[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Dermatological retinoids](https://durgical.com/en/pharmacology/classes/dermatological-retinoids/) › Isotretinoin

# Isotretinoin

## Dermatological retinoids?

Dermatological retinoids

## Pregnancy: contraindicated?

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…

An oral retinoid for severe nodular acne that shrinks the oil glands. It is highly teratogenic, so it is only given inside a pregnancy-prevention programme.

Updated Nov 1, 2026

Also called: 13-cis-retinoic acid

## Quick facts

**Group**
[Dermatological retinoids](https://durgical.com/en/pharmacology/classes/dermatological-retinoids/)

**Target**
Nuclear retinoic acid receptors (RAR), reached mainly through its active metabolites

**Used for**
Severe · Specialist off-label uses

**Key effects**
Dry · Dry skin · Back pain

**Monitor**
Pregnancy tests · Fasting lipid profile · Mood

**ATC**
D10BA01

No doses: the clinician sets them by the current guideline.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Clinical What the labels mean

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**Nuclear retinoic acid receptors (RAR), reached mainly through its active metabolites**Isotretinoin

ⓘ 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.

**Target in 3D:** Nuclear retinoic acid receptors (RAR), reached mainly through its active metabolites. PDB structure 2LBD (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/2LBD) · Drag to rotate · pinch to zoom

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.

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

## Indications

- Severe, recalcitrant nodular acne that has not responded to conventional treatment, including systemic antibiotics [Acne vulgaris →](https://durgical.com/en/conditions/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

### Serious (rare, important)

- Embryo-fetal toxicity: severe birth defects, miscarriage and premature birth
- Depression, psychosis and, rarely, suicidal thoughts or attempts and aggressive behaviour
- Intracranial hypertension (pseudotumor cerebri): headache, blurred vision, nausea, papilloedema
- Very high triglycerides and acute pancreatitis (rarely haemorrhagic and fatal)
- Hepatitis; inflammatory bowel disease
- Hearing loss; decreased night vision and corneal opacities
- Severe skin reactions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Lower bone density, hyperostosis and premature closure of growth plates in teenagers

## 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.

## Memory aid

ISO-PLEDGE: Pregnancy tests, Lipids and liver, Emotions (mood), Dry lips and eyes, Growth plates and bones, Eyes at night. And never with a teTRAcycline.

## Test yourself

Think of the answer, then tap the question to see it.

## Which acne is isotretinoin reserved for?

Severe, recalcitrant nodular acne that has not responded to conventional treatment, including systemic antibiotics.

## What are the key parts of an isotretinoin pregnancy-prevention programme?

Negative pregnancy tests before starting and every month, two contraceptive methods before, during and after treatment, limited supplies without refills, and no sharing or blood donation.

## A teenager on isotretinoin and doxycycline develops headache and blurred vision. What is the concern?

Intracranial hypertension (pseudotumor cerebri); the tetracycline combination is avoided.

## Which laboratory tests are checked before and during isotretinoin?

Fasting lipids (especially triglycerides) and liver tests, plus pregnancy tests in people who can become pregnant.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/isotretinoin/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## What the labels mean

**Pregnancy: contraindicated**
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…

## Connections

## Related drugs 3

- [Adapalene](https://durgical.com/en/pharmacology/adapalene/)
- [Acitretin](https://durgical.com/en/pharmacology/acitretin/)
- [Benzoyl peroxide](https://durgical.com/en/pharmacology/benzoyl-peroxide/)

## Related conditions 1

- [Acne vulgaris](https://durgical.com/en/conditions/acne-vulgaris/)

[← Back to the class: Dermatological retinoids](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a681043.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - ISOTRETINOIN capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e8516dc-a3c6-4d8f-aa14-2c37c6c8f6e6) (DailyMed (U.S. National Library of Medicine), 2026); [Retinoid-containing medicinal products - referral](https://www.ema.europa.eu/en/medicines/human/referrals/retinoid-containing-medicinal-products) (European Medicines Agency (EMA), 2018); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=D10BA01) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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