mitapivat (Pyrukynd)

Indications

• treatment of hemolytic anemia in adults with pyruvate kinase deficiency

Contraindications

• avoid if severe hepatic impairment

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

Adverse effects

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

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