Mitapivat 50mg tablets
Requires a prescription from a doctor or prescriber
Mitapivat is a novel, first-in-class pyruvate kinase activator.
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Safety monitoring data
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Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
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Suspected adverse reactions reported for Mitapivat
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1 branded products available
Therapeutically similar medicines
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
Clinical guidelines and formulary information
British National Formulary
Mitapivat
Source: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(1)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Supply & product information
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Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
None known
Half-life
3 to 5 hours
Mechanism
The pyruvate kinase enzyme is an ATP-generating enzyme involved in the Embden–Me…
Food interactions
1 warning
Human targets
2 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
73%
Half-life
5 mg
[L40528]…
Protein binding
97.7%
[L40528]
Volume of distribution
42.5 L
[L40528]
Metabolism
120 mg
[L40528]…
Elimination
89.2%
[A245478]
After a single oral administration of radiolabeled mitapivat in healthy subjects,…
Clearance
14.4 L/h
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
On February 17, 2022, the FDA approved mitapivat as the first disease-modifying treatment for hemolytic anemia in adults with pyruvate kinase (PK) deficiency, a rare, inherited disorder leading to lifelong hemolytic anemia.[L40533] Mitapivat has also been investigated in other hereditary red blood cell disorders associated with hemolytic anemia, such as sickle cell disease and alpha- and beta-thalassemia.[A245478]
[L40528]
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 674 interactions
Erythrocyte pyruvate kinase is an allosterically regulated homotetrameric enzyme [A245493] that is normally activated by fructose bisphosphate (FBP) in an allosteric fashion. Mitapivat is also an allosteric pyruvate kinase activator but binds to a different allosteric site from FBP on the PKR tetramer. This allows for the activation of both wild-type and mutant forms of erythrocyte pyruvate kinase, including those not induced by FBP.[A245478][L40528] Upon binding to pyruvate kinase, mitapivat stabilizes the active tetrameric form of the enzyme and enhances its affinity for its substrate, phosphoenolpyruvate.[A245488] Mitapivat upregulates erythrocyte pyruvate kinase activity, increases ATP production, and reduces levels of 2,3-DPG.[A245478][L40528]
Interestingly, mitapivat is a mild-to-moderate inhibitor of the aromatase enzyme (CYP19A1),[A245478] which is an enzyme involved in biosynthesis of estrogens from androgen precursors. Inhibition of aromatase is associated with bone density loss, as estrogen mediates suppressive, antiresorptive effects on osteoclasts and generally favours bone formation over resorption. Thus, low estrogen levels can increase bone turnover and osteoclast activity, resulting in net bone loss and decreased bone quality.[A245483] Inhibition of aromatase by mitapivat may have some clinical implications, as patients with pyruvate kinase deficiency have considerably high rate of osteopenia and osteoporosis. The long-term effect of mitapivant on bond mineral density requires further investigation. One study suggests that this off-target effect may have negligible clinical effects on adults, but may potentially have some clinical implications in developing children.[A245478]
How the body processes this drug — absorption, distribution, metabolism, and elimination
The mean (CV%) AUC were 450.4 (28%) ng x h/mL, 1623.8 (28%) ng x h/mL, and 3591.4 (28%) ng x h/mL, respectively. The median Tmax values at steady state were 0.5 to 1.0 hour post-dose across the dose range of 5 mg to 50 mg twice daily.
In healthy subjects, a high-fat meal did not affect the drug exposure but reduced the rate of mitapivat absorption, with a 42% reduction in Cmax and a delay in Tmax of 2.3 hours when compared to dosing under fasted conditions.
[L40528]
[L40528]
[L40528]
[L40528]
[L40528]
It is also a substrate of CYP1A2, CYP2C8, and CYP2C9.
[A245478]
Following a single oral dose administration of 120 mg of radiolabeled mitapivat in healthy subjects, unchanged mitapivat was the major circulating component in plasma.
[L40528]
[A245478]
After a single oral administration of radiolabeled mitapivat in healthy subjects, the total recovery of administered radioactive dose was 89.2%. About 49.6% of radioactivity was recovered in the urine with 2.6% excreted as unchanged mitapivat. About 39.6% of radioactivity was recovered in the feces with less than 1% being the unchanged drug.
[L40528]
[L40528]
Proteins and enzymes this drug interacts with in the body
PMID:27702664 PMID:2848247
Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid .
PMID:20385561
Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen .
PMID:22773874
Also displays 2-hydroxylase activity toward estrone .
PMID:22773874
Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) PMID:20385561 PMID:22773874
Enzymes involved in drug metabolism — important for understanding drug interactions
Proteins that transport this drug across cell membranes
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
ATC G01AE10
ATC B06AX04
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Mitapivat
Additional database identifiers
ChemSpider
29763395
ZINC
ZINC000140430983
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9020
GenAtlas
PKLR
GeneCards
PKLR
GenBank Gene Database
AB015983
GenBank Protein Database
3327365
Guide to Pharmacology
3007
UniProt Accession
KPYR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2594
GenAtlas
CYP19A1
GeneCards
CYP19A1
GenBank Gene Database
M22246
GenBank Protein Database
179002
Guide to Pharmacology
1362
UniProt Accession
CP19A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
Patent information
10 active patents
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
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