Ketoconazole is an imidazole antifungal drug. It comes in two very different forms: oral tablets (200 mg), which are absorbed into the body, and topical products (2% cream, 2% prescription shampoo and 1% over-the-counter shampoo), which act on the skin and scalp and are not measurably absorbed.
The oral form also blocks the enzymes the body uses to make testosterone and cortisol. That is why it caused gynecomastia in early users, why doctors have used it off-label for Cushing’s syndrome and prostate cancer, and why it comes up in bodybuilding and hair-loss discussions. In 2013 the FDA restricted oral ketoconazole to rare systemic fungal infections because of fatal liver injury, and the EU suspended it as an antifungal the same year. The tablet label carries a boxed warning for liver toxicity and for QT prolongation caused by drug interactions.
This page summarizes what the FDA and EMA labels, regulatory notices and clinical studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Imidazole antifungal; inhibitor of steroid-making cytochrome P450 enzymes |
| Forms (US) | Oral 200 mg tablets (generic; brand Nizoral tablets discontinued); 2% cream and 2% shampoo (Rx); 1% shampoo (OTC, Nizoral Anti-Dandruff) |
| Oral indication (US) | Blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis and paracoccidioidomycosis, only when other antifungals have failed or are not tolerated |
| Labeled oral dose | 200 mg once daily, increased to 400 mg once daily if response is insufficient |
| Half-life (oral label) | Biphasic: about 2 h during the first 10 h, then about 8 h |
| Hormonal effects (label) | Lowers testosterone (impaired at 800 mg/day, abolished at 1600 mg/day); decreases adrenal corticosteroid output at 400 mg/day and above |
| Boxed warning (oral) | Hepatotoxicity, including deaths and liver transplants; QT prolongation from drug interactions |
| Topical absorption | Not detected in plasma after months of shampoo use (label) |
| EU status | Oral antifungal use suspended in 2013; Ketoconazole HRA tablets authorized in 2014 for Cushing’s syndrome |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Ketoconazole is a synthetic imidazole with the formula C₂₆H₂₈Cl₂N₄O₄ and a molecular weight of 531.44 (ketoconazole tablets label). The drug is a racemic mixture of two mirror-image forms (enantiomers). One of them, the 2S,4R enantiomer, is sold separately as levoketoconazole (Recorlev) for Cushing’s syndrome (Creemers et al., JCEM 2021). The US approval of ketoconazole dates to 1981 (Recorlev label).
How it kills fungi
Ketoconazole blocks lanosterol 14α-demethylase, a cytochrome P450 enzyme that fungi need to make ergosterol, the main sterol of their cell membranes. Without ergosterol the membrane weakens (tablets label). On the scalp, the shampoo is thought to work by reducing Malassezia yeasts, which are linked to dandruff and seborrheic dermatitis (2% shampoo label).
How it blocks testosterone and cortisol
The same kind of P450 enzymes also make human steroid hormones. Ketoconazole inhibits several of them:
| Enzyme step | What it normally does | Evidence |
|---|---|---|
| Side-chain cleavage (cholesterol to pregnenolone) | First step of all steroid hormone synthesis | Blocked in adrenal mitochondria in vitro (Loose et al., J Clin Invest 1983) |
| 11β-hydroxylase | Final step to the main glucocorticoid | Blocked in isolated adrenal cells in vitro (Loose et al.) |
| 17α-hydroxylase and 17,20-lyase (desmolase) | Steps that lead to androgens such as testosterone | Blocked in rat testis preparations (Sikka et al., Endocrinology 1985) |
In people, the effect was first noticed when two patients developed gynecomastia (breast tissue growth in men). In male volunteers, a single 200, 400 or 600 mg dose made serum testosterone fall markedly, with recovery toward baseline 8–24 hours later as drug levels waned (Pont et al., Arch Intern Med 1982). The authors noted an “escape” from the block in vivo, which may explain why hormonal side effects were uncommon at standard antifungal doses.
The tablet label states that testosterone is impaired at 800 mg/day and abolished at 1600 mg/day, returns to baseline after stopping, and that low testosterone can show up as gynecomastia, impotence and oligospermia (low sperm count). Adrenal corticosteroid secretion falls at 400 mg/day and above, an effect the label says other azoles do not share.
Pharmacokinetics
Oral tablets
From the ketoconazole tablets label (DailyMed):
| Parameter | Value |
|---|---|
| Peak level after 200 mg with a meal | About 3.5 mcg/mL, at 1–2 h |
| Need for stomach acid | Yes; a weak base that dissolves only in acid. After omeprazole, bioavailability fell to 17% (65% when taken with non-diet cola) |
| Protein binding | About 99%, mainly to albumin |
| Cerebrospinal fluid | Only negligible amounts reach it |
| Metabolism | Mainly CYP3A4, to inactive metabolites |
| Elimination half-life | About 2 h in the first 10 h, about 8 h thereafter |
| Excretion | About 57% in feces (via bile); about 13% in urine, 2–4% unchanged |
The short half-life fits the hormone data: in the 1982 volunteer study, testosterone dropped after each dose and recovered as drug levels fell (Pont et al. 1982).
Topical products
Topical ketoconazole does not reach measurable blood levels in the label studies:
- 2% shampoo: not detected in plasma in 39 patients who shampooed 4–10 times a week for 6 months, or in 33 patients who shampooed 2–3 times a week for 3–26 months (2% shampoo label).
- 2% cream: after one application to the chest, back and arms of volunteers, not detected in blood at the 5 ng/mL level over 72 hours (2% cream label).
This is why the hormonal and liver effects of the tablets do not carry over to topical use. The cream label states that hepatitis and, at high doses, lowered testosterone and cortisol responses “have not been seen with topical ketoconazole.”
Approved medical use
Oral tablets (antifungal)
Since July 2013, US labeling limits ketoconazole tablets to five systemic fungal infections (blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis and paracoccidioidomycosis), and only in patients who have failed or cannot tolerate other therapy. The tablets are not indicated for nail fungus, skin dermatophyte infections or Candida infections, and should not be used for fungal meningitis because they penetrate poorly into the cerebrospinal fluid (tablets label).
The labeled adult dose is 200 mg once daily, raised to 400 mg once daily if response is insufficient, usually for 6 months for systemic infection. The label says the 200–400 mg daily range should not be exceeded because of adrenal effects.
Topical products
| Product | Labeled use | Labeled directions |
|---|---|---|
| 2% cream (Rx) | Tinea corporis, cruris and pedis; tinea versicolor; cutaneous candidiasis; seborrheic dermatitis | Once daily for 2 weeks (6 weeks for tinea pedis); twice daily for 4 weeks for seborrheic dermatitis (cream label) |
| 2% shampoo (Rx) | Tinea (pityriasis) versicolor | Single application, left on for 5 minutes (shampoo label) |
| 1% shampoo (OTC) | Flaking, scaling and itching of dandruff | Every 3–4 days for up to 8 weeks, then as needed, in people 12 and older (Nizoral Anti-Dandruff label) |
Hair loss is not a labeled use of any ketoconazole product.
Cushing’s syndrome
Cushing’s syndrome is a disease of chronically high cortisol. Because ketoconazole blocks cortisol synthesis, it has long been used off-label to control it. The US tablet label states that use for Cushing’s syndrome and advanced prostate cancer is not FDA-approved and that safety and effectiveness have not been established.
In the EU, the 2013 suspension allowed national authorities to keep oral ketoconazole available for Cushing’s patients under controlled conditions (EMA referral). In November 2014 the EU authorized Ketoconazole HRA 200 mg tablets for endogenous Cushing’s syndrome in adults and adolescents over 12 (EMA, Ketoconazole HRA).
In the US, the single enantiomer levoketoconazole (Recorlev) was approved on December 30, 2021 for endogenous hypercortisolemia in adults with Cushing’s syndrome when surgery is not an option or has not been curative (Drugs@FDA, NDA 214133). It is dosed from 150 mg twice daily up to 600 mg twice daily and carries its own boxed warning for hepatotoxicity and QT prolongation (Recorlev label).
Regulatory status
| Date | Regulator | Action |
|---|---|---|
| July 26, 2013 | FDA | Limited Nizoral tablets to endemic mycoses when alternatives are not available or tolerated; removed skin and nail indications; revised the boxed warning; added a liver-disease contraindication and an adrenal insufficiency warning (FDA Drug Safety Communication) |
| July 25, 2013 | EMA (CHMP) | Recommended suspension of all oral ketoconazole marketing authorizations in the EU, concluding that liver-injury risk outweighs benefit for fungal infections (EMA referral) |
| October 11, 2013 | European Commission | Legally binding EU-wide decision on the suspension |
| November 2014 | European Commission | Ketoconazole HRA authorized for Cushing’s syndrome |
| December 30, 2021 | FDA | Recorlev (levoketoconazole) approved for Cushing’s syndrome |
Both regulators stated that topical forms (creams, shampoos, gels) were not affected. FDA said they “have not been associated with liver damage, adrenal problems, or drug interactions,” and EMA noted that very little is absorbed into the body from these products. The brand Nizoral tablets (NDA 018533) are listed as discontinued in the US. Generic 200 mg tablets remain available by prescription (Drugs@FDA).
Ketoconazole is not a controlled substance in the US. It is not named on the WADA 2026 Prohibited List.
What the research shows
Cushing’s disease (oral ketoconazole)
The largest study is a French retrospective review of 200 patients treated with ketoconazole alone for Cushing’s disease (Cushing’s caused by a pituitary tumor) (Castinetti et al., JCEM 2014):
| Outcome | Result |
|---|---|
| Normal urinary free cortisol at last follow-up | 49.3% of patients |
| At least 50% reduction (not normalized) | 25.6% |
| Unchanged | 25.4% |
| Median final dose | 600 mg/day |
| Stopped because of poor tolerance | 41 patients (20.5%) |
| Mild liver enzyme rise (under 5× normal) | 13.5% |
| Major liver enzyme rise (over 5× normal) | 2.5% |
| Fatal hepatitis | None observed |
As a retrospective study without a control group, it cannot give precise efficacy figures, but it shows that the cortisol-lowering doses used in Cushing’s are well above the antifungal range.
Levoketoconazole trials
Two phase 3 trials supported Recorlev:
| Trial | Design | Main result |
|---|---|---|
| SONICS (Fleseriu et al., Lancet Diabetes Endocrinol 2019) | Open-label, single-arm, n = 94; 150–600 mg twice daily | 31% had normal mean urinary free cortisol at the end of 6 months of maintenance without a dose increase. ALT rose above 3× normal in 11%; 2 patients had QTcF over 500 ms |
| LOGICS (Pivonello et al., Pituitary 2022) | Randomized withdrawal, n = 44 randomized | Cortisol control was lost in 95.5% switched to placebo vs 40.9% continuing the drug (difference −54.5%, 95% CI −75.7 to −27.4) |
The Recorlev label reports drug-induced liver injury (ALT or AST over 3× normal) in 13% of patients across its trials (Recorlev label).
Prostate cancer (historical, off-label)
Because it lowers androgen production, high-dose ketoconazole was used for advanced prostate cancer. The tablet label reports a trial of 350 men with metastatic prostate cancer in which 11 died within two weeks of starting 1200 mg/day. It was not possible to tell whether the deaths were caused by the drug, adrenal insufficiency or the underlying disease (tablets label).
Topical ketoconazole in androgenetic alopecia
Androgenetic alopecia (pattern hair loss) is driven by DHT. The first-line drugs are finasteride, dutasteride and minoxidil. Ketoconazole shampoo has been studied as an add-on, on the theory that scalp yeast and inflammation contribute to follicle damage. Since topical ketoconazole is not detectable in blood, any effect would be local, not a drop in body-wide testosterone.
The evidence is limited:
- Piérard-Franchimont et al., 1998. This small study compared 2% ketoconazole shampoo with an unmedicated shampoo, used with or without 2% minoxidil. Hair density, hair size and the share of follicles in the growth (anagen) phase improved by about as much with ketoconazole as with minoxidil, and scalp sebum appeared lower. The authors said the clinical significance needed a larger controlled study (Dermatology 1998).
- Khandpur et al., 2002. In an open-label randomized study of 100 men followed for one year, finasteride 1 mg plus 2% ketoconazole shampoo (only 10 men) ranked second after finasteride plus minoxidil, ahead of finasteride alone and minoxidil alone. The trial was not blinded and the ketoconazole group was very small (J Dermatol 2002).
- Fields et al., 2020 systematic review. It found only five human studies (318 participants in total) plus two mouse studies. Human studies reported thicker hair shafts and some clinical improvement. The authors called topical ketoconazole “promising” but concluded that randomized controlled trials are needed (Dermatol Ther 2020).
Guidelines reflect this. A 2025 Canadian Delphi consensus placed ketoconazole shampoo in its “recommended with near consensus” group as part of a regimen, below the seven fully recommended treatments that include oral and topical finasteride, dutasteride and minoxidil (Landells et al., J Cutan Med Surg 2025).
For its labeled uses, the evidence is much stronger. A systematic review of 40 randomized trials (4,566 patients) reported efficacy of 63–90% in seborrheic dermatitis and 71–89% in pityriasis versicolor (Choi et al., J Dermatolog Treat 2019).
Side effects and risks
Boxed warning: liver toxicity (oral)
The tablet label warns that serious hepatotoxicity, including deaths and cases needing a liver transplant, has occurred with oral ketoconazole, sometimes in people with no risk factors. It happened both with high doses for short periods and with low doses for long periods, and has recurred on restarting the drug (tablets label). The label requires:
- baseline liver tests (GGT, alkaline phosphatase, ALT, AST, bilirubin, PT/INR) and testing for viral hepatitis;
- weekly ALT during treatment;
- stopping treatment if ALT rises above the upper limit of normal or 30% above baseline, or if symptoms appear;
- no alcohol, and avoiding other liver-toxic drugs where possible.
Ketoconazole is contraindicated in acute or chronic liver disease. In a UK cohort of 69,830 users of oral antifungals, the rate of acute liver injury with ketoconazole was 134.1 per 100,000 person-months, with a relative risk of 228 (95% CI 33.9–933.0) compared with non-users. That was the highest of the antifungals studied (García Rodríguez et al., Br J Clin Pharmacol 1999).
Boxed warning: QT prolongation and drug interactions (oral)
Ketoconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, so it raises blood levels of many other drugs. At 200 mg twice daily for 3–7 days it lengthened the QTc interval by a mean maximum of about 6–12 ms (tablets label). Combining it with these drugs is contraindicated because of the risk of fatal arrhythmias such as torsades de pointes:
- dofetilide, quinidine, disopyramide, dronedarone, ranolazine;
- pimozide, lurasidone, cisapride, methadone.
The label also contraindicates oral midazolam, triazolam, alprazolam, simvastatin, lovastatin, ergot alkaloids, irinotecan, felodipine, nisoldipine, tolvaptan, eplerenone and colchicine. Other examples it lists:
| Interacting drug | Label finding |
|---|---|
| Sirolimus | Peak level up 4.3-fold and AUC up 10.9-fold |
| Cisapride | Mean 8-fold increase in AUC |
| Tolvaptan | Exposure up 5-fold |
| Sildenafil, tadalafil, vardenafil | Listed as interacting drugs; vardenafil should not exceed a single 5 mg dose |
| Budesonide, dexamethasone, fluticasone | Higher steroid levels; fluticasone not recommended unless benefit outweighs the risk of systemic corticosteroid effects |
| Acid reducers (PPIs, H2 blockers, antacids) | Lower ketoconazole absorption |
| Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) | Lower ketoconazole levels; not recommended |
Hormonal effects (oral)
- Low testosterone: gynecomastia, erectile dysfunction, oligospermia, and azoospermia (no sperm) at doses above 200–400 mg/day (tablets label).
- Adrenal insufficiency: cortisol output falls at 400 mg/day and above. The label advises monitoring adrenal function in people with borderline adrenal function or under prolonged stress such as major surgery or intensive care. Symptoms include tiredness, weakness, dizziness, nausea and vomiting.
Other oral side effects
The most common side effects on the medication guide are nausea, headache, diarrhea, stomach pain and abnormal liver tests. Anaphylaxis has been reported after the first dose. In rats, ketoconazole caused limb malformations at 80 mg/kg/day, and it passes into breast milk; the label says not to breastfeed while taking it.
Topical products
Topical side effects are mostly local. In 11 double-blind trials of 2% shampoo (264 patients), increased hair shedding and irritation each occurred in under 1%. Postmarketing reports include hair discoloration, abnormal hair texture, contact dermatitis, angioedema and hair loss (2% shampoo label). In cream trials, 5.0% of 905 patients reported irritation, itching or stinging, compared with 2.4% on placebo. The cream contains sodium sulfite, which can trigger allergic reactions in sulfite-sensitive people, especially those with asthma (2% cream label).
“Ketoconazole shampoo lowers DHT.” This claim mixes up the oral and topical drug. Oral ketoconazole blocks testosterone production at high doses. The shampoo was not detected in blood after months of use, and there is no evidence that it lowers testosterone or DHT in the body. Any effect on hair loss is likely local and remains weakly supported.
Key takeaways
- Two drugs in one name. Oral ketoconazole is a systemic enzyme inhibitor with serious risks. Topical ketoconazole (cream, 1% and 2% shampoo) is not measurably absorbed and has mostly local side effects.
- Oral use is tightly restricted. Since 2013, US labeling limits tablets to rare systemic fungal infections when nothing else works, and the EU suspended oral antifungal use because liver-injury risk outweighed benefit.
- It blocks testosterone and cortisol. Single 200–600 mg doses lowered testosterone in men. The label notes testosterone is impaired at 800 mg/day and cortisol output falls from 400 mg/day, with gynecomastia, impotence and adrenal insufficiency as consequences.
- Cushing’s is the main hormonal use. About half of 200 French patients normalized cortisol at a median 600 mg/day. The EU approved Ketoconazole HRA in 2014, and the US approved the single enantiomer levoketoconazole (Recorlev) in 2021, both with liver and QT warnings.
- Hair-loss evidence is thin. Small, mostly uncontrolled studies suggest 2% shampoo may help as an add-on to finasteride or minoxidil. No large randomized trial has tested it.
Sources
- Strides Pharma. Ketoconazole tablets USP, 200 mg, prescribing information and medication guide, revised 07/2025. DailyMed.
- ANI Pharmaceuticals. Ketoconazole shampoo, 2%, prescribing information, issued 07/2024. DailyMed.
- E. Fougera & Co. Ketoconazole cream 2%, prescribing information. DailyMed.
- Kramer Laboratories. Nizoral Anti-Dandruff (ketoconazole 1%) shampoo, Drug Facts. DailyMed.
- Xeris Pharmaceuticals. Recorlev (levoketoconazole) tablets prescribing information. DailyMed.
- Food and Drug Administration. NDA 214133 (Recorlev) approval letter, December 30, 2021. FDA.
- Food and Drug Administration. Drugs@FDA: Nizoral (ketoconazole) tablets, NDA 018533. FDA.
- Food and Drug Administration. FDA Drug Safety Communication: FDA limits usage of Nizoral (ketoconazole) oral tablets due to potentially fatal liver injury and risk of drug interactions and adrenal gland problems. July 26, 2013. FDA.
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- European Medicines Agency. Ketoconazole HRA: EPAR. EMA.
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