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Ondansetron Hydrochloride

Pronunciation

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

Trade Names

Ondansetron Hydrochloride
- Tablets 16 mg
- Tablets 24 mg
- Injection 32 mg/50 mL

Zofran
- Tablets 4 mg
- Tablets 8 mg
- Solution, oral 4 mg/5 mL (5 mg as hydrochloride dihydrate)
- Injection 2 mg/mL

Zofran ODT
- Tablets, orally-disintegrating 4 mg
- Tablets, orally-disintegrating 8 mg

Zuplenz
- Film, oral 4 mg
- Film, oral 8 mg

Apo-Ondansetron (Canada)
PMS-Ondansetron (Canada)
ratio-Ondansetron (Canada)
Sandoz Ondansetron (Canada)

Pharmacology

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

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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. C max for the film is 37.28 ng/mL. T max for males is 2 to 4.1 h (8 mg dose). T max for females is 1.7 to 4.9 h (8 mg dose). T max for the film is 1.3 h.

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 half-life for males is 2.1 to 4.5 h (8 mg oral dose). The half-life for females is 1.9 to 6.2 h (8 mg dose). The half-life for injection is 3.5 to 5.5 h. Plasma Cl is 0.262 to 0.381 L/h/kg. The half-life for the film is 4.6 h.

Special Populations

Renal Function Impairment

Mean plasma Cl is reduced by 50% in patients with severe renal impairment.

Severe Renal Function Impairment

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

Hepatic Function Impairment

Cl is reduced 2- to 3-fold and the volume of distribution is increased. The half-life is increased to 20 h in patients with severe hepatic impairment. Bioavailability approaches 100%.

Elderly

In elderly older than 75 y of age, there is a reduction in Cl 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 Cl, a smaller volume of distribution, and higher bioavailability in women.

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

Concomitant use with apomorphine ( Zuplenz only); hypersensitivity to ondansetron.

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 h after the first dose. Alternatively, infuse 32 mg over 15 min, starting 30 min prior to emetogenic chemotherapy.

Adults and children 12 y of age and older

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

Children 4 to 11 y of age

PO 4 mg 3 times daily, starting 30 min prior to chemotherapy, with subsequent doses 4 and 8 h after the first dose; give 4 mg every 8 h for 1 to 2 days after completion of chemotherapy.

Prevention of Nausea and Vomiting due to Moderately 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.

Prevention of Radiotherapy-Induced Nausea and Vomiting
Adults

PO 8 mg 3 times daily.

Total Body Irradiation
Adults

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

Single High-Dose Fraction Radiotherapy to the Abdomen
Adults

PO 8 mg 1 to 2 h prior to radiotherapy, with subsequent doses every 8 h 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 h prior to radiotherapy, with subsequent doses every 8 h 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 h prior to induction of anesthesia.

Children (2 to 12 y of age 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.

Hepatic Function Impairment
Severe Hepatic Impairment

PO Max, 8 mg/day.

IV Single 8 mg/day dose over 15 min beginning 30 min before chemotherapy.

General Advice

  • Film
  • For oral use only. Do not chew or swallow.
  • With dry hands, remove the film from the pouch and immediately place the film on top of the tongue where it dissolves in 4 to 20 sec.
  • Once the film is dissolved, swallow with or without liquid.
  • Wash hands after administration.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

Apomorphine

Concomitant use is contraindicated.

CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampicin)

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

Tramadol

Concomitant use may result in reduced analgesic activity of tramadol.

Incompatibility

Alkaline solutions.

Adverse Reactions

Cardiovascular

Bradycardia (6%); hypotension (5%); chest pain, ECG changes, tachycardia, vascular occlusive events.

CNS

Headache (27%); drowsiness/sedation (20%); malaise/fatigue (13%); dizziness (7%); anxiety/agitation (6%); extrapyramidal symptoms, seizures, tonic-clonic seizures.

Dermatologic

Pruritis (5%); rash (1%); flushing, urticaria (postmarketing).

GI

Constipation (9%); diarrhea (7%); dry mouth, abdominal pain.

Genitourinary

Gynecological disorder (7%); urinary retention (5%); oculogyric crisis (postmarketing).

Hepatic

AST and/or ALT elevated (2%), abnormal LFTs (postmarketing).

Hypersensitivity

Anaphylaxis; hypersensitivity reactions, sometimes severe (eg, angioedema, shortness of breath, hypotension, laryngeal edema, stridor), laryngospasm, shock, cardiopulmonary arrest (postmarketing).

Metabolic

Hypokalemia.

Respiratory

Hypoxia (9%), bronchospasm.

Miscellaneous

Wound problem (28%); fever (8%); shivers (5%); hiccups, transient blindness, weakness (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Dosing in children younger than 4 y of age is not well defined.

Zuplenz

Safety and efficacy for prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, radiotherapy, and/or prevention of postoperative nausea and/or vomiting not established for children; safety and efficacy of prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy not established in children younger than 4 y of age.

Hypersensitivity

Anaphylaxis and bronchospasm have been reported.

Hepatic Function

Reduced doses required in severe hepatic impairment.

ECG changes

Transient ECG changes, including QT interval prolongation, have been reported rarely and predominately with IV use.

GI effects

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

Overdosage

Symptoms

Amaurosis, constipation, hypotension, vasovagal episode with transient second-degree heart block.

Patient Information

  • Advise patient that headache is a common adverse reaction.
  • Advise patient that medication will greatly reduce likelihood of nausea and vomiting, but that these are still possible.
  • Advise patients that hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm, have occurred.

Copyright © 2009 Wolters Kluwer Health.

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