Pharmacology News Digest, July 15th



This week’s clinical pharmacology update includes​​ an​​ expanded​​ FDA​​ indication​​ for​​ a​​ prostate cancer drug,​​ fenfluramine​​ resurfaces for rare epilepsy,​​ PCSK9 inhibitors​​ may not decrease inflammation, and​​ multivitamins​​ appear to​​ have no impact on​​ cardiovascular risk.

-​​ July 15th, 2018










~  ​​ ​​​​ 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.

Link to​​ GSK​​ Press Release​​ 



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.

Link to FDA Press Announcement




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.

Link to Medscape Coverage,​​ Link to FDA Label




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.

Link to FDA Press Release




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.

Link to FDA Press Release



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.

Link to FDA Fact Sheet




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).

Link to Article



~  ​​ ​​​​ 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).

Link to Medscape​​ Coverage



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).

Link to Medscape Coverage




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).

Link to Article



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).

Link to Company News Release


~  ​​ ​​​​ 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).​​ 

Link to​​ First​​ Article,​​ Link to Second Article



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).

Link to Article



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)

Link to article



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).

Link to Article



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).

Link to Article



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).

Link to article



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).

Link to article



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).

Link to Medscape coverage



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).

Link to Article



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).

Link to Article



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).

Link to first article,​​ Link to second article



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).

Link to article




~  ​​ ​​​​ 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.)

Link to study



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).

Link to Article



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).

Link to Article



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).

Link to article







by​​ pharmacologyreview