Pharmacology News Digest, August 5th, 2018



This​​ week in clinical pharmacology news:​​ ​​ the​​ FDA approves​​ iobenguane I-131​​ for​​ adrenal​​ tumors,​​ lusotrombopag​​ for thrombocytopenia.​​ ​​ New research​​ is out​​ on opioid prescribing patterns,​​ ranibizumab​​ improves​​ diabetic retinopathy,​​ budesonide​​ speeds recovery from rhinosinusitis, and​​ chocolate​​ is associated with decreased CVD risk.

-​​ August​​ 8th, 2018









~  ​​ ​​​​ Pharmacology News ​​ ~

FDA & Pfizer Warn Not to Use​​ Azithromycin​​ for Bronchiolitis Obliterans Following Bone Marrow Transplant

August 3rd, FDA: The FDA has issued a warning​​ against the​​ off-label​​ use of azithromycin to​​ prevent bronchiolitis obliterans syndrome (BOS) in patients with hematological/lymphatic cancers who recently received hematopoietic stem cell transplantation. ​​ The warning follows the discontinuation of a clinical trial funded by Pfizer evaluating the use of azithromycin for BOS prevention. ​​ 


Antihypertensive Medications​​ Associated with Lower Risk of Dementia

July 24, AAIC Meeting: Hypertensive individuals who used blood pressure medications of any class were found to have a 12% lower risk of all-cause dementia and 15% lower risk of Alzheimer’s Disease. ​​ Meta-analysis of observational prospective studies (31,090 participants). ​​​​ 



Opioids​​ for Low Back Pain More Likely​​ to Be Prescribed​​ Later in Day

July 2nd, Journal of General Internal Medicine: ​​​​ Physicians were 25% more likely to prescribe opioids in the 2nd​​ hour of a 4-hour clinic session compared to the first hour, and 60% more likely to prescribe opioids in the 4th​​ hour​​ compared with​​ the first hour. ​​ Observational (2772 patient visits). ​​​​ 



More than 1 in 4 First-Time​​ Heroin​​ Users Develop Dependency

August 1st, JAMA Psychiatry: ​​​​ 23-38% of first-time heroin users develop heroin dependency in first 1-12 months after​​ first use, according to an analysis of the National Survey on Drug Use and Health conducted between 2002 and 2016 in the United States. ​​ Observational (837,326 patients). ​​ 



Shorter Course of​​ Rifampin​​ As Good As 9 Months of Isoniazid​​ in Children with Latent Tuberculosis

August 2nd, NEJM:​​ 4 months of rifampin, a bacterial RNA polymerase inhibitor used in the treatment of active mycobacterium tuberculosis (TB) infection, was found to be non-inferior, with similar safety considerations, to the current standard 9 months of isoniazid (INH) therapy in children with​​ latent TB. ​​ Adherence to the drug regimen was higher in the rifampin group. ​​​​ RCT, open-label (844 participants).​​ 



Lowering​​ Default Pill Count in EMR Associated with Decreased Post-Op​​ Opioid​​ Prescription

July 18th, JAMA Surgery: Lowering the default electronic medical record pill count from 30 to 12 was associated with a reduction in the number of opioid pills prescribed to post-operative patients (effect size ~5 opioid pill reduction).  ​​​​ Pre-post interventional (1447 procedures). ​​ 



Iobenguane​​ I-131​​ Approved for the Treatment of Unresectable Pheochromocytomas, Paragangliomas

July 30th, FDA:​​ Iobenguane I-131 is the first systemic anticancer therapy approved for patients with metastatic or locally advanced unresectable pheochromocytoma or paraganglioma (adrenal gland tumors). ​​ Iobenguane is a norepinephrine analog that accumulates in adrenergically innervated tissues. ​​ When radiolabeled with Iodine-123, it​​ is used as a radiolabel​​ in​​ MIBG scaninng​​ for diagnosis of neuroendocrine tumors. ​​ When labeled with I-131, iobenguane accumulates in the adrenal medulla and causes local tissue destruction and tumor regression. ​​ 



FDA Approves​​ Once-Monthly​​ Risperidone​​ Subcutaneous Injection

July 30th, FDA:​​ The FDA has approved the first once-monthly subcutaneous injection of risperidone (Perseris), a 2nd​​ generation antipsychotic, for the treatment of schizophrenia. ​​ Other​​ formulations of risperidone require either daily oral medication adherence or biweekly intramuscular injections with a 3 week of oral risperidone bridge.​​ ​​ The FDA does not​​ require or recommend oral risperidone administration​​ alongside Perseris​​ except to establish drug tolerability.​​ 



More Physicians Using​​ Epidural​​ Methylprednisolone​​ Injections for Back Pain

July 31st, NYTimes:​​ Facing pressure to reduce opioid prescriptions, more physicians are using off-label epidural methylprednisolone injections (Depo-Medrol) despite risks of serious adverse effects including paralysis, stroke, and death. ​​ A number of countries, including Australia, France, Brazil and Canada, have already banned this use of Depo-Medrol. ​​ 



FDA Approves​​ TPO Agonist​​ Lusotrombopag​​ For Patients with Liver Disease Undergoing Procedure

July 31st, FDA:​​ The​​ US FDA has approved lusotrombopag, a small-molecule thrombopoietin (TPO) receptor agonist, for the treatment of thrombocytopenia in patients with​​ chronic​​ liver disease scheduled to undergo a procedure. ​​ Other TPO receptor agonists include eltrombopag, romiplostim and avatrombopag. ​​ 


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

Ranibizumab​​ Associated with Regression of​​ Diabetic Retinopathy

August 1st, Ophthalmology Retina:​​ Ranibizumab, an anti-VEGF monoclonal antibody, was associated with a three-fold lower risk of new proliferative events compared with sham treatments in patients with baseline diabetic retinopathy (DR). ​​ Patients receiving ranibizumab were also significantly more likely to experience clinically meaningful regression of DR compared with those receiving placebo. ​​ Post-hoc analysis of RIDE & RISE RCTs (740 patients). ​​ 


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


Folic Acid​​ Supplementation May Reduce Fetal Side Effects of Antiepileptic Medications

August 1st, Journal Neurology:​​ Folic acid supplementation​​ in women taking antiepileptic medications​​ starting​​ 4 weeks before conception until​​ the end of the first trimester was linked to​​ a​​ decreased​​ risk of later​​ childhood language delays. ​​ Observational retrospective (335 AED-exposed children). ​​ 



Antihypertensive​​ Combination Pill​​ Prescriptions Associated with Higher Risk of Redundant Prescriptions

August 2nd, Journal Heart: Patients who received fixed-dose combination (multiple medications provided in a single pill) antihypertensive prescriptions​​ experienced​​ an up to two-fold increased the risk of therapeutic duplication compared to those who received individual prescriptions. ​​ Therapeutic duplication was defined as the simultaneous prescription of multiple drugs from the same class (e.g., two ACE inhibitors). ​​ Retrospective observational (459,465 prescriptions). ​​​​ 



Idiopathic Inflammatory Myositis Associated with​​ Statin​​ Exposure

July 30th, JAMA Internal Medicine: ​​​​ Patients with histologically confirmed idiopathic inflammatory myositis (IIM)​​ were​​ 79%​​ more​​ likely to have had exposure to a​​ statin​​ medication​​ than control patients who did not have IIM. ​​ Observational, 1:3 case:control (883 patients).​​ 



Ramipril​​ Impact on Proteinuria Predicts Progression of CKD in Children

August 1st, American Society of Nephrology: ​​ In children with chronic kidney disease, the magnitude of proteinuria-lowering by ramipril (an angiotensin-converting enzyme inhibitor) was associated with progression of renal disease. ​​ Children who experienced a >60% reduction of proteinuria were 58% less likely to experience a 50% eGFR decline during 5 years of​​ observation compared with children who experienced a 30% decline in proteinuria. ​​ Observational (280 children).​​ 



Budesonide​​ Irrigation Improves Symptoms in Chronic Rhinosinusitis

July 19th, JAMA Otolaryngology:​​ Addition of budesonide, a synthetic glucocorticoid, to large-volume low-pressure saline sinus irrigation was associated a greater improvement in patient-reported chronic rhinosinusitis (CRS) symptoms (mean effect size ~20%) compared with saline irrigation alone. ​​ RCT (80 patients). ​​​​ 



Cannabis​​ Use Associated with Decreased Anxiety, Pain Following Diagnosis of Head and Neck Cancer​​ 

August​​ 2st,​​ JAMA​​ Otolaryngology:​​ Patients with recently​​ diagnosed​​ head and neck cancer (HNC) who were cannabis users reported 36% lower self-reported anxiety scores and 16% lower pain scores than patients with recent HNC diagnoses who did not use cannabis. ​​ Prospective observational (148 patients). ​​ 



Cannabis​​ Use Associated with Higher Likelihood of Adolescent Psychotic Symptoms

June 6th/August 1st, JAMA Psychiatry: Analysis of a survey study demonstrated a positive association between self-reported cannabis use and​​ the likelihood of experiencing​​ psychosis symptoms​​ in adolescents aged 13-16. ​​ Observational (3,966 participants). ​​ 



Opioids​​ for Chronic Pain Associated with Decreased Sexual Desire

July 2nd, Journal Pain: Individuals with chronic non-cancer pain (CNCP) who used​​ opioids were 81%​​ more likely to report​​ a​​ lack of or low sexual desire compared with​​ individuals with CNCP who did not use opioids. ​​ Observational cross-sectional survey (11,517 participants). ​​​​ 



Methadone​​ Therapy Engagement Associated with Lower Viral Loads in Individuals with HIV and Injection-Drug Use

July 25th, International AIDS Conference:​​ Individuals with HIV who use injection-drugs who​​ also​​ reported accessing methadone therapy were​​ 30% less likely to have viral loads above 1500 copies/mL than individuals who did not use methadone. ​​ Observational prospective (867 participants).​​ 



Methadone​​ Treatment Decreases Likelihood of Death in Patients with Criminal Convictions

July 31st, PLOS Med: ​​​​ Individuals with a history of criminal convictions who filled at least one methadone prescription between 1998 and 2015 were observed to have between 59-73% (depending on cause) lower risk of death during periods when​​ they were filling​​ methadone​​ prescriptions​​ compared with periods​​ when they were not taking methadone.​​ Observational retrospective (14,530 participants).



Drinking​​ Alcohol​​ While Breastfeeding Associated with Lower Cognitive Scores in Children

July 30th, Pediatrics: ​​​​ Exposure of infants to alcohol through breastmilk was associated with mildly decreased cognitive​​ performance​​ (Matrix Reasoning​​ evaluation) at age 6 and 7 compared with those who were not exposed to alcohol. ​​ No difference in​​ cognitive​​ scores was observed at age 10 and 11. ​​ Observational prospective (5107 infants). ​​​​ 



Both Excessive and Abstinent​​ Alcohol​​ Use Associated with Higher Dementia Risk

August 1nd, BMJ: Abstinence from alcohol intake in midlife was associated with a 47% higher risk of dementia compared with consumption of 1-14 units/week. ​​ For those drinking more than 14 units/week, for each 7-unit increase​​ in alcohol consumption​​ the risk of dementia increased by 17%. ​​ 14 United Kingdom alcohol units is equivalent to approximately 1.5 bottles of wine.​​ Prospective cohort, Whitehall II study follow-up (9087 participants). ​​​​ 



Pre-operative​​ Antiviral​​ Treatment in Hepatitis B-Related Liver Cancer Lowers Risk of Tumor Recurrence​​ 

August 1st, JAMA Surgery: ​​​​ Pre-operative antiviral therapy was associated with a 24% lower risk of hepatitis B (HBV)-related microvascular invasion​​ and a 27% lower risk of early tumor recurrence​​ in patients with hepatitis B-associated hepatocellular carcinoma undergoing tumor resection. ​​ Prospective observational (2362 patients). ​​​​ 



Comparison to Peers Lowers​​ Physicians’​​ Quetiapine​​ Prescription Rates

August 1st, 2018:​​ Physicians who frequently prescribe the atypical antipsychotic agent quetiapine reduced their prescription frequency to 11% fewer quetiapine days (per​​ prescriber) following the receipt of a​​ letter​​ contrasting​​ their prescription practices to their peers. ​​ In the control group,​​ high-frequency quetiapine prescribers​​ received a placebo letter. ​​ Up to 75% of all quetiapine prescriptions are estimated to be inappropriate or lack evidence-basis.​​ RCT (5055 highest-volume primary care prescribers of quetiapine). ​​ ​​ ​​​​ 



Antipsychotics​​ in Adolescents with Behavioral Disorders Associated with Metabolic Changes

August 1st, JAMA Psychiatry:​​ The 2nd​​ generation antipsychotic medications aripiprazole, olanzapine, and risperidone (dopamine/serotonin antagonists) were associated with​​ increased total body fat during a 12-week trial in adolescents diagnosed with disruptive behavioral disorders. ​​ Patients treated with olanzapine experienced the most significant increase (+4.12%) in body fat. ​​ Randomized 1:1:1 risperidone:olanzapine:aripiprazole (144 participants). ​​​​ 



~  ​​ ​​​​ Reviews  ​​ ​​​​ ~


Prenatal​​ Acetaminophen​​ Exposure​​ Associated with Increased Risk of ADHD, Autism

April 23rd/August 1st, American Journal of Epidemiology:​​ Children born to women who were exposed to acetaminophen during pregnancy were 34% more likely to have attention​​ deficit hyperactivity disorder, 19% more likely to have autism spectrum disorder, and 24% more likely to have hyperactivity symptoms. ​​ Systematic review and meta-analysis (7 retrospective observational studies, 132,738 mother-child pairs). ​​​​ 



Natalizumab​​ Effective in Moderate-Severe Crohn’s Disease,​​ Increases Risk of Viral Encephalopathy

August 1st, Cochrane: Patients with Crohn’s disease​​ who received natalizumab, an anti-integrin monoclonal antibody,​​ were up to 34% more likely to achieve clinical disease remission than patients who received placebo. ​​ Natalizumab was​​ associated with the development of progressive multifocal encephalopathy in some patients, raising serious concerns about its practical use in most settings.​​ Systematic review and meta-analysis (5 RCTs, 1771 participatns). ​​​​ 




Antenatal​​ Corticosteroids​​ May Decrease Respiratory​​ Risk Following Elective C-Section

August 3rd, Cochrane: Antenatal, maternal intramuscular corticosteroid injections (dexamethasone or betamethasone) were associated with a lower risk of neonatal respiratory complications when administered to women undergoing elective Cesaerean-section surgeries at 37 weeks of gestation or earlier. ​​ Meta-analysis (3956 women, 3893 babies). ​​ 




Chocolate​​ Consumption Associated with Lower Risk of Cardiovascular Disease

July 30th, Journal Heart: ​​​​ Limited chocolate consumption (<100g/week) was associated with a decreased risk of cardiovascular disease, with the largest effect observed at 45​​ g/week. ​​ Standard-size chocolate bars generally weigh 100 g. ​​ Meta-analaysis (23 observational studies, 405,304 participants). ​​​​ 




Antibiotics​​ Effective for Chronic Wet Cough in Children

July 31st, Cochrane: A 7-14 day course of amoxicillin/clavulanate or erythromycin​​ was​​ associated​​ with​​ improve outcomes in children with persistent (>​​ 10 days)​​ wet cough. ​​ The cure rate for antibiotic therapy was estimated to be one child cured for every three children treated. ​​ Meta-analysis (3 RCTs, 190 children). ​​ 



by​​ pharmacologyreview