Prophylactic Trimethoprim-Sulfamethoxazole Does Not Affect Pharmacokinetics or Pharmacodynamics of Methotrexate.

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 given concurrently 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/m/24 h), there was no difference in clearance (110.7 [1.8%] vs. 108.2 [0.9%] mL/min/m, 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/m/24 h), there was slightly higher clearance (95.5 [1.4%] vs. 91.2 [0.8%] mL/min/m, 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/m) 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.

The role of aclidinium bromide in the treatment of chronic obstructive pulmonary disease.

INTRODUCTION: Inhaled bronchodilators remain a cornerstone of treatment for chronic obstructive pulmonary disease (COPD); current guidelines recommend initiating inhaled bronchodilators as either monotherapy or combination therapy depending on disease severity and exacerbation risk to improve air flow and reduce breathlessness. Aclidinium bromide is a twice-daily, long-acting muscarinic antagonist recently approved in the United States and Europe and carries significant promise as an alternative long-acting inhaled antimuscarinic agent for the treatment of moderate-to-severe COPD. OBJECTIVE: This review describes the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of aclidinium bromide. DISCUSSION: Clinical trials have demonstrated improvement in forced expiratory volume in 1 second, nighttime symptom control, disease-related quality of life, and delay in time to first COPD exacerbation with aclidinium use compared with placebo. Commonly reported adverse effects include headache, nasopharyngitis, and cough. One trial reported narrow-angle glaucoma; however, no other serious adverse events have been reported to date. CONCLUSION: Overall, aclidinium bromide has been found to be safe and effective for the treatment of moderate-to-severe COPD. Further clinical trials comparing aclidinium bromide to standard therapies are needed to fully elucidate its role in the treatment of COPD.