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.
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.
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.
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.
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).
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.
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).
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).
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.
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).