Sensitive Cyp3a4 Substrates With Toxicity
Contraindicated
Database
Potent CYP3A4 inhibition
Contraindicated combinations per label
Source: Kimi deep-research + Cla
Drug reference
levoketoconazole
Cortisol synthesis inhibitor (2S,4R enantiomer of ketoconazole) · Steroidogenesis inhibitor
START
150 mg PO twice daily; titrate by cortisol response
TYPICAL MAX
1200 mg/day
STOP IF
ALT >3× ULN, QTc >500 ms, or adrenal insufficiency
WATCH
LFTs (intensive baseline + weekly initial), ECG/QT, K, urinary free cortisol
CDSCO approvedATC H02CA
KDIGO 2024 + manufacturer label
- ONSET
- 1h · absorption
- PEAK
- 2h · Tmax
- t½
- 3.5h · t½
- DURATION
- 12h · twice-daily
EXCRETION
Mainly faecal; minor renal
route + CYP
INTERACTIONS
3 major
incl. contraindicated
PREGNANCY
Contraindicated — embryotoxic.
FDA category + note
Top interactionssee all 5 →
- Sensitive Cyp3a4 Substrates With ToxicityContraindicatedDatabaseKimi deep-research + Cla
- Qt Prolonging DrugsSevereDatabaseKimi deep-research + Cla
- Strong Cyp3a4 InducersSevereDatabaseKimi deep-research + Cla
Mechanism
Inhibits adrenal steroidogenic enzymes (CYP17A1, 11β-hydroxylase, side-chain cleavage), reducing cortisol production; designed as the more steroidogenically active and less hepatotoxic enantiomer of racemic ketoconazole.
Indications
Endogenous Cushing syndrome (adults in whom surgery is not an option or has not been curative)
Dosing
- Adult
- 150 mg PO twice daily; titrate by ~150 mg/day every 2–3 weeks (max 1200 mg/day; usually maintenance 150–600 mg twice daily).
- Pediatric
- Not established.
- Renal adjustment
- No specific adjustment; limited data severe.
- Hepatic adjustment
- Avoid in cirrhosis / significant baseline liver disease; monitor LFTs intensively.
- Geriatric
- No specific adjustment; monitor closely.
- Max dose
- 1200 mg/day
Pharmacokinetics
Onset
Cortisol decline within days
Peak effect
~2 h (Tmax)
Duration
~12 h (twice-daily)
Half-life
~3.5 h
Bioavailability
Improved with food and low gastric pH
Protein binding
>99%
Metabolism
Hepatic CYP3A4 (and inhibits CYP3A4)
Excretion
Mainly faecal; minor renal
Contraindications
- Cirrhosis / acute liver disease / repeated unexplained transaminase elevation
- Co-administration with strong CYP3A4 inhibitors or sensitive CYP3A4 substrates with serious toxicity
- Prolonged QT interval / long-QT syndrome
- Hypersensitivity
- Pregnancy
Side effects
Common
Nausea/vomitingHeadacheAdrenal insufficiencyFatigueHypokalaemiaHypertension
Serious
- Hepatotoxicity (boxed warning — hepatic failure)
- QT prolongation/torsades
- Adrenal insufficiency / hypocortisolism
- Severe hypokalaemia
Pregnancy & lactation
Pregnancy
Contraindicated — embryotoxic.
Lactation
Contraindicated during therapy.
Drug interactions
Qt Prolonging Drugs
Severe
Database
Additive QT prolongation
Avoid; ECG/electrolyte monitoring
Source: Kimi deep-research + Cla
Strong Cyp3a4 Inducers
Severe
Database
Reduced exposure
Avoid combination
Source: Kimi deep-research + Cla
Acid Suppressants
Moderate
Database
Reduced solubility/absorption
Take with acidic drink; avoid PPI if possible
Source: Kimi deep-research + Cla
Hepatotoxic Drugs
Moderate
Database
Additive hepatotoxicity
Avoid combination; monitor LFTs
Source: Kimi deep-research + Cla
Related guidelines
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ESC · Cardiology · 2026
Ask House about levoketoconazole
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: Goodman & Gilman 14e·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20