CLARAVIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).
Isotretinoin, a retinoid, reduces sebum production, inhibits sebaceous gland activity, and normalizes follicular keratinization. It also exhibits anti-inflammatory effects.
| Metabolism | Primarily metabolized by CYP450 enzymes (CYP2C8, CYP3A4, CYP2C9) to major metabolites (4-oxo-isotretinoin, tretinoin, 4-oxo-tretinoin). Undergoes glucuronidation and oxidation. |
| Excretion | Renal: 90% as unchanged drug; fecal: 5%; biliary: <1%. |
| Half-life | Terminal half-life: 19-24 hours in adults; prolonged in renal impairment (up to 50 hours in ESRD). |
| Protein binding | 99.9% bound to albumin, primarily to retinol-binding protein and prealbumin. |
| Volume of Distribution | Vd: 0.95-1.1 L/kg; extensive tissue distribution including sebaceous glands and skin. |
| Bioavailability | Oral (isotretinoin): 25-30% after first-pass metabolism; topical (CLARAVIS gel): approximately 2% systemic absorption. |
| Onset of Action | Oral: 2-4 hours to peak serum concentration; topical: 2-4 weeks for visible improvement in acne. |
| Duration of Action | Clinical effects persist for 2-4 weeks after cessation; systemic concentrations decline slowly with multi-dose accumulation. |
| Molecular Weight | 300.44 |
Oral: 30 mg once daily after a meal for 12 weeks; administration with high-fat meal increases absorption.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe impairment (CrCl <30 mL/min) or ESRD; use with caution. |
| Liver impairment | Child-Pugh Class A (mild): No adjustment. Child-Pugh Class B (moderate): 15 mg once daily. Child-Pugh Class C (severe): Contraindicated. |
| Pediatric use | Approved for children ≥12 years with severe recalcitrant nodular acne: 0.5-1 mg/kg/day orally divided twice daily with food, maximum 2 mg/kg/day, total cumulative dose 120-150 mg/kg. For children <12 years: not recommended. |
| Geriatric use | No specific dose adjustment; use with caution due to potential for increased sensitivity, dry skin/mucous membranes, and hepatic impairment. Monitor renal function and lipids. |
| 1st trimester | Claravis (isotretinoin) is teratogenic; contraindicated in pregnancy. Exposure during first trimester linked to major fetal malformations including CNS, cardiovascular, and facial abnormalities. |
| 2nd trimester | Contraindicated in pregnancy; risk of fetal harm continues throughout all trimesters. |
| 3rd trimester | Contraindicated in pregnancy; may cause premature epiphyseal closure and other skeletal defects. |
Clinical note
Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).
| Placental transfer | Isotretinoin crosses the placenta; fetal exposure is significant, causing teratogenicity. |
| Breastfeeding | Excretion into human breast milk is likely; potential for serious adverse effects in nursing infants. Use is contraindicated during breastfeeding. |
■ FDA Black Box Warning
Contraindicated in pregnancy due to high risk of teratogenicity (major fetal abnormalities). Must not be prescribed to female patients of childbearing potential unless they meet strict conditions: negative pregnancy tests, use of two effective contraceptive methods, and enrollment in the iPLEDGE program.
| Serious Effects |
PregnancyWomen of childbearing potential not using two effective forms of contraceptionHypersensitivity to isotretinoin or any componentConcurrent use of tetracyclinesHistory of pancreatitis
| Precautions | Pseudotumor cerebri (intracranial hypertension) especially with tetracyclines, Psychiatric disorders (depression, psychosis, suicidal ideation), Pancreatitis, hypertriglyceridemia, hepatotoxicity, Inflammatory bowel disease exacerbation, Night vision decrease, corneal opacities, Photosensitivity, skin fragility, cheilitis, dry eyes, Skeletal hyperostosis with long-term use, Musculoskeletal pain, benign intracranial hypertension |
| Food/Dietary | Take isotretinoin with a fat-containing meal (e.g., full glass of milk, high-fat meal) to improve absorption. Avoid grapefruit juice as it may increase drug levels. No other significant food interactions reported. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | CLARAVIS (isotretinoin) is a known human teratogen. First trimester: high risk of major congenital malformations involving central nervous system, cardiovascular system, craniofacial structure, and thymus. Second and third trimesters: spontaneous abortion, preterm delivery, and fetal neurodevelopmental impairment. Contraindicated in pregnancy. |
| Fetal Monitoring | Pregnancy testing (serum HCG) before initiation, monthly during therapy, and at 5 weeks after discontinuation. Effective contraception must be used for 1 month before, during, and 1 month after therapy. Baseline and monthly liver function tests, fasting lipid panel, and complete blood count. Monitor for mood changes and suicidal ideation. |
| Fertility Effects | Isotretinoin does not impair fertility in females when used as recommended. In males, isotretinoin does not affect sperm production or fertility based on clinical studies. However, due to teratogenicity, male patients are advised to use condoms during sexual activity with pregnant or potentially pregnant partners. |
| Clinical Pearls | CLARAVIS (isotretinoin) is a retinoid used for severe nodulocystic acne. Monitor for idiopathic intracranial hypertension; avoid tetracyclines concurrently. Pregnancy category X; two negative pregnancy tests and monthly monitoring required. Check baseline and monthly liver enzymes and lipids. May cause cheilitis; recommend emollients. Dry eyes common; artificial tears advised. Avoid waxing and dermabrasion due to skin fragility. |
| Patient Advice | Do not become pregnant while taking this medication and for one month after stopping; use two forms of effective contraception. · Do not donate blood during therapy and for one month after discontinuation. · Avoid alcohol consumption as it may increase risk of liver damage. · Use sun protection and avoid excessive sun exposure due to increased photosensitivity. · Report any vision changes, severe headache, or mood changes immediately. · Take with food to enhance absorption. · Expect dry lips, skin, and eyes; use moisturizers and artificial tears as needed. · Do not take vitamin A or other retinoid supplements. |