Isotretinoin

Oral:
Severe: As conventional formulation: Initiate at a lower dose (e.g. 10 mg daily), then gradually increase up to 1 mg/kg daily or until the patient is receiving the Max tolerable dose.

Oral:
Contraindicated.

Isotretinoin lidose & micronised formulations: May be taken with or without food. Take w/ a full glass of liqd to minimise oesophageal irritation. Swallow whole, do not chew/suck.
Isotretinoin standard formulation: Should be taken with food. Take w/ a full glass of liqd to minimise oesophageal irritation. Swallow whole, do not chew/suck.

Hypervitaminosis A, hyperlipidaemia (oral). Hepatic impairment (oral). Pregnancy and lactation. Concomitant use with tetracyclines (oral).

Oral: Patient with diabetes mellitus, alcoholism, obesity, dry eye syndrome; history of depression; genetic predisposition for bone loss (e.g. age-related osteoporosis, history of childhood osteoporosis, osteomalacia, other disorders of bone metabolism). Not indicated for prepubertal acne. Avoid concomitant use with vitamin A and topical keratolytic or exfoliative anti-acne agents. Conventional formulation is not bioequivalent to lidose or micronised formulations. Due to variations in bioavailability and dosage, lidose and micronised formulations are not substitutable with one another. Refer to specific product guidelines. Topical: Patient with history of photoallergy or photodermatitis, personal or family history of skin cancer; rosacea, perioral dermatitis; patients who have previously been unable to tolerate similar retinoid products; application to sensitive skin areas (e.g. neck). Severe renal impairment (oral). Children (oral).

Significant: Photosensitivity. Oral: Acute exacerbation of acne (during initial period); osteoporosis, osteopenia, bone fractures, delay in healing of bone fractures, decreased BMD, sacroiliitis, premature epiphyseal closure; cutaneous adverse reactions (e.g. cheilitis, xeroderma), allergic vasculitis often with purpura of the extremities and extracutaneous involvement, inflammatory bowel disease (including regional ileitis); back pain (particularly in adolescents), arthralgia, myalgia, increased serum creatine phosphokinase (particularly in patients who engage in vigorous physical activity); hepatitis, mild to moderate increase in liver enzymes, acute pancreatitis, increased serum triglycerides and cholesterol, decreased HDL; new onset or worsening of depression, psychosis, mood alterations, anxiety, impaired glucose control; hearing impairment; corneal opacities, dry eyes, keratitis, blepharitis, night blindness, visual disturbance, eye irritation, conjunctivitis. Rarely, benign intracranial hypertension (pseudotumour cerebri), anaphylactic reactions, sexual dysfunction (e.g. erectile dysfunction, decreased libido), suicidal ideation or attempts, aggressive and/or violent behaviours. Topical: Irritation (redness, peeling, or discomfort).
Blood and lymphatic system disorders: Anaemia, thrombocytopenia, thrombocytosis (oral).
Investigations: Increased RBC sedimentation rate (oral).
Nervous system disorders: Headache (oral).
Renal and urinary disorders: Haematuria, proteinuria (oral).
Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, epistaxis, nasal dryness (oral).
Skin and subcutaneous tissue disorders: Dry skin; dermatitis, localised exfoliation, pruritus, erythematous rash, skin fragility (oral); application site erythema, pruritus and stinging; skin burning sensation, tenderness and pain (topical).
Potentially Fatal: Oral: Severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme). Rarely, rhabdomyolysis, suicide, haemorrhagic pancreatitis.

PO/Topical: Z (Contraindicated)

This drug may reduce night vision, which may be sudden; be cautious when driving or operating machinery at night. Women of childbearing potential must use at least 1 highly effective birth control method (e.g. intrauterine device or implant) or 2 complementary patient-dependent forms of birth control (e.g. oral contraceptives, barrier method) for at least 1 month before starting treatment, during the entire course, and at least 1 month after stopping the treatment. Avoid or minimise prolonged exposure to sunlight or UV rays; if exposure cannot be avoided, use sunscreen (with protection factor of at least SPF 15) and wear protective clothing. Oral: Do not donate blood during treatment and for 1 month after discontinuation. Avoid aggressive chemical dermabrasion, wax epilation and cutaneous laser treatment during and for ≥6 months after treatment. Topical: Avoid contact of topical cream with the mouth, eyes, mucous membranes and broken skin. Do not apply to sunburned skin. Avoid application to eczematous skin.

Perform pregnancy tests with sensitivity of ≥25 milliunits/mL in patients of childbearing potential before starting treatment (2 tests; the 2nd test is performed ≥19 days after the 1st one and during the 1st 5 days of menstrual period immediately preceding the start of treatment); then, every month during treatment, at the end of the entire course and 1 month after discontinuation of treatment. Assess mental health before treatment initiation and regularly during therapy. Obtain LFTs and fasting lipid tests before treatment and at weekly or biweekly intervals until treatment response is established. Monitor CBC with differential and platelet count, sedimentation rate (at baseline), blood glucose, and creatine phosphokinase. Assess for signs and symptoms of psychiatric effects (e.g. depression, mood alteration, psychosis, aggression, suicidal thoughts), severe skin reactions, vision changes and pseudotumour cerebri (e.g. papilloedema, headache, visual disturbances).

Concomitant use with tetracyclines resulted in benign intracranial hypertension (pseudotumour cerebri). Increased risk of hypervitaminosis A with vitamin A. May increase skin irritation with topical keratolytic or exfoliative anti-acne agents.

Increased bioavailability with food (conventional formulation).

Description:
Overview: Isotretinoin is a synthetic retinoid and the cis configuration of tretinoin.
Mechanism of Action: The exact mechanism of action of isotretinoin has not been fully elucidated; however, it has been noted to be associated with the inhibition of the sebaceous gland function and follicular keratinisation. It also inhibits sebaceous gland differentiation and has anti-inflammatory effect that may be mediated through the inhibition of collagenase and prostaglandin E₂ synthesis. When applied topically, isotretinoin stimulates epidermal mitosis, decreases intercellular cohesion in the stratum corneum, combats hyperkeratosis, aids desquamation, and reduces the cohesiveness of epidermal sebaceous cells.
Pharmacodynamics: Isotretinoin temporarily reduces sebum production, which reflects a decrease in the size of the sebaceous gland. During treatment, the lipid composition of the skin surface is altered and resembles that of prepubertal skin. There is an increase in the percentage of free and esterified cholesterol, primarily of epidermal origin, and a decrease in the percentage of squalene and wax esters, primarily of sebaceous origin.
Pharmacokinetics:
Absorption: Variable absorption from the gastrointestinal tract (oral); minimal systemic absorption after topical application. Increased bioavailability with food (conventional formulation). Time to peak plasma concentration: Conventional formulation: 5.3 hours (fed state); 3.2 hours (fasting state). Lidose formulation: 6.4 hours (fed state); 2.9 hours (fasting state). Micronised formulation: 5 hours (fed state); 3.5 hours (fasting state).
Distribution: Crosses the placenta. Plasma protein binding: 99-100%, mainly to albumin.
Metabolism: Metabolised in the liver by CYP450 isoenzymes, including CYP2B6, CYP2C8, CYP2C9, and CYP3A4 into 4-oxo-isotretinoin (major active metabolite), retinoic acid (tretinoin), and 4-oxo-retinoic acid (4-oxo-tretinoin). Undergoes enterohepatic recycling (including metabolites).
Excretion: Via urine and faeces (in equal amounts). Elimination half-life: Conventional formulation: 21 ± 8.2 hours (isotretinoin); 24 ± 5.3 hours (4-oxo-isotretinoin). Lidose formulation: 18 hours (isotretinoin); 38 hours (4-oxo-isotretinoin). Micronised formulation: Approx 24 hours (isotretinoin); approx 38 hours (4-oxo-isotretinoin).

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5282379, Isotretinoin. https://pubchem.ncbi.nlm.nih.gov/compound/Isotretinoin. Accessed Oct. 28, 2025.

Oral:
Cap: Store between 15-30°C. Protect from light.

Topical:
Cream: Store below 25°C.

Acne Treatment Preparations

D10BA01 - isotretinoin ; Belongs to the class of systemic retinoid preparations used in the treatment of acne.
D10AD04 - isotretinoin ; Belongs to the class of topical retinoid preparations used in the treatment of acne.

Absorica/Absorica LD Capsule (Sun Pharmaceuticals Industries, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/09/2025.

Brayfield A, Cadart C (eds). Isotretinoin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/09/2025.

Douglas Pharmaceuticals Ltd. Oratane Soft Gelatin Capsule data sheet 10 December 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 11/09/2025.

Isotretinoin (Systemic). UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/09/2025.

Isotretinoin (Topical). UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 11/09/2025.

Isotretinoin. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 02/10/2025.

Isotrex 0.05% Cream (GlaxoSmithKline UK Limited Trading as Stiefel). MHRA. https://products.mhra.gov.uk. Accessed 11/09/2025.

Joint Formulary Committee. Isotretinoin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/09/2025.

Roaccutane 10 mg Soft Capsules (Neon Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 11/09/2025.

Roaccutane Capsule (Zuellig Pharma Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 11/09/2025.

Zenatane Capsule, Gelatin Coated (Dr. Reddy's Laboratories Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 11/09/2025.