Medicine for acne: Isotretinoin Side effects

Isotretinoin Side effects
Side effects occur frequently, are dose-dependent, and are reversible shortly after discontinuing treatment. Patients with side effects can be managed at a lower dosage for a period long enough to reach the 120 mg/kg cumulative dose level. Explain to patients that the long-term benefit is related to the cumulative dosage, not to the duration of therapy.
The incidence of side effects was documented in a large study. Patients in that study stopped isotretinoin for the following reasons: mucous/skin effects (2.5), elevated triglyceride levels (2.0), musculoskeletal effects (1.3), headaches (1.1), elevated liver enzyme levels (0.6), amenorrhea (0.4), and other (0.5).
Teratogenicity--pregnancy prevention program.
Isotretinoin is a potent teratogen primarily involving craniofacial, cardiac, thymic, and central nervous system structures. A number of physicians inadvertently prescribed isotretinoin to pregnant women, which resulted in birth defects. For this reason the FDA considered withdrawing isotretinoin in 1988. Roche Laboratories designed the pregnancy prevention program; as a result, isotretinoin is still available.
The pregnancy prevention program is available from Roche Laboratories in a box containing a qualification checklist for patients, information about treatment, contraception counseling and serum pregnancy testing information, an optional referral form for expert counseling on contraception and patient self-evaluation, consent forms, and a follow-up survey.
Women should be educated about the risks to the fetus and the need for adequate contraception. Sexually active women should have a pregnancy test and postpone therapy until their next normal menstrual period. Some physicians will not prescribe isotretinoin to women of child-bearing age unless they are taking oral contraceptives. Others withhold isotretinoin if abortion is not an option. Isotretinoin is not mutagenic, nor is it stored in tissue. It is recommended that contraception be continued for 1 month after stopping isotretinoin. Patients can be reassured that conception is safe after this 1-month period. One study showed that from the fourth month of treatment onward, a statistically significant increase in the mean sperm density, sperm morphology, and motility were not affected. One year after treatment there was no evidence of any negative influence of 6 months of treatment with isotretinoin on spermatogenesis.
Plasma lipid abnormalities.
Accutane therapy induces an elevation of plasma triglycerides. In one study of patients (ages 14 to 40 years) treated for 20 weeks with 1 mg/kg/day, the maximum mean triglyceride levels rose 46.3 mg/dl in men and 52.3 mg/dl in women. In that study, 2 of 53 patients had a triglyceride elevation over 500 mg/dl, and 8 had elevations of 200 to 500 mg/dl. Triglyceride levels rise after 6 weeks of therapy and continue to rise while therapy continues. Age, sex, and weighted dose do not appear to be risk factors for triglyceride elevations. Overweight subjects are 6 times more likely to develop significant elevations in serum triglyceride, and subjects with elevated baseline triglyceride levels are 4.3 times more likely to develop significant elevations. Plasma lipid and lipoprotein levels return to baseline by 8 weeks after treatment. Liver and lipid abnormalities rarely necessitate dosage reduction and the need for repeat laboratory tests after initial normal values has been questioned.
Hyperostoses.
Asymptomatic hyperostoses (spurs) of the spine and extremities can be documented radiographically in some patients but do not seem to be of concern with a standard course of isotretinoin therapy.
Cheilitis.
Cheilitis is the most common side effect, occurring in virtually all patients. Application of emollients should be started with the initiation of therapy to minimize drying.
Approximately 40% of patients develop an elevated sedimentation rate during treatment. Isotretinoin does not specifically affect skeletal or myocardial muscles, 28% of patients complain of musculoskeletal symptoms. Accutane contains the preservative parabens; those patients with a proven allergy to parabens cannot receive Accutane. Exuberant granulation tissue may occur at the sites of healing acne lesions and is more likely to develop in patients who have preexisting crusted, draining, or ulcerated lesions. Granulation tissue can be controlled with intralesional steroid injections or silver nitrate sticks. Severe dry skin or eczema commonly occurs on the backs of the hands. Routine use of moisturizers and infrequent washing is recommended.