Drug reference

Isotretinoin

Retinoid · Dermatology

Also known as 13-cis-retinoic acid, Roaccutane, Accutane

START

Confirm severe nodular acne unresponsive to conventional therapy. Baseline LFTs, fasting lipids, CBC, pregnancy test (two negative tests required before starting in women of childbearing potential). Register in iPLEDGE (or equivalent). Counsel on teratogenicity, mood changes, and dry skin management.

TYPICAL MAX

2 mg/kg/day; cumulative 150 mg/kg. Do not exceed.

STOP IF

Pregnancy (discontinue immediately), ALT/AST >3x ULN, triglycerides >800 mg/dL (pancreatitis risk), severe depression/suicidal ideation, signs of pseudotumor cerebri, severe IBD

WATCH

LFTs and lipids at baseline, then monthly; pregnancy test monthly (women of childbearing potential); mood/mental status (monthly); dry skin/eye management; musculoskeletal symptoms

CDSCO approvedATC D10BA01

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · absorption onset
PEAK: 4h · 3-5 h (oral, with food)
t½: 15h · 10-20 h (mean ~15 h)
DURATION: 120w · Long-term remission (months-years after course)

EXCRETION

Equal urine/fecal (metabolites); hepatic CYP2C8/CYP3A4; <1% unchanged

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

FDA PLLR: ABSOLUTE CONTRAINDICATION. Causes severe, life-threatening birth defects. Two forms of effective contraception required for females of childbearing potential 1 month before, during, and 1 month after therapy. Monthly pregnancy tests mandatory. iPLEDGE registration required.

FDA category + note

Top interactionssee all 12 →

DoxycyclineContraindicatedDatabaseDDInter
TetracyclineContraindicatedDatabaseDDInter
TetracyclinesContraindicatedDatabaseKimi deep-research + Cla
Tetracyclines (e.g., Doxycycline, Minocycline)ContraindicatedDatabase

Available in India

403 branded formulations. Look up specific brands in the Drugs workspace.

Mechanism

Isotretinoin is a retinoid (13-cis-retinoic acid) that is a stereoisomer of tretinoin (all-trans-retinoic acid). It reduces sebaceous gland size and sebum production by ~90% through: (1) inhibition of sebocyte proliferation and differentiation; (2) apoptosis of sebocytes; (3) normalization of keratinization within the follicle, preventing comedone formation; and (4) anti-inflammatory effects including reduction of P. acnes colonization and inhibition of pro-inflammatory cytokines (IL-1, IL-8, TNF-alpha). Isotretinoin also modulates gene expression through binding to nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), affecting transcription of multiple genes involved in cell differentiation and proliferation.

Indications

Severe recalcitrant nodular acneAcne conglobataAcne fulminansGram-negative folliculitisRosacea fulminans (off-label)Hidradenitis suppurativa (off-label)Chemoprevention of skin cancer (off-label, high-risk patients)Neuroblastoma (off-label, high-dose)

Dosing

Adult: 0.5-1 mg/kg/day PO divided BID with meals for 15-20 weeks. Nodular acne: 0.5-2 mg/kg/day. Cumulative dose target: 120-150 mg/kg over course. Some regimens use lower doses (0.25-0.5 mg/kg/day) for longer duration with fewer side effects.
Pediatric: ≥12 years: same as adult dosing. <12 years: not recommended.
Renal adjustment: No adjustment required.
Hepatic adjustment: Contraindicated in hepatic insufficiency. Baseline and periodic LFTs required.
Geriatric: Not typically indicated. If used, standard adult dosing.
Max dose: 2 mg/kg/day; cumulative 150 mg/kg per course

Pharmacokinetics

Onset

Reduced sebum production within 2-4 weeks; clinical improvement in acne within 4-8 weeks.

Peak effect

Oral: peak plasma at 3-5 hours (with high-fat meal increases absorption 1.5-2x).

Duration

Long-term remission after single course (in ~70% of patients).

Half-life

~10-20 hours (mean ~15 hours).

Bioavailability

~25% (oral; highly variable; increased with high-fat meal).

Protein binding

~99.9% (bound primarily to albumin).

Metabolism

Extensive hepatic via oxidation to 4-oxo-isotretinoin (active metabolite) and tretinoin (all-trans-retinoic acid — active), followed by glucuronidation and further oxidation. CYP2C8, CYP2C9, CYP3A4, and CYP2B6 involved.

Excretion

Urine and feces (approximately equal; primarily as metabolites). <1% excreted unchanged.

Contraindications

Pregnancy (absolute contraindication — Category X; causes severe birth defects: craniofacial, cardiac, CNS, thymic abnormalities)
Breastfeeding
Hypersensitivity to isotretinoin, vitamin A, or parabens
Hepatic insufficiency
Hypervitaminosis A
Hyperlipidemia unresponsive to therapy
Concurrent tetracycline use (increased intracranial pressure/pseudotumor cerebri risk)

Side effects

Common

Dry skin, cheilitis (chapped lips — nearly universal)Dry eyes, conjunctivitisDry nose, epistaxisMyalgias, arthralgias (especially with vigorous exercise)Elevated triglycerides, cholesterolElevated liver enzymes (transient)Photosensitivity

Serious

TERATOGENICITY (FDA iPLEDGE program — mandatory for all prescribers/dispensers/patients in US) — severe birth defects
Hepatotoxicity (hepatitis, elevated transaminases >3x ULN)
Pancreatitis (especially with severe hypertriglyceridemia >800 mg/dL)
Pseudotumor cerebri / increased intracranial pressure (especially with tetracyclines — headache, nausea, vomiting, visual disturbances)
Depression, suicidal ideation, psychosis (controversial; monitoring required)
Inflammatory bowel disease (IBD) exacerbation or new onset (controversial)
Night blindness (decreased dark adaptation)
Skeletal hyperostosis, premature epiphyseal closure (with high-dose/long-term use)
Agranulocytosis (rare)

Pregnancy & lactation

Pregnancy

Lactation

Contraindicated during breastfeeding. Excreted in breast milk. Risk of infant toxicity.

Drug interactions

Doxycycline

Contraindicated

Database

Pseudotumor cerebri.

Contraindicated.

Source: DDInter

Tetracycline

Contraindicated

Database

Pseudotumor cerebri: severe headache, papilledema, vision loss.

Never combine.

Source: DDInter

Tetracyclines

Contraindicated

Database

Both isotretinoin and tetracyclines can increase intracranial pressure. Combined use significantly increases risk of pseudotumor cerebri (benign intracranial hypertension) with headache, nausea, vomiting, papilledema, and vision loss.

Absolute contraindication. Do NOT use tetracyclines during isotretinoin therapy. Use alternative antibiotics (macrolides) if needed for acne.

Source: Kimi deep-research + Cla

Tetracyclines (e.g., Doxycycline, Minocycline)

Contraindicated

Database

Increased risk of pseudotumor cerebri (benign intracranial hypertension) with symptoms like headache, nausea, vomiting, and papilledema.

Concomitant use is contraindicated. If a patient on isotretinoin develops symptoms of pseudotumor cerebri, discontinue isotretinoin immediately and refer for neurological evaluation. Avoid starting isotretinoin in patients currently on tetracyclines, and vice versa.

Vitamin A Supplements

Contraindicated

Database

Additive hypervitaminosis A effects — increased risk of hepatotoxicity, intracranial hypertension, bone toxicity, and mucocutaneous side effects.

Avoid vitamin A supplements during isotretinoin therapy. Patient education on avoiding multivitamins containing vitamin A.

Source: Kimi deep-research + Cla

Acitretin

Severe

Database

Clinical effect not specified

Source: DDInter

Aminolevulinic Acid