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| {{drugbox | | | __NOTOC__ |
| |IUPAC_name = 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine
| | {{Pyrimethamine}} |
| | image = Pyrimethamine.svg
| | {{CMG}}; {{AE}} {{chetan}} |
| | width = 160px
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| |CAS_number = 58-14-0
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| | ATC_prefix=P01
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| | ATC_suffix=BD01
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| | PubChem=4993
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| | DrugBank=APRD00599
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| | C = 12 |H = 13 |Cl = 1 |N = 4
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| |molecular_weight = 248.71 [[gram|g]]/[[mole (unit)|mol]]
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| |bioavailability = well-absorbed
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| |protein_bound = 87%
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| |metabolism = [[Liver|Hepatic]]
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| |elimination_half-life = 96 [[hour]]s
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| |excretion = [[Kidney|Renal]]
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| |pregnancy_US = C
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| |pregnancy_AU = B3
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| |legal_status = Rx-only
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| |routes_of_administration = [[Mouth|Oral]]
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| }} | |
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| '''Pyrimethamine''' ('''Daraprim®''') is a [[medication]] used for [[protozoal]] infections. It is commonly used as an [[antimalarial drug]] (for both treatment and prevention), and is also used in the treatment of ''[[Toxoplasma gondii]]'' infections in [[immunocompromise]]d patients, such as [[HIV]]-positive individuals.
| | ==Overview== |
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| ==Mechanism of action== | | ==Category== |
| Pyrimethamine interferes with [[folic acid]] synthesis by inhibiting the enzyme [[dihydrofolate reductase]]. Folic acid is needed for [[DNA]] and [[RNA]] synthesis in many [[species]], including protozoa.
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| ==Mechanism of resistance== | | ==US Brand Names== |
| Resistance to pyrimethamine is widespread. Mutations in the gene for dihydrofolate reductase may reduce the effectiveness of pyrimethamine (PMID 15155209). These mutations decrease the binding affinity between pyrimethamine and dihydrofolate reductase by [[steric]] interactions (PMID 14711307).
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| ==Clinical use== | | ==FDA Package Insert== |
| Pyrimethamine is typically given with a [[sulfonamide]] and [[folinic acid]]:
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| * [[Sulfonamide]]s inhibit [[dihydropteroate synthetase]], an enzyme that participates in folic acid synthesis from [[para-aminobenzoic acid]]. Hence, sulfonamides work synergistically with pyrimethamine by blocking a different enzyme needed for folic acid synthesis.
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| * Folinic acid ([[Leucovorin]]) is a compound that can be converted into folic acid by the human body without relying on dihydrofolate reductase. By doing so, folinic acid reduces side effects related to folate deficiency.
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| ==Side effects==
| | ''' [[Pyrimethamine description|Description]]''' |
| Pyrimethamine may deplete [[folic acid]] in humans, resulting in [[hematology|hematologic]] side effects associated with folate deficiency. | | '''| [[Pyrimethamine clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Pyrimethamine microbiology|Microbiology]]''' |
| | '''| [[Pyrimethamine indications and usage|Indications and Usage]]''' |
| | '''| [[Pyrimethamine contraindications|Contraindications]]''' |
| | '''| [[Pyrimethamine warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Pyrimethamine adverse reactions|Adverse Reactions]]''' |
| | '''| [[Pyrimethamine drug interactions|Drug Interactions]]''' |
| | '''| [[Pyrimethamine overdosage|Overdosage]]''' |
| | '''| [[Pyrimethamine clinical studies|Clinical Studies]]''' |
| | '''| [[Pyrimethamine dosage and administration|Dosage and Administration]]''' |
| | '''| [[Pyrimethamine how supplied|How Supplied]]''' |
| | '''| [[Pyrimethamine labels and packages|Labels and Packages]]''' |
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| Side effects include:
| | ==Mechanism of Action== |
| *[[hypersensitivity]] reactions
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| *[[megaloblastic anemia]]
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| *[[leukopenia]]
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| *[[thrombocytopenia]]
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| *[[pancytopenia]]
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| *[[atrophic glossitis]]
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| *[[hematuria]]
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| *cardiac [[arrhythmia]]s
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| *pulmonary [[eosinophilia]] (rare)
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| *[[hyperphenylalaninemia]] (particularly when used with a sulfonamide)
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| ==Contraindications== | |
| Pyrimethamine is contraindicated in patients with:
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| * hypersensitivity to pyrimethamine
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| * megaloblastic anemia - depletion of folic acid may aggravate this condition
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| ==References== | | ==References== |
| *[http://us.gsk.com/products/assets/us_daraprim.pdf Daraprim - Package insert (PDF file)]
| | {{Reflist|2}} |
| *[http://www.rocheusa.com/products/fansidar/pi.pdf Fansidar - sulfadoxine and pyrimethamine]
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| ==External links==
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| {{Antimalarials}} | |
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| [[Category:Antimalarial agents]]
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| [[Category:Antiprotozoal agents]]
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| [[Category:Dihydrofolate reductase inhibitors]]
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| [[de:Pyrimethamin]] | | [[Category:Antibiotics]] |
| [[pl:Pirymetamina]] | | [[Category:Wikinfect]] |