[Posted 06/29/2012]ISSUE:The U.S. Food and Drug Administration (FDA) is informing healthcare professionals and the public that preliminary results from a recently completed clinical study suggest that a 32 mg single intravenous dose of ondansetron (Zofran, ondansetron hydrochloride, and generics) may affect the electrical activity of the heart (QT interval prolongation), which could pre-dispose patients to develop an abnormal and potentially fatal heart rhythm known as Torsades de Pointes.
GlaxoSmithKline (GSK) has announced changes to the ondansetron drug label to remove the 32 mg single intravenous dose. The updated label will state that ondansetron can continue to be used in adults and children with chemotherapy-induced nausea and vomiting at the lower intravenous dose recommended in the drug label, a dose of 0.15 mg/kg administered every 4 hours for three doses; however, no single intravenous dose should exceed 16 mg. Information from the new clinical study will be included in the updated drug label.
BACKGROUND: Zofran (ondansetron) is in a class of medications called 5-HT3 receptor antagonists. It is used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy and surgery. FDA will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults.
RECOMMENDATION: The new information on QT prolongation does not change any of the recommended oral dosing regimens for ondansetron. It also does not change the recommended lower dose intravenous dosing of ondansetron to prevent post-operative nausea and vomiting.
- The use of a single 32 mg intravenous dose of ondansetron should be avoided. New information indicates that QT prolongation occurs in a dose-dependent manner, and specifically at a single intravenous dose of 32 mg
- Patients who may be at particular risk for QT prolongation with ondansentron are those with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval
- Electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia) should be corrected prior to the infusion of ondansetron.
- The lower dose intravenous regimen of 0.15 mg/kg every 4 hours for three doses may be used in adults with chemotherapy-induced nausea and vomiting. However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation.
- The new information does not change any of the recommended oral dosing regimens for ondansetron, including the single oral dose of 24 mg for chemotherapy induced nausea and vomiting.
For more information visit the FDA website at: Web Siteand Web Site.
Ondansetron injection is used to prevent nausea and vomiting caused by cancer chemotherapy and surgery. Ondansetron is in a class of medications called serotonin 5-HT3receptor antagonists. It works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting.
Ondansetron comes as a solution (liquid) to be injected intravenously (into a vein) or intramuscularly (into a muscle) by a health care provider in a hospital or clinic. When ondansetron is used to prevent nausea and vomiting caused by chemotherapy, it is usually given 30 minutes before the start of chemotherapy. Additional doses may be given 4 hours after the first dose of ondansetron and 8 hours after the first dose of ondansetron, if needed. When ondansetron is used to prevent nausea and vomiting caused by surgery, it is usually given just before the surgery. Ondansetron is also sometimes given after surgery to patients who are experiencing nausea and vomiting and who did not receive ondansetron before surgery.
This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.
Before taking ondansetron,
- tell your doctor and pharmacist if you are allergic to ondansetron, alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), palonosetron (Aloxi), or any other medications.
- tell your doctor if you are receiving apomorphine (Apokyn). Your doctor will probably tell you not to use ondansetron if you are receiving this medication.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention clarithromycin (Biaxin, in Prevpac); erythromycin (E.E.S., Erythrocin, others); medications for irregular heart beat; medications for mental illness; moxifloxacin (Avelox);and tramadol (Ultram, in Ultracet). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects. Many other medications may also interact with ondansetron, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you or anyone in your family has or has ever had long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death), or another type of irregular heart beat or heart rhythm problem, or if you have or have ever had low blood levels of magnesium or potassium in your blood, congestive heart failure (CHF; condition in which the heart cannot pump enough blood to other parts of the body), or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ondansetron, call your doctor.
Unless your doctor tells you otherwise, continue your usual diet.
Ondansetron may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- feeling cold or chills
- pain, burning, numbness, or tingling in the hand or feet
- pain, redness, swelling, warmth, or burning in the place where ondansetron was injected
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:
- swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs
- difficulty breathing or swallowing
- shortness of breath
- noisy, high pitched breathing
- blurred vision or vision loss
Ondansetron may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
This medication will be stored in the hospital or clinic.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include:
- sudden loss of vision for a short time
- dizziness or lightheadedness
- irregular heart beat
Keep all appointments with your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: July 18, 2012.