Isotretinoin is an oral prescription medication primarily used to treat severe acne by affecting sebaceous glands. 

Approved by the US Food and Drug Administration (FDA) in 1982, it is particularly effective for severe, nodular acne that does not respond to conventional treatments, including systemic antibiotics. Isotretinoin is effective for severe acne and has several non-FDA-approved uses, including moderate acne, cutaneous T-cell lymphomas, neuroblastoma, and preventing squamous cell carcinoma in high-risk patients. It is also used to treat rosacea, folliculitis, and pyoderma faciale. 

Mechanism of action 

As a systemic retinoid taken orally, isotretinoin inhibits sebaceous gland function and keratinisation, reducing gland size and sebum production. Though its exact mechanism is unknown, it effectively treats acne at doses of 0.5 to 1mg/kg per day. For neuroblastoma, it decreases cell proliferation and induces differentiation. 

Administration 

Isotretinoin is available in capsule form and is highly lipophilic. To maximise absorption, it should be taken with a meal and a full glass of water to prevent oesophageal irritation. The typical dosing starts at 0.5mg/kg per day, gradually increasing to 1mg/kg per day, with a treatment course lasting 15 to 20 weeks for sustained remission. 

Adverse effects 

Common dose-dependent side effects: cheilitis (dry lips), dry skin, dry mouth, dry nose, and sun sensitivity. Patients should use sun protection, moisturisers, and avoid skin procedures during and six months after treatment. Frequent laboratory monitoring is necessary for hypertriglyceridemia and increased erythrocyte sedimentation rate. Other potential adverse effects include pruritis, irritation, hair thinning, dry eyes, skin infections, rashes, bone or joint pain, and muscle aches. Paediatric patients often report back and joint pain. 

Laboratory abnormalities 

Common laboratory abnormalities include decreased HDL, increased liver function tests, increased creatinine phosphokinase, decreased haemoglobin and haematocrit, decreased erythrocyte and leukocyte counts, and increased platelet counts. Isotretinoin should be discontinued if neutropenia or agranulocytosis occurs. 

Serious reactions and precautions 

Recent studies do not significantly correlate controversial associations with inflammatory bowel disease or depression.Serious skin reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis warrant discontinuation. Acute pancreatitis has also been reported, necessitating cessation if symptoms appear. 

Patients should avoid blood donation during and for one month after treatment due to the risk of embryo-foetal toxicity. Screening for depression and other psychological conditions is recommended, and isotretinoin should not be combined with tetracyclines due to the risk of pseudotumor cerebri.  

Contraindications and monitoring 

Sotretinoin is contraindicated in pregnant women due to severe birth defects. The FDA's iPLEDGE program ensures compliance with pregnancy prevention measures, requiring negative pregnancy tests and the use of two forms of birth control. 

Monitoring: Females of child-bearing potential must have two negative pregnancy tests before starting isotretinoin and monthly tests thereafter. All patients should have baseline liver function tests, lipid profiles, blood glucose, creatinine phosphokinase, and complete blood counts. Biweekly monitoring is necessary during the initial treatment phase. 

Reference:

Pile HD, Sadiq NM. Isotretinoin. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525949/