Pharmacology News Round-Up: June 28th, 2018




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.


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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 3years post-treatment. ​​ PROBONE II Trial, 5 year followup.  65 patients, randomized placebo-controlled. ​​ 



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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. 



by​​ pharmacologyreview