pyrimethamine

pyrimethamine /pyr·i·meth·amine/ (pir?i-meth´ah-men) a folic acid antagonist, used in the treatment of malaria and of toxoplasmosis.

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py·ri·meth·a·mine (pr-mth-mn, -mn)

n.

A potent folic acid antagonist used as a prophylactic antimalarial agent against Plasmodium falciparum and in the treatment of toxoplasmosis.

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pyrimethamine (pir´imeth´mēn),

n a folic acid inhibitor that acts against
T. gondii and
P. spp., which cause toxoplasmosis and malaria.

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pyrimethamine

a folic acid antagonist used in combination with sulfonamides in the treatment of toxoplasmosis and avian coccidiosis.

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pyrimethamine

Daraprim

Pharmacologic class: Folic acid antagonist

Therapeutic class: Antiprotozoal, antimalarial

Pregnancy risk category C

Action

Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid (folinic acid) by binding to and reversibly inhibiting dihydrofolate reductase

Availability

Tablets: 25 mg

⊘Indications and dosages

➣ To control plasmodia transmission and suppress susceptible strains

Adults and children ages 10 and older: 25 mg P.O. daily for 2 days, given with a sulfonamide

➣ Toxoplasmosis

Adults: Initially, 50 to 75 mg P.O. daily for 1 to 3 weeks, given with a sulfonamide. Depending on response and tolerance, reduce dosages of both drugs by 50% and continue therapy for 4 to 5 more weeks.

Children: 1 mg/kg P.O. daily in two equally divided doses for 2 to 4 days, then reduced to 0.5 mg/kg/day for approximately 1 month. Alternatively, 2 mg/kg (up to 100 mg) P.O. daily in two equally divided doses for 3 days, then 1 mg/kg (up to 25 mg) in two equally divided doses for 4 weeks, given with sulfadiazine for 4 weeks.

➣ Prophylaxis of malaria caused by susceptible plasmodia strains

Adults and children older than age 10: 25 mg P.O. weekly

Children ages 4 to 10: 12.5 mg P.O. weekly

Infants and children younger than age 4: 6.25 mg P.O. weekly

Off-label uses

• Isosporiasis
• Prophylaxis of Pneumocystis jiroveci pneumonia

Contraindications

• Hypersensitivity to drug
• Megaloblastic anemia caused by folate deficiency
• Concurrent folate antagonist therapy

Precautions

Use cautiously in:
• anemia, bone marrow depression, hepatic or renal impairment, G6PD deficiency
• history of seizures
• patients more than 16 weeks pregnant
• breastfeeding patients.

Administration

• Administer with meals.
• When giving tablets to young children, crush them and administer as oral suspension in water, cherry syrup, or sweetened solution.
• Know that because of worldwide resistance to pyrimethamine, its use alone to prevent or treat acute malaria is no longer recommended.
• Be aware that fixed combination of pyrimethamine and sulfadoxine is available and has been used for uncomplicated mild to moderate malaria caused by chloroquine-resistant Plasmodium falciparum and for presumptive self-treatment by travelers.

Route	Onset	Peak	Duration
P.O.	Unknown	2-6 hr	2 wk

Adverse reactions

CNS: headache, light-headedness, insomnia, malaise, depression, seizures

CV: arrhythmias

EENT: dry throat

GI: nausea, vomiting, diarrhea, anorexia, atrophic glossitis

GU: hematuria

Hematologic: megaloblastic anemia, leukopenia, pancytopenia, thrombocytopenia

Metabolic: hyperphenylalaninemia

Respiratory: pulmonary eosinophilia

Skin: pigmentation changes, dermatitis, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome

Other: fever, anaphylaxis

Interactions

Drug-drug. Lorazepam: hepatotoxicity

Myelosuppressants (including antineoplastics): increased risk of bone marrow depression

Drug-diagnostic tests. Platelets, white blood cells: decreased counts

Patient monitoring

• Monitor CBC. Watch for evidence of blood dyscrasias.
• Assess for signs and symptoms of folic acid deficiency.
• Closely monitor neurologic and cardiovascular status. Stay alert for seizures and arrhythmias.
☞ Watch for evidence of erythema multiforme, including sore throat, cough, mouth sores, rash, iritic lesions, and fever. Report early signs before condition can progress to Stevens-Johnson syndrome.

Patient teaching

• Advise patient to take with meals.
☞ Tell patient to discontinue drug and contact prescriber at first sign of rash.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.