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.

pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against pneumonia. Pentamidine may be an acceptable alternative for pediatric patients unable to tolerate trimethoprim-sulfamethoxazole. A retrospective review was conducted of pediatric oncology patients who received ≥1 dose of pentamidine for pneumonia prophylaxis between January 2007 and August 2014. Electronic medical records were reviewed to determine the incidence of breakthrough pneumonia or discontinuation of pentamidine associated with adverse events. A total of 754 patients received pentamidine prophylaxis during the period. There were no cases of probable or proven pneumonia, and 4 cases (0.5%) of possible pneumonia. The incidence of possible breakthrough pneumonia was not significantly different between subgroups based on age (<12 months [1.7%] versus ≥12 months [0.4%], = 0.3), route of administration (aerosolized [0%] versus intravenous [1.0%], = 0.2), or hematopoietic stem cell transplant status (transplant [0.4%] versus no transplant [0.8%], = 0.6). Pentamidine was discontinued due to an adverse drug event in 23 children (3.1%), more frequently for aerosolized than for intravenous administration (7.6% versus 2.2%, respectively, = 0.004). Intravenous or inhaled pentamidine may be a safe and effective second-line alternative for prophylaxis against pneumonia in children with cancer receiving immunosuppressive chemotherapy or hematopoietic stem cell transplantation.

Vincristine (VCR) is a vinca alkaloid and common chemotherapeutic that is used to treat multiple pediatric and adult malignancies. Despite its common use, cases of anaphylaxis to VCR are rare and typically isolated to a single individual. We report a series of eight patients with adverse reactions to VCR over the course of 11 months at a single institution, four of which progressed to anaphylaxis and one of which resulted in cardiac arrest. Mass spectrometry analysis of medication lots was concerning for possible contaminant. Our findings highlight the risk of anaphylaxis during therapy with VCR.

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RATIONALE: Drug provocation test (DPT) is the gold standard to diagnose analgesic drugs hypersensitivity reactions (HRs). The purpose of this study was to confirm the diagnosis in patients with NSAIDs and acetaminophen HRs and to find the safe alternatives. METHODS: This is a retrospective study which enrolled adult participants with history of NSAIDs and acetaminophen-induced immediate drug HRs whose skin prick test results were negative. Their DPTs were singleblinded and placebo controlled. The analgesic drugs included acetaminophen, NSAIDs (aspirin, ibuprofen, diclofenac, mefenamic acid, and meloxicam), COX-2 inhibitor (etoricoxib) and tramadol. All participants were challenged with placebo and the analgesic drugs by ingestion of increasing dose every 60 minutes, started from 25%, 50%, 75% and then 100% of their targeted therapeutic dose. RESULTS: Eighteen participants consented to DPTs. We performed 404 DPTs. Sixty-seven (16.58%) tests were positive with 2 of those were anaphylaxis. DPTs confirmed the diagnosis in all of 5 participants with the history of NSAIDs and acetaminophen HRs and 8 participants with the history of only NSAIDs HRs. DPTs were able to diagnose 50% of 4 participants with the history of acetaminophen HRs. Eleven participants had multiple NSIADs positive results. DPTs with etoricoxib and tramadol were negative in 12 (66.66%) and 14 (77.78%) out of 18 participants, respectively. Six participants with etoricoxib positive DPTs had multiple NSIADs positive DPTs too. CONCLUSIONS: This study indicated the DPT was a good diagnostic test for analgesic drugs HRs. Etoricoxib and tramadol were tolerated in the majority but not all participants tested.