THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

(for veterinary information only)

Brand Name: Nizoral

Available in 200 mg tablets 
 
Background

Fungal infections are generally resistant to therapy. Treatment is prolonged and often requires months, depending on how deep the infection is and how strong the patient’s immune system is. Fungal infections can be limited to the skin as happens with ringworm or Malassezia dermatitis, or they can involve more crucial organs such as the lung, bone, and even the nervous system. The superficial infections can generally be treated successfully within in a few weeks while the deeper infections may take over a year.

In the past, the only treatment for life-threatening fungal infections was a medication called Amphotericin B. This medication could only be given intravenously in a fluid drip and it was associated with a high incidence of kidney failure (some sources say up to 50%). Obviously, an innovation in treatment was needed. Ketoconazole represents this innovation. Ketoconazole not only is free from renal side effects, but is also given orally as a tablet, sparing patients expensive hospitalization time.

Since ketoconazole’s introduction, related anti-fungals have been released to improve upon its activity. For example, itraconazole was introduced to reduce the incidence of nausea side effects. Fluconazole was developed to improve penetration of the central nervous system and treat fungal infections there. With the introduction of generic forms ketoconazole and its relatives, treatment of fungal disease can be affordable, safer, and more effective.

How this Medication Works

Ketoconazole works by interfering with the structure of the fungal cell wall. Depending on the fungus and depending on the dose used, ketoconazole may kill the fungus or just inhibit its ability to reproduce. Fungal infections for which ketoconazole is commonly used include:

• Dermatophytosis (ringworm)
• Malassezia dermatitis
• Aspergillosis
• Cryptococcosis
• Coccidioidomycosis (Valley fever)
• Histoplasmosis
• Blastomycosis

There is another effect of ketoconazole that is generally thought of as a side effect but that can be used as a therapeutic goal. Ketoconazole blocks the synthesis of cortisone in the adrenal gland. This means that ketoconazole can be used to treat Cushing's disease, in which an excessive amount of adrenal hormone is produced.

Ketoconazole can also be used to slow the body's removal of the immunomodulating drug cyclosporine. Cyclosporine is a very expensive medication so using ketoconazole to spare its use may reduce the dose requirement enough to make treatment affordable.

Side Effects

• The most common side effects are nausea, vomiting, and diarrhea. These may be reduced by giving ketoconazole with food or by dividing the dose into several smaller doses. If nausea is severe, it should resolve with discontinuation of the medication.
  
• At higher doses or in certain individuals, liver disease can result, but this should go away when the medication is discontinued. This is usually a problem for cats rather than dogs. It can be dose-dependent or independent, and it is a cholangiohepatitis-type inflammation.
  
• The liver enzymes routinely measured on a blood panel commonly increase with ketoconazole use and does not necessarily indicate that the liver reaction mentioned above has developed. When ketoconazole use is long term, liver enzymes should be monitored.
  
• Some individuals show a lightening of the hair coat while taking ketoconazole. This effect reverses when the medication is discontinued.
  
• Ketoconazole interferes with testicular secretion of testosterone and may produce a feminizing effect in males.
  
• Ketoconazole also interferes with the adrenal gland’s production of cortisone and can therefore be used in the treatment of Cushing’s disease.

The lethal dose of this medication is at least 50 times
the usual recommended dose, thus serious side effects are unusual
(nausea and upset stomach are not unusual).

Interactions with Other Drugs

Ketoconazole is better absorbed when there is acid in the stomach, thus it is better not to give ketoconazole while the pet is taking antacids.

Cyclosporine, an immune suppressive agents used in transplant patients as well as in certain immune mediated conditions, will have increased blood levels (stronger effects than normal) when it is given with ketoconazole. Other drugs that may have higher blood levels include: theophylline (an airway dilator), methylprednisolone (a corticosteroid), and warfarin (an anticoagulant).

When ketoconazole and cisapride are used concurrently, dangerous heart rhythm disturbances can result; these medications should not be used together.

Concerns and Cautions

Ketoconazole is best not used in breeding male animals due to its feminization effect. It is also best avoided in patients with pre-existing liver disease or with decreased platelet (blood clotting cell) levels.

Ketoconazole has potential to cause birth defects.

When ketoconazole therapy will continue for months at a time, many veterinarians will monitor liver enzymes with complete blood counts. This is not necessary when medication is used for only a few weeks.

Ketoconazole is absorbed into the body best when it is given with food.

It is our policy not to give dosing information over the Internet.

Date Published: 1/1/2001
Date Reviewed/Revised: 03/13/2009