Primaquine phosphate is an 8-aminoquinoline antimalarial agent with a distinct and critical role in modern parasitology. Its primary function extends beyond the suppression of acute malarial symptoms; it is the therapeutic gold standard for achieving radical cure, specifically targeting the dormant hypnozoite forms of Plasmodium vivax and Plasmodium ovale that reside in the liver. This action prevents relapse, a hallmark of these parasitic species. Its use is a cornerstone of public health strategies in endemic regions and is essential for travelers returning from these areas. Administration requires careful medical supervision due to its specific indications and potential for hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Features

• Active Pharmaceutical Ingredient: Primaquine phosphate.
• Drug Class: 8-Aminoqunoline antimalarial.
• Primary Mechanism: Activity against intrahepatic hypnozoites of P. vivax and P. ovale.
• Secondary Mechanism: Gametocytocidal activity against Plasmodium falciparum.
• Standard Formulation: Oral tablets (typically 26.3 mg of primaquine phosphate, equivalent to 15 mg of primaquine base).
• Prescription Status: Rx-only medication.

Benefits

• Achieves radical cure by eliminating the dormant liver-stage hypnozoites of P. vivax and P. ovale, preventing relapses of malaria weeks or months after the initial infection.
• Significantly reduces the reservoir of transmissible malaria by effectively killing gametocytes, the sexual blood-stage forms of the parasite that are infectious to mosquitoes.
• Provides a targeted therapeutic option that complements blood schizonticides like chloroquine, which only address the acute asexual blood stage infection.
• Contributes to regional malaria control and elimination programs by preventing transmission and recurrent cases.
• Offers a well-established treatment protocol with decades of clinical evidence supporting its efficacy when used appropriately.

Common use

Primaquine is exclusively indicated for the radical cure (anti-relapse therapy) of malaria caused by Plasmodium vivax and Plasmodium ovale. It is never used as a monotherapy for acute treatment; it must be co-administered with a blood schizonticide, such as chloroquine or artemisinin-based combination therapy (ACT), to first clear the asexual blood-stage parasites. A second, critical use is as a single-dose gametocytocide to eliminate Plasmodium falciparum gametocytes, thereby reducing the transmissibility of the infection from the treated patient to mosquitoes. It is not indicated for malaria prophylaxis.

Dosage and direction

Dosing is based on the primaquine base content. G6PD testing is absolutely mandatory prior to initiation to determine eligibility and appropriate dosing.

• Radical Cure for P. vivax and P. ovale Malaria: The standard regimen is 30 mg base (2 tablets) orally once daily for 14 days, given concurrently with a blood schizonticide. For patients with G6PD deficiency, alternative regimens (e.g., 45 mg base once per week for 8 weeks) may be used under strict supervision. Pediatric dosing is weight-based: 0.5 mg base/kg once daily (up to adult dose) for 14 days.
• Gametocytocidal Action for P. falciparum: A single dose of 45 mg base (3 tablets) is administered, typically at the same time as the primary ACT treatment. This is contraindicated in patients with G6PD deficiency.
• Administration: Tablets should be taken with food to minimize gastric upset.

Precautions

The most significant precaution is the risk of dose-related hemolytic anemia in patients with G6PD deficiency. Quantitative G6PD testing must be performed before prescribing. Use with extreme caution in patients with other conditions predisposing to hemolysis (e.g., other enzyme deficiencies, autoimmune diseases) or with pre-existing anemia, neutropenia, or cyanosis. Primaquine should be used cautiously in patients with a history of rheumatoid arthritis or lupus erythematosus, as it may exacerbate these conditions. It is not recommended during pregnancy; the benefits must profoundly outweigh the risks due to the unknown G6PD status of the fetus. Lactating women should not nurse unless the infant has been tested for G6PD deficiency.

Contraindications

• Known G6PD deficiency (for the standard 14-day course; see dosage for exceptions).
• Pregnancy.
• Concomitant use with other drugs known to cause hemolysis or bone marrow suppression (e.g., quinacrine).
• A history of granulocytopenia or methemoglobinemia caused by primaquine.
• Breastfeeding by an untested infant.
• Known hypersensitivity to primaquine or any component of the formulation.

Possible side effect

The most serious adverse reaction is hemolytic anemia, particularly in G6PD-deficient individuals. Other common side effects are typically gastrointestinal and include:

• Abdominal cramps
• Nausea
• Vomiting
• Epigastric distress
• Less common effects include:
• Methemoglobinemia (causing cyanosis)
• Leukopenia (low white blood cell count)
• Granulocytopenia
• Hypertension
• Headache
• Pruritus (itching)

Drug interaction

The most critical and absolutely contraindicated interaction is with quinacrine, which potentiates the toxic effects of primaquine. Concomitant use can lead to severe plasma level elevation of primaquine and a significantly increased risk of toxicity. Use caution with other bone marrow-suppressing or hemolysis-inducing agents. Drugs that are metabolized by or inhibit CYP450 enzymes may potentially interact, though these are less well-defined.

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. They should simply resume the regular dosing schedule with the next planned dose. Maintaining the full 14-day course is critical for efficacy.

Overdose

Symptoms of overdose are an exaggerated extension of its known adverse effects, primarily severe hemolytic anemia, methemoglobinemia, leukopenia, and abdominal distress. Symptoms of hemolysis include dark urine, jaundice, and profound fatigue. Methemoglobinemia presents as cyanosis (bluish skin), shortness of breath, and dizziness. There is no specific antidote. Management is supportive and includes immediate discontinuation of the drug, gastric lavage if ingestion was recent, and treatment of complications (e.g., methylene blue for severe methemoglobinemia, blood transfusions for severe anemia).

Storage

Store at controlled room temperature (20°C to 25°C or 68°F to 77°F). Keep the bottle tightly closed and protect from light and moisture. 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 and publisher are not responsible for any errors or omissions or for any outcomes resulting from the use of this information.

Reviews

• “As an infectious disease specialist, primaquine is an indispensable tool in our arsenal. Its ability to prevent relapse in vivax malaria is unmatched. The necessity for pre-treatment G6PD screening cannot be overstated—it is the key to safe and effective use.” – Dr. A. Sharma, MD
• “From a public health perspective, the gametocytocidal activity of primaquine is a critical component of malaria elimination campaigns. A single dose can drastically reduce transmission potential.” – Public Health Official, SE Asia Region
• “While the side effect profile requires vigilance, when administered correctly to appropriate patients, the benefit of a definitive cure far outweighs the risks. It remains the standard of care for a reason.” – Clinical Pharmacologist
• “The 14-day course can be challenging for patient adherence, but its efficacy is well-documented. Patient education on the importance of completing the full regimen is crucial.” – Travel Medicine Nurse Practitioner