The US FDA has approved the thrombopoietin receptor agonist avatrombopag (Doptelet®, AkaRx Inc) for the prevention of bleeding events in patients with chronic liver disease and thrombocytopenia undergoing a planned medical or dental procedure.

Avatrombopag

  • Thrombopoietin receptor agonist, stimulates platelet production
  • Decreases serious bleed risk 2-3 fold in patients w/ severe thrombocytopenia (<50*109/L) and chronic liver disease undergoing invasive procedures for up to 7 days after procedure
  • Most common adverse events: fever, abdominal pain, fatigue, edema, nausea
  • Current treatment: pre-procedural platelet transfusion 
  • May increase risk of thromboembolism in some patients
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Publication 

  • New England Journal of Medicine
  • Castro & Tohda et al, May 2018

Key Points

  • Dupilumab: monoclonal antibody targets IL-4 receptor (blocks  IL-4, IL-13 response)
  • Biweekly subcutaneous injection
  • 47.7% decrease in severe asthma exacerbations w/ dupilumab vs. placebo
  • Best response (66% fewer exacerbations) if blood eosinophils > 300/mm³
  •  + 0.14 L ΔFEV1 relative to placebo (after 12 weeks)
  • Rate of adverse rxns similar in tx and ctl groups (most common: injection site reaction)

Overview

Atorvastatin is statin-class drug commonly prescribed for the treatment of dyslipidemias and for the prevention of ischemic cardiovascular events.  It works by inhibiting hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a key enzyme in the cholesterol biosynthetic pathway.  Inhibition of HMG-CoA reductase decreases hepatic cholesterol synthesis, increases hepatic cholesterol re-uptake, and decreases serum cholesterol levels.

The US FDA has approved the cation chelator sodium zirconium cyclosilicate (ZS-9, Lokelma®) for the treatment of hyperkalemia.

Sodium Zirconium Cyclosilicate

  • Oral potassium cation-exchange agent, not systemically absorbed
  • Onset of action 1 hour, median 2.2 hours until normokalemic
  • Not approved for life-threatening potassium elevations at this time
  • Daily dosing for 1 year twice as likely as placebo to maintain normokalemia
  • Most common adverse effects: GI distress, hypokalemia, UTI, edema
  • Adverse effects less frequent than patiromer (alternative chelating agent for hyperkalemia)

The US FDA has approved the alpha-adrenergic agonist lofexidine HCl (Lucemyra®) for the treatment of opioid withdrawal symptoms.

Key Points

  • First non-opioid approved for treating opioid withdrawal symptoms
  • Approved for up to 14 days after discontinuation of opioids
  • Alpha-2 adrenergic agonist, suppresses sympathetic outflow
  • Originally developed in 1980s for management of hypertension
  • Most common side effects: hypotension, bradycardia, sedation and dizziness
  • Alternative treatments for opioid withdrawal: gradual opioid dose taper, switch to less addictive opioids (e.g., methadone, buprenorphine), use opioid receptor antagonists (naltrexone)

Overview

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor used in the treatment of hypertension and congestive heart failure.  It acts by inhibiting the conversion of angiotensin I to angiotensin II, lowering serum levels of the vasopressor hormone angiotenin II.  Decreased angiotensin II receptor stimulation also decreases adrenal secretion of aldosterone.