Generic

Ondansetron

Indications

Azithromycin is used to treat infections in the lower respiratory tract, such as bronchitis and pneumonia, as well as infections in the upper respiratory tract, such as sinusitis and pharyngitis/tonsillitis, otitis media, and skin and soft tissue infections. Azithromycin is used to treat non-gonococcal urethritis and cervicitis caused by Chlamydia trachomatis in both men and women with sexually transmitted infections.

Pharmacology

Ondansetron is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. The average bioavailability of healthy subjects was about 56%, and the bioavailability also increased slightly with the presence of food and higher doses, but was not affected by antacids. The volume of distribution of ondansetron is 1.92.6 L/kg, indicating that most of the drug is absorbed by human tissues. Circulating drugs are also distributed in red blood cells. The plasma protein binding rate is 70%, and it can easily pass through the membrane. The biotransformation pathway means that the main metabolic pathway is hydroxylation on the indole ring, followed by glucuronide or sulfate conjugation.Ondansetron is extensively metabolized by the liver and excreted in urine (about 65%) and feces (35%). The plasma half-life is 3.5 hours.Pharmacodinetics: Ondansetron is an effective and highly selective 5HT3 receptor antagonist. The exact mode of action for controlling nausea and vomiting is unclear. Chemotherapeutics and radiation therapy can activate the vagus nerve afferent through the 5HT3 receptor, which triggers the vomiting reflex, which leads to the release of 5HT in the small intestine. Ondansetron prevents this reflex from happening. The activation of the vagus nerve afferent also causes the postmas area at the bottom of the fourth ventricle to release 5HT, which can also promote vomiting through a central mechanism. Therefore, the effect of ondansetron in the treatment of nausea and vomiting caused by cytotoxic chemotherapy and radiotherapy may be due to the antagonism of 5HT3 receptors in neurons located in the central and peripheral nervous system. The mechanism of postoperative nausea and vomiting is not clear, but there may be a common pathway with nausea and vomiting caused by cytotoxicity.

Dosage & Administration

Chemotherapy-induced Nausea and Vomiting-

Adults/Geriatric/Child of 12 years or over:

Highly emetogenic cancer chemotherapy: 30 ml (24 mg) Ondansetron Oral Solution administered 30 minutes before start of emetogenic chemotherapy.

Moderate emetogenic cancer chemotherapy: 10 ml (8 mg) Ondansetron Oral Solution administered 30 minutes before start of emetogenic chemotherapy. A further 10 ml dose should be administered after 8 hours of the first dose. One 10 ml dose should be administered twice a day (every 12 hours) for 1-2 days after completion of chemotherapy.

Pediatric (4-11 years): 5 ml (4 mg) Ondansetron Oral Solution should be taken 30 minutes before the start of chemotherapy. The other 2 doses should be taken 4 and 8 hours after the first dose. Then 5 ml oral solution should be administered 3 times a day (every 8 hours) for 1-2 days after completion of chemotherapy.

Radiotherapy induced Nausea and Vomiting-

Adults/Geriatric/Child of 12 years or over:

The recommended oral dosage: 10 ml (8 mg) Ondansetron Oral Solution 3 times daily.

For total body irradiation: 10 ml (8-mg) Ondansetron Oral Solution 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 10 ml Ondansetron Oral Solution 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: 10 ml (8-mg) Ondansetron Oral Solution 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.

Postoperative Nausea and Vomiting-

Adults/Geriatric/Child of 12 years or over: 20 ml (16 mg) Ondansetron Oral Solution 1 hour before induction of anesthesia

Interaction

The cytochrome P-450 drug-metabolizing enzyme system of the liver does not appear to be induced or inhibited by ondansetron. Because Ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may alter Ondansetron’s clearance and, as a result, its half-life. For patients taking these medicines, no dosage adjustments of Ondasetron are indicated based on existing data.

Contraindications

Ondansetron oral solution is contraindicated for patients known to have hypersensitivity to the drug.

Side Effects

Common adverse events were headache, constipation and diarrhea, but most were mild or moderate. Among chemotherapy-induced nausea and vomiting, approximately 1% of patients receiving ondansetron have a rash. There are also reports of redness or fever, hiccups, and abnormal liver enzymes. Rare allergic reactions, bronchospasm, tachycardia, angina (chest pain), hypokalemia, and shortness of breath have also been reported. In addition to bronchospasm and allergic reactions, the relationship with ondansetron is not clear. There is no evidence of extrapyramidal reactions. In rare cases, it is a stand-alone ophthalmic crisis, and other dystonic reactions for which there is no clear clinical evidence. In the case of PONV, with the exception of headaches, the incidence of these events did not differ significantly between ondansetron and placebo groups.

Pregnancy & Lactation

No carcinogenic effects were observed in the 2-year study in which oral ondansetron doses were as high as 10 and 30 mg / kg per day in rats and mice. In the standard mutagenicity test, ondansetron is not mutagenic. Daily oral ondansetron 15 mg / kg does not affect fertility or general reproductive performance of male and female rats.

Reproduction studies were conducted in pregnant rats and rabbits, with daily oral doses as high as 15 and 30 mg / kg per day, respectively, and no evidence was found that ondansetron caused fertility or harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women. Ondansetron is excreted in the breast milk of rats. Therefore, breastfeeding women should be cautious when taking ondansetron.

Precautions & Warnings

Patients who had previously experienced hypersensitivity to other selective 5-HT3 receptor antagonists have reported hypersensitivity reactions to this drug. Ondansetron is not a stomach or intestinal peristalsis stimulant. It should never be substituted with nasogastric suction. Ondansetron may be used to mask a progressive ileus and/or gastric distension in individuals who have had abdominal surgery or who have chemotherapy-induced nausea and vomiting.

Therapeutic Class

Anti-emetic drugs

Storage Conditions

Store in a cool and dry place below 30ºC. Protect from light. keep out of reach of children.

Pharmaceutical Name

Eskayef Pharmaceuticals Ltd.