The P-I-E-N-O Parkinsn's List Drug Database
ondansetron / ZofranTM
ANTI-EMETIC/
Anti Hallucinating
Description: Ondansetron is an oral and parenteral antiemetic agent. It is the first selective serotonin blocking agent to be marketed. It is similar to granisetron, which was marketed in 1994. Ondansetron is an extremely safe and highly effective antiemetic that has greatly improved the ability to give chemotherapy. The quality of life of patients has been tremendously better with ondansetron than with older, traditional antiemetics. Despite its effectiveness, ondansetron is not recommended for the routine treatment of nausea due to its significant cost. Ondansetron was originally approved for the treatment of chemotherapy-induced nausea/vomiting by the FDA in January 1991 and tablets were approved for the treatment of post-operative nausea/vomiting in April 1995.
Mechanism of Action: Ondansetron may have central and/or peripheral action. Ondansetron selectively blocks the serotonin 5-HTA receptors. (In contrast, sumatriptan stimulates serotonin receptors, albeit of a different type.) 5-HTA receptors are found centrally in the chemoreceptor trigger zone and peripherally at vagal nerve terminals in the intestines. Whether the action of ondansetron is mediated centrally, peripherally, or a combination of both remains to be determined. Emesis during chemotherapy and radiation therapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine. Blocking these nerve endings in the intestines prevents signals to the central nervous system. Ondansetron has no dopamine-receptor blocking activity. Colonic transit time is slowed after multiple oral doses of ondansetron.
Pharmacokinetics: Ondansetron is administered orally and parenterally. Oral bioavailability of the tablets is 59%. The drug is also administered by IV infusion. Animal studies indicate that ondansetron has no teratogenic effects and that it is distributed into breast milk. Approximately 36% of an ondansetron dose is distributed into erythrocytes. The drug is about 70-76% bound to plasma protein. Ondansetron undergoes extensive metabolism, mainly by hydroxylation, followed by glucuronide or sulfate conjugation. For adults, the mean elimination half-life is 4 hours; patients under age 15 years show a shorter half-life of about 2.4 hours. Less than 5% of an intravenous dose is eliminated unchanged in the urine. The inactive metabolites are eliminated in the urine.
CONTRAINDICATIONS/PRECAUTIONS: Ondansetron is extensively metabolized in the liver and should be used with caution in patients with hepatic disease because of possible increased plasma levels and subsequent toxicity. Patients with compromised liver function should receive no more than 8 mg daily.
Ondansetron is classified as pregnancy category B. It should be used during pregnancy only when clearly needed.
Ondansetron is excreted into breast milk and should be used with caution during breast-feeding. If use is essential, then alternative methods of feeding are recommended.
Ondansetron should be used with caution in patients with granisetron hypersensitivity. Cross-sensitivity is possible between these two agents.
The use of ondansetron may mask the symptoms of adynamic ileus or gastric distention after abdominal surgery.
DRUG INTERACTIONS: No drug interactions with ondansetron have been identified yet. Because it is metabolized by the cytochrome P-450 system, concern has been expressed about the ability of enzyme inducers to reduce ondansetron's activity and enzyme inhibitors to increase its toxicity. No such interactions have been reported to date.
From a pharmacology perspective, ondansetron and sumatriptan exert opposing effects on serotonin (5-HT) receptors. A specific drug interaction may not occur, however, because ondansetron is an antagonist at the type 3 receptor (5-HTA) while sumatriptan is an agonist at the type 1d serotonin receptor. Neither agent affects other serotonin receptors.
ADVERSE REACTIONS: Antagonism of serotonin (5HT) receptors and the subsequent increased levels of serotonin have been hypothesized to increase the risk of developing bronchospasm and/or vasoconstriction. This concern is apparently being realized. As of October 15, 1993, the FDA has received no less than 24 reports of anaphylactoid/anaphylactic reactions to ondansetron injection.DD Manifestations have included angioedema, bronchospasm, dyspnea, hypotension, and/or urticaria. It is not clear at this time if these reactions are due to ondansetron alone or a drug interaction between ondansetron and another chemotherapeutic agent.
Other adverse reactions that have been noted during therapy with ondansetron include dizziness (5-41%), constipation (7%), diarrhea (3-13%), hyperbilirubinemia (8-34%), fever, chills, and headache (8-40%). Other adverse effects that occur less frequently include angina, abdominal pain, asthenia and xerostomia. A direct relationship between these effects and ondansetron has not been established, and some of these adverse reactions may result from chemotherapeutic agents or other concomitantly used drugs. In general, ondansetron is well tolerated, with headache being the most troublesome adverse effect.
PATIENT INFORMATION:
What do ondansetron tablets do?
Ondansetron (ZofranTM ) helps to relieve nausea and vomiting, especially when associated with the treatment of cancer (chemotherapy). Generic ondansetron tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take ondansetron?
They need to know if you have any of these conditions:
How should I take this medicine?
Take ondansetron tablets by mouth. Swallow the tablets with a drink of water. The first dose of ondansetron is given 30 minutes before chemotherapy, followed by a dose at regular intervals for one or two days after chemotherapy. Take your doses at regular intervals. Do not take your medicine more often than directed..
Special precautions for use in children:
Safe use of this medicine for children under 4 years old has not been studied.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with ondansetron?
No interactions have been recorded between ondansetron and other medicines.
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking ondansetron?
Serious side effects with ondansetron are uncommon, but severe allergic reactions can occur; they include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with ondansetron include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take ondansetron?
Check with your doctor as soon as you can if you have any sign of an allergic reaction.
Do not take alcohol while taking ondansetron.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store between 2 and 30C (36 and 86F). Protect from light. Throw away any unused medicine after the expiration date.
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