|Acitretin should only be prescribed by physicians who are experienced in the use of systemic retinoids and understand the risk of teratogenicity associated with acitretin therapy.Acitretin is highly teratogenic. The risk of giving birth to a deformed child is exceptionally high if Acitretin is taken before or during pregnancy, no matter for how long or at what dosage. Foetal exposure to Acitretin always involves a risk of congenital malformation.Acitretin is contra-indicated in women of childbearing potential unless the following criteria are met:1. Pregnancy has been excluded before instituting therapy with Acitretin (negative pregnancy test within 2 weeks prior to therapy). Whenever practicable a monthly repetition of the pregnancy test is recommended during therapy.2. She starts Acitretin therapy only on the second or third day of the next menstrual cycle.3. Having excluded pregnancy, any woman of childbearing potential who is receiving Acitretin must practice effective contraception for at least one month before treatment, during the treatment period and for at least 2 years following its cessation.Even female patients who normally do not practice contraception because of a history of infertility should be advised to do so, while taking Acitretin.4. The same effective and uninterrupted contraceptive measures must also be taken every time therapy is repeated, however long the intervening period may have been, and must be continued for 2 years afterwards.5. Any pregnancy occurring during treatment with Acitretin, or in the 2 years following its cessation, carries a high risk of severe foetal malformation. Therefore, before instituting Acitretin the treating physician must explain clearly and in detail what precautions must be taken. This should include the risks involved and the possible consequences of pregnancy occurring during Acitretin treatment or in the 2 years following its cessation.6. She is reliable and capable of understanding the risk and complying with effective contraception, and confirms that she has understood the warnings.Full patient information about the teratogenic risk and the strict pregnancy prevention measures should be given by the physician to all patients, both male and female.Due to the risk of foetal malformations, the medicine must not be passed on to other people. Unused or expired products should be returned to a pharmacy for disposal.If oral contraception is chosen as the most appropriate contraceptive method for women undergoing retinoid treatment, then a combined oestrogen-progestogen formulation is recommended.Women of childbearing potential must not receive blood from patients being treated with acitretin. Theoretically there would be a small risk to a woman in the first trimester of pregnancy who received blood donated by a patient on Acitretin therapy. Therefore donation of blood by a patient being treated with acitretin is prohibited during and for two years after completion of treatment with acitretin.Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin. Women of childbearing age must therefore not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy. Contraceptive measures and pregnancy tests must also be taken for 2 years after completion of acitretin treatment (see section 4.6 and 5.2).Acitretin has been shown to affect diaphyseal and spongy bone adversely in animals at high doses in excess of those recommended for use in man. Since skeletal hyperostosis and extraosseous calcification have been reported following long-term treatment with etretinate in man, this effect should be expected with acitretin therapy.Since there have been occasional reports of bone changes in children, including premature epiphyseal closure, skeletal hyperostosis and extraosseous calcification after long-term treatment with etretinate, these effects may be expected with acitretin. Acitretin therapy in children is not, therefore, recommended. If, in exceptional circumstances, such therapy is undertaken the child should be carefully monitored for any abnormalities of musculo-skeletal development and growth parameters and bone development must be closely monitored.In adults, especially elderly, receiving long-term treatment with Acitretin, appropriate examinations should be periodically performed in view of possible ossification abnormalities (see section 4.8 Undesirable effects). Any patients complaining of atypical musculo-skeletal symptoms on treatment with Acitretin should be promptly and fully investigated to exclude possible acitretin-induced bone changes. If clinically significant bone or joint changes are found, Acitretin therapy should be discontinued.The effects of UV light are enhanced by retinoid therapy, therefore patients should avoid excessive exposure to sunlight and the unsupervised use of sun lamps. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used.Hepatic function should be checked before starting treatment with Acitretin, every 1 - 2 weeks for the first 2 months after commencement and then every 3 months during treatment. If abnormal results are obtained, weekly checks should be instituted. If hepatic function fails to return to normal or deteriorates further, Acitretin must be withdrawn. In such cases it is advisable to continue monitoring hepatic function for at least 3 months (see section 4.8).Serum cholesterol and serum triglycerides (fasting values) must be monitored before starting treatment, one month after the commencement and then every 3 months during treatment, especially in high-risk patients (disturbances of lipid metabolism, diabetes mellitus, obesity, alcoholism) and during long-term treatment.In diabetic patients, retinoids can alter glucose tolerance. Blood sugar levels should therefore be checked more frequently than usual at the beginning of the treatment period.Patients should be warned of the possibility of alopecia occurring (see section 4.8 Undesirable effects).Decreased night vision has been reported with acitretin therapy. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Visual problems should be carefully monitored (see section 4.8).There have been rare reports of benign intracranial hypertension. Patients with severe headache, nausea, vomiting, and visual disturbances should discontinue acitretin immediately and be referred for neurologic evaluation and care (see section 4.8).It should be emphasized that, at the present time, not all the consequences of life-long administration of acitretin are known.Treatment with high dose retinoids can cause mood changes including irritability, aggression and depression.|
High risk patients:In patients with diabetes, alcoholism, obesity, cardiovascular risk factors or a lipid metabolism disorder undergoing treatment with acitretin, more frequent checks are necessary of serum values for lipids,and/or glycaemia and other cardiovascular risk indicators, e.g. blood pressure. In diabetics, retinoids can either improve or worsen glucose tolerance. Blood-sugar levels must therefore be checked more frequently than usual in the early stages of treatment.For all high risk patients where cardiovascular risk indicators fail to return to normal or deteriorate further, dose reduction or withdrawal of acitretin should be considered.