Isotretinoin

Mechanism of action

◎Nuclear retinoic acid receptors (RAR), reached mainly through its active metabolitesIsotretinoin

ⓘ The figure shows the ligand-binding domain of human RAR-γ holding all-trans retinoic acid (tretinoin), one of the active metabolites of isotretinoin found in plasma; isotretinoin itself is not in this crystal.

Isotretinoin is the 13-cis isomer of retinoic acid. Its exact mechanism in acne is not fully known. It and its active metabolites (4-oxo-isotretinoin, tretinoin) act through nuclear retinoid receptors in the pilosebaceous unit: sebaceous glands shrink and stop differentiating, sebum output falls sharply and follicular keratinisation returns to normal. With less sebum and fewer plugs, the follicle is a poor home for Cutibacterium acnes and inflammation settles.

1. Isotretinoin and its metabolites act on nuclear retinoid receptors
2. Sebaceous glands shrink and make far less sebum
3. Follicular keratinisation normalises: fewer comedones
4. Less C. acnes and inflammation: nodules clear

Indications

• Severe, recalcitrant nodular acne that has not responded to conventional treatment, including systemic antibiotics Acne vulgaris →
• Specialist off-label uses in other disorders of keratinisation and follicular disease

Adverse effects

Common

• Dry, cracked lips (cheilitis), the most common effect
• Dry skin, eyes, mouth and nose; nosebleeds
• Back pain, joint and muscle pain; raised creatine kinase
• Sun sensitivity
• Thinning hair, nail changes, slow wound healing
• Early flare of acne

Contraindications

• Pregnancy
• Breastfeeding
• Hypersensitivity to isotretinoin, to vitamin A (chemically similar) or to any component

Key interactions

Tetracyclines (doxycycline, minocycline)

Cases of intracranial hypertension; the combination is avoided.

Vitamin A supplements

Additive vitamin A toxicity; avoided.

Progestin-only 'minipill'

Isotretinoin interferes with its action, so it is not accepted as one of the contraceptive methods.

St John's wort

Can make hormonal contraceptives fail, which is critical during isotretinoin treatment.

What is monitored

• Pregnancy tests in people who can become pregnant: two negative tests before starting, then every month, at the end and after the last dose
• Fasting lipid profile and liver tests before starting and at intervals until the response is known
• Mood, sleep and behaviour at every visit, with the family told which warning signs to report
• Headache with visual change, abdominal pain, rectal bleeding, hearing or vision problems

Administration and safety

• Capsules are swallowed whole with a full glass of liquid, never chewed or opened, to avoid oesophageal irritation.
• Dispensed only within the registered programme: limited supply, no refills, never shared with anyone.
• Different isotretinoin products differ in bioavailability and are not substituted one for another.
• No blood donation during treatment and for one month after, because the blood could reach a pregnant patient.

Pregnancy and breastfeeding

Contraindicated. Even brief exposure carries an extremely high risk of severe birth defects, so pregnancy is excluded and prevented before, during and after the course; if pregnancy occurs, the drug is stopped at once and the patient is referred.

Nursing care

• Before each prescription, confirm the negative pregnancy test and the two contraceptive methods documented in the programme.
• Ask about low mood, irritability, withdrawal or thoughts of self-harm at every contact, and teach the family to report them.
• Teach sun protection, lip and eye care, and care when driving at night (night vision can drop suddenly).
• Teach to avoid waxing, laser treatments and dermabrasion during treatment and for six months after (scarring risk).
• Report severe headache, blurred vision, abdominal pain, rectal bleeding or yellow skin at once.

Pharmacokinetics

Absorption

Oral capsule; standard capsules are absorbed better with food. Different oral products are not interchangeable.

Distribution

Almost entirely bound to plasma albumin.

Metabolism

Liver (several CYP enzymes) to active metabolites: 4-oxo-isotretinoin, tretinoin and 4-oxo-tretinoin.

Elimination

Metabolites leave in urine and faeces in similar amounts.

Half-life

Under a day for isotretinoin; its main 4-oxo metabolite lasts about twice as long.

Onset and duration

Improvement over weeks to months; acne can flare at first and keeps improving after the course ends.

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Connections

← Back to the class: Dermatological retinoids

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Isotretinoin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - ISOTRETINOIN capsule (DailyMed (U.S. National Library of Medicine), 2026); Retinoid-containing medicinal products - referral (European Medicines Agency (EMA), 2018); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.