This week's clinical pharmacology highlights include several groundbreaking FDA approvals. Metformin is associated with lower all-cause mortality in patients with comorbid diabetes and dementia, statins are underprescribed to African-American patients, and classic insulin NPH may be as effective as the more-expensive basals.
~ Pharmacology News ~
Binimetinib + Encorafenib - Approved for Advanced Melanoma
June 27th, FDA: MEK inhibitor binimetinib (Mektovi) and BRAF inhibitor encorafenib (Braftovi) combination therapy have been approved for the treatment of metastatic melanomas with V600E/V600K mutations.
Plazomicin (Zemdri®) - Approved for UTI
June 25th, FDA: The FDA has approved the aminoglycoside antibiotic plazomicin for the treatment of complicated UTIs in patients with limited alternative treatment options. It is administered intravenously, once-daily.
Cannabidiol (Epidiolex®) - Approved for Seizure Disorders
June 25th, FDA: The FDA has approved cannabidiol (Epidiolex®) for the treatment of the severe childhood epilepsy disorders Lennox-Gastaut syndrome and Dravet syndrome.
Chronic Opioid Use - A Predictor of 2016 Trump Preference
June 22nd, JAMA: Individuals with chronic (>90 day) opioid prescriptions were more likely to have supported Donald Trump in the 2016 presidential election. Retrospective observational, > 3 million individuals from Medicare Part D claims databank.
25% of Diabetes Patients Underuse Insulin Due to Cost
June 22nd, ADA Meeting: 1 out of 4 individuals were found to have not used insulin as prescribed to due concerns about medication cost. Cross-sectional observational, 199 patients.
~ Clinical Trials - New Horizons ~
Canakinumab (IL-1β Inhibitor) - Acute Gout Flare
June 13th, EULAR Conference: Canakinumab lowers the risk of acute gout flares by 50-60%, without lowering serum urate levels. Secondary analysis of CANTOS RCT.
Estradiol-Progesterone Single-Capsule Combo - Menopausal Vasomotor Symptoms
June 28th, Obstetrics and Gynecology: 1 - 2.5 million women in the US are taking unapproved compounded hormone therapy, with unknown safety and efficacy profiles. Single-capsule estradiol-progesterone combination therapy (TX-001HR) improved moderate-to-severe vasomotor symptoms. REPLENISH Trial. RCT double-blind, 1,845 participants.
Elagolix (GNRH Antagonist) - Endometriosis
June 28th, Obstetrics and Gynecology: Daily elagolix for women with endometriosis was effective over a 12 month treatment period, with sustained reduction in dysmenorrhea, non-menstrual pelvic pain, and dyspareunia. Decreases in bone mineral density occurred at an increased rate in the treatment arm. EM-III, EM-IV (extension of EM-I and EM-II trials). RCT, 569 patients.
Carbetocin (Uterotonic) - Post-Partum Hemorrhage
June 27th, NEJM: Oxytocin is effective in controlling bleeding in post-partum hemorrhage but requires cold-storage. A heat-stable formulation of carbetocin has demonstrated efficacy in the reducing post-partum hemorrhage severity. Randomized-controlled trial, 29,645 patients.
Enzalutamide (Androgen Receptor Antagonist) - Prostate Cancer
June 27th, NEJM: Once-daily enzalutamide led to a 71% reduction of metastasis risk in men with castration-resistant, non-metastatic prostate cancer with rapidly rising PSA levels. PROSPER Trial. Randomized-controlled trial, 1,401 patients.
~ Clinical Pharmacology Research ~
Canagliflozin (SGLT2 Inhibitor) - Amputation Risk
June 25th, ADA Conference: No evidence of a higher risk of amputation following use of the SGLT2-inhibitor canagliflozin compared with other antidiabetic agents, in contrast with CANVAS study results. OBSERVE 4-D trial. Observational retrospective, >700,000 patients.
Evolocumab (PCSK9 Inhibitor) - Hyperlipidemia & Type II Diabetes
June 24th, ADA Meeting: Evolocumab (Repatha®) lowers LDL-C by 64% relative to baseline after 12 weeks. BANTING study, Randomized placebo-controlled, 421 patients.
Insulin NPH vs. Glargine/Detemir - Type II Diabetes Mellitus
June 23rd, JAMA: Basal insulin analogs (e.g., glargine or determir) did not reduce the risk of ED visits or hospital admissions for hypoglycemia, or improve glycemic control compared with insulin NPH (neutral protamine hagedorn - older, less expensive form of insulin). Retrospective Observational, 25,489 patients.
Dulaglutide (GLP-1 Receptor Agonist) - Glycemic Control in CKD
June 14th, The Lancet: Once-weekly dulaglutide has been found to provide comparable glucose control to insulin glargine in patients with CKD. AWARD-7 study. Randomized, open-label trial, 577 patients.
Metformin - Diabetes + Dementia
June 18th, EAN Meeting: Metformin was observed to lower all-cause mortality in patients with both diabetes and dementia. Insulin was associated with a higher risk of heart failure. Observational, >75,000 patients.
Statins - CV Event Prevention Among African-American Patients
June 13th, JAMA Cardiology: African-American patients are less likely than white patients (33% vs. 44%) to receive guideline-appropriate statin therapy for 1º and 2º prevention of cardiovascular events. Observational retrospective, 5,689 patients.
Zolendronic Acid (Bisphosphonate) - Bone Loss From Breast Cancer Tx
June 13th, Journal Bone: IV zolendronate given periodically over 2 years prevented cancer-treatment induced bone loss in premenopausal women with breast cancer and maintained bone mineral density up to 3 years post-treatment. PROBONE II Trial, 5 year followup. 65 patients, randomized placebo-controlled.
~ Reviews ~
Intranasal Saline - Allergic Rhinitis
June 18th, Cochrane: Patient-reported symptoms of allergic rhinitis improved following the use of intranasal saline rinses or sprays when compared with no nasal saline irrigation. Systematic review, 112 adults and 332 children.
Antidepressants During Pregnancy - Motor Development
June 25th, Pediatrics: In-utero antidepressant use was associated with an increased risk of worse motor function scores during infancy and childhood. The authors urge further, larger studies. Meta-analysis, 18 randomized and non-randomized trials.
Botulinum Toxin - Chronic Migraine
June 25th, Cochrane: In chronic migraine (> 15 headache days/month), botulinum toxin type A injections may reduce the number of migraine days per month by 2 days compared with placebo treatment. Meta-analysis, 28 trials (4190 participants).
Lithium - Congenital Malformation Risk
June 18th, The Lancet Psychiatry: Lithium exposure during the first trimester of pregnancy was associated with a 70% increased risk of congenital malformations. 22, 124 pregnancies, 6 cohorts - Meta-analysis.