mitapivat

Action and Spectrum

Actions and Spectrum

Actions: 

Mitapivat is an oral allosteric activator of red blood cell pyruvate kinase (PKR). It increases PKR activity, improve glycolysis and ATP production in red blood cells which enhances red cell survival and reduces hemolysis. 

Spectrum: 

Mitapivat is used to treat adults who have pyruvate kinase (PK) deficiency linked to hemolytic anemia. Its therapeutic effect is limited to disorders involving PK enzyme dysfunction and is not a broad-spectrum hematologic agent. 

Drug Interaction

Adverse Reaction

>10%: 

Back pain, all grades 

Estrone reduced in men 

Estradiol reduced in men 

1-10%: 

Arthralgia 

Gastroenteritis 

Hypertriglyceridemia 

Paresthesia 

Dry mouth  

Constipation 

Arrhythmia 

Hypertension 

Breast discomfort 

Oropharyngeal pain 

Hot flush 

Hypertriglyceridemia 

Black Box Warning

Black Box Warning 

It has warning for acute hemolysis and severe anemia after abrupt interruption or discontinuation of therapy. Sudden discontinuation can lead to rapid worsening of hemolysis, so treatment should be tapered gradually and patients should be closely monitored for any signs of hemolysis and anemia during dosage reduction or discontinuation. 

Contraindication / Caution

Contraindication / Caution

Contraindication: 

None 

Cautions: 

Abrupt discontinuation of Pyrukynd in PK deficiency can cause acute hemolysis and anemia, so the dose should be tapered and patients monitored for related symptoms. In thalassemia, higher doses have been linked to liver injury within the first six months; liver function should be regularly monitored, therapy held for significant enzyme elevations and discontinued if hepatotoxicity is suspected. 

Pregnancy / Lactation

Pregnancy/Lactation 

Pregnancy consideration:  

Insufficient data is available regarding the use of drug in pregnant women. 

Breastfeeding warnings:  

No data is available regarding the excretion of the drug in breast milk. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        

• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        

• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       

• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        

• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        

• Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology

Mitapivat is an oral allosteric activator of red blood cell pyruvate kinase that increases ATP production, improves erythrocyte energy balance, reduces hemolysis and prolongs red cell survival in pyruvate kinase deficiency. It is hepatically metabolized by CYP enzymes shows dose-dependent pharmacokinetics with potential drug interactions, and abrupt discontinuation may trigger acute hemolysis. 

Pharmacokinetics: 

Absorption: 

Peak plasma absorption occurs at 0.5 to 1 hour after dosage in dosage range of 5 to 100 mg BID and absolute bioavailability at 73%. 

Peak plasma concertation:  

• 100 mg BID: 1641.7 ng/mL 

• 50 mg BID: 935.2 ng/mL 

• 20 mg BID: 389.9 ng/mL 

• 5 mg BID: 101.2 ng/mL 

Trough concentration: 

• 100 mg BID: 71 ng/mL 

• 50 mg BID: 62.1 ng/mL 

• 20 mg BID: 32.3 ng/mL 

• 5 mg BID: 10.1 ng/mL 

AUC: 

• 100 mg BID: 4835.6 ng⋅h/mL 

• 50 mg BID: 3591.4 ng⋅h/mL 

• 20 mg BID: 1623.8 ng⋅h/mL 

• 5 mg BID: 450.4 ng⋅h/mL 

Distribution: 

Protein bound at 97.7% in plasma 

RBC-to-plasma ratio: 0.37 

Vd: 42.5 Litre 

Metabolism: 

It mainly metabolized by CYP3A4. 

Elimination 

The half-life of mitapivat is 3 to 5 hours. 

Clearance 

• 100 mg BID: 17.7 L/hr 

• 50 mg BID: 14.4 L.hr 

• 20 mg BID: 12.7 L/hr 

• 5 mg BID: 11.5 L/hr 

Excretion 

• Feces: 39.6% (below 1% unchanged) 

• Urine: 49.6% (2.6% unchanged) 

Adminstartion

Administration

Oral Administration:

Mitapivat should be taken with or without food. It should be swallowed whole and must not be split, crushed, chewed or dissolved. If a dosage is missed by 4 hours or less, it should be taken as soon as possible. If > 4 hours have passed, missed dosage should be skipped and next dose taken at the regularly scheduled time. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mitapivat 

Pronounced: mit-a-piv-at 

Why do we use mitapivat? 

Mitapivat is used to treat hemolytic anemia in adults with PK deficiency or specific types of thalassemia. It helps red blood cells produce more energy which reduces their breakdown and improves anemia. Take this medicine by mouth twice daily with or without food and swallow the tablets whole. Do not stop taking mitapivat suddenly, as this may cause worsening anemia, always follow your healthcare provider’s instructions to stop or change the dosage. Regular blood tests is needed to monitor hemoglobin and liver function during the treatment.