AUDIENCE: Internal Medicine, Infectious Disease
ISSUE: The FDA is cautioning that differences in dosing regimens between the two oral formulations of the antifungal posaconazole (Noxafil) have resulted in dosing errors. To help prevent additional medication errors, the drug labels were revised to indicate that the two oral formulations cannot be directly substituted for each other but require a change in dose. Direct mg for mg substitution of the two formulations can result in drug levels that are lower or higher than needed to effectively treat certain fungal infections.
Since the approval of posaconazole delayed-release tablets in November 2013, FDA received eleven reports of the wrong oral formulations being prescribed and/or dispensed to patients. One case resulted in death, and an additional case resulted in hospitalization. According to the reports, these outcomes were a result of health care professionals not knowing that the two oral formulations cannot be substituted for each other without adjusting the dose due to differences in how the medicine is absorbed and handled by the body.
In addition to changes to the outer carton of posaconazole (see /Drugs/DrugSafety/ucm479352.htm in Drug Safety Communication), its manufacturer Merck revised the prescribing information and the patient information in the drug label to alert patients and their health care professionals that the two oral formulations of posaconazole cannot be substituted for each other.
BACKGROUND: posaconazole is approved in two oral formulations: an oral suspension and a delayed-release tablet. It is also approved as an intravenous solution for injection. Posaconazole is used to help prevent certain invasive fungal infections caused by fungi called Aspergillus and Candida. Posaconazole is used in patients who have an increased chance of getting these infections due to weakened immune systems. Posaconazole oral suspension is also used to treat a fungal infection called thrush caused by Candida in the mouth or throat area.
RECOMMENDATION: Prescribers should specify the dosage form, strength, and frequency on all prescriptions they write for Noxafil. Pharmacists should request clarification from prescribers when the dosage form, strength, or frequency is not specified. Patients should talk to their health care professional before they switch from one oral formulation to the other. For additional information for health care professionals, patients and caregivers, refer to the /Drugs/DrugSafety/ucm479352.htm.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Posaconazole is used to prevent serious fungal infections in people with a weakened ability to fight infection. Posaconazole is also used to treat yeast infections of the mouth and throat including yeast infections that could not be treated successfully with other medications. Posaconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
How should this medicine be used?
Posaconazole comes as a suspension (liquid) to take by mouth. Each dose should be taken with a full meal or liquid nutritional supplement. When posaconazole is used to prevent fungal infections, it is usually taken three times a day. When posaconazole is used to treat yeast infections of the mouth and throat, it is usually taken once or twice a day. The length of your treatment depends on your general health, the type of infection you have, and how well you respond to this medication. Take posaconazole at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take posaconazole exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Shake the liquid well before each use to mix the medication evenly.
Posaconazole comes with a dosing spoon to measure your dose. The spoon should be rinsed thoroughly with water after each use and before storing.
Continue to take posaconazole until your doctor tells you that you should stop, even if you feel better. Do not stop taking posaconazole without talking to your doctor. If you stop taking posaconazole too soon, your infection may not be completely treated.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking posaconazole,
- tell your doctor and pharmacist if you are allergic to posaconazole; other antifungal medications such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend); simethicone; any other medications; or any of the ingredients in posaconazole. Ask your pharmacist for a list of the ingredients.
- do not take posaconazole if you are taking any of the following medications: astemizole (Hismanal) (not available in the U.S.); cisapride (Propulsid); ergot-type medications such as bromocriptine (Parlodel), cabergoline (Dostinex), dihydroergotamine (D.H.E. 45, Migranal), ergoloid mesylates (Germinal, Hydergine), ergonovine (Ergotrate), ergotamine (Bellergal-S, Cafergot, Ergomar, Wigraine), methylergonovine (Methergine), and pergolide (Permax); halofantrine (Halfan) (not available in the U.S.); pimozide (Orap); quinidine; or terfenadine (Seldane) (not available in the U.S.).
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: benzodiazepines such as alprazolam (Xanax), diazepam (Valium), midazolam (Versed), and triazolam (Halcion); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac, others), felodipine (Plendil), nifedipine (Adalat, Procardia), nisoldipine (Sular), and verapamil (Calan, Isoptin, Verelan); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor), lovastatin (Mevacor), and simvastatin (Zocor); cimetidine (Tagamet); cyclosporine (Gengraf, Neoral, Sandimmune); erythromycin (E.E.S., E-Mycin, Erythrocin), glipizide (Glucotrol); phenytoin (Dilantin, Phenytek); rifabutin (Mycobutin); sirolimus (Rapamune); tacrolimus (Prograf); vinblastine; and vincristine. Many other medications may also interact with posaconazole, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you cannot eat a full meal or liquid nutritional supplement and if you have or have ever had an irregular heartbeat; kidney or liver disease; or low levels of calcium, magnesium, or potassium in your blood.Also tell your doctor if you develop severe diarrhea or vomiting at any time during your treatment.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking posaconazole, call your doctor.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Posaconazole may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- chills or shaking
- swelling of the hands, feet, ankles, or lower legs
- stomach pain
- weight loss
- back or muscle pain
- sores on the lips, mouth, or throat
- difficulty falling asleep or staying asleep
- increased sweating
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- unusual bruising or bleeding
- extreme tiredness
- lack of energy
- loss of appetite
- pain in the upper right part of the stomach
- yellowing of the skin or eyes
- flu-like symptoms
- dark urine
- pale stools
- fast, pounding, or irregular heartbeat
- sudden loss of consciousness
- shortness of breath
- decreased urination
Posaconazole may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze this medication. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
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.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to posaconazole.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription. If you still have symptoms of infection after you finish taking posaconazole, call 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.