Trimethoprim-sulfamethoxazole (TMP/SMX) is used as prophylaxis against Pneumocystis jiroveci during chemotherapy. Many groups recommend withholding TMP/SMX during high-dose methotrexate (HDMTX) for concerns that it will delay methotrexate clearance. We compared methotrexate exposure following HDMTX (NCT00549848) in 424 patients including 783 courses that were and 602 courses that were not given concurrently with TMP/SMX. Among 176 patients (555 courses) on the low-risk arm (HDMTX = 2.5 g/m2/24 hours), there was no difference in clearance (110.7 (1.8%) vs. 108.2 (0.9%) mL/min/m2, p=0.3) nor in 42 hour methotrexate concentration (0.37 (5.1%) vs. 0.40 (5.0%) μM, p=0.23). Among 248 patients (830 courses) on the standard/high-risk arm (HDMTX ~5 g/m2/24 hours), there was slightly higher clearance (95.5 (1.4%) vs. 91.2 (0.8%) mL/min/m2, p=0.005) in those receiving TMP/SMX, with no difference in the 42 hour methotrexate concentration (0.59 (4.1%) vs. 0.66 (4.2%) μM, p=0.06). There was no difference in neutrophil counts based on TMP/SMX during HDMTX (p = 0.83). TMP/SMX also did not have a significant impact on myelosuppression of low-dose methotrexate (40 mg/m2) given during continuation therapy among 230 patients enrolled on a prior study (NCT00137111). Thus, we found no evidence for an interaction between methotrexate and TMP/SMX given prophylactically.
Four patients with rheumatoid arthritis received a combination of methotrexate and sulfasalazine for a mean of 24 months (range 20–28 months). All 4 patients experienced clinical improvement, with a reduction in the number of involved joints and in morning stiffness. In all 3 patients who had previously taken methotrexate, we were able to reduce the dosage, and the prednisone dosage was reduced in 2 of 3 patients who had previously taken that drug. No serious toxicity was observed in any patient.
BackgroundRhabdomyolysis is a condition characterized by leakage of muscle cell contents and is associated with necrosis and acute kidney injury, which can lead to morbidity and mortality. 1 Though rhabdomyolysis is often caused by direct injury and prolonged immobilization, several medications, including succinylcholine, have been implicated in muscle damage. 2 Succinylcholine is a depolarizing neuromuscular blocker that is used for intubation and carries a black box warning in pediatric patients due to a risk of rhabdomyolysis, hyperkalemia, ventricular arrhythmias, and cardiac arrest in patients with skeletal muscle myopathy. 2 Rhabdomyolysis from succinylcholine is caused by the upregulation of acetylcholine receptors, leading to the depolarization of the muscle and rapid release of potassium. 3 To date, there have been few reports of adult patients with no underlying muscular disorder experiencing rhabdomyolysis attributable to succinylcholine. We describe a patient who experienced cardiac arrest, rhabdomyolysis, hyperkalemia, and acute kidney injury after receipt of succinylcholine for rapid sequence intubation. The Naranjo adverse drug reaction probability scale for this case is 5, which is considered probable.
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