Pharmacology News Digest, August 20th, 2018



This week in​​ clinical pharmacology news: ​​ FDA approves​​ cyclosporine​​ for​​ dry eye,​​ nivolumab​​ for​​ small cell lung cancer, and​​ lenvatinib​​ for hepatocellular carcinoma. ​​​​ Talazoparib​​ shows efficacy in​​ BRCA+ breast cancer,​​ fasinumab​​ decreases osteoarthritis pain, and​​ thiamine lowers mortality in septic shock.

-​​ August​​ 20th, 2018









~  ​​ ​​​​ Pharmacology News ​​ ~

FDA Approves​​ Cyclosporine​​ Drops for Dry Eye

August 17th, Medscape:​​ The US FDA has approved a cyclosporine A (calcineurin inhibitor used for immunosuppression) solution for the treatment of keratoconjunctivitis sicca.​​ 



FDA Expands​​ Ivacaftor​​ to Include Children > 12 Months with Cystic Fibrosis

August 15th, Vertex Pharmaceuticals:​​ The FDA has expanded the indication of ivacaftor (Kalydeco) monotherapy to include children as young as 12 months with cystic fibrosis and a CFTR mutation response to ivacaftor. ​​ 



FDA Approves​​ Nivolumab​​ for Treatment of Refractory Small Cell Lung Cancer

August 17th, FDA:​​ The US FDA has approved intravenous nivolumab, a PD-1 checkpoint inhibitor, for the treatment of metastatic small cell lung cancer that has progressed on both first-line platinum-based chemotherapy and on a second-line agent. ​​ 



FDA Expands Indication of​​ Lenvatinib​​ to Include Liver Cancer

August 16th, FDA: The FDA has expanded the indication of lenvatinib, a VEGF receptor inhibitor previously approved for the treatment of renal cell carcinoma and thyroid cancer, to include first-line treatment of unresectable hepatocellular carcinoma. ​​ 



1/10 Surgery or Endoscopy Patients Experience Adverse​​ Opioid​​ Related Events

August 16th, JAMA Surgery:​​ 10.6% of patients undergoing hospital-based surgical or endoscopic procedures were found to have a had at least one opioid-related adverse drug event (ORADE). ​​ Patients who experienced an ORADE were more likely to have worse outcomes, including higher inpatient mortality, longer length of stay, and a higher likelihood of readmission within 30 days. Observational retrospective (135,379 patients). ​​​​ 



AHA Recommends​​ Low-Calorie Sweetened Beverages​​ in Some Adults, Not Children

July 30th, Circulation:​​ The American Heart Association (AHA) issued a recommendation that low-calorie sweetened beverages​​ should​​ be considered in adults who consume large volumes of sugar-sweetened beverages. ​​ The organization advises against consumption of these beverages by children. ​​ 



Addiction Meds​​ Associated with Decreased Suicidality, Crime, Overdose

August 2nd, American Journal of Psychiatry: Individuals with alcohol or opioid use disorder who received naltrexone were​​ less likely to experience accidental overdose​​ while on treatment​​ than during periods without treatment. ​​ Buprenorphine therapy was associated with decreased arrest rates and accidental overdose, and methadone was associated with decreased risk of suicide. ​​ Patients who received acamprosate therapy were not observed to have altered risk of suicide, overdose or arrest while receiving treatment compared to periods when they​​ were​​ not receiving treatment.​​ ​​ Observational retrospective (21,218 individuals).



DDT Exposure​​ Associated with Increased Risk of Autism

August 16th, American Journal of Psychiatry:​​ High maternal serum levels of​​ p,p-DDE, a metabolite of the insecticide DDT, were associated with increased risk of autism among offspring (odds ratio in 75th​​ percentile of DDE levels: 1.32). ​​ Observational retrospective (778 case-control pairs). ​​​​ 


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

PARP Inhibitor​​ Talazoparib​​ Extends Progression-Free Survival in BRCA+ Breast Cancer

August 15th, NEJM:​​ Patients with advanced breast cancer and germline BRCA1/2 mutations were observed to have a 3 month longer progression-free survival when treated with the poly(adenosine diphosphate–ribose) inhibitor talazoparib as those treated with standard single-agent therapy (capecitabine, eribulin, gemcitabine, or vinorelbine). ​​ RCT (431 patients).​​ 



Anti-CD4 Antibody​​ Ibalizumab​​ Demonstrates Efficacy Against Drug-Resistant HIV

August 16th, NEJM:​​ In patients with multi-drug resistant HIV, the humanized monoclonal IgG4 anti-CD4 antibody was associated with a significant viral load reduction in 83% of​​ patients. ​​ Open-label Phase III, not controlled (31 patients completed trial). ​​​​ 



Botulinum Toxin​​ Improves Urinary Incontinence in Multiple Sclerosis

August 14th, Journal Neurology:​​ Intradetrusor injections of onabotulinumtoxinA in patients with multiple sclerosis were​​ found to​​ reduce urinary incontinence (-3.3 fewer episodes per day) compared with placebo injections (-1.1 fewer episodes per day). ​​ RCT, double-blind phase III (144 patients). ​​​​ 



Fasinumab​​ Shows Efficacy in Osteoarthritis of Knee, Hip

August 16th, Teva/Regeneron:​​ Fasinumab, a monoclonal anti-nerve growth factor antibody, was associated with decreased pain in patients with osteoarthritis of the knee and hip, compared with placebo. ​​ RCT, Phase III (646 patients). ​​​​ 


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

Levetiracetam​​ Seizure Prophylaxis After Intracerebral Hemorrhage Associated with Worse Outcomes

August 16th, Critical Care Medicine:​​ Levetiracetam seizure prophylaxis in hospitalized patients with intracerebral hemorrhage was associated with decreased cognitive function-related quality of life, and​​ an​​ increased risk of lobar hematoma,​​ compared with​​ patients who received no seizure prophylaxis. ​​ Prospective observational (394 patients). ​​​​ 



Edoxaban​​ Associated with Lower Mortality Risk Than Warfarin in Korean Patients with Atrial Fibrillation

August 14th, JACC: ​​​​ In Korean patients with atrial fibrillation, edoxaban anticoagulation was associated with a 30% lower risk of stroke,​​ decreased​​ all-cause mortality, and a lower risk of major bleeding compared with warfarin. ​​ Observational (16,244 patients). ​​​​ 



Oral Steroids​​ Not Associated with Improved Hearing in Most Children with Otitis Media

August 18th, The Lancet:​​ Administration of oral prednisolone in children with acute otitis media was associated with improved hearing in 1 out of 14 patients after 5 weeks, with no overall effect on quality of life. ​​ RCT, OSTRICH trial (389 children). ​​​​ 



Very High and Low​​ Sodium Intake​​ Associated with Increased Risk of Stroke, Mortality

August 11th, The Lancet: ​​ In an epidemiological study in China, ​​ increased stroke risk was correlated with sodium intake​​ in individuals whose​​ sodium consumption was very high (>5g/day). ​​ Individuals in communities where salt intake was very low (<4 g/day) were also found to have an increased risk​​ of cardiovascular events. ​​ No correlation between salt intake and stroke risk was observed in the middle tertile (mean 4.7 g/day). ​​ Observational (95,767 pariticpants). ​​​​ 



Discontinuation of Mass​​ Azithromycin​​ Administration in Ethiopa Associated with ​​ Trachoma Rebound

August 14th, PLOS Medicine: ​​​​ Mass administration of azithromycin in Ethiopa for an additional 3 years​​ -​​ after an initial 4 year treatment period​​ -​​ led to sustained lower rates of ocular chlamydia trachomatis, but did not eliminate the disease. ​​ In subgroups where mass azithromycin was​​ discontinued, disease rates doubled over three years. ​​​​ TANA II trial, re-randomization of TANA I RCT (3,938 children). ​​​​ 



Radioactive Iodine​​ May Not Improve Outcomes in Recurrent Papillary Thyroid Cancer

August 15th, JAMA Surgery:​​ In patients undergoing​​ re-operation for persistent or recurrent papillary thyroid cancer, radioactive iodine therapy did not appear to improve mortality compared with patients who received re-operation alone. ​​ Observational retrospective (102 patients). ​​ 



Cetuximab + Radiation​​ Inferior to Standard Care in HPV+ Oropharyngeal Cancer

August 14th, NIH News Release:​​ Cetuximab, an EGFR inhibitor, + radiation was associated with worse overall and progression-free survival than the current standard of care, cisplatin + radiation, in patients with HPV+ oropharyngeal cancer. ​​ Interim analysis of Phase III RCT (987 patients). ​​​​ 



Fludrocortisone​​ Helps Normalize Sodium, Does Not Improve Outcomes in Tuberculous Meningitis

August 13th, JAMA Neurology:​​ Addition of oral fludrocortisone to oral and intravenous sodium​​ supplementation in patients with tuberculous meningitis and cerebral salt wasting was associated with earlier normalization of serum sodium levels, but was not​​ associated with​​ improved outcomes within 6 months. ​​ RCT (36 patients). ​​​​ 



Patients with​​ IBD​​ on​​ Anti-TNF​​ Therapy​​ Less Likely to Develop Parkinson’s​​ 

April 23rd/August​​ 13th, JAMA Neurology: ​​​​ Although patients with inflammatory bowel disease (IBD) are more likely to develop Parkinson’s than patients without IBD, individuals​​ with IBD​​ who are treated with anti-tumor necrosis factor​​ (anti-TNF) therapies are 78% less likely to develop the disease than patients with IBD who are not treated with anti-TNF drugs. ​​ Observational retrospective (144,018 patients). ​​ 



SGLT-2 Inhibitors​​ Associated with Increased Risk of Amputations

August 13th, JAMA Internal Medicine:​​ Patients with type II diabetes who received SGLT-2 inhibitor therapy were more likely than patients who used older antidiabetic drugs (e.g., sulfonylurea, metformin hydrochloride, or thiazolidinediones) to undergo lower extremity amputation. ​​ SGLT-2 use was not associated with a higher rate of amputation compared with​​ DPP-I and GLP-I inhibitor use. ​​ Observational retrospective (953,906 individuals). ​​ 



Benzodiazepine​​ Use Associated with Increased Risk for Alzheimer’s Disease

May 31st, Acta Psychiatra Scandinavica: ​​​​ Benzodiazepine use was associated with a 6% increased risk of Alzheimer’s disease in a Finnish population. ​​ Observational retrospective (353,581 participants). ​​ 



Thiamine​​ in Septic Shock Associated with Lower Mortality

June 18th, Journal CCM: ​​​​ Intravenous thiamine administration in ICU patients with septic shock was associated with​​ an​​ increased​​ likelihood of lactate clearance and a 33% decrease in 28-day mortality compared with patients who did not receive thiamine. ​​ Observational retrospective (269 patients). ​​​​ 



TNF Inhibitors​​ in Rheumatoid Arthritis​​ Not Associated with​​ Increased​​ Risk of Cancer Recurrence

August 14th, Annals of Internal Medicine:​​ Tumor necrosis factor inhibitors (TNFi) prescribed for​​ patients​​ with rheumatoid arthritis (RA) who had previously received a cancer diagnosis did not appear to increase the risk of cancer recurrence compared with RA patients who were not given TNFi. ​​ Observational (467 patients).​​ 



Fetal​​ Quetiapine​​ Exposure Not Associated with Increased Risk of Malformations

August 16th, American Journal of Psychiatry: ​​​​ Maternal first-trimester exposure to quetiapine​​ was​​ not associated with​​ an​​ increased risk of fetal malformations relative to unexposed patients.​​ ​​ Observational prospective (357 eligible participants). ​​ 


Remifentanil​​ More Effective Than Pethidine in Reducing Epidural Use During Delivery

August 13th, The Lancet:​​ Intravenous remifentanil, a short-acting opioid, decreased the number of epidural conversions during labor and delivery by 52% relative to intramuscular pethidine (meperidine, Demerol), a commonly used opioid for labor and delivery anesthesia in the UK. ​​ RCT (201 patients). ​​​​ 



Skepticism, Stigma Top Barriers to​​ Alcohol Use Disorder​​ Treatment

August 17th, Journal of General Internal Medicine: ​​​​ Among patients with alcohol use disorder, 21% reported wanting treatment while <15% received treatment. ​​ Among those who did not receive treatment, nearly half reported skepticism about efficacy and concerns about stigma as barriers to pursuing treatment. ​​ Observational, survey (5547 respondents, 555 with alcohol use disorder). ​​​​ 


~  ​​ ​​​​ Reviews  ​​ ​​​​ ~


Corticosteroids​​ May Decrease Mortality in Sepsis

August 16th, Critical Care Medicine:​​ Critically ill patients with sepsis​​ who received intravenous corticosteroids​​ were found to have a lower risk of death (relative risk 0.93) in the short term (28-31 days), but had a 16% higher rate of hyperglycemia and​​ an​​ increased risk of neuromuscular weakness. ​​ Systematic review and meta-analysis (42 RCTs, 10,194 patients). ​​​​ 




Higher-Dose​​ Rivaroxaban​​ Associated with Increased Risk of Intracranial Hemorrhage

August 13th, JAMA Neurology:​​ Patients who received 15-20 mg daily doses of rivaroxaban, a non-vitamin K antagonist oral anticoagulant, for stroke prevention were more likely to develop intracranial hemorrhage than patients who used only aspirin, a lower​​ (10 mg)​​ daily dose of rivaroxaban, or 5 mg of apixaban. ​​ Systematic review and meta-analysis (5 RCTs, 39,398 patients).​​ 



Vitamin D​​ Only Dietary Supplement At This Time​​ with Clear​​ Benefit in Multiple Sclerosis

April 23rd/August​​ 13th, JAMA Neurology: ​​ Although large trials of other dietary modifications and supplements (e.g., biotin) are currently being conducted, current data​​ supports​​ only vitamin D for routine supplementation in patients with multiple sclerosis. ​​ Literature review. ​​ 




Both Low and High Intake of​​ Carbohydrates​​ Associated with Increased Mortality

August 16th, The Lancet Public Health: ​​ In a prospective cohort study and meta-analysis, individuals who report both low carbohydrate intake (<40% of energy derived from carbohydrates) and high carbohydrate intake (>70% of calories derived from carbs) had a higher 25-year mortality than those who reported 50-55% of their energy as coming from carbohydrate sources. ​​ Prospective cohort study (15,428 participants) and meta-analysis (432,179​​ participants). ​​​​ 




by​​ pharmacologyreview