[Posted 07/26/2013]ISSUE: FDA is taking several actions related to Nizoral (ketoconazole) oral tablets, including limiting the drug's use, warning that it can cause severe liver injuries and adrenal gland problems, and advising that it can lead to harmful drug interactions with other medications. FDA has approved label changes and added a new Medication Guide to address these safety issues. As a result, Nizoral oral tablets should not be a first-line treatment for any fungal infection. Nizoral should be used for the treatment of certain fungal infections, known as endemic mycoses, only when alternative antifungal therapies are not available or tolerated.
Liver Injury (Hepatotoxicity): Nizoral tablets can cause liver injury, which may potentially result in liver transplantation or death. FDA has revised the Boxed Warning, added a strong recommendation against its use (contraindication) in patients with liver disease, and included new recommendations for assessing and monitoring patients for liver toxicity.
Adrenal Insufficiency: Nizoral tablets may cause adrenal insufficiency by decreasing the body's production of corticosteroids.
Drug Interactions: Nizoral tablets may interact with other drugs a patient is taking and can result in serious and potentially life-threatening outcomes, such as heart rhythm problems.
See the FDA Drug Safety Communication for additional information, including a Data Summary.
BACKGROUND: Nizoral (ketoconazole) is indicated for the treatment of fungal infections when alternatives are not available or not tolerated. The topical formulations of Nizoral have not been associated with liver damage, adrenal problems, or drug interactions. These formulations include creams, shampoos, foams, and gels applied to the skin, unlike the Nizoral tablets, which are taken by mouth.
RECOMMENDATION: Nizoral tablets should be used only for the treatment of certain life-threatening mycoses when the potential benefits outweigh the risks and alternative therapeutic options are not available or tolerated. Healthcare professionals should assess the liver status of the patient before starting oral ketoconazole, and monitor serum ALT levels during treatment. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients under prolonged periods of stress (major surgery, intensive care, etc.). Review all concomitant medications for the potential for drug interactions with Nizoral tablets.
Ketoconazole may cause liver damage. Tell your doctor if you drink or have ever drunk large amounts of alcohol and if you have or have ever had liver disease. Tell your doctor and pharmacist if you are taking acetaminophen (Tylenol, others); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), or simvastatin (Zocor); isoniazid (INH, Nydrazid); methotrexate (Rheumatrex); niacin (nicotinic acid); or rifampin. If you experience any of the following symptoms, call your doctor immediately: extreme tiredness, loss of appetite, nausea, vomiting, yellowing of the skin or eyes, dark yellow urine, pale stools, pain in the upper right part of the stomach, or flu-like symptoms.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to ketoconazole.
Do not take astemizole (Hismanal) (not available in the US), cisapride (Propulsid), or terfenadine (Seldane) (not available in the US) while you are taking ketoconazole.
Ketoconazole is used to treat fungal infections. Ketoconazole is most often used to treat fungal infections that can spread to different parts of the body through the bloodstream such as yeast infections of the mouth, skin, urinary tract, and blood, and certain fungal infections that begin on the skin or in the lungs and can spread through the body. Ketoconazole is also used to treat fungal infections of the skin or nails that cannot be treated with other medications. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Ketoconazole comes as a tablet to take by mouth. It is usually taken once a day. To help you remember to take ketoconazole, take it at around the same time 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 ketoconazole exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
If you have certain medical conditions, your doctor will tell you to take ketoconazole tablets dissolved in an acid solution. Your doctor will tell you exactly how to do this. Follow these directions carefully.
Your doctor will probably start you on an average dose of ketoconazole. Your doctor may increase your dose if your infection is very serious or your condition does not improve.
You may need to take ketoconazole for several weeks or months to cure your infection completely. Your doctor will probably order laboratory tests to be sure your infection has been treated. Continue to take ketoconazole until your doctor tells you that you should stop, even if you feel better. Do not stop taking ketoconazole without talking to your doctor. If you stop taking ketoconazole too soon, your infection may come back after a short time.
Ketoconazole is also sometimes used to treat vaginal yeast infections, tinea versicolor (spots on skin caused by yeast), eumycetoma (a severe fungal skin infection that often affects the foot), leishmaniasis (a disease caused by the bite of an infected sand fly), prostate cancer (cancer that begins in a male reproductive organ), high blood levels of calcium in patients with certain conditions, Cushing's syndrome (high blood levels of a natural substance called cortisol), and excessive hair growth in women. Talk to your doctor about the possible risks of using this drug for your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking ketoconazole,
- tell your doctor and pharmacist if you are allergic to ketoconazole, other antifungal medications such as fluconazole (Diflucan), itraconazole (Sporanox), or voriconazole (Vfend); any other medications; or corn.
- do not take ketoconazole if you are taking any of the medications listed in the IMPORTANT WARNING section or triazolam (Halcion).
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: alprazolam (Xanax); anticoagulants ('blood thinners') such as warfarin (Coumadin); buspirone (BuSpar); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac), felodipine (Plendil), nifedipine (Adalat, Procardia), nisoldipine (Sular),and verapamil (Calan, Covera, Isoptin, Verelan); clarithromycin (Biaxin); clopidogrel (Plavix);cyclosporine (Neoral, Sandimmune); diazepam (Valium); digoxin (Lanoxin); erythromycin (E.E.S., E-Mycin, Erythrocin); HIV protease inhibitors such as indinavir (Crixivan), ritonavir (Norvir),and saquinavir (Invirase, Fortovase); loratadine (Claritin); medications for diabetes; medications for erectile dysfunction such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra); methadone (Dolophine); methylprednisolone (Medrol); midazolam (Versed); phenytoin (Dilantin); pimozide (Orap); quinidine (Quinidex, Quinaglute); quinine; tacrolimus (Prograf); tamoxifen (Nolvadex); telithromycin (Ketek); trazodone (Desyrel); and vincristine (Vincasar). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- if you are taking antacids; antihistamines; medications for heartburn or ulcers such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), or ranitidine (Zantac); or medications for irritable bowel disease, motion sickness, Parkinson's disease, ulcers, or urinary problems, take them 2 hours after you take ketoconazole.
- tell your doctor if you have or have ever had the conditions mentioned in the IMPORTANT WARNING section or any condition that decreases the amount of acid in your stomach.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking ketoconazole, call your doctor. Do not breast-feed while you are taking ketoconazole.
- ask your doctor about the safe use of alcoholic beverages while you are taking ketoconazole. You may experience unpleasant symptoms such as flushing, rash, nausea, headache, and swelling of the hands, feet, ankles, or lower legs if you drink alcohol while you are taking ketoconazole.
Unless your doctor tells you otherwise, continue your normal diet.
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.
Ketoconazole may cause side effects. Tell your doctor if either of these symptoms is severe or does not go away: Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- difficulty breathing or swallowing
- thinking about harming or killing yourself or planning or trying to do so
A small number of patients who were taking high doses of ketoconazole for prostate cancer died soon after they began taking the medication. It is not known whether they died because of their disease or their treatment with ketoconazole or for other reasons. Talk to your doctor about the risks of taking ketoconazole.
Ketoconazole may cause a decrease in the number of sperm (male reproductive cells) produced, especially if it is taken at high doses. Talk to your doctor about the risks of taking this medication if you are a man and would like to have children.
Ketoconazole may cause other side effects. Call your doctor if you have any unusual problems while 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].
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). 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 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.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking ketoconazole.
Do not let anyone else take your medication. Ask your pharmacist if you have any questions about refilling your prescription. If you still have symptoms of infection after you finish the ketoconazole, 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.
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: August 15, 2013.