Mitapivat

Mitapivat is a prescription medicine used for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency.

• Mitapivat is available under the following different brand names: Pyrukynd

Common side effects of Mitapivat include:

• back pain
• joint pain
• estrone decreased (men)
• estradiol decreased (men) 
• increased urate
• high triglycerides
• gastroenteritis
• hot flushes
• mouth and throat pain
• high blood pressure (hypertension)
• irregular heartbeat (arrhythmia)
• breast discomfort
• constipation
• dry mouth
• numbness and tingling

Serious side effects of mitapivat include:

• hives
• difficult breathing
• swelling of the face, lips, tongue, or throat
• jaundice (yellowing of the skin or eyes)
• dark urine
• dizziness
• confusion
• tiredness
• shortness of breath

Rare side effects of mitapivat include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 5 mg
• 20 mg
• 50 mg

Hemolytic anemia

Adult dosage

• 5 mg orally two times a day initially; gradually increase to 20 mg two times a day, and then to a maximum dose of 50 mg two times a day according to the following titration schedule
• Discontinue (taper gradually) if no benefit is observed by 24 weeks, as determined by hemoglobin (Hb) and hemolysis laboratory results and transfusion requirements
• Dose titration schedule
  • Weeks 1–4: 5 mg two times a day
  • Weeks 5–8
    • Hb below normal range or transfusion required within last 8 weeks: Increase to 20 mg two times a day and maintain for 4 weeks
    • Hb within normal range and no transfusion required within last 8 weeks: Maintain 5 mg two times a day
  • Weeks 9–12
    • Hb below normal range or transfusion required within last 8 weeks: Increase to 50 mg two times a day and maintain thereafter
    • Hb within normal range and no transfusion required within last 8 weeks: Maintain current dose (5 mg two times a day or 20 mg two times a day)
    • Maintenance: If Hb decreases, consider up-titration to 50 mg two times a day according to the above schedule
• Dose interruption or discontinuation
  • Gradually taper dose: avoid abrupt interruption or abrupt discontinuation to reduce the risk of acute hemolysis and monitor for acute hemolysis and worsening of anemia
• The current dose is 5 mg two times a day
  • Days 1–7: 5 mg once a day
  • Day 8 and thereafter: Discontinue
• Current dose 20 mg two times a day
  • Days 1–7: 20 mg once a day
  • Days 8–14: 5 mg once a day
  • Day 15: Discontinue
• Current dose 50 mg two times a day
  • Days 1–7: 50 mg two times a day
  • Days 8–14: 20 mg once a day
  • Day 15: Discontinue

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Mitapivat has severe interactions with the following drugs:
  • mavacamten
  • pacritinib
• Mitapivat has serious interactions with the following drugs:
  • elacestrant
  • ganaxolone
  • lenacapavir
  • leniolisib
  • lumateperone
  • olutasidenib
  • omaveloxolone
  • vonoprazan
  • zanubrutinib
• Mitapivat has moderate interactions with the following drugs:
  • lenacapavir
  • warfarin
• Mitapivat has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Mitapivat?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Mitapivat?”

Cautions

• Acute hemolysis with abrupt treatment interruption
• Acute hemolysis with subsequent anemia was observed following an abrupt interruption or discontinuation
• Avoid abrupt discontinuation
• Gradually taper the dose to discontinue treatment if possible
• When discontinuing treatment, monitor for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath
• Drug interaction overview
  • Substrate of CYP3A4
    • Induces CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 enzymes
    • Also, induces UGT1A1
    • Substrate and inhibitor of P-glycoprotein
  • Strong or moderate CYP3A4 inhibitors
    • Strong CYP3A4 inhibitors: Avoid coadministration
    • Moderate CYP3A4 inhibitors: Monitor Hb for increased risks of adverse reactions with mitapivat; do not titrate Mitapivat beyond 20 mg two times a day
    • Strong or moderate CYP3A inhibitors increase plasma concentrations and risks of adverse reactions of mitapivat
  • Strong or moderate CYP3A4 inducers
    • Strong CYP3A4 inducers: Avoid coadministration
    • Moderate CYP3A4 inducers: Consider other drugs that are not moderate CYP3A inducers when coadministered with mitapivat; if coadministration is unavoidable, monitor Hb and titrate beyond 50 mg two times a day, if necessary (not to exceed 100 mg two times a day)
    • Strong or moderate CYP3A inducers decrease plasma concentrations and efficacy of mitapivat
  • Sensitive CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 substrates
    • Monitor for loss of therapeutic effect of sensitive CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 substrates with narrow therapeutic index when coadministered with mitapivat
    • Mitapivat may decrease systemic concentrations of sensitive CYP3A4 (eg, hormonal contraceptives), CYP2B6, CYP2C8, CYP2C9, and CYP2C19 substrates
    • Advise patients using hormonal contraceptives to use a nonhormonal contraceptive method or add a barrier method of contraception during treatment
  • UGT1A1 substrates
    • Monitor for loss of therapeutic effect of UGT1A1 substrates with narrow therapeutic index when coadministered with mitapivat
    • Mitapivat may decrease systemic concentrations of UGT1A1 substrates with a narrow therapeutic index
  • P-gp substrates
    • Monitor for adverse reactions of P-gp substrates with a narrow therapeutic index when coadministered with mitapivat
    • Mitapivat may increase systemic concentrations of drugs that are P-gp substrates

Pregnancy and Lactation

• Available data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Clinical considerations
  • PK deficiency in pregnant women may precipitate acute hemolysis, preterm labor, miscarriage, and severe anemia requiring frequent transfusion
  • Preeclampsia and severe hypertension were also reported
• Lactation
  • There is no data on the presence of mitapivat or its metabolites in human or animal milk, its effects on breastfed children, or on milk production
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need and any potential adverse effects on the breastfed child or from the underlying maternal condition