Isotretinoin teratogenicity

Some chemical exposures, such as dimethyl mercury (neurocognitive impairment), isotretinoin (teratogenicity), or aflatoxin (cancer), may have mild or absent immediate effects, despite their long term toxicity... 

Isotretinoin Capsules 10, 20, 40 mg 0.5-1 mg/kg/per day in two divided doses Maximum dose 2 mg/kg per day Cumulative dose 120-150 mg/day Dry skin and mucous membranes, muscle and joint pain, elevated liver enzymes and triglycerides, depression, teratogenicity... 

Blood donation Because of isotretinoin s teratogenic potential, patients receiving the drug should not donate blood for transfusion during treatment and for 1 month after discontinuing therapy. 

The most serious toxicity of isotretinoin is teratogenicity. Pregnant women should never receive the drug, and women should not conceive for at least 1 month after its discontinuation. Other toxicities ... 

Nau HJ (2001) Teratogenicity of isotretinoin revisited species variation and the role of all-trans-retinoic acid. J Am Acad Dermatol 45(5) S183-S187... 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

Isotretinoin (1) works extremely well for severe acne, and is efficacious for 75% of all patients. However, like all oral retenoids, isotretinoin (1) has a spectrum of toxicity. Most prevalent of all is its profound teratogenic properties. The risk of a major congenital abnormality in the first tnmester in pregnant women is increased by 25-fold. Therefore, it is mandatory for women of child-bearing potential who are taking... 

Systemically administered retinoids such as isotretinoin (1, Accutane ) have several disadvantages such as a relatively narrow therapeutic index and a variety of toxic effects including teratogenicity. Topically administered retinoids may avoid some of those drawbacks. For instance, tazarotene (2, Tazorac ) is a topical receptor-selective retenoid that normalizes differentiation and proliferation of keratinocytes. Its major metabolite, tazarotenic acid (11), binds to retinoic acid receptors (RARs) with high affinity. 

Isotretinoin is a potent teratogen, and when it is prescribed it is vital to use one or more reliable contraceptive methods. It is therefore important to determine whether isotretinoin itself might interfere with the efficacy of hormonal contraception. In 26 women who were to be treated with isotretinoin and expected to use oral contraceptives, serum concentrations of the two components of Ortho Novum (ethinylestradiol and norethin-drone) were used as markers for any direct kinetic effect of isotretinoin, while concentrations of serum... 

The macaque embryofetal development study design has been shown to be appropriate for detecting the teratogenic effects of the small molecular weight drugs thalidomide and isotretinoin [35,36]. For large molecular weight biopharmaceuticals that do not cross the placenta the standard macaque... 

Directly (thalidomide, cytotoxic drugs, antithyroid drugs, aromatic retinoids, e.g. isotretinoin) any drug affecting cell division, enzymes, protein synthesis or DNA s)mthesis, is a potential teratogen, e.g. many antimicrobials. 

Drugs known to be teratogenic include cytotoxics, warfarin, alcohol, lithium, methotrexate, phenytoin, valproate, ACE inhibitors and isotretinoin. Selective interference can produce characteristic anatomical abnormalities, and the phocomelia (flipper-Uke) limb defect was one factor that caused thalidomide to be so readily recognised. (For an account of thalidomide see p. 81.)... 

Isotretinoin Fatigue headache nausea and vomiting pruricis Teratogenic cheilitis xerostomia rash conjunctivitis and eye irritation anorexia hypertriglyceridaemia pseudotumour cerebri... 

Although the various retinoids have similar toxicity profiles, they differ in the extent to which they affect various body systems. Cutaneous and mucous membrane symptoms (up to 70%) are by far the most prominent adverse effects patients who use isotretinoin have a 50% incidence of conjunctivitis and irritation of the eyes. Musculoskeletal symptoms occur in up to 15% of users. Hypersensitivity reactions are rare and consist of occasional drug rashes. The occurrence of sarcomas in patients treated with isotretinoin may well be a chance finding (SEDA-21, 164) retinoids may prevent or even cure certain malignancies (20). All the retinoids are strongly teratogenic (21-23). 

Retinoids are strongly teratogenic (21). Pregnancy should be ruled out and an effective form of contraception must be used for at least 1 month before starting therapy, during therapy, and for at least 1 month (isotretinoin) or 2 years (acitretin) after therapy is stopped. Retinoid-induced teratogenicity has been reviewed (22,23). 

Accutane is a potent rat and rabbit developmental toxin (teratogen). Testicular atrophy and evidence of lower spermatogenesis was noted in dogs given isotretinoin for 30 weeks at 20 or 60 mg kg day Fischer 344 rats dosed at 8 or 32 mg kg day for over 18 months had a dose-related raised incidence of pheochromocytoma, an adrenal gland tumor. The relevance in man is unknown since this animal develops spontaneous pheochromocytoma at a significant rate. 

Honein MA, Moore CA, Erickson JD. 2004. Can we ensure the safe use of known human teratogens Introduction of generic isotretinoin in the US as an example . Drug Safety 27 1069-1080. 

Oral isotretinoin is available for severe acne refractive to other forms of treatment. It is effective but is teratogenic and can have severe side-effects. 

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