Formulary
Ketoconazole: Indications, Dosing, Side Effects and Interactions
With oral use: An imidazole derivative which acts as a potent inhibitor of cortisol and aldosterone synthesis by inhibiting the activity of 17-hydroxylase,...
MedNext Academy | 6 min read
Ketoconazole: Indications, Dosing, Side Effects and Interactions
With oral use: An imidazole derivative which acts as a potent inhibitor of cortisol and aldosterone synthesis by inhibiting the activity of 17-hydroxylase,...
Drug action
With oral use: An imidazole derivative which acts as a potent inhibitor of cortisol and aldosterone synthesis by inhibiting the activity of 17-hydroxylase, 11-hydroxylation steps and at higher doses the cholesterol side-chain cleavage enzyme. It also inhibits the activity of adrenal C17-20 lyase enzymes resulting in androgen synthesis inhibition, and may have a direct effect on corticotropic tumour cells in patients with Cushing's disease.
Indications and dose
**Endogenous Cushing's syndrome (specialist use only)**
- **Adult** (By Mouth): Initially 400-600 mg daily in 2-3 divided doses, increased to 800-1200 mg daily; maintenance 400-800 mg daily in 2-3 divided doses, for dose titrations in patients with established dose, adjustments in adrenal insufficiency, or concomitant corticosteroid replacement therapy, consult product literature; maximum 1200 mg per day.
**Tinea pedis**
- **Adult** (To The Skin Using Cream): Apply twice daily.
**Fungal skin infection (not Tinea pedis)**
- **Adult** (To The Skin Using Cream): Apply 1-2 times a day.
**Treatment of seborrhoeic dermatitis and dandruff**
- **Child** (To The Skin Using Shampoo): 12-17 years Apply twice weekly for 2-4 weeks, leave preparation on for 3-5 minutes before rinsing.
- **Adult** (To The Skin Using Shampoo): Apply twice weekly for 2-4 weeks, leave preparation on for 3-5 minutes before rinsing.
**Prophylaxis of seborrhoeic dermatitis and dandruff**
- **Child** (To The Skin Using Shampoo): 12-17 years Apply every 1-2 weeks, leave preparation on for 3-5 minutes before rinsing.
- **Adult** (To The Skin Using Shampoo): Apply every 1-2 weeks, leave preparation on for 3-5 minutes before rinsing.
**Treatment of pityriasis versicolor**
- **Child** (To The Skin Using Shampoo): 12-17 years Apply once daily for maximum 5 days, leave preparation on for 3-5 minutes before rinsing.
- **Adult** (To The Skin Using Shampoo): Apply once daily for maximum 5 days, leave preparation on for 3-5 minutes before rinsing.
**Prophylaxis of pityriasis versicolor**
- **Child** (To The Skin Using Shampoo): 12-17 years Apply once daily for up to 3 days before sun exposure, leave preparation on for 3-5 minutes before rinsing.
- **Adult** (To The Skin Using Shampoo): Apply once daily for up to 3 days before sun exposure, leave preparation on for 3-5 minutes before rinsing.
**Endogenous Cushing's syndrome (specialist use only) for ketoconazole**
- **Child 12-17 years** (By mouth): Initially 400-600 mg daily in 2-3 divided doses, increased to 800-1200 mg daily; maintenance 400-800 mg daily in 2-3 divided doses, for dose titrations in patients with established dose, adjustments in adrenal insufficiency, or concomitant corticosteroid replacement therapy, consult product literature; maximum 1200 mg per day.
**Treatment of seborrhoeic dermatitis and dandruff for ketoconazole**
- **Child 12-17 years** (To the skin using shampoo): Apply twice weekly for 2-4 weeks, leave preparation on for 3-5 minutes before rinsing.
**Prophylaxis of seborrhoeic dermatitis and dandruff for ketoconazole**
- **Child 12-17 years** (To the skin using shampoo): Apply every 1-2 weeks, leave preparation on for 3-5 minutes before rinsing.
**Treatment of pityriasis versicolor for ketoconazole**
- **Child 12-17 years** (To the skin using shampoo): Apply once daily for maximum 5 days, leave preparation on for 3-5 minutes before rinsing.
**Prophylaxis of pityriasis versicolor for ketoconazole**
- **Child 12-17 years** (To the skin using shampoo): Apply once daily for up to 3 days before sun exposure, leave preparation on for 3-5 minutes before rinsing.
Cautions
With oral use Pre-treatment liver enzymes should not exceed 2 times the normal upper limit; risk of adrenal insufficiency With topical use Avoid contact with eyes; avoid contact with mucous membranes
Contraindications
General contra-indications: Acute porphyrias Specific contra-indications: With oral use Acquired QTc prolongation; avoid concomitant use of hepatotoxic drugs; congenital QTc prolongation
Side effects
General side-effects: Common or very common Skin reactions Uncommon Alopecia; angioedema Rare or very rare Taste altered Specific side-effects: Common or very common With oral use Adrenal insufficiency; diarrhoea; gastrointestinal discomfort; nausea; vomiting Uncommon With oral use Allergic conditions; asthenia; dizziness; drowsiness; headache; thrombocytopenia With topical use Excessive tearing; folliculitis; hair changes Rare or very rare With oral use Fever; hepatic disorders With topical use Eye irritation Frequency not known With oral use Alcohol intolerance; appetite abnormal; arthralgia; azoospermia; dry mouth; epistaxis; flatulence; fontanelle bulging; gynaecomastia; hot flush; insomnia; intracranial pressure increased; malaise; menstrual disorder; myalgia; nervousness; papilloedema; paraesthesia; peripheral oedema; photophobia; photosensitivity reaction; tongue discolouration Side-effects, further information Potentially life-threatening hepatotoxicity reported rarely with oral use. Manufacturer advises reduce dose if hepatic enzymes increased to less than 3 times the upper limit of normal-consult product literature; discontinue permanently if hepatic enzymes at least 3 times the upper limit of normal.
Interactions
**Severe interactions:**
- Other active substances The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and thus clinical efficacy may be impaired.
- CYP3A4 and P-gp inhibitors Co-administration of rivaroxaban with ketoconazole (400 mg once a day) or ritonavir (600 mg twice a day) led to a 2.6 fold / 2.5 fold increase in mean rivaroxaban AUC and...
- Ketoconazole and erythromycin significantly inhibited the formation of nevirapine hydroxylated metabolites.
- The absence of a significant pharmacokinetic interaction with pravastatin has been specifically demonstrated for several products, particularly those that are substrates/inhibitors of CYP3A4 e.g.
- Ketoconazole Steady-state administration of ketoconazole (a strong inhibitor of CYP3A4) did not result in a clinically significant increase in exposure to ambrisentan (see section 5.2).
- Increase in plasma concentrations of loratadine has been reported after concomitant use with ketoconazole, erythromycin, and cimetidine in controlled trials, but without clinically significant...
- For this reason, it is possible that potent CYP3A4 inhibitors (i.e.
- Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels.
**Other interactions (206):**
- Concomitant uses with drugs that inhibit P-gp (e.g.
- Enzyme inhibitors such as cimetidine, erythromycin, itraconazole, ketoconazole and ritonavir impair the elimination of felodipine, and Cardioplen XL 2.5 mg Prolonged Release Tablets dosage may need...
- In vivo studies: Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole,...
- Stronger CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have greater effects.
- Concomitant use of P-gp inhibitors may increase the exposure of relugolix, including certain anti-infective medicinal products (e.g.
- AUC = area under curve; C max = maximum concentration; QD = once daily; BID = twice daily; TID = three times daily; QID = four times daily Estradiol and norethisterone acetate CYP3A4 inhibitors:...
Pregnancy
With oral use: Manufacturer advises avoid-teratogenic in animal studies.
Breast feeding
With oral use: Manufacturer advises avoid-present in breast milk.
Hepatic impairment
With oral use: Manufacturer advises avoid.
Medicinal forms
Suspension,Tablet,Cream
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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