mitapivat (Pyrukynd, Aqvesme)

Indications

• treatment of hemolytic anemia in adults with pyruvate kinase deficiency
  • treatment of adults with alpha-thalassemia or beta-thalassemia (Aqvesme)

Contraindications

• avoid if severe hepatic impairment (cirrhosis)

Dosage

• start: 5 mg BID with or without food
• titrate* upward at 4 week intervals to maximum of 50 mg BID at 12 weeks
• taper to discontinue over period of 14 days

Tablets: 5 mg. 20 mg, 50 mg (swallow tablet whole)

* titrate to blood hemoglobin

Pharmacokinetics

• metabolized by CYP3A4

Monitor

• liver function tests every 4 weeks first 24 weeks of treatment

Adverse effects

• increased serum uric acid
• back pain, arthralgia
• hypertriglyceridemia
• gastroenteritis
• hypertension
• arrhythmia
• constipation
• dry mouth
• paresthesia
• acute hemolysis with abrupt discontinuation

* Boxed warning: hepatocellular toxicity (Aqvesme)

Drug interactions

• inducers & inhibitors of CYP3A4

Mechanism of action

• pyruvate kinase activator
  • allosterically binds to pyruvate kinase tetramer thus increasing pyruvate kinase activity

More general terms

• hematologic agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=59634741
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=134693700
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=139593419