Pregnancy contraindications related

Nausea and mucosal ulcers are the most common toxicities. Progressive dose-related hepatotoxicity in the form of enzyme elevation occurs frequently, but cirrhosis is rare (< 1%). Liver toxicity is not related to serum methotrexate concentrations, and liver biopsy follow-up is only recommended every 5 years. A rare hypersensitivity-like lung reaction with acute shortness of breath is documented, as are pseudolymphomatous reactions. The incidence of gastrointestinal and liver function test abnormalities can be reduced by the use of leucovorin 24 hours after each weekly dose or by the use of daily folic acid, although this may decrease the efficacy of the methotrexate. This drug is contraindicated in pregnancy. 

Adverse reactions include dose-related peripheral neuropathy (primarily sensory), nausea, vomiting, constipation, dry mouth, headache, and erythematous rashes. Dose-related central nervous system depression is relatively common. Thalidomide is contraindicated in pregnancy and in women of childbearing age. 

Diarrhea, with or without abdominal pain and cramps, occurs in up to 30% of patients who take misoprostol. Apparently dose-related, it typically begins within the first 2 weeks after therapy is initiated and often resolves spontaneously within a week more severe or protracted cases may necessitate drug discontinuation. Misoprostol can cause clinical exacerbations of inflammatory bowel disease (see Chapter 38) and should be avoided in patients with this disorder. Misoprostol is contraindicated during pregnancy because it can increase uterine contractility. 

Despite these promising clinical data, the toxicities, cost, and complexities of administration have limited the use of radioimmunotherapy. The murine antibodies induce an immune response. This may manifest as acute infusion reactions and human anti-murine antibodies (HAMA), which occur in approximately 2% of patients treated with Y ibritumomab tiuxetan and 9% of patients treated with I tositumomab. Myelosuppression 6-9 weeks after administration is common. Ten percent of patients treated with I tositumomab develop hypothyroidism [92]. The most feared complication of radioimmunotherapy is treatment-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Rates of these late, generally incurable toxicities range 1.5—2.5% for Y ibritumomab tiuxetan and 3.5—6.4% for tositumomab [63, 93, 94]. Because ionizing radiation is teratogenic, radioimmunotherapy is contraindicated in all stages of pregnancy. 

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