Tretinoin is a skin irritant. Topical application may cause transitory stinging and a feeling of warmth and in normal use it produces some erythema and peeling similar to that of mild sunburn. Sensitive individuals may experience oedema, blistering, and crusting of the skin. Excessive application can cause severe erythema, peeling, and discomfort with no increase in efficacy. Photosensitivity may occur. Temporary hypopigmentation and hyperpigmentation have been reported.
Oral doses of tretinoin (ISOTREX, ISOTROIN, ROACCUTANE) may produce similar adverse effects to those of isotretinoin. Adverse cardiovascular effects have also been reported; the most common were arrhythmias, flushing, hypotension, hypertension, and heart failure. Less common events were cardiac arrest, myocardial infarction, cardiomegaly, heart murmur, ischaemia, stroke, myocarditis, pericarditis, pulmonary hypertension, and secondary cardiomyopathy. A potentially life-threatening ‘retinoic acid syndrome’ has been described after oral use.
Studies in mice suggested that tretinoin could enhance photocarcinogenesis.1 However, other studies refuted this2 and evidence indicates that topical tretinoin is not carcinogenic in humans.
Tretinoin is contra-indicated in pregnancy and in breast-feeding mothers. Contact of tretinoin with the eyes, mouth, or other mucous surfaces should be avoided. It should not be applied to eczematous, sunburnt, or abraded skin and the effects of other topical treatment, especially with keratolytics, should be allowed to subside before topical use of tretinoin. Exposure to UV light and excessive exposure to sunlight should be avoided hence recommended for use at night only.
Absorption does not seem to occur to any great extent with topical use. When tretinoin is given by mouth the precautions described under isotretinoin should be adopted.
Although there have been isolated reports of congenital abnormalities in infants born to mothers who used Retin A tretinoin 0.05% topically before and during pregnancy, studies involving a total of 309 women showed no increased risk for major congenital disorders in infants who had been exposed in the first trimester.