About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.
Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:
- Kidney and liver damage. People at particular risk for liver damage from methotrexate include diabetics with existing liver or kidney problems, alcoholics, those who are obese, the elderly, and (at very high risk) those with psoriasis.
- Osteoporosis may possibly develop at high doses. (A 2001 study reported no higher risk for bone loss at low doses.)
- Increased risk for infections, particularly herpes zoster and pneumonia.
- Lung disease occurs in up to 5% of people who take methotrexate and deserves special mention. There are five key risk factors for methotrexate-induced lung diseases: Age, diabetes, existing rheumatoid involvement in the lung, protein in the urine, and previous use of other DMARDs, (particularly sulfasalazine, oral gold and d-penicillamine). Patients with multiple risk factors should notify their doctor about any symptoms, such as coughing, that might indicate lung injury.
- The drug increases the risk for birth defects when taken by pregnant women.
- There have been a few reports of lymphomas in some patients taking methotrexate. In such cases, the disease appears to go into remission when the drug is stopped. Most studies have found no significant risk for cancer in patients taking this drug.
Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:
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