By Counterforce Health Team —

All About PYRUKYND

What is PYRUKYND?

PYRUKYND is a prescription medication approved for the treatment of hemolytic anemia in adults with Pyruvate Kinase (PK) Deficiency. This is a rare inherited disorder in which red blood cells (RBCs) break down (hemolyze) earlier than normal, leading to anemia and related complications. It is the first therapy approved that targets a key mechanism of this condition.

Why is PYRUKYND needed?

People with PK deficiency have a defect in an enzyme called pyruvate kinase in their red blood cells. Because that enzyme isn’t working properly, RBCs cannot generate enough energy, become fragile, and break down prematurely.This results in symptoms such as: fatigue, yellowing of the skin/eyes (jaundice), enlarged spleen, need for frequent transfusions, iron overload, and other complications.Until treatments like PYRUKYND, management was largely supportive (transfusions, managing symptoms) rather than disease-modifying.

How does PYRUKYND work?

PYRUKYND (mitapivat) is what’s called a pyruvate kinase activator. Put simply:

  • It binds to the defective pyruvate kinase enzyme in RBCs and helps increase its activity. 
  • With more enzyme activity, the RBCs generate more energy (ATP), which helps them survive longer rather than breaking down prematurely. 
  • By reducing hemolysis (premature RBC breakdown), the goal is to increase the hemoglobin level (the oxygen-carrying molecule in RBCs) and reduce need for transfusions over time. 

Dosage & Administration

Here are the typical guidelines (always follow your healthcare provider’s instructions):

  • Starting dose: 5 mg taken twice daily, with or without food.
  • After about 4 weeks, if hemoglobin remains low or the patient has needed a transfusion in the prior 8 weeks, dose can be increased to 20 mg twice daily. 
  • After another ~4 weeks (so ~8 weeks from start) if still insufficient response, dose may be increased to the maximum of 50 mg twice daily. 
  • Tablets must be swallowed whole; do not split, chew, or dissolve. 
  • If no benefit (hemoglobin improvement, reduced transfusion need) is observed by ~24 weeks, discontinuation may be considered. 

Safety & Important Precautions

Key warnings/precautions:

  • Acute hemolysis on abrupt discontinuation: If PYRUKYND is stopped suddenly, there have been cases of rapid RBC breakdown and worsening anemia. Therefore, it should be tapered if possible and closely monitored.
  • Liver injury risk: In patients treated with doses higher than recommended (in other conditions), serious liver injury (hepatocellular injury) was observed within the first 6 months. For PK deficiency patients, liver tests are recommended prior to starting, then monthly for the first 6 months.
  • Patients with moderate or severe hepatic impairment should avoid use of PYRUKYND.

Common side effects:According to available data:

  • Decrease in reproductive hormones (estrone and estradiol) in males.
  • Increased urate levels. 
  • Back pain, joint pain (arthralgia). 
  • Other possible lab abnormalities and effects depending on individual patient profile.

Other noteworthy safety details:

  • Use in children: Safety and efficacy in pediatric patients has not been established. 
  • Drug interactions: PYRUKYND has interactions with drugs affecting CYP3A, CYP2B6, CYP2C, P-glycoprotein, and UGT1A1. These need consideration when co-prescribing. 
  • Monitoring: Regular lab monitoring of hemoglobin, liver enzymes, and other parameters is essential during therapy.

Who Might Be a Candidate for PYRUKYND?

Given the nature of PK deficiency and the way PYRUKYND works, potential candidates are adult patients who:

  • Have a confirmed diagnosis of PK deficiency.
  • Have hemolytic anemia resulting from RBC breakdown associated with the enzyme defect.
  • May have been receiving transfusions or have a transfusion history and/or are suffering from anemia symptoms.
  • Are under a hematologist’s care familiar with managing rare diseases like PK deficiency.

Because this is a rare condition, often patients will be seen in specialized centers or by providers experienced in hemolytic anemias.

The Bottom Line

PYRUKYND is a significant step forward in the treatment of adult patients with PK deficiency—the first therapy that aims at the underlying enzyme defect rather than only managing symptoms. For the right patient, it offers real potential to improve hemoglobin levels, reduce transfusion burden, and reduce the burden of hemolysis.

However, it requires careful monitoring, understanding of risks (especially concerning abrupt discontinuation and liver safety), and coordination with a skilled hematologist. If you or someone you care for has PK deficiency, discussing PYRUKYND with a specialist may be worthwhile to determine if this treatment is appropriate.