Methotrexate dose reduction

When Methotrexate is discontinued, the arthritis usually worsens within 3 to 6 weeks. Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more.

Dose reduction or cessation is guided by patient response and hematologic monitoring.

As the time interval between Methotrexate administration and leucovorin initiation increases, the effectiveness of leucovorin in counteracting toxicity decreases.

Dosages ranged up to 25 mg per week and treatment was administered for up to four years.

Close attention to renal function including adequate hydration, urine alkalinization and measurement of serum Methotrexate and creatinine levels are essential for safe administration. This lesion can occur at all dosages.

When a patient presents with pulmonary symptoms, the possibility of Pneumocystis carinii pneumonia should be considered. Immunization may be ineffective when given during Methotrexate therapy.

Methotrexate side effects

Methotrexate should be used with extreme caution in the presence of debility. If vomiting, diarrhea, or stomatitis occur, which may result in dehydration, Methotrexate should be discontinued until recovery occurs. Post-marketing experience suggests that the occurrence of bone marrow suppression, thrombocytopenia, and pneumonitis may increase with age. In chronic use situations, certain toxicities may be reduced by folate supplementation.

Elderly patients should be closely monitored for early signs of hepatic, bone marrow and renal toxicity. Serum Methotrexate levels may also be helpful. Since decline in renal function may be associated with increases in adverse events and serum creatinine measurements may over estimate renal function in the elderly, more accurate methods should be considered. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic and renal function, decreased folate stores, concomitant disease or other drug therapy in this population. Clinical studies of Methotrexate did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects.

Methotrexate causes

Methotrexate causes embryotoxicity, abortion, and fetal defects in humans. Benefits should be weighed against the potential risks before using Methotrexate alone or in combination with other drugs, especially in pediatric patients or young adults. However, there have been instances of malignant lymphoma arising during treatment with low-dose oral Methotrexate, which have regressed completely following withdrawal of Methotrexate, without requiring active anti-lymphoma treatment. Non-Hodgkin's lymphoma and other tumors have been reported in patients receiving low-dose oral Methotrexate. Although there is evidence that Methotrexate causes chromosomal damage to animal somatic cells and human bone marrow cells, the clinical significance remains uncertain. Methotrexate has been evaluated in a number of animal studies for carcinogenic potential with inconclusive results. No controlled human data exist regarding the risk of neoplasia with Methotrexate. Trimethoprim/sulfamethoxazole has been reported rarely to increase bone marrow suppression in patients receiving Methotrexate, probably by an additive antifolate effect. Certain side effects such as mouth sores may be reduced by folate supplementation with Methotrexate. Methotrexate may decrease the clearance of theophylline; theophylline levels should be monitored when used concurrently with Methotrexate.

Methotrexate dose

With the exception of alopecia, photosensitivity, and "burning of skin lesions" , the adverse reaction rates in these reports were very similar to those in the rheumatoid arthritis studies. Dosages ranged up to 25 mg per week and treatment was administered for up to four years. There are two literature reports describing large series of psoriasis patients treated with Methotrexate. There are no recent placebo-controlled trials in patients with psoriasis. Two other controlled trials of patients with Rheumatoid Arthritis on 7.5 mg to 15 mg/wk oral doses showed an incidence of interstitial pneumonitis of 1%. Hepatic histology was not examined in these short-term studies. Virtually all of these patients were on concomitant nonsteroidal anti-inflammatory drugs and some were also taking low dosages of corticosteroids. The approximate incidences of Methotrexate attributed adverse reactions in 12 to 18 week double-blind studies of patients with rheumatoid arthritis treated with low-dose oral pulse Methotrexate are listed below. Anaphylactoid reactions have been reported. Other rarer reactions related to or attributed to the use of Methotrexate such as nodulosis, vasculitis, arthralgia/myalgia, loss of libido/impotence, diabetes, osteoporosis, sudden death, reversible lymphomas, tumor lysis syndrome, soft tissue necrosis and osteonecrosis.

Methotrexate dose rheumatoid arthritis

Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more. Although there is experience with doses up to 30 mg/m2/wk in children, there are too few published data to assess how doses over 20 mg/m2/wk might affect the risk of serious toxicity in children. Limited experience shows a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression, at doses greater than 20 mg/wk in adults. For either adult RA or polyarticular-course JRA dosages may be adjusted gradually to achieve an optimal response. The recommended starting dose is 10 mg/m2 given once weekly. Dose reduction or cessation is guided by patient response and hematologic monitoring.