Ketoconazole

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Systemic mycotic infections, e.g. systemic candidiasis
• Chronic and recurrent vaginal candidiasis not responding to topical treatment
• Serious chronic infections of the skin, hair and nails caused by sensitive dermatophytes, e.g. Trichophyton rubrum, T. mentagrophytes; and/or yeasts (dermatomycoses, paronychia, serious chronic mucocutaneous candidiasis, etc.)
• When topical treatment is ineffective owing to the involvement of large areas of the skin, or lesions penetrating the deeper dermal layers, nails and hair
• Serious mycoses of the gastro-intestinal tract not responsive to other therapy or when the organism is resistant to other therapy
• Serious chronic mucocutaneous candidiasis not responsive to other therapy or when the organism is resistant to other therapy
• Paracoccidioidomycosis
• Pulmonary, oral and/or disseminated histoplasmosis
• Coccidioidomycosis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Hepatic impairment
• QT prolongation
• Coadministration with HMG-coA reductase inhibitors
• Coadministration with eplerenone
• Coadministration with QT prolonging agents
• Coadministration with dabigatran
• Coadministration with benzodiazepines
• Coadministraton with ergot alkaloids
• Coadministration with lurasidone
• Coadministration with quetiapine
• Coadministration with telithromycin and clarithromycin in patients with severe renal impairment
• Coadministration with felodipine and nisoldipine
• Coadministration with colchicine in patients with renal impairment
• Coadministration with irinotecan
• Coadministration with everolimus and sirolimus
• Coadministration with vardenafil
• Coadministraion with ritonavir
• Coadministration with fesoterodine and solifenacin in patient with renal impairment

Cautions

• Physiological stress
• Inflammatory disorders
• Autoimmune disorders
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Infections caused by: Dermatophytes; Candida spp.; Trichophyton spp.; Coccidioides immitis; Histoplasma capsulatum; Paracoccidioides brasiliensis

General dosing range

• Oral (tab): 200-400mg, dly

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Consider the risks and benefits very carefully before using ketoconazole for minor conditions such as skin and nail fungal infections. Skin and nail fungal infections in otherwise healthy individuals are not life-threatening, and therefore the risks associated with oral ketoconazole (serious liver damage, adrenal gland problems, and potentially harmful drug-drug interactions) potentially outweigh the benefits

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Take with meals

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Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Endogenous Cushing's syndrome

• Oral (tab): Initial 400-600mg/day, in 2-3 divided doses; Maintenance: 400-1200mg/day, in 2-3 divided doses

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In the case of adrenal insufficiency and depending on the severity of the event, the dose of ketaconazole should be decreased by at least 200mg/day or the treatment should be temporarily discontinued

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NOTE: This drug is rarely used; It has significant drug-drug interactions and cannot be used in patients taking antiretrovirals or anti-tuberculosis drugs

Not established for use in children

Pregnancy

• Contraindicated
• There are insufficient clinical data regarding the use of ketoconazole in pregnant women. Preclinical data show that ketoconazole crosses the placenta and is teratogenic. Ketoconazole is contraindicated during pregnancy and it should not be used in women of childbearing potential not using an effective method of contraception

Breastfeeding

• Contraindicated
• Since ketoconazole is excreted in the milk, mothers who are under treatment must not breastfeed whilst being treated with ketoconazole

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Nervousness
• Headache
• Dizziness
• Somnolence
• Increased intracranial pressure
• Paraesthesia
• Malaise

Cardiovascular Disorders

• Oedema

Respiratory Disorders

• Epistaxis

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Flatulence
• Dry mouth
• Tongue discolouration
• Abdominal pain
• Dysgeusia

Hepatobiliary Disorders

• Jaundice
• Hepatitis
• Hepatic necrosis
• Hepatic cirrhosis
• Hepatic failure

Genitourinary Disorders

• Erectile dysfunction
• Azoospermia

Endocrine and Metabolic Disorders

• Adrenal insufficiency
• Alcohol intolerance
• Anorexia
• Increased appetite
• Menstrual disorders
• Gynaecomastia

Musculoskeletal Disorders

• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Urticaria
• Alopecia
• Photosensitivity
• Erythema multiforme
• Dermatitis
• Erythema
• Xeroderma

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Anaphylactic shock
• Anaphylactoid reaction
• Angioedema
• Pyrexia

Sensory Disorders

• Photophobia

• Alcohol
• Analgesic opioids
• HMG-coA reductase inhibitors
• Eplerenone
• QT prolonging agents
• Dabigatran
• Benzodiazepines
• Antimigraine agents
• Ergot alkaloids
• Lurasidone
• Temsirolimus
• Rifabutin
• Rifampicin
• Telithromycin
• Clarithromycin
• Isoniazid
• Anticonvulsants
• Anticoagulants
• Antiarrhythmics
• Antiplatelet agents
• Antidiabetic agents
• Antineoplastics
• Tacrolimus
• Antipsychotics
• Praziquantel
• Anxiolytics 
• Hypnotics
• Ciclosporine
• Calcium channel blockers
• Beta blockers
• Antivirals
• Budesonide
• Ciclesonide
• Colchicine
• Irinotecan
• Everolimus 
• Phosphodiesterase inhibitors
• Ritonavir
• Dexamethasone
• Fluticasone
• Methylprednisolone
• Fesoterodine
• Solifenacin
• Salmeterol
• Tolterodine
• CYP3A4 inducers
• CYP3A4 inhibitors
• P-glycoprotein 1 substrates
• Hepatotoxic medications
• Pasireotide
• Breast cancer resistance protein
• Digoxin
• Quetiapine
• Sirolimus 
• Domperidone
• Naloxegol
• Risperidone
• Aprepitant
• Ranolazine
• Aliskiren
• Bosentan
• Idinavir
• Nevirapine
• Bosentan
• Sildenafil
• Tadalafil
• Vardenafil
• Tolvaptan
• Cinacalcet
• Ebastine
• Mizolastine
• Halofantrine
• Agents affecting gastric acidity
• Statins

• Hepatic function
• Signs of hypocortisolism
• ECG

Ketoconazole is a synthetic imidazole dioxolane, which has antimycotic activity against dermatophytes. Ketoconazole acts at the level of the CYP450 system to inhibit the conversion of lanosterol to ergosterol. Decreased ergosterol levels result in cell wall defects and thus increased fungal cellular permeability. It also acts through several other mechanisms including inhibition of several fungal enzymes that results in accumulation of toxic concentrations of hydrogen peroxide, inhibition of trigylceride and phospholipid synthesis and inihibition of yeast transformation into mycelial forms.

Spectrum of activity: Dermatophytes; Candida spp.; Trichophyton spp.; Coccidioides immitis; Histoplasma capsulatum; Paracoccidioides brasiliensis

Tablet 200mg

• Ketazol (Pharmacare)
• Sandoz ketoconazole (Sandoz)

Also available in the following forms: Shampoo and cream.