CURACNE

Isotretinoin is a retinoid derivative of vitamin A used in the treatment of severe recalcitrant acne.

Label It was most widely marketed under the brand name Accutane, which has since been discontinued.

Isotretinoin is associated with major risks in pregnancy and is therefore only available under the iPLEDGE program in the United States.

The first isotretinoin-containing product was

FDA approved on 7 May 1982.

Isotretinoin is indicated to treat severe recalcitrant nodular acne and patients ≥12 years enrolled in the iPLEDGE program.

Label,

The pharmacodynamics of isotretinoin are poorly understood.

Patients reach a maximum concentration of 74-511ng/mL after 1-4 hours following a 100 mg oral dose.

Isotretinoin is better absorbed with a high fat meal and bioavailability may change from one brand to another.

Following a 40 mg oral dose, fasted subjects reached a maximum concentration of 314ng/mL in 2.9 hours with an area under the curve of 4055ng/mL*hr.

The volume of distribution in humans is unknown because there is no intravenous preparation.

In a study of pediatric patients with neuroblastoma the volume of distribution was found to be 85 L.

The volume of distribution was also found to be 2432 mL/kg in guinea pigs and 1716 mL/kg in obese rats.

Isotretinoin, or 13-cis-retinoic acid can undergo reversible cis-trans isomerization to all-trans-retinoic acid.

Isotretinoin undergoes 4-hydroxylation to 4-hydroxy-13-cis-retinoic acid, which is oxidized to the main metabolite 4-oxo-13-cis-retinoic acid. 8, 3.

All-trans-retinoic acid undergoes 4-hydroxylation to 4-hydroxy-all-trans-retinoic acid, which is oxidized to 4-oxo-all-trans-retinoic acid. 8 4-oxo-13-cis-retinoic acid can undergo reversible cis-trans isomerization to 4-oxo-all-trans-retinoic acid.

Hover over products below to view reaction partners Isotretinoin all-trans-retinoic acid 4-hydroxy-all-trans-retinoic acid 4-oxo-all-trans-retinoic acid 4-oxo-13-cis-retinoic acid 4-hydroxy-13-cis-retinoic acid 4-oxo-13-cis-retinoic acid 4-oxo-all-trans-retinoic acid.

Isotretinoin and its metabolites are conjugated and excreted in the urine and feces in similar amounts.

Label 53-74% of an oral dose is eliminated as unchanged isotretinoin in the feces.

The half life ranges from 7-39 hours with a mean elimination half life of 20 hours.

The half life of 4-oxo-13-cis-retinoic acid ranges from 17-50 hours with a mean elimination half life of 25 hours.

The clearance of isotretinoin is 15.9 L/h in pediatric patients with neuroblastoma.

Clearance is also 21.3 mL/min/kg in guinea pigs and 7.2 mL/min/kg in obese rats.

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Patients experiencing an overdose may present with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia.

These symptoms may rapidly resolve.

Generally no treatment is required for these overdoses.

The oral lowest dose causing toxic effect (TDLO) for children is 30 mg/kg/21W, oral TDLO for men is 24 mg/kg/4W, oral TDLO for women is 56 mg/kg/8W.

The intraperitoneal

LD for rats is 901 mg/kg, oral LD for mice is 3389 mg/kg, oral LD for rats is >4000 mg/kg.

Isotretinoin is associated with major congenital malformations, spontaneous abortion, and premature birth.

It is unknown if isotretinoin is expressed in breast milk but due to the associated hazards a decision should be made to either stop nursing or stop taking isotretinoin.

In animal studies, isotretinoin was associated with an increased risk of pheochromocytoma and adrenal medullary hyperplasia at doses above the recommended clinical dose.

Label Isotretinoin was negative for the

Ames test of mutagenicity once and weakly positive a second time.

It has not been shown to be clastogenic.

A study in dogs noted testicular atrophy after doses of 10-30 times the recommended clinical dose for 30 weeks.

In trials with men there were no effects seen on sperm count, motility, morphology, ejaculate volume, and seminal plasma fructose.