CLARAVIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).

How it works

Isotretinoin, a retinoid, reduces sebum production, inhibits sebaceous gland activity, and normalizes follicular keratinization. It also exhibits anti-inflammatory effects.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).

Breastfeeding	Isotretinoin is excreted in human milk; M/P ratio unknown. Due to potential for serious adverse effects in breastfed infants, breast-feeding is contraindicated during therapy with CLARAVIS.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Pregnancy or potential pregnancy (absolute)","Female patients of childbearing potential not meeting iPLEDGE requirements","Hypersensitivity to isotretinoin or any component","Concurrent use with tetracyclines (increased risk of pseudotumor cerebri)"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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CLARAVIS

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).

How it works

Isotretinoin, a retinoid, reduces sebum production, inhibits sebaceous gland activity, and normalizes follicular keratinization. It also exhibits anti-inflammatory effects.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CLARAVIS (CLARAVIS).

Breastfeeding	Isotretinoin is excreted in human milk; M/P ratio unknown. Due to potential for serious adverse effects in breastfed infants, breast-feeding is contraindicated during therapy with CLARAVIS.
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.