Primaquine phosphate is an 8-aminoquinoline antimalarial agent with a distinct and critical role in the management of Plasmodium vivax and Plasmodium ovale malaria. Unlike blood schizonticides that only address the acute, symptomatic phase of the disease, primaquine’s unique mechanism of action targets the dormant hypnozoite forms residing in the liver. This action is essential for achieving a radical cure—the complete eradication of the parasite from the human host—and preventing relapses, which are a hallmark of these specific malaria species. Its use represents a cornerstone of public health strategies in endemic regions and is a vital tool for travel medicine.

Features

• Active Ingredient: Primaquine phosphate.
• Pharmacologic Class: 8-Aminoquinoline antimalarial.
• Primary Indication: Radical cure (anti-relapse therapy) of Plasmodium vivax and P. ovale malaria.
• Secondary Indication: Terminal prophylaxis (for individuals with recent exposure in endemic areas); primary prophylaxis (in specific, limited scenarios); and off-label use for Pneumocystis jirovecii pneumonia prophylaxis.
• Mechanism of Action: Active metabolites interfere with the mitochondrial electron transport chain in the parasite, generating oxidative stress that is lethal to both the hypnozoite (dormant liver stage) and the gametocyte (sexual blood stage).
• Dosage Forms: Oral tablets (typically 26.3 mg of primaquine phosphate, equivalent to 15 mg of primaquine base).
• Prescription Status: Prescription-only medication.

Benefits

• Achieves Radical Cure: Eradicates the dormant liver-stage hypnozoites of P. vivax and P. ovale, preventing the cycles of relapse that can occur months or even years after the initial infection.
• Reduces Transmission: Demonstrates potent gametocytocidal activity against Plasmodium falciparum, thereby reducing the infectious reservoir and helping to interrupt malaria transmission within communities.
• Enables Simplified Prophylaxis: Serves as a effective terminal prophylactic agent, allowing for a short course of treatment after leaving an endemic area to eliminate any potential hypnozoites acquired during travel.
• Oral Administration: Convenient oral tablet formulation facilitates outpatient treatment and improves adherence to the prescribed regimen.
• Critical Public Health Tool: Its targeted action is indispensable for malaria control and elimination programs in regions where relapsing malaria is prevalent.

Common use

Primaquine is unequivocally indicated for the radical cure of malaria caused by Plasmodium vivax and Plasmodium ovale. It is always administered concurrently with or following a blood schizonticide (such as chloroquine or artemisinin-based combination therapy) to treat the acute blood-stage infection. It is never used as monotherapy for acute malaria. A second common use is for terminal prophylaxis (“presumptive anti-relapse therapy”) in individuals who have had significant exposure in an endemic area and are now departing, aiming to eliminate any hypnozoites that may have been acquired. It is also used off-label as a second-line agent for prophylaxis against Pneumocystis jirovecii pneumonia in immunocompromised patients, particularly those intolerant to first-line therapies like trimethoprim-sulfamethoxazole.

Dosage and direction

Dosing is based on the primaquine base. The standard adult dose for radical cure is 30 mg base (52.6 mg phosphate) orally once daily for 14 days, taken with food to minimize gastrointestinal upset. For terminal prophylaxis, the dose is 30 mg base orally once daily for 14 days after leaving the endemic area. Dosing in children is weight-based: 0.5 mg base/kg (maximum 30 mg) once daily for 14 days.

Crucially, testing for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is mandatory prior to initiation. For patients with intermediate G6PD deficiency, a modified, once-weekly regimen (e.g., 45 mg base once weekly for 8 weeks) may be used under strict supervision. Primaquine is contraindicated in patients with severe G6PD deficiency and in pregnant women. Adherence to the full 14-day course is paramount for efficacy, even if the patient feels completely recovered.

Precautions

• G6PD Testing: The single most important precaution. G6PD deficiency must be ruled out before prescribing to avoid life-threatening hemolytic anemia.
• Pregnancy and Lactation: Contraindicated in pregnancy due to the unknown G6PD status of the fetus and risk of hemolytic anemia. Use during breastfeeding is generally avoided unless the infant has been confirmed to have normal G6PD levels.
• Cyanosis: The drug can cause methemoglobinemia, which may present as cyanosis (bluish discoloration of the skin). This requires monitoring, though it is often mild and self-limiting.
• Comorbidities: Use with caution in patients with pre-existing conditions that predispose them to hemolysis (e.g., rheumatoid arthritis, lupus) or NADPH deficiency.
• Supervision: The initial doses are ideally administered under clinical supervision in settings where G6PD testing is not immediately available.

Contraindications

• Known severe G6PD deficiency (absolute contraindication).
• Pregnancy.
• Breastfeeding by an infant with known or suspected G6PD deficiency.
• Known hypersensitivity to primaquine or any other 8-aminoquinoline drug (e.g., tafenoquine).
• Concomitant use of other agents with significant hemolytic potential (e.g., dapsone, nitrofurantoin) or that can cause methemoglobinemia.

Possible side effect

The most serious adverse effect is dose-dependent hemolytic anemia in G6PD-deficient individuals. Other potential side effects include:

• Gastrointestinal: Nausea, vomiting, epigastric distress, abdominal cramps. (Taking the drug with food can mitigate this).
• Hematologic: Methemoglobinemia (usually asymptomatic, but can cause cyanosis, headache, fatigue, and dyspnea), leukocytosis.
• Cardiovascular: Rare reports of cardiac arrhythmias.
• General: Headache, visual disturbances, pruritus (itching).

Drug interaction

• Other Hemolytic Agents: Concurrent use with drugs like dapsone, sulfonamides, nitrofurantoin, or quinidine can significantly increase the risk of hemolysis and methemoglobinemia.
• Myelosuppressive Agents: Drugs that suppress bone marrow function could potentially exacerbate hematologic toxicity.
• QT-Prolonging Agents: Primaquine may have a minor potential to prolong the QT interval; caution is advised when co-administering with other drugs known to have this effect (e.g., certain antifungals, antiarrhythmics, macrolide antibiotics).

Missed dose

If a dose is missed, it should be taken as soon as it is remembered on the same day. If it is not remembered until the next day, the patient should not double the dose but should simply resume the regular dosing schedule. Maintaining the full 14-day course is critical for efficacy. Inform the prescribing physician of any significant non-adherence.

Overdose

Symptoms of overdose are primarily an exaggeration of its known adverse effects: severe abdominal cramps, vomiting, burning epigastric distress, central nervous system and cardiovascular disturbances, cyanosis, methemoglobinemia, and profound hemolytic anemia in all individuals (not just those with G6PD deficiency), which can lead to granulocytopenia and acute renal failure. There is no specific antidote. Management is strictly supportive and symptomatic, including gastric lavage (if presented early), monitoring and supporting vital functions, and treatment of severe hemolysis and methemoglobinemia, which may require methylene blue administration and blood transfusions.

Storage

Store at room temperature (20°C to 25°C or 68°F to 77°F) in a tight, light-resistant container. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned.

Reviews

• Infectious Disease Specialist, Southeast Asia: “Primaquine is non-negotiable in our fight against vivax malaria. The 14-day course is a challenge for adherence, but its efficacy in preventing relapses is unmatched. Universal G6PD screening is the barrier we must overcome.”
• Tropical Medicine Physician, UK: “For the returning traveler with vivax malaria, a full course of primaquine is the standard of care. It closes the chapter on the infection. The side effect profile is manageable with proper patient selection and education.”
• Public Health Official, South America: “As we push for elimination, primaquine’s gametocytocidal activity is as important as its anti-relapse properties. It’s a key drug in our arsenal, but its use requires a robust healthcare infrastructure for safety monitoring.”
• Clinical Pharmacist, USA: “The necessity of G6PD testing cannot be overstated. It transforms primaquine from a potentially dangerous drug into a safe and life-saving one. Patient counseling on the importance of the full course is equally critical.”