See Contraindications and Special Precautions)Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. The teratogenic effect of lenalidomide cannot be ruled out. For lenalidomide no clinical data on exposed pregnancies are available. Studies in animals have shown embryofoetal toxicity. Therefore, lenalidomide is contraindicated during pregnancy. Women of childbearing potential should use effective method of contraception. If pregnancy occurs in a woman treated with lenalidomide, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for eva luation and advice. If pregnancy occurs in a partner of a male patient taking lenalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for eva luation and advice. For male patients taking lenalidomide, there is no clinical data available on the presence of lenalidomide in human semen. Therefore male patients taking lenalidomide should use condoms if their partner is of childbearing potential and has no contraception. Lactation It is not known whether lenalidomide is excreted in human milk. Therefore breast-feeding should be discontinued during therapy with lenalidomide.
Adverse Reactions
In two Phase III placebo-controlled studies, 353 patients with multiple myeloma were exposed to the lenalidomide/dexamethasone combination and 351 to the placebo/dexamethasone combination. The median duration of exposure to study treatment was significantly longer (44.0 weeks) in the lenalidomide/dexamethasone group as compared to placebo/dexamethasone (23.1 weeks). The difference was accounted for by a lower rate of discontinuation from study treatment due to lower progression of disease in patients exposed to lenalidomide/dexamethasone (39.7%) than in placebo/dexamethasone patients (70.4%). 325 (92%) of the patients in the lenalidomide/dexamethasone group experienced at least one adverse reaction compared to 288 (82%) in the placebo/dexamethasone group. The most serious adverse reactions were: • venous thromboembolism (deep vein thrombosis, pulmonary embolism) (See Special Precautions) • Grade 4 neutropenia (sSee Special Precautions). The most frequently observed adverse reactions which occurred significantly more frequently in the lenalidomide/dexamethasone group compared to the placebo/dexamethasone group were neutropenia (39.4%), fatigue (27.2%), asthenia (17.6%), constipation (23.5%), muscle cramp (20.1%), thrombocytopenia (18.4%), anaemia (17.0%), diarrhoea (14.2%) and rash (10.2%). The adverse reactions observed in patients treated with lenalidomide/dexamethasone are listed below by system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as: very common (= 1/10); common (= 1/100, < 1/10); uncommon (= 1/1,000, < 1/100); rare (= 1/10,000, < 1/1,000), very rare (< 1/10,000 including isolated reports). In the majority of cases, there was no significant difference in the incidence of specific adverse events between the two treatment arms. Only those adverse reactions marked with * occurred significantly more frequently in the lenalidomide/dexamethasone arm compared to the placebo/dexamethasone arm. Adverse Drug Reactions (ADR
