Nizoral (ketoconazole) is a powerful medication that is used to treat fungal infections. Unfortunately, the U.S. Food and Drug Administration (FDA) has warned that oral Nizoral pills should never be used as a first-line treatment due to the potential risk of severe, life-threatening side effects. They have added a “Black Box” warnings about the risk of fatal liver injury, drug interactions, and adrenal gland problems.
What is Nizoral?
Nizoral (ketoconazole) is a broad-spectrum anti-fungal medication manufactured by Johnson & Johnson. It comes in oral and topical formulations (shampoos, creams, etc.), but only the oral forms of Nizoral are affected by the new warnings. Nizoral treats fungal infections by blocking an enzyme that weakens key components of the fungal cell membrane, which destroys the fungus.
FDA Adds Black Box Warning to Nizoral Prescribing Information
On July 26, 2013, the FDA issued a Drug Safety Communication to restrict oral Nizoral and warn about serious side effects. They added the following “Black Box” warning to the Prescribing Information for Nizoral:
“Nizoral tablets should be used only when other effective anti-fungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks.”
Nizoral Suspended by European Medicines Agency
The largest European health regulatory organizations have issued a statement to recommend suspending Nizoral in the European Union (EU). According to the Committee for Medicinal Products for Human Use (CHMP) and the European Medicines Agency (EMA):
“Doctors should no longer prescribe oral ketoconazole and should review patients’ treatment options. … Taking into account the increased rate of liver injury and the availability of alternative antifungal treatments, the CHMP concluded that the benefits did not outweigh the risks.”
According to the EMA, problems with Nizoral include:
- Liver injury with oral Nizoral is more common and more serious than with other anti-fungal medications.
- Liver injury can occur as early as one month after starting treatment at recommended doses of Nizoral, and there is no way to reduce this risk.
- Data on the effectiveness and clinical benefit of oral Nizoral is uncertain and does not meet current standards.
Nizoral and Liver Injury (Hepatoxicity)
The link between Nizoral and liver injury has been known for more than a decade. In 1999, the British Journal of Clinical Pharmacology published a study that found the incidence and seriousness of liver injury from oral Nizoral was higher than for other anti-fungals. In addition, liver injury can occur between 1 and 6 months after staring Nizoral, even in patients with no risk-factors, and even at the recommended dose of 200-mg.
Nizoral and liver injury Black Box warning:
“Serious hepatoxicity, including cases with a fatal outcome or requiring liver transplantation has occurred with the use of oral ketoconazole. Some patients had no obvious risk factors for liver disease.”
Liver injuries associated with Nizoral include:
- Cirrhosis of the liver
- Liver failure
- Liver transplantation
Nizoral and Adrenal Gland Problems (Adrenal Insufficiency)
Nizoral can increase the risk of an adrenal gland problem called adrenal insufficiency. This occurs when the adrenal glands do not produce enough corticosteroids. Normally, corticosteroids help maintain blood pressure, cardiovascular functions, metabolism, and the balance of salt, water, and minerals in the bloodstream.
Symptoms of adrenal insufficiency include:
- Nausea, vomiting
- Loss of appetite
- Weight loss
- And more
Nizoral and Drug Interactions
Nizoral can interact with many other medications and cause life-threatening complications. In some cases, Nizoral can cause the blood-concentration of these medications to rise, which can interfere with electrical activity in the heart. Nizoral is contraindicated with dofetilide, quinidine, pimozide, and cisapride due to the risk of heart problems.
Nizoral drug interaction complications:
- Abnormal heart rhythm
- Cardiac arrhythmia
- QT interval prolongation
- Torsades des pointes
- Ventricular dysrhythmia