DrugindexOnline^{2nd edition}

Pronouncation: (ahn-DAN-SEH-trahn HIGH-droe-KLOR-ide)
Class: 5-HT ₃ receptor antagonist

Trade Names:
Zofran
- Tablets 4 mg (as HCl dihydrate)
- Tablets 8 mg (as HCl dihydrate)
- Tablets 24 mg (as HCl dihydrate)
- Solution, oral 4 mg/5 mL (5 mg as HCl dihydrate)
- Injection 2 mg/mL (as HCl dihydrate)
- Injection 32 mg/50 mL (as HCl dihydrate)

Trade Names:
Zofran ODT
- Tablets, orally-disintegrating 4 mg (as base)
- Tablets, orally-disintegrating 8 mg (as base)

Mechanism of Action

Pharmacology

Selective serotonin (5-HT ₃ ) receptor antagonist that inhibits serotonin receptors in GI tract or chemoreceptor trigger zone.

Pharmacokinetics

Absorption

Passively and completely absorbed from GI tract. Bioavailability is 48% to 75% and is slightly enhanced with food.

C _max for males is 24.1 to 37 ng/mL (8 mg oral dose). C _max for females is 42.7 to 52.4 ng/mL (8 mg oral dose). C _max for injection is 102 to 170 ng/mL. T _max for males is 2 to 4.1 hr (8 mg dose). T _max for females is 1.7 to 4.9 hr (8 mg dose).

Distribution

Plasma protein binding is 70% to 76%.

Metabolism

Extensively metabolized in the liver by hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, CYP3A4 are the main hepatic enzymes.

Elimination

Approximately 5% is eliminated as parent compound in urine. The t _½ for males is 2.1 to 4.5 hr (8 mg oral dose). The t _½ for females is 1.9 to 6.2 hr (8 mg dose). The t _½ for injection is 3.5 to 5.5 hr. Plasma clearance is 0.262 to 0.381 L/hr/kg.

Special Populations

Elderly

In elderly over 75 yr, there is a reduction in clearance and an increase in elimination half-life. No dosage adjustment is necessary.

Gender

The extent and rate of absorption is greater in women than in men. There is slower clearance, a smaller volume of distribution, and higher bioavailability in women.

Severe Hepatic Insufficiency

Clearance is reduced 2- to 3-fold. The volume of distribution is increased. The half-life is increased to 20 hr. Bioavailability approaches 100%. A total daily dose of 8 mg should not be exceeded.

Severe Renal Insufficiency

There is a reduction in clearance. Oral plasma clearance was reduced by 50%. No dosage adjustment is necessary.

Indications and Usage

Parenteral and oral

Prevention of nausea and vomiting with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin; prevention of postoperative nausea or vomiting.

Oral

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 nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin 50 mg/m ² or more.

Unlabeled Uses

Treatment of nausea and vomiting associated with acetaminophen poisoning or prostacyclin therapy; treatment of acute levodopa-induced psychosis (visual hallucinations); reduction in bulimic episodes due to bulimia nervosa; treatment of spinal or epidural morphine-induced pruritus; management of social anxiety disorder.

Contraindications

Standard considerations.

Dosage and Administration

Prevention of Chemotherapy-Induced Nausea and Vomiting
Adults

IV 0.15 mg/kg infused over 15 min beginning 30 min before emetogenic chemotherapy with 2 additional 0.15 mg/kg doses 4 and 8 hr after the first dose. Alternatively, infuse 32 mg over 15 min, starting 30 min prior to emetogenic chemotherapy.

Adults and children 12 yr and older

PO (moderately emetogenic cancer chemotherapy) 8 mg bid, administering the first dose 30 min prior to starting emetogenic chemotherapy and the second dose 8 hr after the first dose; subsequent 8 mg doses may be given q 12 hr for 1 to 2 days after completion of chemotherapy.

Children 4 to 11 yr

PO 4 mg tid, starting 30 min prior to chemotherapy, with subsequent doses 4 and 8 hr after the first dose; give 4 mg q 8 hr for 1 to 2 days after completion of chemotherapy.

Prevention of Radiotherapy-Induced Nausea and Vomiting
Adults

PO 8 mg tid.

Total Body Irradiation
Adults

PO 8 mg 1 to 2 hr prior to each fraction of radiotherapy administered each day.

Single High-Dose Fraction Radiotherapy to the Abdomen
Adults

PO 8 mg 1 to 2 hr prior to radiotherapy, with subsequent doses q 8 hr after the first dose for 1 to 2 days after completion of radiotherapy.

Daily Fractionated Radiotherapy to the Abdomen
Adults

PO 8 mg 1 to 2 hr prior to radiotherapy, with subsequent doses q 8 hr after the first dose for each day radiotherapy is given.

Prevention of Postoperative Nausea and Vomiting
Adults

IV 4 mg (undiluted) over 30 sec (preferably over 2 to 5 min) or IM 4 mg (undiluted) as a single injection. PO 16 mg as a single dose 1 hr prior to induction of anesthesia.

Children (2 to 12 yr weighing 40 kg or less)

IV 0.1 mg/kg

Children (more than 40 kg)

IV 4 mg single dose. Administer over 30 sec or longer, preferably over 2 to 5 min.

Prevention of Nausea and Vomiting due to Highly Emetogenic Cancer Chemotherapy
Adults

PO 24 mg given 30 min prior to start of single-day highly emetogenic chemotherapy, including 50 mg/m ² or more cisplatin.

Drug Interactions

Rifamycins (eg, rifampin)

Plasma levels of ondansetron may be reduced, decreasing the antiemetic effect.

Incompatibility

Alkaline solutions.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Chest pain; tachycardia.

CNS

Headache; seizures.

Dermatologic

Rash.

GI

Dry mouth; constipation; abdominal pain.

Metabolic

Hypokalemia.

Respiratory

Bronchospasm.

Miscellaneous

Fever; anaphylaxis; weakness.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Dosing in children younger than 4 yr is not well defined.

Hepatic Function

In patients with severe hepatic impairment, do not exceed 8 mg/day oral dose. For IV use, give single 8 mg/day dose over 15 min beginning 30 min before chemotherapy.

Peristalsis

Ondansetron does not stimulate gastric or intestinal peristalsis; may mask progressive ileus or gastric distention.

Overdosage

Symptoms

Hypotension, constipation.

Patient Information

• Advise patient that headache is a common side effect.
• Advise patient that medication will greatly reduce likelihood of nausea and vomiting, but that these are still possible.