mitapivat (Rx)

Brand and Other Names:Pyrukynd
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 5mg
  • 20mg
  • 50mg

Hemolytic Anemia

Indicated for treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency

5 mg PO BID initially; gradually increase to 20 mg BID, and then to maximum dose of 50 mg BID according to following titration schedule

Discontinue (taper gradually) if no benefit observed by 24 weeks, as determined by hemoglobin (Hb) and hemolysis laboratory results and transfusion requirements

Dose titration schedule

  • Weeks 1-4: 5 mg BID
  • Weeks 5-8
    • Hb below normal range or transfusion required within last 8 weeks: Increase to 20 mg BID and maintain for 4 weeks
    • Hb within normal range and no transfusion required within last 8 weeks: Maintain 5 mg BID
  • Weeks 9-12
    • Hb below normal range or transfusion required within last 8 weeks: Increase to 50 mg BID and maintain thereafter
    • Hb within normal range and no transfusion required within last 8 weeks: Maintain current dose (5 mg BID or 20 mg BID)

Maintenance: If Hb decreases, consider uptitration to 50 mg BID according to above schedule

Dose interruption or discontinuation

  • Gradually taper dose; avoid abrupt interruption or abrupt discontinuation to reduce risk of acute hemolysis and monitor for acute hemolysis and worsening of anemia
  • Current dose 5 mg BID
    • Days 1-7: 5 mg qDay
    • Day 8 and thereafter: Discontinue
  • Current dose 20 mg BID
    • Days 1-7: 20 mg qDay
    • Days 8-14: 5 mg qDay
    • Day 15: Discontinue
  • Current dose 50 mg BID
    • Days 1-7: 50 mg qDay
    • Days 8-14: 20 mg qDay
    • Day 15: Discontinue

Dosage Modifications

Adverse reaction or Hb levels above normal

  • Dose may be reduced to next lower dose level (eg, 20 mg BID or 5 mg BID)
  • If patient needs to discontinue drug, follow taper schedule listed above
  • If sudden withdrawal is necessary, may stop without taper with careful monitoring for acute hemolysis

Coadministration with CYP3A inhibitors

  • Strong inhibitors: Avoid coadministration
  • Moderate inhibitors: Do not titrate mitapivat beyond 20 mg BID; monitor Hb and for increased risks of adverse reactions

Coadministration with CYP3A inducers

  • Strong inducers: Avoid coadministration
  • Moderate inducers
    • Consider other therapies that are not moderate CYP3A inducers during treatment
    • If unable to avoid coadministration, monitor Hb and titrate beyond 50 mg BID, if necessary (not to exceed 100 mg BID)

Renal impairment

  • Mild (eGFR 60 to <90 mL/min/1.73 m2): No dosage adjustment recommended
  • Moderate (eGFR 30 to <60 mL/min/1.73 m2): Limited data available
  • Severe (eGFR <30 mL/min/1.73 m2): No data available

Hepatic impairment

  • Mitapivat undergoes extensive hepatic metabolism
  • Mild: No recommendations provided
  • Moderate-to-severe: Avoid; increased systemic exposure expected

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and mitapivat

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (2)

            • mavacamten

              mitapivat will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              mitapivat will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pacritinib

              mitapivat will decrease the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            Serious - Use Alternative (3)

            • ganaxolone

              mitapivat will decrease the level or effect of ganaxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ganaxolone with moderate or strong CYP3A4 inducers. If coadministration unavoidable, consider increasing ganaxolone dose; however, do not exceed maximum daily dose for weight.

            • lumateperone

              mitapivat will decrease the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • vonoprazan

              mitapivat will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (1)

            • warfarin

              mitapivat will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            Minor (0)

              Previous
              Next:

              Adverse Effects

              >10%

              Estrone decreased in males (56.3%)

              Back pain, all grades (15%)

              Estradiol decreased in males (12.5%)

              1-10%

              Blood testosterone increased in males (6.3%)

              All grades

              • Arthralgia (10%)
              • Hypertriglyceridemia (8%)
              • Gastroenteritis (8%)
              • Hot flush (8%)
              • Oropharyngeal pain (8%)
              • Hypertension (5%)
              • Arrhythmia (5%)
              • Breast discomfort (5%)
              • Constipation (5%)
              • Dry mouth (5%)
              • Paresthesia (5%)

              Grades ≥3

              • Hypertriglyceridemia (5%)
              • Hypertension (5%)
              • Gastroenteritis (3%)
              Previous
              Next:

              Warnings

              Contraindications

              None

              Cautions

              Acute hemolysis with abrupt treatment interruption

              • Acute hemolysis with subsequent anemia observed following abrupt interruption or discontinuation
              • Avoid abruptly discontinuation
              • Gradually taper 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 (P-gp)
              • Strong or moderate CYP3A4 inhibitors
                • Strong CYP3A4 inhibitors: Avoid coadministration
                • Moderate CYP3A4 inhibitors: Monitor Hb and for increased risks of adverse reactions with mitapivat; do not titrate mitapivat beyond 20 mg BID
                • 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 unavoidable, monitor Hb and titrate beyond 50 mg BID, if necessary (not to exceed 100 mg BID)
                • 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 narrow therapeutic index
              • P-gp substrates
                • Monitor for adverse reactions of P-gp substrates with narrow therapeutic index when coadministered with mitapivat
                • Mitapivat may increase systemic concentrations of drugs that are P-gp substrates
              Previous
              Next:

              Pregnancy & Lactation

              Pregnancy

              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 also reported

              Animal data

              • Oral administration to pregnant rats and rabbits during organogenesis was not teratogenic at doses up to 13x and 3x the maximum recommended human dose (MRHD) of 50 mg twice daily, respectively
              • Oral administration to pregnant rats twice daily during organogenesis through lactation did not result in adverse developmental effects at doses up to 13x MRHD

              Lactation

              There are no data on presence of mitapivat or its metabolites in human or animal milk, effects on breastfed children, or effects on milk production

              Consider 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

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

              Previous
              Next:

              Pharmacology

              Mechanism of Action

              Pyruvate kinase (PK) activator that acts by allosterically binding to pyruvate kinase tetramer and increasing PK activity

              Red blood cell (RBC) form of pyruvate kinase (PK-R) is mutated in PK deficiency, which leads to reduced adenosine triphosphate, shortened RBC lifespan, and chronic hemolysis

              Absorption

              Peak plasma time: 0.5-1 hr post dose across dosage range of 5-50 mg BID

              Absolute bioavailability: 73%

              Peak plasma concentration

              • 5 mg BID: 101.2 ng/mL
              • 20 mg BID: 389.9 ng/mL
              • 50 mg BID: 935.2 ng/mL

              Trough concentration

              • 5 mg BID: 10.1 ng/mL
              • 20 mg BID: 32.3 ng/mL
              • 50 mg BID: 62.1 ng/mL

              AUC

              • 5 mg BID: 450.4 ng⋅h/mL
              • 20 mg BID: 1623.8 ng⋅h/mL
              • 50 mg BID: 3591.4 ng⋅h/mL

              Distribution

              Protein bound: 97.7% in plasma

              Low RBC distribution; RBC-to-plasma ratio of 0.37

              Vd: 42.5 L

              Metabolism

              Primarily metabolized by CYP3A4

              Elimination

              Half-life: 3-5 hr

              Clearance

              • 5 mg BID: 11.5 L/hr
              • 20 mg BID: 12.7 L/hr
              • 50 mg BID: 14.4 L.hr

              Excretion

              • Urine: 49.6% (2.6% unchanged)
              • Feces: 39.6% (<1% unchanged)
              Previous
              Next:

              Administration

              Oral Administration

              Take with or without food

              Swallow tablets whole; do not split, crush, chew, or dissolve

              Missed dose

              • Missed dose by ≤4 hr: Take missed dose as soon as possible
              • Missed by >4 hr: Do not replace dose; wait until next scheduled dose

              Storage

              Tablets: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

              Store blister wallets in original carton until use

              Previous
              Next:

              Images

              No images available for this drug.
              Previous
              Next:

              Patient Handout

              A Patient Handout is not currently available for this monograph.
              Previous
              Next:

              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
              Additional Offers
              Email to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Email Forms to Patient

              From:

              To:

              The recipient will receive more details and instructions to access this offer.

              By clicking send, you acknowledge that you have permission to email the recipient with this information.

              Previous
              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.