Ketoconazole

What it is

Ketoconazole is a synthetic broad-spectrum imidazole antifungal, a white or almost white powder soluble in acids. It exists in two very different products that should not be run together: a 200 mg oral tablet, which is absorbed into the whole body, and topical creams and shampoos, from which systemic absorption is not detectable. The oral tablet carries a boxed warning for fatal liver injury and QT prolongation; the topical forms do not.

What the research says

Ketoconazole kills fungi by blocking the enzyme that converts lanosterol to ergosterol, so the fungal cell membrane fails. For topical use on seborrhoeic dermatitis and dandruff, a Cochrane review of 51 studies found 2% ketoconazole beat placebo (31% lower risk of failed clearance at four weeks, low-quality evidence) with fewer side effects than steroids. For oral use, the picture is reversed: two population cohorts found the highest rate of acute liver injury of any oral antifungal, with a relative risk of 228 in one UK cohort, and the EMA suspended oral ketoconazole in 2013 on exactly those grounds while explicitly keeping the topical forms. It also lowers cortisol and testosterone, which is why it is used off-label in Cushing's syndrome despite the liver risk.

Evidence grade: Disputed.

How it works

Drug class: Imidazole antifungal; inhibitor of fungal lanosterol 14-alpha-demethylase (a cytochrome P450 enzyme). Also a potent human CYP3A4 and P-glycoprotein inhibitor and, at higher doses, an inhibitor of human steroid synthesis.

Ketoconazole blocks a fungal cytochrome P450 enzyme, lanosterol 14-alpha-demethylase, which fungi need to make ergosterol - the sterol that keeps their cell membrane working. Methylated precursors pile up and ergosterol runs out, so the membrane weakens and fails. The same family of enzymes exists in humans, which is why high oral doses also suppress cortisol and testosterone production and why the drug blocks human CYP3A4 so strongly. (Source 1)

Boxed warning

Because ketoconazole tablets have been associated with serious adverse reactions (see WARNINGS section), ketoconazole tablets are not indicated for treatment of onychomycosis, cutaneous dermatophyte infections, or Candida infections.

(Source 2)

What it is used for

• This is now a last-resort indication only. The US label restricts it to people who have failed or are intolerant to other therapies and states it is not indicated for nail, skin or Candida infections at all. The CHMP went further in 2013, concluding that the clinical benefit was uncertain because the effectiveness data are limited and do not meet current standards. Evidence: disputed. (Source 3)
• The best-supported use. A Cochrane review of 51 trials (9,052 participants) found topical 2% ketoconazole reduced the risk of failed clearance by 31% against placebo at four weeks, from a median placebo failure rate of 69%, on low-quality evidence; remission was similar to topical steroids with 44% fewer side effects. A quarter of the included trials had a declared conflict of interest. Evidence: established. (Source 4)
• A Cochrane review of 129 trials (18,086 participants) pooled data for terbinafine and naftifine against placebo and found them effective (NNT 3 for each); azoles as a class were no different from benzylamines (RR 1.01, 95% CI 0.94 to 1.07), but most individual azole comparisons rested on single studies and the body of evidence was rated low to very low. Evidence: limited. (Source 5)
• Used because high-dose ketoconazole blocks adrenal steroid synthesis. In a 52-patient retrospective series using rapid titration, ketoconazole got morning cortisol to target in only 39% (95% CI 24-56%) versus 74% for metyrapone, while 22% had a liver enzyme reach three times the upper limit of normal. The US label states safety and effectiveness have not been established in this setting. Evidence: limited. (Source 6)
• The label records that in a trial of 350 men with metastatic prostate cancer given 1200 mg/day, eleven died within two weeks of starting, with causality undetermined. Safety and effectiveness have not been established. Evidence: not-supported. (Source 7)
• Explicitly de-indicated. The boxed warning states oral ketoconazole is not indicated for these conditions because of its serious adverse reactions, and the label records fatal liver injury and transplants in people who took it for exactly these infections. Evidence: not-supported. (Source 2)

Interactions

• Antacids, H2 blockers and proton pump inhibitors (and any cause of low stomach acid) (pharmacokinetic study): Oral ketoconazole needs stomach acid to dissolve. After omeprazole pretreatment its bioavailability fell to 17% of normal - a fivefold loss. Taking it with a non-diet cola brought that back to 65%. (Source 8)
• Acidic drinks such as non-diet cola (pharmacokinetic study): A measured, usable food effect: an acidic beverage restores absorption of oral ketoconazole in people whose stomach acid is suppressed. Oral bioavailability is also maximal when the tablet is taken with a meal. (Source 8)
• Alcohol (label): Two separate issues. Alcohol intolerance - a flushing, disulfiram-like reaction - is a reported adverse reaction of oral ketoconazole. And because the drug's main serious harm is liver injury, the label advises against drinking during treatment. (Source 9)
• Red yeast rice (monacolin K) (theoretical): No study of red yeast rice taken with oral ketoconazole was found, so this is an expectation rather than a documented interaction - but the mechanism is concrete. Red yeast rice's active cholesterol-lowering compound, monacolin K, is chemically and functionally a statin that inhibits HMG-CoA reductase, and the oral ketoconazole label contraindicates lovastatin and simvastatin because blocking CYP3A4 raises statin levels and causes myopathy. The expectation comes from putting those two facts together. It concerns the oral tablet only; the cream and shampoo are not absorbed enough for it to apply. (Source 10)
• Lovastatin and simvastatin (label): Contraindicated with oral ketoconazole: blocking CYP3A4 raises statin levels and the label lists myopathy as the reason. (Source 11)
• St John's wort and other strong CYP3A4 inducers (theoretical): The oral label names rifampicin, isoniazid, rifabutin, carbamazepine, phenytoin, efavirenz and nevirapine as inducers that can cut ketoconazole's bioavailability enough to lose efficacy, and says they should be avoided from two weeks before and during treatment. St John's wort is a well-known CYP3A4 inducer but is not named in this label and no study of the pair was found, so for this drug the interaction is mechanistic expectation only. (Source 12)
• Drugs that prolong the QT interval (dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine) (label): All contraindicated with oral ketoconazole. It raises their blood levels, and the combination can cause torsades de pointes, a fatal arrhythmia. (Source 2)
• Any drug cleared by CYP3A4 or moved by P-glycoprotein (pharmacokinetic study): Oral ketoconazole is one of the strongest CYP3A4 inhibitors in use - it is the reference inhibitor in interaction studies - and also blocks P-glycoprotein, so a very wide range of other medicines rise in concentration. The contraindication list runs to more than twenty drugs. (Source 13)
• Topical ketoconazole and anything systemic (pharmacokinetic study): None of the above applies to the cream or shampoo in the same way: ketoconazole was not detectable in blood at 5 ng/mL after topical use, which is why the EMA kept the topical forms when it suspended the tablets. (Source 14)

Stopping it

• There is no dependence or withdrawal syndrome. Stopping is instead a safety action with a defined trigger: the label requires weekly ALT monitoring and interruption if ALT goes above the upper limit of normal or 30 percent above baseline, or if symptoms appear. (Source 9)
• Restarting is the specific danger. Hepatotoxicity has recurred on rechallenge, so if the drug is restarted the label requires frequent monitoring. (Source 9)
• The endocrine effects reverse on stopping: serum testosterone returns to baseline once ketoconazole is discontinued. Adrenal function is the opposite concern - it needs monitoring during treatment and under stress, not after stopping. (Source 15)
• When the EMA suspended oral ketoconazole in 2013 it did not treat stopping as urgent: patients were told to make a non-urgent appointment to discuss alternatives, which is the clearest published statement that abrupt cessation carries no rebound risk. (Source 16)

What goes wrong

In a UK general-practice cohort, oral ketoconazole had by far the highest rate of clinical acute liver injury of the oral antifungals studied. (Source 17)

• Cohort study, Moderate certainty.
• Size: 69,830 patients aged 20-79 free of liver and systemic disease; 16 validated cases of acute liver injury.
• Who: General Practice Research Database users of oral fluconazole, griseofulvin, itraconazole, ketoconazole or terbinafine.
• How long: Prescriptions 1991-1996.
• Result: Incidence 134.1 per 100,000 person-months (95% CI 36.8-488.0) for ketoconazole versus a background rate of 0.6 per 100,000 person-months (0.3-1.1); relative risk 228.0 (95% CI 33.9-933.0) versus non-users. Only two ketoconazole cases drove this, so the confidence interval is very wide.
• Funding: not stated.

Ketoconazole was the antifungal associated with the highest relative risk, 228.0 (95% confidence interval 33.9,933.0), when compared with the risk among nonusers

The same cohort shows how rare the event is in absolute terms: just two ketoconazole cases among tens of thousands of antifungal users. (Source 18)

• Cohort study, Moderate certainty.
• Size: 69,830 patients; 16 validated cases.
• Who: As above.
• How long: 1991-1996.
• Result: Five cases occurred during current antifungal use, of which two were on ketoconazole; ten cases occurred during non-use with a background rate of 0.6 per 100,000 person-months.
• Funding: not stated.

Sixteen cases of acute liver injury were identified and validated. Ten cases occurred during nonuse of oral antifungals with a background rate of 0.6 per 100,000 person-months (95% confidence interval 0.3,1.1). Five cases occurred during current use of oral antifungals. Two were using ketoconazole, another two itraconazole, and one terbinafine.

A Taiwanese national cohort of 90,847 oral antifungal users found ketoconazole accounted for the most drug-induced liver injury cases and the steepest rise in risk with longer exposure. (Source 19)

• Cohort study, Moderate certainty.
• Size: 90,847 oral antifungal users; 52 cases of drug-induced liver injury, 28 on ketoconazole.
• Who: Taiwan National Health Insurance Database.
• How long: 2002-2008.
• Result: At 60 or more defined daily doses of exposure, 170.9 cases per 10,000 persons for ketoconazole versus 62.5 for itraconazole and 36.1 for terbinafine; 28 of the 52 drug-induced liver injury cases in the cohort were in ketoconazole users; antifungal users versus controls relative risk 2.38, P < 0.001.
• Funding: not stated.

Limit of this finding: The paper's abstract lists its overall per-drug incidence rates in a different order from its case counts: the cases are listed ketoconazole first, but the rates sentence reads "31.6, 4.9, 4.3, 3.6 and 1.6 for fluconazole, ketoconazole, griseofulvin, itraconazole and terbinafine". Read literally that gives ketoconazole 4.9 per 10,000 and fluconazole 31.6, which is the opposite of what the order of the previous sentence suggests. The paper's tables could not be reached to settle it, so no overall incidence rate is quoted here for ketoconazole. The figures above - the case count, the long-exposure rate and the overall relative risk - do not depend on that ordering.

Longer exposure duration increased the risk of DILI, with IR for exposure duration ≥ 60 defined daily dose (DDD) of 170.9, 62.5, and 36.1 per 10,000 persons for ketoconazole, itraconazole and terbinafine, respectively.

Topical ketoconazole cream causes local irritation in about one patient in twenty, roughly double the placebo rate, and systemic absorption is undetectable. (Source 20)

• Official position, Certainty not rated.
• Size: 905 patients on ketoconazole cream 2% and 208 on placebo in clinical trials.
• Who: Patients treated for tinea, candidiasis or seborrhoeic dermatitis.
• How long: Trial duration, typically two to four weeks.
• Result: Side effects in 45/905 (5.0%) versus 5/208 (2.4%) - an absolute excess of 2.6 percentage points - mainly severe irritation, pruritus and stinging; contact dermatitis rare in postmarketing reports.
• Funding: industry (sponsor label)

During clinical trials 45 (5.0%) of 905 patients treated with ketoconazole cream, 2% and 5 (2.4%) of 208 patients treated with placebo reported side effects consisting mainly of severe irritation, pruritus and stinging.

Oral ketoconazole prolongs the QT interval measurably even at standard doses. (Source 21)

• Blood level study, Moderate certainty.
• Size: Clinical PK/PD and drug-interaction studies; numbers not given in the label.
• Who: Adults given ketoconazole 200 mg twice daily.
• How long: 3 to 7 days.
• Result: Mean maximum QTc increase of about 6 to 12 msec at peak plasma concentrations 1 to 4 hours after dosing.
• Funding: industry (sponsor label)

oral dosing with ketoconazole at 200 mg twice daily for 3 to 7 days can result in an increase of the QTC interval: a mean maximum increase of about 6 to 12 msec was seen at ketoconazole peak plasma concentrations about 1 to 4 hours after ketoconazole administration.

Serious and sometimes fatal liver injury from oral ketoconazole has occurred in people with no risk factors, at both high short courses and low long courses. (Source 22)

• Case series, Certainty not rated.
• Size: Postmarketing reports and label review; denominator not given.
• Who: People taking oral ketoconazole.
• How long: Both short high-dose and long low-dose exposure.
• Result: No rate given in the label; outcomes include death and liver transplantation, usually but not always reversible on stopping, and hepatitis has been reported in children.
• Funding: industry (sponsor label)

Serious hepatotoxicity was reported both by patients receiving high doses for short treatment durations and by patients receiving low doses for long durations.

Oral ketoconazole suppresses adrenal steroid production at 400 mg daily and above - the basis for the Cushing's use and a hazard in everyone else. (Source 23)

• Official position, Certainty not rated.
• Size: Not a study.
• Who: People taking oral ketoconazole, especially under physiological stress.
• How long: Dose-dependent.
• Result: Adrenal corticosteroid secretion decreases at 400 mg and higher; the label states the 200-400 mg daily range should not be exceeded and that this effect is not shared with other azoles.
• Funding: industry (sponsor label)

Ketoconazole tablets decrease adrenal corticosteroid secretion at doses of 400 mg and higher. This effect is not shared with other azoles. The recommended dose of 200 mg to 400 mg daily should not be exceeded.

Oral ketoconazole lowers testosterone dose-dependently, with gynaecomastia, impotence and low sperm counts as consequences; this reverses on stopping. (Source 15)

• Official position, Certainty not rated.
• Size: Not a study.
• Who: People taking oral ketoconazole.
• How long: Reverses after discontinuation.
• Result: Testosterone impaired at 800 mg/day and abolished at 1600 mg/day; returns to baseline after the drug is stopped.
• Funding: industry (sponsor label)

Testosterone levels are impaired with doses of 800 mg per day and abolished by 1600 mg per day. Clinical manifestations of decreased testosterone concentrations may include gynecomastia, impotence and oligospermia.

Eleven men died within two weeks of starting high-dose oral ketoconazole in a prostate-cancer trial, with causality unresolved. (Source 7)

• Official position, Very low certainty.
• Size: 350 patients with metastatic prostatic cancer.
• Who: Men with metastatic prostate cancer given 1200 mg/day.
• How long: Deaths within two weeks of starting.
• Result: 11 deaths reported within two weeks; the label states it is not possible to tell whether these were drug-related, due to adrenal insufficiency, or due to the underlying disease.
• Funding: industry (sponsor label)

In a clinical trial involving 350 patients with metastatic prostatic cancer, eleven deaths were reported within two weeks of starting treatment with high doses of ketoconazole tablets (1200 mg/day).

What the evidence supports

Topical 2% ketoconazole clears seborrhoeic dermatitis better than placebo, but the evidence is low quality and heterogeneous. (Source 4)

• Systematic review, Low certainty.
• Size: Eight studies for the placebo comparison, within a review of 51 studies and 9,052 participants.
• Who: Adolescents and adults with seborrhoeic dermatitis of the face or scalp.
• How long: Four weeks of follow-up for the main comparison; only six of 51 trials looked beyond five weeks.
• Result: Risk of failed clearance 31% lower than placebo, RR 0.69 (95% CI 0.59 to 0.81), low-quality evidence, substantial heterogeneity (I2 = 74%); median non-clearance in placebo groups 69%; side effects RR 0.97 (0.58 to 1.64) on very low-quality evidence.
• Funding: industry-funded in part - the review authors believed 24 of the 51 trials had some form of conflict of interest such as pharmaceutical-company funding.

Topical ketoconazole 2% treatment showed a 31% lower risk of failed clearance of rashes compared with placebo (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.59 to 0.81, eight studies, low-quality evidence) at four weeks of follow-up

Against topical steroids, ketoconazole worked about as well with substantially fewer side effects. (Source 4)

• Systematic review, Low certainty.
• Size: Six studies for remission, eight for side effects, within the 51-study review.
• Who: Adolescents and adults with seborrhoeic dermatitis.
• How long: Mostly five weeks or less.
• Result: Remission RR 1.17 (95% CI 0.95 to 1.44), low-quality evidence - i.e. no significant difference; side effects 44% lower than with steroids, RR 0.56 (0.32 to 0.96), moderate-quality evidence.
• Funding: as above - half the included trials had declared conflicts of interest.

Ketoconazole treatment resulted in a remission rate similar to that of steroids (RR 1.17, 95% CI 0.95 to 1.44, six studies, low-quality evidence), but occurrence of side effects was 44% lower in the ketoconazole group than in the steroid group (RR 0.56, 95% CI 0.32 to 0.96, eight studies, moderate-quality evidence).

The reason the topical and oral risk profiles differ is measured, not assumed: ketoconazole was not detectable in blood after topical application. (Source 14)

• Blood level study, Moderate certainty.
• Size: Normal volunteers (single application) plus a 28-day dog study.
• Who: Healthy volunteers, chest, back and arms.
• How long: 72 hours of blood sampling after a single application.
• Result: Systemic absorption not detected at the 5 ng/mL level over 72 hours in volunteers; no detectable plasma levels at a 2 ng/mL limit in dogs dosed 28 days.
• Funding: industry (sponsor label)

After a single topical application to the chest, back and arms of normal volunteers, systemic absorption of ketoconazole was not detected at the 5 ng/mL level in blood over a 72-hour period.

What the evidence does not support

The European regulator concluded in July 2013 that the risk of liver injury from oral ketoconazole outweighed its benefit, and that the benefit itself was uncertain. (Source 24)

• Official position, Certainty not rated.
• Size: Not a study - a regulatory review of the available data.
• Who: People treated with oral ketoconazole for fungal infection in the EU.
• How long: Review concluded 26 July 2013.
• Result: Recommendation to suspend marketing authorisations EU-wide; the Committee found the incidence and seriousness of liver injury higher than with other antifungals and effectiveness data limited.
• Funding: independent (public regulator)

the CHMP concluded that, although liver injury such as hepatitis is a known side effect of antifungal medicines, the incidence and the seriousness of liver injury with oral ketoconazole were higher than with other antifungals.

The seborrhoeic dermatitis review found no evidence that ketoconazole beats other antifungals in its class, and no trial measured quality of life. (Source 25)

• Systematic review, Low certainty.
• Size: 51 studies, 9,052 participants.
• Who: Adolescents and adults with seborrhoeic dermatitis.
• How long: Very few studies went beyond four weeks.
• Result: Ketoconazole versus ciclopirox remission failure RR 1.09 (95% CI 0.95 to 1.26), low-quality evidence; no study assessed quality of life.
• Funding: half the trials had declared conflicts of interest.

Ketoconazole and ciclopirox are more effective than placebo, but limited evidence suggests that either of these agents is more effective than any other agent within the same class.

For ringworm and jock itch, the Cochrane review's pooled evidence named terbinafine and naftifine as effective; the azole class as a whole was no better than benzylamines, and ketoconazole itself was mostly assessed in single studies. (Source 5)

• Systematic review, Low certainty.
• Size: 129 studies, 18,086 participants.
• Who: People with proven dermatophyte infection of the body or groin.
• How long: Treatment one week to two months; follow-up one week to six months.
• Result: Azoles versus benzylamines, mycological cure RR 1.01 (95% CI 0.94 to 1.07), low-quality evidence; terbinafine versus placebo clinical cure RR 4.51 (3.10 to 6.56), NNT 3 (2 to 4); half the studies at high risk of bias and the overall evidence rated low to very low.
• Funding: independent (the review reports non-commercial support)

There was no difference in mycological cure between azoles and benzylamines (RR 1.01, 95% CI 0.94 to 1.07). The quality of the evidence was rated as low for this comparison.

Where the evidence is mixed

That cohort also contradicts the simple story: all six fatal liver-injury cases were on fluconazole, not ketoconazole. (Source 19)

• Cohort study, Moderate certainty.
• Size: 90,847 users; 6 fatal cases.
• Who: Taiwan National Health Insurance Database.
• How long: 2002-2008.
• Result: All 6 fatal drug-induced liver injury cases used fluconazole; old age and fluconazole predicted fatal injury.
• Funding: not stated.

Limit of this finding: Within the same abstract this is hard to reconcile: it reports only 12 fluconazole liver-injury cases in total, yet says all six fatal cases were on fluconazole - a case-fatality of half. The paper's tables could not be reached to check it, so read this as the authors' statement about which drug the fatal cases involved, not as a reliable fatality rate for fluconazole.

All of the six patients with fatal DILI used fluconazole. Old age and fluconazole increased the risk of oral antifungal-induced fatal DILI.

The same regulatory review drew a sharp line between oral and topical ketoconazole, keeping the topical forms available because systemic absorption from them is very low. (Source 24)

• Official position, Certainty not rated.
• Size: Not a study.
• Who: Users of ketoconazole creams, ointments and shampoos.
• How long: 26 July 2013.
• Result: Topical formulations were allowed to continue in use unchanged.
• Funding: independent (public regulator)

Topical formulations of ketoconazole (such as creams, ointments and shampoos) can continue to be used as the amount of ketoconazole absorbed throughout the body is very low with these formulations.

For Cushing's syndrome, ketoconazole normalised morning cortisol in well under half of patients and raised liver enzymes in about one in five. (Source 6)

• Case series, Low certainty.
• Size: 52 patients treated for ACTH-dependent Cushing syndrome at one tertiary centre.
• Who: ACTH-dependent Cushing syndrome, 2004-2023.
• How long: Rapid titration; maximal ketoconazole effect within 2 days of a dose increase.
• Result: Target morning cortisol (12 mcg/dL or less) reached by 39% (95% CI 24-56%) on ketoconazole versus 74% (49-90%) on metyrapone; a liver enzyme reached or exceeded three times the upper limit of normal in 22% (10-39%) on ketoconazole; bilirubin reached twice normal in 3% (0-15%)
• Funding: not stated.

KTZ achieved target AM F in 39% (95% CI 24%-56%) of patients, compared to 74% (95% CI 49%-90%) on MET.

Where the research disagrees

Whether oral ketoconazole should be available at all for fungal infection

• EMA Committee for Medicinal Products for Human Use (26 July 2013), Regulatory review of postmarketing liver-injury data and effectiveness evidence: The European Medicines Agency's (EMA's) Committee on Medicinal Products for Human Use (CHMP) has recommended that the marketing authorisations of oral ketoconazole-containing medicines should be suspended throughout the European Union (EU). The CHMP concluded that the risk of liver injury is greater than the benefits in treating fungal infections. (Source 16)
• The US label (version effective 2025-12-17), which retains a restricted indication, Regulatory position restricting rather than removing the indication: Ketoconazole tablets are indicated for the treatment of the following systemic fungal infections in patients who have failed or who are intolerant to other therapies: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. (Source 3)

Which oral antifungal poses the greatest liver risk

• Garcia Rodriguez and colleagues, UK GPRD cohort (1999), Cohort of 69,830 patients, 16 validated cases - only two on ketoconazole, hence the very wide interval: Ketoconazole was the antifungal associated with the highest relative risk, 228.0 (95% confidence interval 33.9,933.0), when compared with the risk among nonusers (Source 17)
• The Taiwanese national cohort (2014), Cohort of 90,847 oral antifungal users with 52 liver-injury cases; 28 of those cases were in ketoconazole users and all six fatal cases were on fluconazole, but the abstract lists its per-drug incidence rates in an order that contradicts its own case counts, so no overall rate can be attributed to either drug: All of the six patients with fatal DILI used fluconazole. Old age and fluconazole increased the risk of oral antifungal-induced fatal DILI. (Source 19)

How much

• Reference intake: Dosing is set by the prescriber, not the reader. As a position, the US ketoconazole tablet label (version effective 2025-12-17) states a recommended starting dose of 200 mg once daily, with the usual duration of therapy for systemic infection being 6 months, and 3.3 to 6.6 mg/kg once daily used in small numbers of children over 2 years of age. The topical cream label states it is applied once daily to the affected and surrounding area. (Source 26)
• Upper limit: The oral label allows an increase to 400 mg once daily if response is insufficient, and separately warns that the 200 to 400 mg daily range should not be exceeded because adrenal steroid secretion falls at 400 mg and above. Oral ketoconazole has not been studied in children under 2 years of age. (Source 23)
• Studied: Twelve placebo- or vehicle-controlled trials of topical ketoconazole in seborrhoeic dermatitis (3,253 participants) were pooled in the Cochrane review; the placebo comparison used 2% ketoconazole assessed at four weeks. (Source 27)
• Studied: The QT studies gave oral ketoconazole 200 mg twice daily for 3 to 7 days. (Source 21)
• Studied: The off-label prostate cancer trial recorded in the label used 1200 mg/day, six times the starting dose for infection. (Source 7)

A common belief, and what the research shows

The belief: Ketoconazole is dangerous, so the anti-dandruff shampoo and cream are dangerous too.

What the research shows: The risk belongs to the swallowed tablet, not the product on the skin. Ketoconazole "was not detected at the 5 ng/mL level in blood over a 72-hour period" after topical application, and the European regulator that suspended the tablets in 2013 wrote at the same time that "Topical formulations of ketoconazole (such as creams, ointments and shampoos) can continue to be used as the amount of ketoconazole absorbed throughout the body is very low with these formulations." The cream's own trial data show side effects in 5.0% versus 2.4% on placebo, almost all of it local irritation. The boxed warning for fatal liver injury and QT prolongation applies to the oral tablet.

Questions and answers

What is it?

Ketoconazole is a synthetic broad-spectrum imidazole antifungal - a white or almost white powder, soluble in acids. It comes in two very different forms: a 200 mg oral tablet that reaches the whole body, and creams and shampoos applied to the skin or scalp from which almost nothing is absorbed. The two have different indications and very different risks. (Source 2)

What does it do in the body?

It blocks a fungal enzyme, lanosterol 14-alpha-demethylase, which fungi need to turn lanosterol into ergosterol - the sterol that holds their cell membrane together. Methylated precursors accumulate while ergosterol runs out, so the membrane weakens and the fungus cannot function. Because the enzyme belongs to the cytochrome P450 family, high oral doses also interfere with human steroid synthesis and strongly block human CYP3A4. (Source 1)

Is it good or bad for you?

It depends entirely on the form. Topically for seborrhoeic dermatitis the balance is favourable: a Cochrane review of 51 trials found 2% ketoconazole cut the risk of failed clearance by 31% against placebo, with 44% fewer side effects than topical steroids, and the cream's own trials showed side effects in 5.0% versus 2.4% on placebo. Orally it is a last resort: the boxed warning covers fatal liver injury and QT prolongation, a UK cohort put its relative risk of acute liver injury at 228 against non-users, and the EMA suspended the tablets in Europe in 2013. (Source 16)

How do you get more of it?

Ketoconazole is a medicine, prescribed or bought as a shampoo; there is no dietary source. For the oral tablet, how much gets in depends sharply on stomach acid - it needs acidity to dissolve, bioavailability is maximal when taken with a meal, and after omeprazole it fell to 17% of normal, recovering to 65% when taken with a non-diet cola. (Source 8)

If it is harmful, what reduces it?

Stopping the drug. Oral ketoconazole clears quickly - a biphasic half-life of about 2 hours then 8 hours - mainly through bile into the stool, with about 13% in the urine. Liver injury is usually but not always reversible once the drug is stopped, and testosterone returns to baseline. Restarting is what has caused injury to recur. (Source 22)

Why might someone be low in it or missing it?

Not applicable in the nutrient sense - nobody is low in ketoconazole. For the oral tablet the practical equivalent is losing the drug's effect: anything that reduces stomach acid cuts absorption, and strong CYP3A4 inducers such as rifampicin, isoniazid, rifabutin, carbamazepine, phenytoin, efavirenz and nevirapine can lower blood levels enough to lose efficacy, which is why the label says to avoid them from two weeks before treatment. (Source 12)

Which whole foods contain it or feed it?

No food contains ketoconazole - it is a manufactured imidazole. Food matters only to absorption of the oral tablet: it is best absorbed with a meal, and an acidic drink such as a non-diet cola restores absorption in people on acid-suppressing medicines. Alcohol is the one dietary item the label tells people to avoid during treatment, because of the liver risk and because alcohol intolerance is a reported reaction. (Source 8)

What happens if you do not have it?

Nothing happens from not having ketoconazole; it is a treatment, not a requirement. If a systemic fungal infection goes untreated that is the infection's consequence, not the drug's absence - and for most such infections other antifungals are now preferred. The EMA's view in 2013 was that alternative treatments are available and deemed safer, and patients were told to make a non-urgent appointment to switch. (Source 28)

How can you test for it?

Blood levels of ketoconazole are not routinely measured, though the label says they should be measured when appropriate in people also taking a potent CYP3A4 inhibitor. What is tested is harm: a full baseline panel including ALT, AST, alkaline phosphatase, bilirubin, prothrombin time, INR and viral hepatitis serology, then weekly ALT for the whole course, plus adrenal function in anyone with borderline adrenal reserve or under prolonged stress. These tests detect injury rather than predict it. (Source 9)

References

1. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
2. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
3. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
4. Cochrane Database of Systematic Reviews. Topical antifungals for seborrhoeic dermatitis.. 2015. PMID 25933684, DOI 10.1002/14651858.CD008138.pub3. Read the source
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10. World Journal of Clinical Cases. Red yeast rice with monacolin K for the improvement of hyperlipidemia: A narrative review.. 2025. PMID 40881894, DOI 10.12998/wjcc.v13.i27.105415. Read the source
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17. British Journal of Clinical Pharmacology. A cohort study on the risk of acute liver injury among users of ketoconazole and other antifungal drugs - relative-risk sentence of the Results section. 1999. PMID 10594489, DOI 10.1046/j.1365-2125.1999.00095.x. Read the source
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22. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
23. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
24. European Medicines Agency (CHMP press release, 26 July 2013). European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole. 2013. Read the source
25. Cochrane Database of Systematic Reviews. Topical antifungals for seborrhoeic dermatitis.. 2015. PMID 25933684, DOI 10.1002/14651858.CD008138.pub3. Read the source
26. DailyMed / US FDA Structured Product Label, label version effective 2025-12-17. KETOCONAZOLE TABLET - prescribing information (Strides Pharma Science Limited). 2025. Read the source
27. Cochrane Database of Systematic Reviews. Topical antifungals for seborrhoeic dermatitis.. 2015. PMID 25933684, DOI 10.1002/14651858.CD008138.pub3. Read the source
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