Thalidomide adverse effects

Lenalidomide is an immunomodulating agent related to thalidomide that was recently approved for the treatment of patients with multiple myeloma and myelodysplastic syndrome (MDS). Lenalidomide lacks the common side effects of thalidomide, such as constipation and peripheral neuropathy. Interim analyses of two phase III trials show that lenalidomide in combination with dexamethasone produces higher response rates than dexamethasone alone in relapsed and refractory myeloma. Adverse effects of lenalidomide include diarrhea, nausea, muscle cramps, hematologic side effects and deep vein thrombosis.42... 

Evaluate the patient for adverse effects, including peripheral neuropathy and deep vein thrombosis. Prophylactic anticoagulation therapy should be considered in thalidomide or lenalidomide based therapy. 

The adverse effect profile of thalidomide is extensive. The most important toxicity is teratogenesis. Because of this effect, thalidomide prescription and use is closely regulated by the manufacturer. Other adverse effects of thalidomide include peripheral neuropathy, constipation, rash, fatigue, hypothyroidism, and increased risk of deep vein thrombosis. Thrombosis is sufficiently frequent, particularly in the hematologic malignancy population, that most patients are placed on some type of anticoagulant when thalidomide treatment is initiated. 

Phocomelia The syndrome of having shortened arms and legs due to an adverse effect on the embryo such as caused by thalidomide. 

Other diseases that show a strong relationship between exposure to a chemical and an effect are thalidomide-induced malformations in babies and asbestos-related cancer (mesothelioma) (see pp. 56-9, 178-82). In all these cases, the disease or adverse effect was extremely rare, which helped in the detection and determation of the cause. 

Aside from teratogenicity, the main adverse effects of thalidomide include somnolence, dizziness, fatigue, tremor, rash, constipation, and edema. Although these adverse effects are generally mild and reversible, more severe adverse effects, such as peripheral neuropathy, deep vein thrombosis, and neutropenia, have occasionahy been reported. 

Adverse effect Polyneuropathy with thalidomide Dose-relation Collateral reaction Time-course Long-term... 

Febrile reactions are common in patients taking thahdo-mide. In one study of 56 patients with HIV infection who took thalidomide for 14-21 days, 24 discontinued therapy owing to adverse reactions. Cutaneous and/or febrile reactions, which occurred in 20 patients, were the most frequent adverse effects (96). 

The frequency in Bonn in 1962 was 3.56 per 1000 of all newborn children (200 times the frequency in 1960-61). In Liverpool, the frequency during 1960 and 1961 was lower (0.778 per 1000), but nevertheless considerably higher than in other countries. Cases have been reported from Australia, Scotland, and Sweden (149). The USA was relatively free from this adverse effect, since thalidomide (as Kevadon) failed to pass the Food and Drug Administration because of another adverse effect, namely polyneuropathy (119). 

There was a high incidence (17.5%) of abnormal embryos in mice treated during the sixth to eighth days of pregnancy, whilst thalidomide-treated animals had a higher incidence of fetal resorption (168). Others, however, failed to find any malformations or other adverse effects when using doses ranging from 2 mg/kg up to 400 mg/kg (169). 

A 64-year-old man with myeloma took dexamethasone and thalidomide 200 mg/day for 14 days and had no adverse effects. The dosage was increased to 400 mg/ day and 10 days later a rash occurred thalidomide was withdrawn. Within 3 days he developed toxic epidermal necrolysis. 

Distillers advertized thalidomide as a treatment for morning sickness that could be given with complete safety to pregnant women... without adverse effect on mother or child . 

The fear that toxic agents in the maternal environment might harm the unborn child is an ancient one that was reinforced by the thalidomide tragedy. Although toxicology and teratology are far more advanced sciences now than 20 years ago, it is still not known what factors with an adverse effect... 

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