Pyrimethamine: Uses, Mechanism of Action, Side Effects, Dosage and Precautions

Generic names: Pyrimethamine

Brand names: Daraprim

Drug class: antiparasitic agents

Uses   |   Mechanism of Action   |   Side Effects   |   Dosage   |   Precautions   |   Interactions   |   Overdose   |   FAQs

What is pyrimethamine?

Pyrimethamine is a medication with a wide array of applications. It primarily falls under the category of antiparasitic drugs, making it effective in the treatment of malaria, toxoplasmosis and other parasitic infections.

What is pyrimethamine used for?

• Malaria treatment: Pyrimethamine is used in combination with other antimalarial drugs, such as sulfadoxine, to treat uncomplicated malaria. This combination therapy is particularly effective in regions where the malaria parasite has developed resistance to other drugs. Pyrimethamine works by inhibiting the growth and replication of the Plasmodium parasite in the red blood cells, thereby reducing the severity of the infection.
• Malaria prophylaxis: Pyrimethamine is also used for malaria prophylaxis, especially in travelers visiting areas where malaria is endemic. It can be taken as a preventative measure before, during, and after traveling to such regions to reduce the risk of contracting the disease.
• Toxoplasmosis: Pyrimethamine, often in combination with sulfadiazine and leucovorin, is used to treat toxoplasmosis, a parasitic infection caused by the protozoan Toxoplasma gondii. This condition can be particularly dangerous for individuals with weakened immune systems, such as those with HIV/AIDS.
• Treatment of cystoisosporiasis: Pyrimethamine can be used to treat cystoisosporiasis, a parasitic infection of the intestines caused by the protozoan Cystoisospora belli. This condition can lead to severe diarrhea and is more common in people with compromised immune systems.

What is the mechanism of action of pyrimethamine?

The mechanism of action pyrimethamine revolves around inhibiting the dihydrofolate reductase (DHFR) enzyme in parasites. This enzyme is crucial for the production of tetrahydrofolate (THF), an essential cofactor for DNA, RNA, and amino acid synthesis. By selectively targeting the parasite’s DHFR enzyme while sparing the human DHFR enzyme, pyrimethamine disrupts the folate metabolism pathway in parasites, starving them of the necessary building blocks for growth and replication.

This selective action minimizes harm to human cells and makes pyrimethamine a potent weapon against malaria and other parasitic infections. As part of combination therapies, like sulfadoxine-pyrimethamine (SP), pyrimethamine further enhances its effectiveness in treating malaria. This mechanism of action underscores its significance in the fight against parasitic infections, particularly in regions where drug-resistant strains of malaria are prevalent.

What are the side effects of pyrimethamine?

The side effects can vary in severity, with some being relatively common and mild, while others are more serious and less frequent.

Common Side Effects:

• Gastrointestinal Disturbances: Side effects include nausea, vomiting, diarrhea, and abdominal pains. These symptoms are usually mild and can often be managed by taking the medication with food.
• Mouth Ulcers: Some individuals may experience mouth sores or ulcers while taking pyrimethamine. Maintaining good oral hygiene can help alleviate this side effect.
• Skin Reactions: Mild skin rashes or itching may occur in response to pyrimethamine. These reactions are generally not severe and often resolve on their own without the need to discontinue the medication.
• Headache: Pyrimethamine may cause mild to moderate headaches in some people. These headaches are usually manageable with over-the-counter pain relievers.
• Elevated Liver Enzymes: In rare cases, pyrimethamine can lead to elevated liver enzymes, which can be detected through blood tests. It’s important to monitor liver function during treatment.

Serious Side Effects:

• Blood Disorders: Pyrimethamine can cause bone marrow suppression, leading to a decrease in red blood cells, white blood cells, and platelets. This condition can result in anemia, increased susceptibility to infections, and a higher risk of bleeding. Regular blood tests are necessary to monitor for these side effects.
• Allergic Reactions: Although rare, severe allergic reactions to pyrimethamine can occur. Symptoms may include difficulty breathing, swelling of the face or throat, severe rash, or hives. Immediate medical attention is required if any of these symptoms occur.
• Liver and Kidney Damage: In very rare cases, pyrimethamine has been associated with severe liver and kidney damage. Signs of liver or kidney problems, such as jaundice (yellowing of the skin or eyes) or changes in urine output, should be reported to a healthcare provider promptly.
• Folate Deficiency: Pyrimethamine’s mechanism of action involves inhibiting folate metabolism. While this is the desired effect against parasites, it can lead to folate deficiency in the patient. In pregnant women, this can pose risks to the developing fetus, so careful monitoring is essential.

What is the dosage for pyrimethamine?

The dosage for pyrimethamine varies depending on the specific medical condition it is being used to treat and the patient’s age, weight, and overall health. It is crucial to follow the dosing instructions provided by a healthcare professional, and to take the prescribed dosage to ensure the medication’s effectiveness and minimize the risk of side effects.

Malaria treatment:

• The standard dosage for pyrimethamine in the treatment of uncomplicated malaria is usually 2 or 3 tablets taken orally as a single dose, following the third day course of quinine.
• For children, the dosage is weight-based and may range from 1 mg to 2 mg per kilogram of body weight as a single dose.

Malaria prophylaxis:

• When used for malaria prevention in adults, the typical dosage is 25 mg once a week.
• For children, the dosage is weight-based, and it is usually 1 mg to 2 mg per kilogram of body weight once a week.
• The prophylactic treatment should begin one to two weeks before traveling to a malaria-endemic region and continue during the trip and for four weeks after returning.

Toxoplasmosis:

• In the treatment of toxoplasmosis, the usual adult dosage 50-75 mg q.d PO for 1-3 weeks, then 25-37.5 mg q.d PO for 4-5 weeks
• The specific dosage may vary based on the severity of the infection and individual patient factors.
• It is often administered in combination with other medications like sulfadiazine and leucovorin.

Cystoisosporiasis:

• For the treatment of cystoisosporiasis, the recommended adult dosage is 50-75 mg per day.
• The dosage for children is weight-based, generally ranging from 1 mg to 2 mg per kilogram of body weight per day.

What are the precautions to consider when taking pyrimethamine?

When taking pyrimethamine, it’s essential to observe certain precautions to ensure the safe and effective use of the medication.

Pyrimethamine is a prescription medication. It should only be taken under the guidance of a qualified healthcare professional who can assess the appropriateness of its use for your specific condition and medical history.

Inform your healthcare provider of any known allergies or sensitivities you may have, especially to sulfa drugs or other antimalarial medications. This information is crucial in determining the safety of pyrimethamine for you.

Pyrimethamine should be used cautiously during pregnancy. It can lead to folate deficiency, which may be harmful to the developing fetus. The benefits and risks should be discussed with your healthcare provider. If you are breastfeeding, consult your doctor, as pyrimethamine may be excreted in breast milk, potentially affecting the nursing infant.

To mitigate the risk of folate deficiency, your healthcare provider may recommend folate supplementation, especially in pregnant women and individuals at higher risk of folate depletion.

For certain conditions like malaria, regular blood tests are necessary to monitor your blood cell counts and liver function. This helps detect potential side effects, such as bone marrow suppression.

Inform your healthcare provider about all medications, including over-the-counter drugs and herbal supplements, that you are taking. Some medications may interact with pyrimethamine, potentially altering its effectiveness or increasing the risk of side effects.

If you have kidney or liver problems, your healthcare provider will need to adjust the dosage of pyrimethamine accordingly. Impaired organ function can affect the drug’s metabolism and clearance from the body.

What drugs interact with pyrimethamine?

Pyrimethamine, like many medications, can interact with other drugs, potentially affecting its effectiveness or increasing the risk of side effects.

• Sulfonamide antibiotics: Pyrimethamine should be used cautiously in combination with sulfonamide antibiotics like sulfadoxine. This combination is often used in the treatment of malaria. When taken together, these drugs can enhance their respective effects but may also increase the risk of adverse reactions, particularly related to the blood cells.
• Trimethoprim: Combining pyrimethamine with trimethoprim, a medication used to treat various bacterial infections, can increase the risk of folate deficiency and bone marrow suppression. Trimethoprim has a similar mechanism of action to pyrimethamine in inhibiting dihydrofolate reductase (DHFR).
• Methotrexate: Methotrexate, commonly used in cancer treatment and for certain autoimmune diseases, also inhibits DHFR. When taken with pyrimethamine, there is a risk of additive effects, potentially leading to severe folate deficiency. Close monitoring and dose adjustments may be necessary.
• Phenytoin: Phenytoin, an anticonvulsant used in the treatment of epilepsy, may interfere with the metabolism of pyrimethamine. This can result in decreased effectiveness of pyrimethamine in the treatment of parasitic infections. Dose adjustments or alternative anticonvulsants may be considered.
• Other antimalarial medications: When used in combination therapy for malaria, pyrimethamine may interact with other antimalarial medications. These combinations are designed to enhance effectiveness and reduce the risk of drug resistance. Sulfadoxine-pyrimethamine (SP) is a notable example, and any changes or additions to this combination should be made under medical supervision.

It’s important to note that the above list is not exhaustive, and drug interactions can vary depending on the specific drugs, dosages, and individual patient factors.

Overdose

An overdose of pyrimethamine can be a serious medical emergency and may result in a range of symptoms and complications. Common symptoms of an overdose include nausea, vomiting, diarrhea, confusion, and severe abdominal pain. In severe cases, it may even result in seizures and methemoglobinemia, a condition causing oxygen deficiency. If you suspect an overdose or experience any unusual symptoms after taking pyrimethamine, it’s essential to seek immediate medical attention.

Takeaway

Pyrimethamine is a valuable medication used in the treatment and prevention of malaria. Its mechanism of action involves disrupting the folic acid synthesis pathway in malaria parasites. While generally safe when used as prescribed, it can cause side effects and interact with other drugs. It is essential to take pyrimethamine as directed by a healthcare professional and be aware of potential precautions and drug interactions.

Frequently Asked Questions (FAQs)