Clinical Effects:

  • USES: Isotretinoin is indicated for the treatment of severe recalcitrant nodular acne. PHARMACOLOGY: Isotretinoin (13-cis retinoic acid, RO-43,780) is classified as a retinoid, which is a synthetic analogue of vitamin A. Its exact mechanism of action is not known. When administered in pharmacologic dosages, isotretinoin inhibits sebaceous gland function and keratinization. Retinoids affect the keratinization process, and therefore without specificity exhibit effectiveness in all types of hyperkeratotic conditions. EPIDEMIOLOGY: Overdose is rare and most cases develop only minor symptoms. OVERDOSE: Isotretinoin is unlike vitamin A in that it is not stored in the liver and is less toxic. Vitamin A and retinoic acid cause more CNS toxicity, GI symptoms, and bone, joint, and muscle pain than isotretinoin. Overdose data are limited. Vomiting, cheilitis, abdominal pain, mild tachycardia, hypertension, tachypnea, facial flushing, abdominal discomfort, headache, dizziness, ataxia, dryness of the lips and scaly patches on the skin, and hallucinations have been reported with overdose. ADVERSE EFFECTS: COMMON (5% or greater): Dry mouth and skin, back pain, dry eye, arthralgia, epistaxis, headache, nasopharyngitis, dermatitis, increased blood creatine kinase, cheilitis, musculoskeletal discomfort, upper respiratory tract infection, reduced visual acuity. OTHER EFFECTS: Nausea, vomiting, lethargy, fatigue, pruritus, back pain, and myalgia. RARE: Eruptive xanthomas, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, paronychia, conjunctivitis, corneal opacity, night blindness, tinnitus, vasculitis, mild to moderate increases in liver enzymes, acute allergic reaction, pseudotumor cerebri, papilledema, hypercalcemia, pancreatitis, thrombocytopenia, neutropenia, leukopenia, anemia, agranulocytosis, rhabdomyolysis, seizures, hallucinations, and psychosis. Isotretinoin is a human teratogen (pregnancy category X).

Range of Toxicity:

  • TOXICITY: Acute overdoses of 440 mg and 1,600 mg on 2 consecutive days produced minimal symptoms in one patient. An estimated ingestion of 63.3 mg/kg of isotretinoin produced symptoms of facial flushing and mild tachycardia, tachypnea, and hypertension in a 21-month-old, 17.7 kilogram child. THERAPEUTIC DOSE: ADULTS AND CHILDREN 12 YEARS AND OLDER: 0.5 to 1 mg/kg/day given in 2 divided doses; adults with severe scarring acne or trunk acne may require up to 2 mg/kg/day. CHILDREN YOUNGER THAN 12 YEARS: Safety and efficacy have not been established.


  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
  • Decontamination: PREHOSPITAL: Prehospital gastrointestinal decontamination is generally not required. HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
  • Airway management: Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions or persistent seizures.
  • Antidote: None.
  • Rhabdomyolysis: Rhabdomyolysis has been reported rarely with isotretinoin therapy in postmarketing surveillance. Administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output. Urinary alkalinization is NOT routinely recommended.
  • Monitoring of patient: Plasma concentrations are not readily available or clinically useful in the management of overdose. Monitor vital signs and mental status. Monitor serum electrolytes in patients with significant vomiting. Monitor CBC with differential with platelet count in symptomatic patients. Monitor CK, renal function, and urine output in patients with rhabdomyolysis. Symptoms of vitamin A toxicity are theoretically possible with isotretinoin, and liver enzymes and should be monitored in substantial overdoses. Evaluate patient for clinical evidence of benign increased intracranial pressure (pseudotumor cerebri) such as headache, vomiting, blurred vision, and papilledema. Guidelines for management of Vitamin A overdoses should be followed in such cases when appropriate. A serum pregnancy test should be performed in any female of childbearing age.
  • Enhanced elimination procedure: Hemodialysis is UNLIKELY to be of value because of the high degree of protein binding of isotretinoin.
  • Patient disposition: HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. If there is any possibility the patient is pregnant she should be referred for a pregnancy test and for counseling if the test is positive. OBSERVATION CRITERIA: Symptomatic patients, and those with deliberate ingestion should be referred to a healthcare facility for evaluation. ADMISSION CRITERIA: Patients should be admitted for severe vomiting, severe abdominal pain, dehydration, electrolyte abnormalities, persistent seizures, severe neutropenia or allergic reaction. CONSULT CRITERIA: Consult a medical toxicologist or poison center in patients with severe toxicity or in whom the diagnosis is unclear. Any pregnant patient who is exposed to isotretinoin should be referred to a specialist in teratology.