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Home > Drug Category > Anti-Malarial > Primaquine and Equivalent

Primaquine (Primaquine Phosphate) Information

Primaquine (primaquine phosphate) is a foundational 8-aminoquinoline antimalarial medication, historically developed to combat the persistent forms of malaria. It is the only widely available drug, besides tafenoquine, indicated for the radical cure (prevention of relapse) of malaria caused by Plasmodium vivax and Plasmodium ovale. These species are characterized by dormant liver stages, known as hypnozoites, which cause recurring illness months or years after the initial infection. Primaquine is also crucial for transmission blocking, using a single low dose (SLD) to sterilize the infectious sexual forms of all Plasmodium species, especially P. falciparum. Dosing is carefully determined based on the patient's weight and species of parasite. Treatment must always be preceded by or concurrent with a blood schizonticide (like chloroquine or an ACT) to treat the acute phase of the illness.

The unique mechanism of action for primaquine centers on its status as a prodrug. It must be metabolized in the liver, primarily by the cytochrome P450 enzyme CYP2D6, into active, highly oxidizing metabolites. These metabolites are believed to generate reactive oxygen species (ROS) and interfere with mitochondrial respiration in both the hypnozoites (in the liver) and the gametocytes (in the blood). This oxidative process destroys the parasites, thereby preventing relapse and blocking transmission. The drug must be taken with food to enhance its oral bioavailability and reduce gastrointestinal side effects. The standard regimen for radical cure is 15 milligrams base daily for 14 days.

Primaquine Side Effects

Primaquine is generally well-tolerated at recommended doses, but specific side effects can occur. Common side effects are often associated with the initiation of therapy. They are usually mild, including nausea, vomiting, abdominal cramps, and epigastric distress. These gastrointestinal effects are dose-related and can often be minimized by taking the drug with a full meal. Dizziness and mild rash may also be reported.

However, more serious side effects can occur, particularly those related to the blood. If any of the following symptoms are experienced, the patient should stop taking the medication and seek immediate medical attention:

• Acute Hemolytic Anemia (Boxed Warning): The most critical adverse effect is severe, potentially fatal destruction of red blood cells. This reaction occurs predominantly in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. Symptoms include sudden fatigue, pallor, dark/black urine (hemoglobinuria), and jaundice.

• Cardiac Events: Primaquine has the potential to prolong the QT interval, a measure of heart rhythm. This can lead to serious arrhythmias, particularly in patients with pre-existing heart conditions, bradycardia, or uncorrected electrolyte imbalances (hypokalemia, hypomagnesemia).

• Hematological Complications: Leukopenia (a decrease in white blood cells) has been observed, particularly at higher doses.

• Methemoglobinemia: Can occur in any patient, but is more common in those with co-existing deficiencies (e.g., NADH methemoglobin reductase). This condition reduces the blood's ability to carry oxygen, potentially causing cyanosis (bluish-grey discoloration of the skin and lips), headache, and difficulty breathing.

Primaquine Precautions

Due to the high risk of severe hematological adverse effects, a detailed discussion of the patient's ethnic and family history is crucial. Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme activity testing is mandatory before prescribing primaquine to any patient. Treatment is absolutely contraindicated in severe G6PD deficiency, and primaquine is also contraindicated in pregnant women (due to unknown fetal G6PD status and risk of fetal hemolysis) and in nursing mothers whose infant is G6PD deficient. Even in patients with mild-to-moderate deficiency or those with unknown G6PD status, treatment should only proceed if the potential benefits outweigh the risks, and close hematological monitoring (including hemoglobin and hematocrit checks) can be performed. This often requires an alternative weekly dosing regimen of 0.75 milligrams per kilogram base once a week for 8 weeks. Caution is necessary in patients with pre-existing heart conditions due to the risk of QT prolongation, as well as in acutely ill patients suffering from systemic diseases (e.g., lupus erythematosus, rheumatoid arthritis) that predispose them to bone marrow suppression or granulocytopenia. Patients who are poor metabolizers of the liver enzyme CYP2D6 may have reduced efficacy, increasing the risk of malaria relapse, and this should be considered during treatment.

Do I need a prescription to order Primaquine?

Yes, a prescription is required from your physician to order Primaquine.