The oral LD50 of isotretinoin is greater than 4000 mg/kg in rats and mice (>600 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the rat dose for total body surface area and >300 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1.0 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. All symptoms quickly resolved without apparent residual effects.
Isotretinoin causes serious birth defects at any dosage (see boxed CONTRAINDICATIONS AND WARNINGS). Females of childbearing potential who present with isotretinoin overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the boxed CONTRAINDICATIONS AND WARNINGS. Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in the boxed CONTRAINDICATIONS AND WARNINGS. Educational materials for such patients can be obtained by calling Bertek Pharmaceuticals Inc. Because an overdose would be expected to result in higher levels of isotretinoin in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a female who is or might become pregnant, for 30 days after the overdose. All patients with isotretinoin overdose should
not donate blood for at least 30 days.