Fansidar

Pyrimethamine is a prescription medication used to malaria or toxoplasmosis, a disease caused by parasites. Pyrimethamine belongs to a group of drugs called diaminopyrimidines. These help to fight against parasites.

This medication is comes in tablet form and is taken up to 2 times a day, with or without food. 

Common side effects of pyrimethamine include anorexia, vomiting, or anemia. 

Pyrimethamine is a prescription medication used to prevent and treat malaria. It is also used to treat toxoplasmosis, a disease caused by parasites. This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. 

In the U.S.

• Fansidar

Available Dosage Forms:

• Tablet

Therapeutic Class: Antimalarial Sulfonamide Combination

Pharmacologic Class: Folic Acid Antagonist

Chemical Class: Sulfonamide

If this medicine causes skin rash, itching, redness, sores in the mouth or on the genitals (sex organs), or sore throat, check with your doctor immediately. These may be early warning signs of more serious skin or related problems that could develop later.

Malaria is spread by mosquitoes. If you are living in, or will be traveling to, an area where there is a chance of getting malaria, the following mosquito-control measures will help to prevent infection:

• If possible, sleep under mosquito netting to avoid being bitten by malaria-carrying mosquitoes.
• Wear long-sleeved shirts or blouses and long trousers to protect your arms and legs, especially from dusk through dawn when mosquitoes are out.
• Apply mosquito repellant to uncovered areas of the skin from dusk through dawn when mosquitoes are out.

For patients taking this medicine to prevent malaria :

• It is very important that your doctor check your progress at regular visits. This medicine may cause blood problems, especially if it is taken for a long time.
• If this medicine causes anemia, your doctor may want you to take leucovorin (e.g., folinic acid, Wellcovorin) to help clear up the anemia. If so, it is important to take the leucovorin every day while you are taking this medicine. Do not miss any doses.
• Sulfadoxine and pyrimethamine combination may cause blood problems. These problems may result in a greater chance of certain infections, slow healing, and bleeding of the gums. Therefore, you should be careful when using regular toothbrushes, dental floss, and toothpicks. Dental work should be delayed until your blood counts have returned to normal. Check with your medical doctor or dentist if you have any questions about proper oral hygiene (mouth care) during treatment.
• Sulfadoxine and pyrimethamine combination may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:
  • Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.
  • Wear protective clothing, including a hat. Also, wear sunglasses.
  • Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.
  • Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.
  • Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

For patients taking this medicine to self-treat presumed malaria:

• Seek medical help as soon as possible, especially if your symptoms do not improve within 48 hours.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Fever
• increased sensitivity of skin to sunlight
• irritation or soreness of tongue
• skin rash

• Black, tarry stools
• bleeding or crusting sores on lips
• blood in urine or stools
• chest pain
• chills
• cough or hoarseness
• loss of appetite
• lower back or side pain
• muscle cramps or pain
• nausea
• painful or difficult urination
• pinpoint red spots on skin
• redness, blistering, peeling, or loosening of skin
• sore mouth
• sore throat
• sores, ulcers, and/or white spots in mouth
• sores on lips
• swelling in upper abdominal area
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

• Abdominal or stomach pain
• changes in facial skin color
• constipation
• fast or irregular breathing
• tenderness, itching, or burning of skin
• puffiness or swelling of the eyelids or around the eyes
• shortness of breath, troubled breathing, tightness in chest, and/or wheezing
• swelling of front part of neck

• Bleeding or bruising (severe)
• clumsiness or unsteadiness
• convulsions (seizures)
• fever and sore throat
• irritation or soreness of tongue
• loss of appetite
• unusual tiredness or weakness
• trembling
• vomiting (severe)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Anxiety
• diarrhea
• drowsiness
• headache
• nervousness

• Pain in joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

WARNING: FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF Fansidar HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS. Fansidar PROPHYLAXIS MUST BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH, IF A SIGNIFICANT REDUCTION IN THE COUNT OF ANY FORMED BLOOD ELEMENTS IS NOTED, OR UPON THE OCCURRENCE OF ACTIVE BACTERIAL OR FUNGAL INFECTIONS.

Microbiology

Sulfadoxine and pyrimethamine, the constituents of Fansidar, are folic acid antagonists. Sulfadoxine inhibits the activity of dihydropteroate synthase whereas pyrimethamine inhibits dihydrofolate reductase.

Sulfadoxine and pyrimethamine are active against the asexual erythrocytic stages of Plasmodium falciparum. Fansidar may also be effective against strains of P. falciparum resistant to chloroquine.

Strains of P. falciparum with decreased susceptibility to sulfadoxine and/or pyrimethamine can be selected in vitro or in vivo. P. falciparum malaria that is clinically resistant to Fansidar occurs frequently in parts of Southeast Asia and South America, and is also prevalent in East and Central Africa. Therefore, Fansidar should be used with caution in these areas. Likewise, Fansidar may not be effective for treatment of recrudescent malaria that develops after prior therapy (or prophylaxis) with Fansidar.

Treatment of Acute Malaria

Fansidar is indicated for the treatment of acute, uncomplicated P. falciparum malaria for those patients in whom chloroquine resistance is suspected. However, strains of P. falciparum (see CLINICAL PHARMACOLOGY: Microbiology) may be encountered which have developed resistance to Fansidar, in which case alternative treatment should be administered.

Prevention of Malaria

Malaria prophylaxis with Fansidar is not routinely recommended and should only be considered for travelers to areas where chloroquine-resistant P. falciparum malaria is endemic and sensitive to Fansidar, and when alternative drugs are not available or are contraindicated (see CONTRAINDICATIONS). However, strains of P. falciparum may be encountered which have developed resistance to Fansidar.

General

Oral Fansidar has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria, including hyperparasitemia, pulmonary edema or renal failure. Patients with severe malaria are not candidates for oral therapy. In the event of recrudescent P. falciparum infections after treatment with Fansidar or failure of chemoprophylaxis with Fansidar, patients should be treated with a different blood schizonticide.

Fansidar should be given with caution to patients with impaired renal or hepatic function, to those with possible folate deficiency and to those with severe allergy or bronchial asthma. As with some sulfonamide drugs, in glucose-6-phosphate dehydrogenase-deficient individuals, hemolysis may occur. Urinalysis with microscopic examination and renal function tests should be performed during therapy of those patients who have impaired renal function. Excessive sun exposure should be avoided.

Information for the Patient

Patients should be warned that at the first appearance of a skin rash, they should stop use of Fansidar and seek medical attention immediately. Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation.

Patients should also be warned that the appearance of sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura, jaundice or glossitis may be early indications of serious disorders which require prophylactic treatment to be stopped and medical treatment to be sought.

Females should be cautioned against becoming pregnant and should not breastfeed their infants during Fansidar therapy or prophylactic treatment.

Patients should be warned to keep Fansidar out of reach of children.

Patients also should be advised:

• that malaria can be a life-threatening infection;
• that Fansidar is being prescribed to help prevent or treat this serious infection;
• that no chemoprophylactic regimen is 100% effective, and protective clothing, insect repellents, and bednets are important components of malaria prophylaxis;
• to seek medical attention for any febrile illness that occurs after return from a malarious area and inform their physician that they may have been exposed to malaria;
• that in a small percentage of cases, patients are unable to take this medication because of side effects, and it may be necessary to change medications;
• that when used as prophylaxis, the first dose of Fansidar should be taken 1 or 2 days prior to arrival in an endemic area;
• that if the patient experiences any symptom that may affect the patient's ability to take this drug as prescribed, the physician should be contacted and alternative antimalarial medication should be considered.

Laboratory Tests

Regularly scheduled complete blood counts, liver enzyme tests and analysis of urine for crystalluria should be performed whenever Fansidar is administered for more than three months.

Drug Interactions

There have been reports which may indicate an increase in incidence and severity of adverse reactions when chloroquine is used with Fansidar as compared to the use of Fansidar alone. Fansidar is compatible with quinine and with antibiotics. However, antifolic drugs such as sulfonamides, trimethoprim, or trimethoprim-sulfamethoxazole combinations should not be used while the patient is receiving Fansidar for antimalarial prophylaxis. Fansidar has not been reported to interfere with antidiabetic agents.

If signs of folic acid deficiency develop, Fansidar should be discontinued. When recovery of depressed platelets or white blood cell counts in patients with drug-induced folic acid deficiency is too slow, folinic acid (leucovorin) may be administered in doses of 5 to 15 mg intramuscularly daily for 3 days or longer.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Pyrimethamine was not found carcinogenic in female mice or in male and female rats. The carcinogenic potential of pyrimethamine in male mice could not be assessed from the study because of markedly reduced life-span. Pyrimethamine was found to be mutagenic in laboratory animals and also in human bone marrow following 3 or 4 consecutive daily doses totaling 200 mg to 300 mg. Pyrimethamine was not found mutagenic in the Ames test. Testicular changes have been observed in rats treated with 105 mg/kg/day of Fansidar and with 15 mg/kg/day of pyrimethamine alone. Fertility of male rats and the ability of male or female rats to mate were not adversely affected at dosages of up to 210 mg/kg/day of Fansidar. The pregnancy rate of female rats was not affected following their treatment with 10.5 mg/kg/day, but was significantly reduced at dosages of 31.5 mg/kg/day or higher, a dosage approximately 30 times the weekly human prophylactic dose or higher.

Pregnancy

Fansidar has been shown to be teratogenic in rats when given in weekly doses approximately 12 times the weekly human prophylactic dose. Teratology studies with pyrimethamine plus sulfadoxine (1:20) in rats showed the minimum oral teratogenic dose to be approximately 0.9 mg/kg pyrimethamine plus 18 mg/kg sulfadoxine. In rabbits, no teratogenic effects were noted at oral doses as high as 20 mg/kg pyrimethamine plus 400 mg/kg sulfadoxine.

There are no adequate and well-controlled studies in pregnant women. However, due to the teratogenic effect shown in animals and because pyrimethamine plus sulfadoxine may interfere with folic acid metabolism, Fansidar therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential who are traveling to areas where malaria is endemic should be warned against becoming pregnant, and should be advised to practice contraception during prophylaxis with Fansidar and for three months after the last dose.

See CONTRAINDICATIONS

Nursing Mothers

See CONTRAINDICATIONS

Pediatric Use

Fansidar should not be given to infants less than 2 months of age because of inadequate development of the glucuronide-forming enzyme system.

Geriatric Use

Clinical studies of Fansidar did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pyrimethamine is excreted into human milk. In three women treated with a combination of dapsone and pyrimethamine, the milk: serum ratio of pyrimethamine ranged from 0.46 to 0.66. The American Academy of Pediatrics considers pyrimethamine to be compatible with breast-feeding. Sulfonamides in general are excreted into human milk. For healthy, full-term neonates, sulfonamide excretion into breast milk does not pose a significant risk. Sulfonamides should be avoided if the infant being breast-fed is ill, premature, or has hyperbilirubinemia or glucose-6-phosphate dehydrogenase deficiency. The American Academy of Pediatrics considers some other sulfonamides compatible with breast-feeding of full-term healthy infants. The manufacturer states that sulfadoxine-pyrimethamine therapy is contraindicated during breast-feeding due to the risk of kernicterus from the excretion of sulfonamide into breast milk.