Pyrimethamine

Name: Pyrimethamine

How supplied

White, scored tablets containing 25 mg pyrimethamine, imprinted with “DARAPRIM” and “A3A” in bottles of 100 (NDC 69413-330-10) and bottles of 30 (NDC 69413-330-30).

Store at 15° to 25°C (59° to 77°F) in a dry place and protect from light.

Distributed by: Turing Pharmaceuticals LLC New York, New York 10036. Revised: Mar 2017

What is the most important information i should know about pyrimethamine (daraprim)?

Stop taking pyrimethamine and seek medical attention at the first sign of a skin rash, sore throat, paleness of the skin, unusual bruising under the skin, or swelling of the tongue. These may be early symptoms of serious side effects of pyrimethamine.

Pyrimethamine may cause stomach upset or vomiting. Take each dose with food to lessen this side effect.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of pyrimethamine can be fatal, especially to a child.

Overdose symptoms may include stomach pain, severe vomiting, coughing up blood or vomit that looks like coffee grounds, feeling anxious or excited, seizure (convulsions), and weak or shallow breathing (breathing may stop).

Uses for Pyrimethamine

Cystoisosporiasis

Pyrimethamine (and leucovorin) used alone for treatment of cystoisosporiasis caused by Cystoisospora belli† (formerly Isospora belli) when drug of choice (co-trimoxazole) cannot be used.134 155 156 192 Recommended by CDC, NIH, IDSA, and AAP as preferred alternative for treatment of acute C. belli infections in HIV-infected adults, adolescents, and children who fail to respond to or cannot tolerate co-trimoxazole.155 156

Pyrimethamine (and leucovorin) used alone for chronic maintenance therapy (secondary prophylaxis) of cystoisosporiasis† in HIV-infected adults, adolescents, and children when drug of choice (co-trimoxazole) cannot be used.155 156 Recommended by CDC, NIH, IDSA, and AAP as preferred alternative in those who cannot tolerate co-trimoxazole.155 156

Malaria

Pyrimethamine has been used in the past for prevention (prophylaxis) of malaria caused by susceptible Plasmodium.167 Pyrimethamine-resistant strains prevalent worldwide;167 no longer suitable for prevention of malaria in most areas167 and not included in CDC recommendations for prevention of malaria.115

Pyrimethamine has been used in the past for treatment of acute uncomplicated malaria.167 Pyrimethamine-resistant strains prevalent worldwide;167 cannot be used alone for treatment of malaria161 167 and not included in CDC recommendations for treatment of malaria.143

Fixed-combination preparation containing sulfadoxine and pyrimethamine (sulfadoxine/pyrimethamine; Fansidar) has been used for prevention of malaria and treatment of acute uncomplicated malaria caused by chloroquine-resistant P. falciparum.128 139 168 188 189 Resistance to sulfadoxine/pyrimethamine is widespread (e.g., Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, large parts of Africa);44 45 115 126 127 128 160 161 severe and sometimes fatal adverse reactions reported when fixed combination used for malaria prevention (see Dermatologic and Hypersensitivity Reactions under Cautions).111 112 113 114 132 139 144 145 168 Fixed combination no longer commercially available in US and not included in CDC recommendations for prevention or treatment of malaria.115 143 Fixed combination may still be used for treatment of uncomplicated P. falciparum malaria in some countries where the disease is endemic,161 usually in conjunction with artesunate in artemisinin-based combination therapy (ACT).161

Information on risk of malaria in specific countries and mosquito avoidance measures and recommendations regarding whether prevention of malaria is indicated and choice of antimalarials for prevention are available from CDC at and .115

Assistance with diagnosis or treatment of malaria is available from CDC Malaria Epidemiology Branch at 770-488-7788 or 855-856-4713 from 9:00 a.m. to 5:00 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours and on weekends and holidays.143

Pneumocystis jiroveci Pneumonia

Pyrimethamine (and leucovorin) used in conjunction with dapsone for prevention of initial episodes (primary prophylaxis) of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia† (PCP) in HIV-infected adults and adolescents.134 155 171 173 174 175 176 177 178 179

Pyrimethamine (and leucovorin) used in conjunction with dapsone for chronic maintenance therapy to prevent recurrence (secondary prophylaxis) of PCP† in HIV-infected adults and adolescents.134 155

Co-trimoxazole generally drug of choice for primary and secondary prophylaxis of PCP in HIV-infected adults, adolescents, and children.134 155 156

If co-trimoxazole cannot be used (e.g., because of intolerance), alternative regimens recommended by CDC, NIH, IDSA, and others for primary or secondary prophylaxis of PCP in HIV-infected adults and adolescents are dapsone, dapsone in conjunction with pyrimethamine (and leucovorin), aerosolized pentamidine, or atovaquone (with or without pyrimethamine and leucovorin).134 155

Pyrimethamine regimens not included in CDC, NIH, IDSA, and AAP recommendations for primary or secondary prophylaxis of PCP in HIV-infected children.156

Toxoplasmosis

Pyrimethamine (and leucovorin) used in conjunction with sulfadiazine, clindamycin, atovaquone, or azithromycin for treatment of toxoplasmosis caused by Toxoplasma gondii.134 155 156 167

CDC, NIH, IDSA, and others recommend pyrimethamine (and leucovorin) used in conjunction with sulfadiazine as the regimen of choice for initial treatment of toxoplasmosis, including toxoplasmosis in HIV-infected adults, adolescents, and children.134 155 156

Pyrimethamine (and leucovorin) used in conjunction with clindamycin is the preferred alternative for treatment of toxoplasmosis in HIV-infected adults, adolescents, and children unable to tolerate sulfadiazine or who fail to respond to or relapse after treatment with regimen of choice.134 155 156 Other alternatives for treatment of toxoplasmosis in HIV-infected adults and adolescents include pyrimethamine (and leucovorin) in conjunction with atovaquone, atovaquone alone or in conjunction with sulfadiazine, pyrimethamine (and leucovorin) in conjunction with azithromycin, or co-trimoxazole;155 these regimens not studied in children.156

Pyrimethamine (and leucovorin) used in conjunction with sulfadiazine is the regimen of choice for treatment of congenital toxoplasmosis.156 Empiric treatment of congenital toxoplasmosis should be strongly considered if the mother had symptomatic or asymptomatic Toxoplasma infection during pregnancy, even if the mother received toxoplasmosis treatment during the pregnancy.156

Pyrimethamine (and leucovorin) used in conjunction with dapsone is the recommended alternative for prevention of T. gondii encephalitis (primary prophylaxis)† in HIV-infected adults, adolescents, and children ≥1 month of age when the regimen of choice (co-trimoxazole) cannot be used.155 156 178 195 210 211 Pyrimethamine (and leucovorin) used in conjunction with atovaquone is another alternative for primary prophylaxis of toxoplasmosis in HIV-infected adults, adolescents, and children 4–24 months of age when the regimen of choice (co-trimoxazole) cannot be used.134 155 156

Pyrimethamine (and leucovorin) used in conjunction with sulfadiazine is the regimen of choice for chronic maintenance therapy (secondary prophylaxis) to prevent relapse of T. gondii encephalitis† in HIV-infected adults, adolescents, and children who have completed treatment for the disease.155 156

Pyrimethamine (and leucovorin) used in conjunction with clindamycin is an alternative for secondary prophylaxis in HIV-infected adults, adolescents, and children when the regimen of choice cannot be used;155 156 pyrimethamine (and leucovorin) used in conjunction with atovaquone is another alternative in HIV-infected adults and adolescents.155

Actions

  • Inhibits folic acid synthesis by inhibiting dihydrofolate reductase.125 161 Because reduction of dihydrofolic acid to tetrahydrofolic acid (folinic acid) is inhibited, the drug indirectly blocks synthesis of nucleic acids in susceptible organisms.161 167

  • Blood schizonticidal agent active against asexual erythrocytic forms of susceptible P. falciparum, P. malariae, P. ovale, and P. vivax.125 161

  • Active against T. gondii.125 Concomitant use of pyrimethamine and sulfadiazine results in synergistic activity against T. gondii;125 concomitant use with atovaquone or azithromycin also potentiates antitoxoplasma activity of pyrimethamine.125

  • Pyrimethamine resistance may be induced in plasmodia and frequently occurs in areas where the drug has been widely used.125 161 Pyrimethamine resistance reported in P. falciparum, P. malariae, and P. vivax.125

Advice to Patients

  • Advise patients to take pyrimethamine with meals if anorexia or vomiting occurs.167

  • Advise patients not to exceed recommended dosage.167

  • Advise patients to discontinue pyrimethamine and inform clinicians at the first appearance of rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura, jaundice, or glossitis.167

  • Importance of keeping pyrimethamine out of the reach of children.167

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.167

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.167 (See Pregnancy under Cautions.)

  • Importance of informing patients of other important precautionary information.167 (See Cautions.)

Commonly used brand name(s)

In the U.S.

  • Daraprim

Available Dosage Forms:

  • Tablet

Therapeutic Class: Antimalarial

Pharmacologic Class: Folic Acid Antagonist

Uses For pyrimethamine

Pyrimethamine is an antiprotozoal medicine. Antiprotozoals work by killing protozoa (tiny, one-celled animals) or preventing their growth. Some protozoa are parasites that can cause many different kinds of infections in the body.

pyrimethamine is used with one or more other medicines to treat and prevent malaria and to treat toxoplasmosis. pyrimethamine may also be used for other problems as determined by your doctor.

Pyrimethamine is available only with your doctor's prescription.

Pharmacology

Inhibits parasitic dihydrofolate reductase, resulting in inhibition of vital tetrahydrofolic acid synthesis

Absorption

Well absorbed

Distribution

Vd: Adults: 2.9 L/kg; distributed to the kidneys, lung, liver, and spleen

Excretion

Urine (16% to 32%)

Time to Peak

Serum: 2 to 6 hours

Half-Life Elimination

80 to 95 hours (White 1985)

Protein Binding

87%

Contraindications

Hypersensitivity to pyrimethamine or any component of the formulation; megaloblastic anemia secondary to folate deficiency

Administration

Oral: Administer with meals to minimize GI distress.

Storage

Store at 15°C to 25°C (59°F to 77°F). Protect from light.

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiac arrhythmia (large doses)

Dermatologic: Erythema multiforme, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis

Gastrointestinal: Anorexia, glossitis (atrophic), vomiting

Hematologic & oncologic: Leukopenia, megaloblastic anemia, pancytopenia, thrombocytopenia

Genitourinary: Hematuria

Hypersensitivity: Anaphylaxis

Respiratory: Eosinophilic pneumonitis

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

No monograph available at this time.

Missed Dose

Consult your pharmacist.

Storage

Consult your pharmacist.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2016. Copyright(c) 2016 First Databank, Inc.

Usual Adult Dose for Pneumocystis Pneumonia Prophylaxis

50 to 75 mg orally once a week. Pyrimethamine is used in combination with dapsone and leucovorin. This is considered an alternative regimen for patients who do not tolerate trimethoprim-sulfamethoxazole.

Usual Pediatric Dose for Toxoplasmosis

Newborns and infants:
Initial: 2 mg/kg/day orally divided every 12 hours for 2 days, then 1 mg/kg/day once daily given with sulfadiazine for the first 6 months; next 6 months: 1 mg/kg/day 3 times per week with sulfadiazine; oral folinic acid 5 to 10 mg 3 times per week should be administered to prevent hematological toxicity.

1 to 12 years: 2 mg/kg/day divided every 12 hours for 3 days followed by 1 mg/kg/day (maximum 25 mg/day) once daily or divided twice daily for 4 weeks given with sulfadiazine; oral folinic acid 5 to 10 mg 3 times per week should be administered to prevent hematological toxicity.

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