnancy Teratogenic Effects Pregnancy Category B.
Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively, and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron.
There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed
NUSRING MOTHERS
Nursing Mothers Ondansetron is excreted in the breast milk of rats.
It is not known whether ondansetron is excreted in human milk.
Because many drugs are excreted in human milk, caution should be exercised when ondansetron is administered to a nursing woman.
DOSAGE AND ADMINISTRATION
Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy The recommended adult oral dosage of ondansetron tablets is 24 mg given as three 8 mg tablets administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥ 50 mg/m 2 .
Multiday, single-dose administration of a 24 mg dosage has not been studied.
Pediatric Use There is no experience with the use of a 24 mg dosage in pediatric patients.
Geriatric Use The dosage recommendation is the same as for the general population Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy The recommended adult oral dosage is one 8 mg ondansetron tablet given twice a day.
The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose.
One 8 mg ondansetron tablet should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy.
Pediatric Use For pediatric patients 12 years of age and older, the dosage is the same as for adults.
For pediatric patients 4 through 11 years of age, the dosage is one 4 mg ondansetron tablet or one 4 mg given 3 times a day.
The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose.
One 4 mg ondansetron tablet should be administered 3 times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy.
Geriatric Use The dosage is the same as for the general population.
Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen The recommended oral dosage is one 8 mg ondansetron tablet given 3 times a day.
For total body irradiation , one 8 mg ondansetron tablet should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.
For single high-dose fraction radiotherapy to the abdomen , one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.
For daily fractionated radiotherapy to the abdomen , one 8 mg ondansetron tablet should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.
Pediatric Use There is no experience with the use of ondansetron tablet in the prevention of radiation-induced nausea and vomiting in pediatric patients.
Geriatric Use The dosage recommendation is the same as for the general population.
Postoperative Nausea and Vomiting The recommended dosage is 16 mg given as two 8 mg ondansetron tablets 1 hour before induction of anesthesia.
Pediatric Use There is no experience with the use of ondansetron tablets in the prevention of postoperative nausea and vomiting in pediatric patients.
Geriatric Use The dosage is the same as for the general population.
Dosage Adjustment for Patients With Impaired Renal Function The dosage recommendation is the same as for the general population.
There is no experience beyond first-day administration of ondansetron.
Dosage Adjustment for Patients With Impaired Hepatic Function In patients with severe hepatic impairment (Child-Pugh 2 score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life.
In such patients, a total daily dose of 8 mg should not be exceeded.