Pyrimethamine

Pyrimethamine Uses, Dosage, Side Effects, Food Interaction and all others data.

Pyrimethamine is a folic acid antagonist structurally similar to trimethoprim. It inhibits parasitic dihydrofolate reductase, thus inhibiting vital tetrahydrofolic acid synthesis. It is active against pre-erythrocytic forms and is also a slow-acting schizontocide.

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Trade Name Pyrimethamine
Availability Prescription only
Generic Pyrimethamine
Pyrimethamine Other Names Chloridine, Chloridyn, Diaminopyritamin, Ethylpyrimidine, Pirimetamina, Primethamine, Pyriméthamine, Pyrimethamine, Pyrimethaminum
Related Drugs doxycycline, azithromycin, clindamycin, hydroxychloroquine, sulfamethoxazole / trimethoprim, Bactrim, Zithromax, Plaquenil, clarithromycin, Bactrim DS
Weight 25mg
Type Oral tablet
Formula C12H13ClN4
Weight Average: 248.711
Monoisotopic: 248.082874143
Protein binding

87%

Groups Approved, Investigational, Vet approved
Therapeutic Class Anti-malarial drugs
Manufacturer
Available Country United States
Last Updated: September 19, 2023 at 7:00 am
Pyrimethamine
Pyrimethamine

Uses

Treatment of Toxoplasmosis: Pyrimethamine is used for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination.

Treatment of Acute Malaria: Pyrimethamine is also used for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are used and preferable for the treatment of acute malaria. However, conjoint use of Pyrimethamine with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia.

Chemoprophylaxis of Malaria: Pyrimethamine is used for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas.

Pyrimethamine is also used to associated treatment for these conditions: Plasmodium Infections, Toxoplasmosis, Acute Malaria

How Pyrimethamine works

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.

Dosage

Pyrimethamine dosage

For Treatment of Toxoplasmosis: The dosage of Pyrimethamine for the treatment of toxoplasmosis must be carefully adjusted so as to provide maximum therapeutic effect and a minimum of side effects. At the dosage required, there is a marked variation in the tolerance to the drug. Young patients may tolerate higher doses than older individuals. Concurrent administration offolinic acidis strongly recommended in all patients.

The adultstartingdose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g. sulfadoxine. This dosage is ordinarily continued for 1 to 3 weeks, depending on the response of the patient and tolerance to therapy. The dosage may then be reduced to about one half that previously given for each drug and continued for an additional 4 to 5 weeks.

The pediatric dosage of Pyrimethamine is 1 mg/kg/day divided into 2 equal daily doses; after 2 to 4 days this dose may be reduced to one half and continued for approximately 1 month. The usual pediatric sulfonamide dosage is used in conjunction with Pyrimethamine.

For Treatment of Acute Malaria: Pyrimethamine is NOT recommended alone in the treatment of acute malaria. Fast-acting schizonticides, such as chloroquine or quinine, are indicated for treatment of acute malaria. However, Pyrimethamine at a dosage of 25 mg daily for 2 days with a sulfonamide will initiate transmission control and suppression of non-falciparum malaria.Pyrimethamine is only recommended for patients infected in areas where susceptible plasmodia exist. Should circumstances arise wherein Pyrimethamine must be used alone in semi- immune persons, the adult dosage for acute malaria is 50 mg for 2 days; children 4 through 10 years old may be given 25 mg daily for 2 days. In any event, clinical cure should be followed by the once-weekly regimen described below for chemoprophylaxis. Regimens which include suppression should be extended through any characteristic periods of earlyrecrudescenceand late relapse, i.e., for at least 10 weeks in each case.

For Chemoprophylaxis of Malaria:

  • Adults and pediatric patients over 10 years: 25 mg (1 tablet) once weekly
  • Children 4 through 10 years:12.5 mg (½ tablet) once weekly
  • Infants and children under 4 years: 6.25 mg (¼ tablet) once weekly.

Side Effects

Hypersensitivity reactions, occasionally severe (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and anaphylaxis), and hyperphenylalaninemia, can occur particularly when pyrimethamine is administered concomitantly with a sulfonamide. Consult the complete prescribing information for the relevant sulfonamide for sulfonamideassociated adverse events. With doses of pyrimethamine used for the treatment of toxoplasmosis, anorexia and vomiting may occur. Vomiting may be minimized by giving the medication with meals; it usually disappears promptly upon reduction of dosage. Doses used in toxoplasmosis may produce megaloblastic anemia, leukopenia, thrombocytopenia, pancytopenia, neutropenia, atrophic glossitis, hematuria, and disorders of cardiac rhythm.

Precaution

The recommended dosage for chemoprophylaxis of malaria should not be exceeded. Pyrimethamine should be used with caution in patients with impaired renal or hepatic function or in patients with possible folate deficiency, such as individuals with malabsorption syndrome, alcoholism, or pregnancy, and those receiving therapy, such as phenytoin, affecting folate levels

Interaction

Pyrimethamine may be used with sulfonamides, quinine and other antimalarials, and with other antibiotics. However, the concomitant use of other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim-sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression. If signs of folate deficiency develop, pyrimethamine should be discontinued. Folinic acid (leucovorin) should be administered until normal hematopoiesis is restored

Food Interaction

  • Administer folic acid supplement. Folic acid need is increased.
  • Take with food. Food reduces irritation.

Elimination Route

Well absorbed with peak levels occurring between 2 to 6 hours following administration

Half Life

96 hours

Pregnancy & Breastfeeding use

Pregnancy Category C. Pyrimethamine has been shown to be teratogenic in rats when given in oral doses 7 times the human dose for chemoprophylaxis of malaria or 2.5 times the human dose for treatment of toxoplasmosis. At these doses in rats, there was a significant increase in abnormalities such as cleft palate, brachygnathia, oligodactyly, and microphthalmia. Pyrimethamine has also been shown to produce terata such as meningocele in hamsters and cleft palate in miniature pigs when given in oral doses 170 and 5 times the human dose, respectively, for chemoprophylaxis of malaria or for treatment of toxoplasmosis.

There are no adequate and well-controlled studies in pregnant women. Pyrimethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Concurrent administration of folinic acid is strongly recommended when used for the treatment of toxoplasmosis during pregnancy.

Nursing Mothers: Pyrimethamine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from pyrimethamine and from concurrent use of a sulfonamide with Pyrimethamine for treatment of some patients with toxoplasmosis, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Contraindication

Use of Pyrimethamine is contraindicated in patients with known hypersensitivity to pyrimethamine or to any component of the formulation. Use of the drug is also contraindicated in patients with documented megaloblastic anemia due to folate deficiency.

Special Warning

Geriatric Use: Clinical studies of Pyrimethamine 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.

Innovators Monograph

You find simplified version here Pyrimethamine

Pyrimethamine contains Pyrimethamine see full prescribing information from innovator Pyrimethamine Monograph, Pyrimethamine MSDS, Pyrimethamine FDA label

FAQ

What is Pyrimethamine used for?

Pyrimethamine is usually used together with a sulfonamide to treat toxoplasmosis.The treatment of Toxoplasma gondii infection.

How does Pyrimethamine work?

Pyrimethamine works by stopping this parasite from reproducing once it is in the bloodstream. It does this by blocking the action of a compound that is found in the parasite.

What are the common side effects of Pyrimethamine?

Common side effects of Pyrimethamine are include:

  • nausea,
  • vomiting,
  • loss of appetite,
  • insomnia,
  • headache,
  • lightheadedness, or.
  • dry mouth

Is Pyrimethamine safe during pregnancy?

Pyrimethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Pyrimethamine should also be given if it is used for the treatment of toxoplasmosis during pregnancy.

Is Pyrimethamine safe during breastfeeding?

Pyrimethamine can pass into breast milk and may cause side effects in the nursing baby. Tell your doctor if you are breast-feeding.

Can I drink alcohol with Pyrimethamine?

Do not drink alcohol while you are using Pyrimethamine. Do not take other medicines unless they have been discussed with your doctor.

When should be best taken of Pyrimethamine?

Pyrimethamine should be taken 1 or 2 days before arrival in an endemic area; administration should be continued during the stay and for 4 to 6 weeks after return.

How long does Pyrimethamine take to work?

Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration.

Who should not take Pyrimethamine?

You should not use Pyrimethamine if you are allergic to it, or if you have: a blood cell disorder called megaloblastic anemia that has been caused by folate deficiency.

Can I take Pyrimethamine for a long time?

Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. It is best to take this medicine with food to help prevent vomiting and loss of appetite.

How long can I take Pyrimethamine?

The recommended adult starting dose is 50 to 75 mg of daily with 1 to 4 g daily of a sulfonamide for 1 to 3 weeks depending on the response of the patient and tolerance to therapy.

How do I take Pyrimethamine?

Take Pyrimethamine by mouth usually once or twice daily or as directed by your doctor.

How often should I take Pyrimethamine?

Take this medication by mouth usually once or twice daily or as directed by your doctor.

What happens if I miss a dose of Pyrimethamine?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose on Pyrimethamine?

Seek emergency medical attention. 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 , and weak or shallow breathing.

What happen If I stop taking Pyrimethamine?

Do not stop taking it before completing this prescription unless directed to do so by your doctor, even if you feel better. Skipping or changing your dose without approval from your doctor may cause the amount of parasites to increase, make the infection more difficult to treat (resistant), or worsen side effects.

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*** Taking medicines without doctor's advice can cause long-term problems.
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