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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RECORLEV (RECORLEV).
| Breastfeeding | No data on human milk excretion. Levoketoconazole is lipophilic and likely present in breast milk. Because of potential for serious adverse effects (e.g., adrenal suppression, hepatotoxicity) in nursing infants, breastfeeding is not recommended during treatment and for at least 5 half-lives (approximately 5-7 days) after last dose. M/P ratio: Unknown. |
| 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. |
■ FDA Black Box Warning
No FDA-issued black box warning currently exists for RECORLEV.
| Serious Effects |
["Hypersensitivity to levoketoconazole or any component of the formulation","QTc interval >470 msec at baseline or congenital long QT syndrome","Concomitant use with drugs that are strong CYP3A4 inhibitors or inducers","Severe hepatic impairment (Child-Pugh class C)"]
| 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."] |
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| 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. |