ADVERSE DRUG EVENTS

User-friendly dashboard now available

To improve access to information about adverse drug events, the FDA has launched the FDA Adverse Events Reporting System (FAERS) Public Dashboard, a highly interactive web-based tool designed to make data collected by the FDA easily accessible to healthcare professionals and the public. The dashboard lets the user search for data using such criteria as drug/biologic product, age of patient, type of adverse event, and year or time frame in which the adverse event occurred. The FDA hopes that increasing access to these data will encourage more adverse event reporting by healthcare professionals and the public alike. To access the site, visit http://www.fda.gov and search for FAERS public dashboard.

Source: Food & Drug Administration. FDA improves access to reports of adverse drug reactions. News release. September 28, 2017.

YESCARTA

FDA approves cell-based gene therapy

Classified as a chimeric antigen receptor (CAR)-T cell therapy, Yescarta is the second gene therapy approved by the FDA. It's indicated to treat adults with certain types of large B-cell lymphoma who haven't responded to or have relapsed after at least two other kinds of treatment. Types of large B-cell lymphoma for which Yescarta is indicated are diffuse large B-cell lymphoma (DLBCL), which is the most common type of non-Hodgkins lymphoma in adults, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Each dose of Yescarta is customized for the patient: T cells are collected from the patient and genetically modified to include a new gene that directs the T cells to attack lymphoma cells. In a multicenter clinical trial of more than 100 patients, the complete remission rate was 51%.

Yescarta can cause severe adverse reactions and carries a boxed warning for cytokine release syndrome (CRS), a systemic response to the activation and proliferation of CAR-T cells, and neurologic toxicities. It's available only through a restricted program under a Risk Evaluation and Mitigation Strategy, and staff involved in prescribing, dispensing, or administering the drug must be trained to recognize and treat CRS and neurologic toxicities. The FDA is requiring the manufacturer to conduct a postmarketing observational study of patients treated with Yescarta.

Sources: Food & Drug Administration. FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. News release. October 18, 2017. Yescarta (axicabtagene ciloleucel) suspension for intravenous infusion. Prescribing information. http://www.gilead.com.

ANTICOAGULANTS

DOACs are a viable option for treating VTE

Because they don't require frequent blood monitoring and dose adjustments, direct oral anticoagulants (DOACs) such as dabigatran, apixaban, or rivaroxaban have advantages over warfarin for treating patients with venous thromboembolism (VTE) who require anticoagulation. However, little research has been performed to investigate the relative safety of DOACs for treating VTE. Using healthcare data from six jurisdictions in the United States and Canada, researchers conducted a retrospective matched cohort study involving over 59,500 adults with a new VTE diagnosis and a prescription for warfarin or a DOAC within 30 days of diagnosis. Outcomes included hospital admission or an ED visit for major bleeding and all-cause mortality within 90 of starting treatment.

Results showed that the risk of bleeding and all-cause mortality was similar for DOACs and warfarin. The authors write, "our results suggest that DOACs may be considered as a treatment option for patients with venous thromboembolism who are candidates for anticoagulation."

Source: Jun M, Lix LM, Durand M, et al. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study. BMJ. 2017;359:j4323.

VAGINAL ESTROGEN

Study supports safety of suppositories, creams

Research involving over 45,600 postmenopausal women has shown that use of vaginal estrogen creams or suppositories is safe for these patients. Based on data from the Women's Health Initiative Observational Study, the prospective cohort study investigated the association between use of vaginal estrogen and risk of a global index event (GIE), defined as coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, or death from any cause. Use of vaginal estrogen was self-reported by the women, none of whom used systemic estrogen therapy during the median follow-up period of 7.2 years. No association was found between vaginal estrogen use and any GIE.

Currently the FDA requires all estrogen formulations, including topical products, to be labeled with a warning about the increased risks of cardiovascular events, certain cancers, and other potentially serious adverse reactions. According to lead author Carolyn J. Crandall, MD, MS, these findings should reassure clinicians and patients about the safety of vaginal estrogens, but she cautions that a possible link between prolonged use of these agents and endometrial cancer requires more study.

The study was funded by the National Institutes of Health and reported at the annual meeting of the North American Menopause Society.

Sources: Crandall CJ, Hovey K, Andrews C, et al. Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the WHI observational study. North American Menopause Society. Abstract presentation. October 12, 2017. Monaco K. No risk for CVD, Ca with vaginal estrogen use. MedPage Today. October 13, 2017.

MIGRAINE

Opioid shouldn't be initial treatment in ED

In a study conducted in two New York City EDs, researchers compared outcomes among patients with migraine who were treated with I.V. hydromorphone (1 mg) versus those receiving I.V. prochlorperazine (10 mg) plus diphenhydramine (25 mg). Hydromorphone is an opioid analgesic; prochlorperazine is a propylpiperazine derivative of phenothiazine. Like other phenothiazines, it exerts an antiemetic effect through a depressant action on the chemoreceptor trigger zone. It also has a clinically useful antipsychotic effect. Diphenhydramine, a histamine-1 receptor antagonist, is administered with prochlorperazine to prevent akathisia, a common adverse reaction to I.V. prochlorperazine.

The primary outcome was sustained headache relief, defined as a headache level of mild to none within 2 hours of treatment, maintained for 48 hours without the need for rescue medication. The primary outcome was achieved by 60% of patients in the prochlorperazine group, compared with 31% of those in the hydromorphone group. Based on these significant results, the data monitoring committee halted the study after 127 patients had been enrolled. The study authors concluded that "I.V. hydromorphone is substantially less effective than I.V. prochlorperazine for treatment of acute migraine in the ED and should not be used as first-line therapy."

Sources: Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. [e-pub Oct. 18, 2017.] Prochlorperazine Edisylate Injection, USP. Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089903s018lbl.pdf.