Zofran

Drugs , Gastrointestinal System / October 20, 2016

Class: Gastrointestinal System
Dosage Form: Various
Description: Proton pump inhibitor for management of nausea and vomiting
Stock: Available
Manufacturer: GlaxoSmithKline (GSK)

Composition:

Tablets
Ondansetron……………….4 mg or 8 mg
Ampoule
Ondansetron…………………….2 mg/ 1ml

Properties:

Ondanesteron is a potent, highly selective 5-HT3 receptor antagonist. Its precise mode of action in the control of nausea and vomiting is not known.
Chemotherapeutic agents and radiotherapy may cause release of 5-HT in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. Ondanesteron blocks the initiation of this reflex.
Activation of vagal afferents may also cause a release of 5HT in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism.
The efect of ondanesteron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and raidotherapy is therefore probably due to antagonism of 5-HT3 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.
Ondanesteron does not alter plasma prolactin concentrations.

Indications:

Ondansetron is indicated in:

  • Management of nausea and vomiting induced by cytotoxic chemotherapy and raidotherapy
  • Prevention of post-operative nausea and vomiting

Contraindicatons:

Hypersensitivity to any component of the preparation.

Drug Interactions:

There is no evidence that ondanesteron either induces or inhibits the metabolism of other drugs commonly coadministered with it. Specific studies have shown that ondanesteron does not interact with alcohol, temazepam, frusemide, tramadol and propofol.

Side Effects:

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>= 1/10), common (>= 1/100 and < 1/10), uncommon (>= 1/1000 and < 1/100), rare (>= 1/10,000 and < 1/1000) and very rare (< 1/10,000) including isolated reports. Very common, common and uncommon events were generally determined from clinical trial data. The incidence in placebo was taken into account. Rare and very rare events were generally determined from post-marketing spontaneous data.
The following frequencies are estimated at the standard recommended doses of ondansetron according to indication and formulation.
1. Immune System Disorders:

  • Rare: Immediate hypersensitivity reactions sometimes severe, including anaphylaxis

2. Nervous System Disorders:

  • Very common: Headache
  • Uncommon: Extrapyramidal reactions (such as oculogyric crisis/dystonic reactions) have been observed without definite evidence of persistent clinical sequelae, seizures
  • Rare: Dizziness during rapid I.V. administration

3. Eye Disorders:

  • Rare: Transient visual disturbances (e.g. blurred vision) during rapid I.V. administration.

4. Cardiac Disorders:

  • Uncommon: Arrhythmias, chest pain with or without ST segment depression, bradycardia

5. Vascular Disorders:

  • Common: Sensation of warmth or flushing
  • Uncommon: Hypotension

6. Respiratory, Thoracic and Mediastinal Disorders:

  • Uncommon: Hiccups

7. Hepatobiliary Disorders:

  • Uncommon: Asymptomatic increases in liver function tests
  • These events were observed commonly in patients receiving chemotherapy with cisplatin

8. General Disorders and Administration Site Conditions:

  • Common: Local I.V. infection site reactions

Dosage and Administration:

1. Chemotherapy and Radiotheray Induced Nausea and Vomiting:

  • Adults: The emetogenic potential of cancer treatment varies according to the doses and combinations of chemotherapy and radiotherapy regimens
  • Emetogenic chemotherapy and radiotherapy: The recommended oral dose is 8 mg 1-2 hours before treatment, followed by 8 mg orally 12 hours later. To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with Zofran should be continued for up to 5 days after a course of treatment. The recommended oral dose is 8 mg to be taken twice daily
  • Highly emetogenic chemotherapy: Zofran can be given by oral, intravenous or intramuscular route. The recommended oral dose is 24 mg taken together with oral dexamethasone sodium phosphate 12 mg, 1-2 hours before treatment.
    To protect against delayed or prolonged emesis after the first 24 hours, oral treatment with Zofran should be continued for up to 5 days after a course of treatment. The recommended oral dose is 8 mg to be taken twice daily
  • Children: In children, Zofran is administered as a single intravenous dose immediately before chemotherapy, followed by 4 mg orally twelve hours later, 4 mg orally twice daily should be continued for up to 5 days after a course of treatment
  • Elderly: Zofran is well tolerated by patients over 65 years old and no alteration of dosage, dosing frequency or route of administration is required

2. Post-Operative Nausea and Vomiting:

  • Adults: For prevention of post-operative nausea and vomiting, the recommended oral dose is 16 mg given one hour prior to anesthesia
  • For treatment of established post-operative nausea and vomiting, Zofran administration by injection is recommended
  • Children: For prevention of treatment of post-operative nausea and vomiting, Zofran may be administered by slow intravenous injection
  • Elderly: There is limited experience in the use of Zofran in the prevention and treatment of post-operative nausea and vomiting in the elderly, however, Zofran is well tolerated in patients over 65 years receiving chemotherapy

3. Patients with Renal Impairment:

  • No alteration of daily dosage or frequency of dosing, or route of administration are required

4. Patients with Hepatic Impairment:

  • Clearance of Zofran is significantly reduced and serum half-life significantly prolonged in subjects with moderate or severe impairment of hepatic function. In such patients, a total daily dose of 8 mg should not be exceeded

5. Patients with Poor Spartein/debrisoquine metabolism:

  • The elimination half-life of ondanesteron is not altered in subjects classified as poor metabolites of sparteine and debrisoquine
  • Consequently, in such patients repeat dosing will give drip exposure levels no different from those of the general population
  • No alteration of daily dosage or frequency of dosing are required

Overdosage:

There is limited experience of ondanesteron overdose. In the majority of cases, symptoms were similar to those already reported in patients receiving recommended doses. There is no specific antidote for ondanesteron, therefore in cases of suspected overdose, symptomatic and supportive therapy should be given as appropriate. The use of ipecacuanha to treat overdose with ondanesteron is not recommended as patients are unlikely to respond due to the anti-emetic action of Zofran itself.

Pregnancy and Lactation:

Pregnancy
The safety of odansetron 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 fetus, the course of gestation and peri- and post-natal development. However, as animal studies are not always predictive of human response the use of ondansetron in pregnancy is not recommended.

Lactation
Tests have shown that ondansetron passes into the milk of lactating animals. It is therefore recommended that mothers receiving ondansetron should not breast-feed their babies.

Warnings:

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists.
As ondanesteron is known to increase large bowel transit time, patients with signs of subacute intestinal obstruction should be monitored following administration.

Packaging:

Box of 5 vials of 2 ml (4 mg) or 4 ml (8 mg) each.
Pack of  strip of 10 tablets each.

Storage:

Store at room temperature, below 25°C.

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