Pharmacology News Round-Up | July 6th, 2018



This week’s​​ clinical​​ pharmacology​​ update​​ includes​​ FDA​​ approvals​​ for excessive sweating​​ and​​ drooling, phase III trial results for new​​ hepatocellular carcinoma​​ and​​ PNH​​ drugs, and more good news for​​ coffee​​ drinkers.

-​​ July​​ 6th, 2018








~  ​​ ​​​​ Pharmacology News ​​​​ ~

Glycopyrronium​​ Approved for the Treatment of Excessive Underarm Sweating

June 28th:​​ The FDA has approved​​ Glycopyrronium (QbrexaTM) for the treatment of primary axillary​​ hyperhidrosis​​ – excessive underarm sweating -​​ in patients ages​​ 9 and​​ older.



Rapid Onset,​​ Long-Acting​​ Aripiprazole​​ Approved​​ for Psychosis

June 29th:​​ The United States FDA has approved a quicker-onset formulation of the long-acting injectable antipsychotic agent aripiprazole lauroxil (Aristada Initio) that does not require 3 weeks of orally dosed aripiprazole​​ before therapeutic onset.​​ 



Incobotulinumtoxin A​​ Approved for Excessive Drooling

July 4th:​​ The United States FDA has approved injectable incobotulinumtoxin A​​ (a neuronal acetylcholine release inhibitor)​​ previously approved for cervical dystonia and blepharospasm, for the treatment of sialorrhea, or excessive drooling.




Coffee​​ Drinking Again Associated with Decreased Mortality

July 5th, 2018:​​ Coffee drinking was associated with decreased mortality over 10 years. ​​ Mortality benefits were observed in participants drinking 1 – 8 or more cups per day, ground coffee, decaffeinated coffee, and instant coffee.​​ Prospective​​ observational​​ (498,134 participants).




~  ​​ ​​​​ Clinical Trials: New Horizons ​​ ​​ ​​​​ ~

Ravelizumab​​ for PNH Effective When Dosed Q8 Weeks

June 17th, EHA Conference:​​ A new C5 inhibitor, ravelizumab, has demonstrated non-inferiority to eculizumab in treating paroxysmal nocturnal hemoglobinuria when dosed intravenously at 8 week intervals. ​​ Eculizumab​​ is​​ currently administered every two weeks.​​ RCT (245 patients).




Cabozantinib, Novel Tyrosine Kinase Inhibitor, Improves Survival in Hepatocellular Carcinoma

July 5th, NEJM:​​ Oral, once daily cabozantinib (VEGF receptor, MET and AXL tyrosine kinase inhibitor) extended median survival in patients with advanced hepatocellular carcinoma by 2.2 months relative to placebo.​​ RCT, Phase III Clinical Trial (707 patients).



Patisiran,​​ Hepatically Targeted​​ RNAi Agent, Improves Outcomes in Hereditary Transthyretin Amyloidosis

July 5th, NEJM:​​ Patisiran, an interference-RNA therapy that reduces expression of​​ the​​ transthyretin protein, improves clinical outcomes of hereditary transthyretin amyloidosis, including gait speed and​​ polyneuropathy​​ symptoms.​​ RCT, Phase III Clinical Trial (225 patients).





Quizartinib,​​ FLT3 Inhibitor, Improves Survival​​ in​​ Refractory​​ AML​​ 

June 16th, EHA​​ Meeting: ​​​​ A selective tyrosine kinase inhibitor quizartinib (fms-like tyrosine kinase 3​​ -​​ FLT3​​ ​​ inhibitor) has​​ shown efficacy in a subset of relapsed/refractory acute myeloid leukemia patients with FLT3 mutations. ​​ Median overall survival was 1.5 months longer in the quizartinib group than the standard chemotherapy group. ​​ RCT​​ (367 patients) – QuANTUM-R trial.




~  ​​ ​​​​ Clinical​​ Research ​​ ​​ ​​​​ ~


Ramelteon​​ May​​ Lower​​ Delirium Risk &​​ ICU Duration of Stay

July​​ 5th,​​ Journal​​ CCM:​​ Ramelteon​​ (melatonin receptor agonist often used as a sleep aid) given nightly to patients in intensive care decreased risk of delirium and may shorten ICU length of stay.​​ RCT​​ ​​ (88 participants).​​ 





Increased Diabetes Risk Associated with​​ Oral Contraceptive​​ Use

June 24th, ADA Meeting: ​​​​ Past use of oral contraceptives for > 6 months was associated with a 1/3 higher risk of insulin resistanse and diabetes in postmenopausal women. ​​​​ Observational Retrospective (6554 participants)




Antibiotic​​ Use Before, During, and After Pregnancy Associated with Childhood Asthma Risk

July 4th, European Respiratory Journal: ​​​​ Maternal antibiotic use during the 9 months before beginning of pregnancy, during the pregnancy, and for 9 months after delivery was associated with a 23% increased risk of childhood asthma. ​​ Observational retrospective (213,661 mother-child dyads).​​ 



Prenatal Exposure to​​ Folic Acid​​ May Protect Against Later​​ Psychosis

July 3rd, JAMA Psychiatry: ​​​​ Alterations in cortical development and, subsequently, decreased incidence of psychosis-spectrum disorders were observed following widespread folic acid grain fortification in the United States during the 1990’s. ​​ Observational retrospective (292 participants).




Liraglutide​​ Lowers​​ HbA1c​​ More​​ Than Bolus Insulin When HbA1c​​ Very High

July 4th, ADA Meeting:​​ Liraglutide (GLP-1 agonist) + metformin + basal insulin was more effective at lowering HbA1c levels over 6 months than bolus insulin + metformin + basal insulin in patients with baseline HbA1c > 10%. ​​​​ RCT, SIMPLE Trial (120 patients).




IVIg​​ Speeds Recovery in Childhood ITP

June 26th, Journal Blood:​​ Intravenous immunoglobulin (IVIg) treatment of children with newly diagnosed immune thrombocytopenia (ITP) resulted in increased complete response rate and a 36% lower likelihood of developing chronic ITP than in children not receiving IVIg.​​ RCT (206 participants).




First Oral Formulation of​​ GLP-1 Agonist​​ Lowers HbA1c

June 25th, ADA Meeting:​​ The first oral GLP-1 agonist, a novel formulation of semaglutide, has produced a median reduction in HbA1c of 1.5% and 4.3 kg of weight loss in patients with diabetes mellitus type II after 26 weeks of treatment. ​​ RCT, PIONEER-1 trial ​​ (703 participants).



Metformin​​ Not Associated with Lactic Acidosis in Diabetic Patients with Kidney Disease​​ 

July 2nd, JAMA Internal Medicine:​​ Two large studies have found that metformin use in patients with diabetes and eGFR between​​ 30 to 60 mL/min/1.73 m2​​ was not associated with an increased incidence of metabolic acidosis. ​​ Two observational retrospective studies (75,413 and 82,017 patients, respectively). ​​​​ 




Sodium Bicarbonate​​ Decreased Mortality in ICU Patients with Severe Metabolic Acidosis and AKI

June 14th, The Lancet:​​ Sodium bicarbonate decreased 28-day mortality and organ failure in patients in intensive care with severe metabolic acidosis (pH ≤ 7.20, NaHCO3 ≤ 20 mmol/L) and acute kidney injury (AKI). ​​ In patients with severe metabolic acidosis without AKI, sodium bicarbonate did not improve clinical outcomes. ​​ RCT (389 patients).




Apixaban​​ Safer than Warfarin in Patients on Dialysis

Circulation, June 28th: Apixaban was associated with a lower risk of major bleeding in end-stage kidney disease patients compared with warfarin, as well as reductions in thromboembolism event rate and overall mortality. ​​ Retrospective observational (25,523 patients).



Norepinephrine​​ Superior to Epinephrine In Cardiogenic Shock Following MI

July 2nd, JACC:​​ In patients with cardiogenic shock following MI, norepinephrine had comparable effects on blood pressure and cardiac index, but was​​ associated with lower rates of refractory shock. ​​ RCT​​ ​​ (57 patients).​​ 



~  ​​ ​​​​ Reviews  ​​ ​​​​ ~


Vitamin D​​ Supplementation During Pregnancy Associated with Improved Infant Growth​​ 

July 2nd,​​ JAMA Pediatrics:​​ Vitamin D supplementation during pregnancy was associated with decreased risk of​​ fetal/neonatal mortality, and improved infant growth.​​ Systematic review and meta-analysis (24​​ RCTs, 5405 participants). ​​​​ 




Gabapentin​​ &​​ Pregabalin​​ Ineffective in Treating Low Back Pain

July 3rd, CMAJ:​​ The anticonvulsants gabapentin and pregabalin were found to be ineffective in reducing chronic low back and lumbar radicular pain and were associated with increased risks of adverse events.​​ Systematic Review and Meta-Analysis (15 studies, 859 patients)





MRA​​ Therapy Associated with Improved Survival After​​ MI​​ (without Heart Failure)

July 2nd, JAMA Internal Medicine:​​ Aldosterone antagonist therapy (spironolactone,​​ eplerenone,​​ canrenoate) following ST-segment elevation myocardial infarction in patients without heart failure (or ejection​​ fraction < 40%) led to decreased mortality. ​​ Systematic review and meta-analysis (10 studies, 4147 patients).



Corticosteroids​​ Associated with Improved Outcomes in Severe Community-Acquired Pneumonia

June 22nd, Annals of Emergency Medicine:​​ Corticosteroids appear to reduce morbidity and mortality in adults with severe community-acquired pneumonia (CAP). ​​ In pediatric patients and nonsevere CAP, morbidity was improved but mortality was​​ unaffected. ​​ Systematic review and meta-analysis (17 RCTs, 2,264 patients).​​ 




LABA​​ + Inhaled Glucocorticoid As Safe as Inhaled Glucocorticoid Alone for Asthma

June 28th, NEJM:​​ Combination long-acting beta agonist and inhaled glucocorticoid therapy was associated with as many adverse asthma-related events as inhaled glucocorticoid therapy alone in patients with asthma,​​ and reduced the number of severe asthma exacerbations. ​​ Combined RCTs (4​​ trials, 36,010 patients)



by​​ pharmacologyreview