Ketoconazole – Uses and Dose

Background

Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections. It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus. Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981.9 At this time it was considered a significant improvement over previous antifungals, miconazole and clotrimazole, due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis. These effects combined with waning efficacy led to its eventual replacement by triazole agents, fluconazole, itraconazole, voriconazole, and posaconazole. Ketoconazole and its predecessor clotrimazole continue to be used in topical formulations.

Properties and Characteristics of Ketoconazole

Drug class	Azole antifungals
Brand Names	Extina, Ketodan, Ketoderm, Nizoral, Xolegel
Synonyms	Ketoconazol, Ketoconazole, Ketoconazolum, Ketozole, Levoketoconazole, Panfungol, Ketoisdin
Molecular Formula	C26H28Cl2N4O4
Molecular Weight	531.4 g/mol
IUPAC Name	1-[4-[4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone
Structural formula of main components
Pure active ingredient	Ketoconazole
Appearance	Colourless crystals or powder
Melting point	146 °C
Solubility	In water, 0.29 mg/L at 20 °C (est)
Excretion	Excreted in the urine
Storage	Store at controlled room temperature 15 deg – 25 °C (59 deg – 77 °F)
Available Forms	Cream, Capsule liquid filled, Powder, Solution, Aerosol, foam, Shampoo
Prescription	Doctor prescription is required

What is Ketoconazole cream used for?

• Ringworm
• Jock itch
• Athlete’s foot
• Tinea versicolor (a fungal infection that causes discolored patches on the skin)
• Seborrheic dermatitis
• Skin yeast infection caused by Candida

What side effects may I notice from receiving this medication?

Side effects that you should report to your care team as soon as possible:

• Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
• Burning, itching, crusting, or peeling of treated skin

Side effects that usually do not require medical attention (report to your care team if they continue or are bothersome):

• Irritation at application site

This list may not describe all possible side effects. Call your doctor for medical advice about side effects.

Mechanism of action

Ketoconazole interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability due to reduced amounts of ergosterol present in the fungal cell membrane. This metabolic inhibition also results in accumulation of 14α-methyl-3,6-diol, a toxic metabolite. The increase in membrane fluidity is also thought to produce impairment of membrane-bound enzyme systems as components become less closely packed.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For cream dosage form

For cutaneous candidiasis, tinea corporis, tinea cruris, tinea pedis, or pityriasis versicolor:

• Adults—Apply to the affected area of the skin and the surrounding area once a day.
• Children—Use and dose must be determined by your doctor.

For seborrheic dermatitis:

• Adults—Apply to the affected area of the skin and the surrounding area two times per day.
• Children—Use and dose must be determined by your doctor.

For foam dosage form

For seborrheic dermatitis:

• Adults—Apply to the affected area of the skin and the surrounding area two times per day for 4 weeks.
• Children—Use and dose must be determined by your doctor.

For gel dosage form

For seborrheic dermatitis:

• Adults, teenagers, and children 12 years of age and older—Apply to the affected area of the skin and the surrounding area once a day for 2 weeks.
• Children younger than 12 years of age—Use and dose must be determined by your doctor.

For 1% shampoo dosage form

For dandruff:

• Adults—Use every 3 or 4 days for up to 8 weeks. Then use only as needed to keep dandruff under control.
• Children—Use and dose must be determined by your doctor.

For 2% shampoo dosage form

For pityriasis versicolor:

• Adults—Use once.
• Children—Use and dose must be determined by your doctor.

Overdose of ketoconazole

If you take too much

You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

• Nausea
• Vomiting
• Diarrhea

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call your nearest emergency room right away.

Precautions

Before taking ketoconazole, tell your doctor or pharmacist if you are allergic to it; or to levoketoconazole; or to other azole antifungal drugs (such as fluconazole, itraconazole); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, alcohol use, low testosterone levels, decreased adrenal gland function problems (such as low cortisol levels, Addison’s disease, adrenal insufficiency), little or no stomach acid production (achlorhydria).

Ketoconazole may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.

The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using ketoconazole, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).

Pregnancy and breastfeeding

Ketoconazole and pregnancy

You can use ketoconazole cream or shampoo if you’re pregnant. Only tiny amounts are absorbed into your body so it will not affect your baby.

Ketoconazole and breastfeeding

If you want to breastfeed and are using ketoconazole on your chest, wash any cream off your breasts and nipples and then wash your hands before feeding your baby.