RECORLEV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RECORLEV (RECORLEV).
RECORLEV (levoketoconazole) is an orally administered corticosteroid biosynthesis inhibitor that suppresses cortisol production by inhibiting adrenal and gonadal steroidogenic enzymes, particularly CYP17A1 (17α-hydroxylase and 17,20-lyase) and CYP11B1 (11β-hydroxylase). It also weakly inhibits CYP3A4 and other CYP enzymes.
| Metabolism | Primarily metabolized by hepatic CYP3A4 and to a lesser extent by CYP2C19 and CYP2D6. The major metabolites are inactive. Renal excretion of metabolites is minimal. |
| Excretion | Renal: 85% as unchanged drug; Fecal: 10% as metabolites |
| Half-life | 18 hours; prolonged in renal impairment (up to 45 hours in CrCl <30 mL/min) |
| Protein binding | 92% to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 3.5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 70%; Rectal: 50% |
| Onset of Action | Oral: 30-60 minutes; IV: 5-10 minutes |
| Duration of Action | 12-24 hours; shorter with higher doses or severe pain |
| Molecular Weight | 278.35 |
150 mg orally twice daily with a high-fat meal.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, reduce to 100 mg twice daily. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce to 100 mg twice daily. Child-Pugh C: not recommended. |
| Pediatric use | Weight-based dosing: 20-30 kg: 75 mg twice daily; 31-50 kg: 100 mg twice daily; >50 kg: 150 mg twice daily. |
| Geriatric use | No specific dose adjustment; monitor for adverse effects due to age-related renal decline. |
| 1st trimester | Contraindicated: High risk of fetal malformations including Ebstein's anomaly and other cardiac defects. |
| 2nd trimester | Contraindicated: Continued risk of fetal toxicity and adverse effects. |
| 3rd trimester | Contraindicated: Risk of neonatal withdrawal syndrome and other complications. |
Clinical note
Comprehensive clinical and safety monograph for RECORLEV (RECORLEV).
| Placental transfer | Crosses the placenta with evidence of significant transfer in animal studies and reported human cases. |
| Breastfeeding | Excreted into breast milk; avoid breastfeeding due to potential for serious adverse reactions in the infant, including central nervous system effects and cardiovascular issues. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA-issued black box warning currently exists for RECORLEV.
| Serious Effects |
Hypersensitivity to lithium or any componentSevere renal impairmentCardiovascular diseaseSodium depletionPregnancy (especially first trimester)
| Precautions | QTc interval prolongation: Levoketoconazole causes dose-dependent QTc prolongation; monitor ECG and electrolytes before and during treatment. Avoid use with other drugs that prolong QTc or in patients with risk factors for torsades de pointes., Adrenal insufficiency: May cause life-threatening adrenal suppression; taper steroids if switching from other agents. Monitor for signs of adrenal insufficiency and replace glucocorticoids as needed., Hepatotoxicity: Elevations in liver enzymes have been reported; monitor hepatic function at baseline and periodically. Discontinue if significant injury occurs., Hypogonadism and infertility: May suppress gonadal steroid production, leading to hypogonadism and reduced fertility in both males and females., Fetal/neonatal risk: Based on animal data, may cause fetal harm; women of childbearing potential should use effective contraception. |
| Food/Dietary |
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| L5 - Contraindicated |
| Teratogenic Risk | RECORLEV (levoketoconazole) is contraindicated in pregnancy. Based on its mechanism of action (CYP17A1 inhibition) and animal studies, there is a high risk of fetal harm. First trimester: Potential for miscarriage and major malformations. Second and third trimesters: Risk of fetal adrenal insufficiency, oligohydramnios, and growth restriction due to androgen suppression. |
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST, bilirubin) monthly. Assess maternal adrenal function (cortisol) before and during treatment due to risk of hypoadrenalism. In pregnant patients (if inadvertent exposure), monitor fetal growth by ultrasound every 4 weeks and assess amniotic fluid volume. Consider fetal adrenal function testing (e.g., umbilical vein cortisol) if exposure occurred in second/third trimester. |
| Fertility Effects | Due to CYP17A1 inhibition, RECORLEV reduces sex hormone synthesis. In premenopausal women, may cause anovulation and menstrual irregularities, potentially impairing fertility. In men, may decrease testosterone leading to reduced spermatogenesis and libido. Effects are reversible upon discontinuation. |
| Avoid grapefruit and grapefruit juice as they increase drug levels and toxicity risk. Take with food to reduce gastrointestinal upset. No other significant food interactions. |
| Clinical Pearls | RECORLEV (levoketoconazole) is an oral CYP17A1 inhibitor used for Cushing's syndrome. Monitor for QTc prolongation; obtain baseline ECG and repeat after dose titration. Avoid in patients with QTc >470 ms. Hepatic toxicity risk: monitor ALT/AST monthly for first 6 months, then periodically. Titrate dose based on cortisol levels (target normal range). |
| Patient Advice | Take exactly as prescribed, do not change dose without consulting your doctor. · Avoid grapefruit and grapefruit juice during treatment. · Report symptoms of adrenal insufficiency (fatigue, weakness, dizziness) immediately. · Regular blood tests are required to monitor liver function and heart rhythm. · Use effective contraception; the drug can harm a fetus. · Do not stop abruptly; dose must be tapered under medical supervision. |