Methotrexate

Methotrexate (MTX) is used in our pediatric population for steroid unresponsive or dependent patients despite the addition of 6-MP/AZA, or in children intolerant of 6-MP/AZA. Its effectiveness in this setting has been described in children.

There is extensive literature on the efficacy and safety of MTX in pediatric rheumatology and there is growing acceptance of its use in children with CD (Mack et al 1998; Woo et al, 2000; Giannini et al, 1992; Ravelli et al, 1998). Although uncommon, the potential risk of hepatic fibro-sis with advancing accumulated dose should be monitored. Potential bone marrow toxicity and interstitial pneu-monitis are also a concern. Dosing in children involves weekly parenteral administration, either via subcutaneous or intramuscular injection. Taking MTX orally often leads to intolerable nausea and absorption is variable, but no studies have been done in children comparing oral MTX with parenteral use for maintenance therapy in CD. Parenteral MTX has the added benefit of improved compliance. Because the mechanism of action of MTX is via inhibition of folate metabolism, supplementation with folate at a dose of 1 mg/d is a recommended. We typically dose MTX at weekly subcutaneous injections of 10 mg (for 20-29 kg of body weight), 15 mg (30-39 kg), 20 mg (40-49 kg), or 25 mg (> 50 kg) and give 50% of this dose the first week, 75% the next week, and the full dose by the third week if tolerated. Our maximum dose is 25 mg in children over 50 kg in weight. The dose can be gradually reduced after steroid withdrawal is achieved. We monitor the CBCs and alanine aminotransferase (ALT) weekly for the first 4 weeks then every 2 months, if stable. The dose is reduced by 50% for an ALT greater than 2 times baseline, white blood cells (WBC) < 4,000, absolute neutrophil count (ANC) < 1,500, or platelet count < 120,000. The dose is held for ALT > 3 times baseline, WBC < 3,000, ANC < 1,000, or platelet count < 100,000. Additionally, a chest radiograph and pulmonary function test are obtained if a child has a nonproductive cough for longer than 1 week and might be considered annually for patients on a maintenance regimen. Liver biopsy is considered when accumulated lifetime dose exceeds 1.5 g, but the data is not available to say this is necessary. Adolescent girls of child-bearing age are educated about the potential teratogenic effects of MTX and appropriate contraceptive measures.

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Constipation Prescription

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