Pharmacology News Digest, September 4th, 2018


This week in clinical pharmacology: ​​ 


The FDA approves​​ eravacycline​​ for abdominal infections and​​ doravirine​​ for HIV. ​​ Low-dose​​ rivaroxaban​​ does not lower cardiovascular risk in HF​​ without atrial fibrillation,​​ tafamidis​​ demonstrates efficacy in transthyretin amyloidosis, and​​ brexanolone​​ shows promise in post-partum depression.


-​​ September 4th, 2018




FDA Rejects​​ Volanesorsen​​ for Familial Chylomicronemia

August 28th, FDA:​​ The US FDA has rejected volanesorsen (Waylivra) for familial chylomicronemia despite a recent​​ advisory panel ruling in favor of the drug. ​​ 



Endocrinology/Infectious Diseases

FDA Warns About Genital Infection Risk Associated with​​ SGLT2 Inhibitors

August​​ 29th, FDA:​​ The US FDA has issued a warning about a rare but serious genital infection, Fournier’s gangrene associated with antidiabetic SGLT2 inhibitor medications. ​​ 



Infectious Diseases

FDA Approves Novel Antibiotic​​ Eravacycline​​ for Intra-Abdominal Infections

August 28th, FDA:​​ The US FDA has approved the fluorocycline (a tetracycline derivative) antibiotic eravacycline for complicated intra-abdominal infections​​ in individuals 18 years and older.​​ 



Infectious Diseases

FDA Approves Two New​​ Doravirine-Based HIV Antiretroviral Therapies

August 31st, FDA:​​ The US FDA has​​ approved doravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV in combination with other​​ antiretrovirals (Pifeltro) and in a fixed dose combination with lamivudine and tenofovir disoproxil fumarate (Delstrigo). ​​ 




FDA Approves New​​ Factor VIII​​ Product for Hemophilia

August 30th, Bayer: The US FDA has approved a recombinant, pegylated form of factor VIII (Jivi) for​​ maintenance and on-demand treatment of hemophilia A in adults 12 and older. ​​ This formulation allows flexible dosing according to individualized patient requirements. ​​ 




FDA Expands​​ Ibrutinib​​ Indication to Include Combo Therapy with Rituximab

August 27th, Janssen:​​ The FDA has expanded the indication of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, previously approved as monotherapy for Waldenstrom’s macroglobulinemia, to include combination therapy with rituximab for the same disease. ​​ 




FDA Rejects​​ Dasotraline, ADHD Treatment Candidate

August 31st, FDA:​​ The US FDA has rejected the new drug application for dasotraline, a dopamine-norepinephrine reuptake inhibitor (NDRI) for the treatment of ADHD, citing safety and efficacy concerns. ​​ 



Public Health

FDA Does Not Support​​ Coffee​​ Cancer Warning

August 30th, FDA:​​ The FDA has issued a statement that supports exempting coffee being labeled as​​ carcinogenic under California’s cancer warning law. ​​ 





Aspirin​​ Lowers Vascular Event Rates, Increases Bleed Risk in Patients with Diabetes

August 26th, NEJM: Patients with diabetes mellitus and no history of cardiovascular​​ disease who were treated with 100 mg of aspirin daily had fewer cardiovascular events but had an increased risk of serious bleeding compared with patients who received placebo. ​​ RCT (15,480 participants).




Ticagrelor​​ Not Superior to Dual Antiplatelet Therapy After Stent

August 27th, The Lancet:​​ In patients with coronary artery disease who received a drug-eluting stent, ticagrelor + aspirin for 1 month followed by​​ ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy (followed by 12 months of aspirin alone) in the prevention of all-cause mortality or new Q-wave myocardial infarction. ​​ RCT, GLOBAL LEADERS clinical trial (15,968 participants). ​​​​ 




Low-Dose​​ Rivaroxaban​​ Does Not Lower CV Risk in HF without Atrial Fibrillation

August 27th, NEJM:​​ 2.5 mg twice-daily rivaroxaban was not associated with improved cardiovascular outcomes or mortality compared with placebo in patients with chronic heart failure and coronary artery disease in the absence atrial fibrillation. ​​ RCT (5,022 patients). ​​ 




Tafamidis​​ Shows Efficacy in Transthyretin Amyloidosis

August 27th, NEJM:​​ Tafamidis (Vyndaqel), a transthyretin stabilizer, was associated with a 30% reduction in mortality​​ after 30 months compared with placebo in patients with transthyretin amyloid cardiomyopathy. ​​ RCT, Phase III double-blind (441 patients). ​​​​ 




Spironolactone​​ Associated with Improved Diastolic Function, No Change in Mortality in HFpEF

August 31st, Medicine:​​ Patients with heart failure with preserved ejection fraction (HFpEF) who received spironolactone were found to have improved diastolic function compared with those treated with placebo. ​​ No change was observed in all-cause mortality or hospitalization. ​​ Systematic review and meta-analysis (7 RCTs, 4147 patients). ​​​​ 



Infectious Diseases/Cardiology

Switching to​​ Oral Antibiotics​​ in Endocarditis as Effective as Continuing Intravenous Therapy

August 28th, NEJM:​​ In patients with left-sided endocarditis, switching to oral​​ antibiotics after 10 days was as effective as continuing intravenous antibiotics for 2-3 weeks. ​​ RCT (400 patients). ​​​​ 




Melatonin​​ Hastens Sleep​​ Onset by a Half-Hour

June 18th, PLOS Medicine:​​ In patients with delayed melatonin rhythm, sleep onset occurred a median of 34 minutes earlier in patients who received melatonin compared with those who received placebo. ​​ RCT (307 participants). ​​​​ 




Small Study Suggests Risks of​​ Zolpidem​​ Use at High Altitude

August 30th, Journal Sleep:​​ Study participants who were not acclimated to high​​ altitude settings who used​​ zolpidem at 1,000 meters elevation were found to have a higher risk of acute mountain sickness and daytime sleepiness compared to those who did not use the drug. ​​ RCT (22 participants). ​​ 




Emicizumab, Factor VIII Mimicking Antibody, Shows Efficacy in Hemophilia A

August 30th, NEJM: ​​​​ Weekly and biweekly subcutaneous injections emicizumab, a monoclonal antibody that mimics Factor VIII action by crosslinking Factor​​ IX and X resulted in a 97% lower bleeding than placebo injections. ​​ RCT, HAVEN III trial (152 patients). ​​​​ 




Terlipressin​​ More Effective than Norepinephrine in Hepatorenal Syndrome + Acute on Chronic Liver Failure

August 3rd, Hepatology:​​ Patients with hepatorenal syndrome​​ and​​ acute-on-chronic liver failure who received intravenous terlipressin, a vasopressin analogue, experienced improved survival and decreased need for renal replacement therapy compared with those who received intravenous norepinephrine. ​​ RCT, open-label (120 patients). ​​ 




Febuxostat​​ May Protect​​ Kidneys, Increase Cardiovascular Risk in Hyperuricemia

August 29th, ESC 2018 Meeting:​​ Febuxostat, a xanthine oxidase inhibitor, was associated with improved renal outcomes compared with placebo in patients with hyperuricemia, but may also increase risk for​​ cardiovascular events. ​​ RCT (1070 patients). ​​​​ 




Brexanolone​​ Demonstrates Efficacy in Post-Partum Depression

August 31st, The Lancet: Patients with​​ post-partum depression who received a single intravenous dose of brexanolone, a novel GABA-A receptor modulator, experienced significant reductions in depressive symptoms at 60 hours compared with patients who received placebo. ​​ Two RCTs, double blind (246​​ patients). ​​​​ 




Bevacizumab, Ranibizumab​​ Associated with Lower Endophthalmitis Risk than Aflibercept

August 30th, Clinical Opthalmology:​​ A retrospective comparison of intravitreal VEGF inhibitors found that bevacizumab and ranibizumab were associated with lower rates of endophthalmitis than aflibercept in patients with neovascular (wet) age-related macular degeneration (AMD). ​​ Retrospective observational (156,594 patients). ​​​​ 




Cannabinoids​​ Detectable in Breastmilk of Mothers Who Used Marijuana

August 31st, Pediatrics: ​​​​ ∆9-THC, the primary psychoactive ingredient in marijuana, was detectable in 63% of breast milk samples of women who used marijuana within the preceding 6 days. ​​ 50 participants. ​​ 



Pediatrics/Infectious Diseases

Fewer Neonatal​​ Antibiotic Prescriptions​​ Following External Stewardship Efforts

August 31st, Pediatrics: Rates of neonatal antibiotic use in neonatal intensive care units declined at a 70% greater rate following enrollment in externally-organized antibiotic stewardship programs compared with hospitals with internally-organized or no antibiotic stewardship​​ efforts. ​​ Retrospective cohort (>54,000 neonates, >130 NICUs). ​​​​ 



Pediatrics/Public Health

1 in 5 US Children Used Prescription​​ Medications in 2013

August 31st, Pediatrics:​​ 19.8% of children in the United States used at least 1 prescriptions medication between 2013 and 2014. ​​ 8.2% of children who used several medications were found to be at risk for drug-drug interactons. ​​ Descriptive analysis, NHANES database (23,152 participants). ​​ 



Pulmonology & Critical Care

Simvastatin​​ May be Effective in ARDS Hyperinflammatory Subtype

August 2nd,​​ The Lancet Respiratory Medicine:​​ Patients with a hyperinflammatory subtype of acute respiratory distress syndrome experienced greater 28-day survival when treated with simvastatin than those treated with placebo. ​​ HARP-2 RCT secondary analysis (539 patients). ​​ 




Surgery & Anesthesia

Short-Term​​ Dexamethasone​​ Therapy Not Associated with Higher Infection Risk After Surgery

August 28th,​​ Cochrane:​​ A single dose of dexamethasone was not associated with increased risk of infection after surgery. ​​ It is unclear whether it delays wound healing. ​​ Meta-analysis and systematic review (27 studies, 4,931 patients). ​​​​ 



Surgery & Anesthesia

Intravenous​​ Diclofenac​​ Comparable to Oral NSAIDS for Post-Surgical Pain

August 28th, Cochrane: Single-dose intravenous diclofenac was found to have similar efficacy in post-surgical pain relief when compared with other, orally administered non-steroidal anti-inflammatory drugs.​​ Meta-analysis and systematic review (8 studies, 1,756 patients). ​​ 





Surgery & Anesthesia

Dexamethasone​​ Associated with Decreased Pain After Knee Replacement

August 31st, Medicine:​​ Patients​​ undergoing total knee arthroplasty who received post-surgical dexamethasone experienced less pain than those who received placebo. ​​ Systematic review and meta-analysis (6 RCTs). ​​​​ 



Surgery & Anesthesia

Ursodeoxycholic Acid + Glucocorticoids​​ May Improve Outcomes Following Kasai Surgery

August 31st, Medicine:​​ Patients with biliary atresia undergoing hepatoportoenterostomy (Kasai procedure) were found to have lower rates of post-operative​​ jaundice compared to patients who received placebo or other interventions. ​​ Systematic review and meta-analysis (8 mixed-type studies, 530 patients). ​​​​ 



Surgery & Anesthesia

Midazolam​​ Premedication Not Associated Decreased Anxiety

August 31st, Medicine:​​ Patients undergoing surgery who received midazolam premedication prior to induction of anesthesia did not report lower levels of anxiety 30 minutes after receiving the drug, but did show higher levels of analgesia and hemodynamic stability compared with patients who did not receive midazolam. ​​ RCT, single-blind (128 patients). ​​​​ 



Surgery & Anesthesia

Epidural Anesthetics​​ Slightly More Effective than Patient-Administered Intravenous Opioids

August 30th, Cochrane:​​ Patients undergoing intra-abdominal surgery who received epidural anesthesia (local anesthetics and opioids) experienced marginally better pain control compared with patients who used patient-administered intravenous opioids (IVPCA). ​​ Systematic review and meta-analysis (32 studies, 1716 patients). ​​​​ 




Baseline Corticosteroid Use Associated with Worse Outcomes on​​ Anti-PD-1L​​ Therapies

August 30th, Journal of Clinical Oncology:​​ Baseline prednisone equivalent use of > 10 mg​​ daily was associated with worse outcomes in patients with non-small cell lung cancer treated with single-agent PD-(L)1 inhibitors. ​​ Observational retrospective (640 patients). ​​​​ 




Continuing​​ Bevacizumab​​ After Disease Progression Not Effective in NSCLC

August 30th, JAMA Oncology: ​​​​ Patients with non-small cell lung cancer (NSCLC) who had previously received bevacizumab (a VEGF inhibitor) therapy and who​​ continued to receive bevacizumab plus standard-of-care after disease progression did not experience survival benefit compared with those who received standard-of-care alone following disease progression. ​​ RCT, AvaALL Phase IIIb (485 patients). ​​​​ 











Multivitamin & Lipid-based​​ Prenatal Supplements​​ Associated with Similar Outcomes

August 31st, Cochrane:​​ Prenatal lipid-based and multiple micronutrient supplements (i.e.,​​ multivitamin) nutritional supplements were associated with improved newborn length and weight compared with iron-folate supplements. ​​ Multiple micronutrient and iron-folate supplements were, however, were found to have a lower risk of maternal anemia than​​ lipid-based supplementation.​​ Systematic review and meta-analysis (4 studies, 8018 women). ​​​​ 



Surgery and Anesthesia

Immunonutrition​​ Associated with Decreased Risk of Fistula After Head and Neck Surgery

August 30th, Cochrane: Patients undergoing head and neck surgery who received “immunonutrition” (amino acids, omega-3 fatty acids or nucleotide-enriched nutrition) were less likely to experience post-surgical pharyngocutaneous fistula than patients who received standard nutrition. ​​ Other outcomes did not appear to vary between the standard and nutritionally supplemented groups. ​​ Systematic review and meta-analysis (1099 participants).​​ 




Lactoferrin​​ Supplementation Could Improve Outcomes in Premature Infants

August 31st, Medicine:​​ Premature infants who received prophylactic lactoferrin were observed to have a lower risk of late-onset sepsis, necrotizing enterocolitis, and infection-related mortality compared to those who did not receive lactoferrin. ​​ Systematic review and meta-analysis (9 RCTs, 1834 patients). ​​​​ 



Public Health

Sharp Decline in​​ Opioid​​ Prescriptions Associated with 2016 CDC Guidelines

August 28th, Annals of Internal Medicine:​​ Opioid prescription rates, which have declined by​​ 3.56% per month since January 2012, declined more sharply (by 8%) following changes in the CDC guidelines for opioid prescription in early 2016. ​​ 



Public Health/Psychiatry

Prazosin​​ Associated with Decreased Drinking in Alcohol Use Disorder

August 29th, American Journal of Psychiatry:​​ Patients with alcohol use disorder who received three-times daily oral prazosin, an alpha-adrenergic antagonist, consumed​​ less alcohol than those who received placebo. ​​ RCT, double blind (80 participants). ​​ 





by pharmacologyreview