~ Pharmacology News ~
FDA Panel Endorses Efficacy and Safety of Tafenoquine, New Antimalarial Drug
July 12th: The US FDA has voted 13-0 that one of the first new antimalarial drugs in decades, the hypnozoite-targeting tafenoquine, has demonstrated significant efficacy, and 12-1 that there is adequate evidence of its safety, for the prevention of relapse of Plasmodium vivax malaria in patients 16 years and older.
FDA Issues Recall on Some Valsartan Products Due to Carcinogenic Contaminant
July 13th: The US FDA has issued a recall of valsartan products from Major Pharmaceuticals, Solco Healthcare and Teva Pharmaceuticals, and Valsartan/HCTZ combination products from Solco Healthcare and Teva. The presence of the suspected human carcinogen N-nitrosodimethylamine (NDMA) prompted the recall.
FDA Expands Approval of Enzalutamide for Earlier-Stage Prostate Cancer
July 13th: The United States FDA has expanded the indication of enzalutamide (Xtandi™, an androgen receptor antagonist) to include castration-resistant non-metastatic prostate cancer.
FDA Approves Tecovirimat, First Drug to Treat Smallpox
July 13th: The US FDA has approved tecovirimat (an inhibitor of the p37 orthopoxvirus envelope protein) for the treatment of smallpox virus infection. Smallpox has been eradicated from global circulation, but concerns remain that it could be employed as a biological weapon.
FDA Enhances Fluoroquinolone Side-Effect Warnings
July 10th: The FDA has updated fluoroquinolone antibiotic (DNA gyrase/topoisomerase IV inhibitors) label requirements to include a clearer warning about mental health adverse effects (separately listed from other adverse neurological effects), as well as explicitly reference the risk of hypoglycemic coma in diabetic patients.
Room-Temperature Stable Plasma Product, “French FDP”, Approved for U.S. Military Use
July 9th: The U.S. FDA has announced an emergency use authorization for the treatment of acute hemorrhage in a military setting with Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma (French FDP) when frozen or fresh plasma is not available. French FDP, unlike other forms of plasma, may be stored at a range of ambient temperatures for up to two years.
1 in 4 Surgical Patients Report Pre-Operative Opioid Use
July 11, JAMA Surgery: In a study of surgical patients presenting at a large Midwestern academic center, 23.1% reported pre-operative opioid use. Cross-sectional observational (34,186 patients).
~ Clinical Trials: New Horizons ~
Rimegepant Better than Placebo in Acute Headache
June 30th, CIHS Meeting: An oral CGRP antagonist, rimegepant, eliminated pain in 20% of acute migraine patients and photosensitivity in 38%, about twice as many as those who received placebo. RCT (1,186 patients).
Sumatriptan Low-Dose Autoinjector Better Tolerated Than Higher Dose
June 30th, AHS Meeting: 3 mg subcutaneous autoinjector-delivered sumatriptan, a 5HT1B/D agonist, has demonstrated reasonable safety and efficacy and is better tolerated than the commonly used 6 mg autoinjected dose. RCT (248 patients).
IV Ketamine Associated with Favorable Outcomes in ICU Patients Experiencing Ethanol Withdrawal
July 13th, Journal CCM: A small study has found that adjunctive intravenous ketamine (an NMDA receptor antagonist), in addition to guideline benzodiazepine/barbiturate therapy reduced likelihood of intubation and ICU length of stay in intensive care patients with DSM-V delirium tremens. RCT (63 patients).
Fenfluramine, Discontinued Weight Loss Drug, Shows Efficacy in Dravet Syndrome
July 12th, Zogenix News Release: Fenfluramine, a serotonin reuptake inhibitor formerly marketed as a weight-loss drug, has demonstrated a 62.7% decrease in seizure frequency in children with Dravet syndrome compared with 1.2% in the placebo group. RCT (87 patients).
~ Clinical Research ~
Topical Sirolimus Effective in Treating Angiofibromas in Tuberous Sclerosis
July 11th, JAMA Dermatology: Sirolimus (an mTOR inhibitor/immunosuppressant also called rapamycin) has demonstrated efficacy in treating facial angiofibromas in patients with tuberous sclerosis complex, with 85% of pediatric and 41% of adult patients experiencing positive responses after 12 weeks of treatment, compared with 0% of placebo patients. A second trial published in the same JAMA Dermatology issue found similar results. RCT (62 participants).
Oral Cephalexin as Good as IV Cephazolin + Probenecid for Skin and Soft Tissue Infections
July 13th, Emergency Medicine Journal: Oral cephalexin (1st-generation cephalosporin) was found to be non-inferior to intravenous cefazolin (also, 1st-gen) + probenecid (OAT & renal drug excretion inhibitor) as safe as QID oral cephalexin in the treatment of mild-to-moderate skin and soft tissue infections presenting to the ED. RCT (206 patients).
Testosterone Prescriptions Down More than 50% Since Thromboembolism Warnings in 2013
July 10th, JAMA: Testosterone prescriptions appear to have fallen by between 53% and 69% in men ages 30 and older between 2013, when the FDA issued warnings that testosterone therapy increased risk of myocardial infarction and stroke. Observational retrospective (9,962,538 patient records in commercial insurance database)
Rituximab Associated with Lower Risk of Follicular Lymphoma Transforming to Aggressive Form
July 4th, The Lancet Hematology: Rituximab, an anti-CD20 monoclonal antibody, decreases the risk of follicular lymphoma transforming into aggressive cancer by 27%. Retrospective pooled analysis (8,116 patients).
Follicular Lymphoma Outcomes Improved by Systemic Immunochemotherapy
July 5th, JCO: Addition of six cycles of cyclophosphamide, vincristine, and prednisolone to involved-field radiotherapy (IFRT) in patients with stage I/stage II follicular lymphoma resulted in more patients with 10-year progression-free survival compared with IFTR alone. RCT (150 patients).
Sacubitril/Valsartan Improves Blood Pressure and Cardiac Biomarkers Relative to Irbesartan in CKD Patients
July 12th, Circulation: Sacubitril (a neprilysin inhibitor)/valsartan combination therapy demonstrated similar effects on eGFR and albuminuria compared to irbesartan therapy (an angiotensin II receptor blocker). Patients taking the combination drug were observed to have lower blood pressure and decreased N-terminal pro-BNP and troponin I compared to those assigned to irbesartan. RCT (207 patients).
ACEI/ARB Lower Risk of Atrial Fibrillation in Hypertrophic Cardiomyopathy
July 13th, Journal Heart: ACE Inhibitor and angiotensin II receptor blockers both the risk of new-onset atrial fibrillation by 44% in patients with hypertrophic cardiomyopathy. Observational retrospective (18,266 patients).
Liraglutide Shows Promise in Decreasing HBA1c and Blood Pressure in Type 1 Diabetes
June 24th, ADA Meeting: Liraglutide, a GLP-1 agonist currently approved for treating type 2 diabetes, has demonstrated efficacy in a small cohort of type 1 diabetes, patients, lowering HbA1c by 0.05% after 52 weeks of therapy and blood pressure by 9 mmHg. RCT (46 patients).
Penicillin Allergy Documentation Associated with Increased Risk of MRSA and C. Difficile Infections
June 27th, BMJ: Patients with documented penicillin allergies were 69% and 26% more likely to develop MRSA or C. Difficile infections, respectively, during a 6 year follow-up period. Retrospective observational (301,399 patients).
HBV Antiviral Tenofovir Alafenamide Shows Decreased Bone Loss Compared to Tenofovir Disoproxil
June 19th, Journal CGH: HBV antiviral tenofovir disoproxil fumarate (a reverse transcriptase inhibitor) results in greater bone loss after two years than its pro-drug form, tenofovir alafenamide fumarate. RCT (1,298 patients).
PCSK9 Inhibitor + Statin Therapy Does Not Decrease Levels of Inflammatory Marker
July 10th, Circulation: Post-hoc analysis of the FOURIER and SPIRE-1/SPIRE-2 trials demonstrated no change in high-sensitivity C-reactive protein levels in patients receiving evolocumab/statin (FOURIER) or bococizumab/statin (SPIRE) therapy. Bococizumab development was discontinued in 2016 due to adverse effects and long-term efficacy. Post-hoc analysis of FOURIER RCT (27, 564 patients) and SPIRE RCTs (9,738 patients).
NSAIDs + Oral Anticoagulants in Atrial Fibrillation Increases Bleeding and Stroke Risk
July 9th, JACC: Addition of NSAID therapy to oral anticoagulation with dabigatran etexilate or warfarin resulted a 68% increased risk of major bleeding and 50% increased risk of stroke or systemic embolism in patients with atrial fibrillation. Post-hoc analysis of RE-LY RCT (18,113 patients).
~ Reviews ~
Vegetarian Diets Improve Metabolic Factors in Patients with Diabetes
June 6th, JCN: Vegetarian diets appear to improve glycemic control, lower LDL-C, and decrease body weight and adiposity compared with non-vegetarian diets. Meta-analysis (9 RCTs, 664 participants.)
Multivitamin Use Not Associated with Improved Cardiovascular Outcomes
July 10th, Circulation: A review has found no correlation between daily multivitamin use and cardiovascular disease outcomes. 18 prospective observational and RCTs, (2,019,862 particpants).
Aspirin Primary Prevention of Cardiovascular Events Depends on Dose, Body Weight
July 12, The Lancet: Low-dose (75-100mg) aspirin was effective in reducing cardiovascular event rates only in patients weighing less than 70 kg. In patients weighing more than 70 kg, only higher doses of aspirin (≥ 325 mg) lowered cardiovascular event rate, with lower doses actually increasing the case fatality of the first cardiovascularevent. Systematic review and meta-analysis (10 RCTs, 110,279 participants).
Antibiotics Appear to Be Effective in Children with MDR-Tuberculosis
July 11th, PLOS Medicine: Children with multi-drug resistant tuberculosis (MDR-TB) were effectively treated with high-dose isoniazid and second-line injectable agents, with a 78% disease resolution rate. Therapy was significantly less effective in children with MDR-TB + untreated HIV, and earlier literature has shown lower treatment efficacy in adults with MDR-TB. Systematic review and meta-analysis (28 studies, 975 patients).