pyrimethamine
enUKpyrimethamine
[pir″ĭ-meth´ah-mēn]pyrimethamine
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 chloroquineresistant Plasmodium falciparum and for presumptive self-treatment by travelers.
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.
See 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.
See 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.