Primaquine

Primaquine phosphate is an 8-aminoquinoline antimalarial agent with a unique and critical role in modern parasitology. Unlike most antimalarials that target the asexual blood stages of Plasmodium parasites, primaquine’s primary clinical value lies in its potent activity against dormant hypnozoites of P. vivax and P. ovale, preventing relapses and achieving a true radical cure. It also exhibits gametocytocidal activity against P. falciparum, making it a vital tool for reducing malaria transmission in elimination programs. Its mechanism of action, though not fully elucidated, is believed to involve the generation of reactive oxygen species that are toxic to the parasite.

Features

• Active Pharmaceutical Ingredient: Primaquine phosphate
• Chemical Class: 8-Aminoquinoline
• Available Formulations: Oral tablets (typically 7.5 mg and 15 mg base equivalent)
• Mechanism of Action: Believed to interfere with mitochondrial electron transport and generate oxidative stress within the parasite
• Key Indications: Radical cure of Plasmodium vivax and P. ovale malaria; gametocytocidal clearance in P. falciparum malaria
• Prescription Status: Prescription-only medication

Benefits

• Eradicates Dormant Liver Stages: Uniquely targets and eliminates hypnozoites of P. vivax and P. ovale, preventing the characteristic relapses of these malaria species and providing a definitive cure.
• Interrupts Malaria Transmission: Effectively kills gametocytes of P. falciparum, rendering the patient non-infectious to mosquitoes and thus reducing community transmission.
• Oral Administration: Convenient tablet form allows for outpatient treatment and adherence to full course therapy outside a clinical setting.
• Proven Efficacy: Decades of clinical use and study have confirmed its critical role in malaria control and elimination strategies worldwide.
• Complementary Action: Works synergistically with blood schizonticides like chloroquine or artemisinin-based combination therapies (ACTs) to address all parasitic life stages.

Common use

Primaquine is exclusively used for the prophylaxis and treatment of malaria. Its primary use is for the “radical cure” of malaria caused by Plasmodium vivax or P. ovale. This involves co-administration with a blood schizonticide (e.g., chloroquine) to clear the acute blood-stage infection, followed by a course of primaquine to eliminate the dormant liver-stage hypnozoites and prevent future relapses. A secondary, but equally important, use is as a single dose to eliminate P. falciparum gametocytes, a strategy employed in mass drug administration programs to reduce transmission in areas moving toward malaria elimination. It is also used (with caution) for terminal prophylaxis in individuals with extensive exposure in endemic areas.

Dosage and direction

Dosing is weight-based and must be calculated as milligrams of primaquine base. A crucial prerequisite is testing for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency before administration.

• Radical Cure for P. vivax and P. ovale malaria: 0.5 mg base/kg/day (or 0.8 mg base/kg/day in Oceania and Southeast Asia due to emerging resistance) orally for 14 days. This is always preceded by an appropriate blood schizonticide.
• Gametocytocidal dose for P. falciparum: A single dose of 0.75 mg base/kg (max 45 mg), typically given alongside the primary ACT treatment.
• Administration: Tablets should be taken with food to minimize gastrointestinal upset. Adherence to the full prescribed course, especially the 14-day regimen, is absolutely critical for efficacy.

Precautions

• G6PD Testing Mandatory: Primaquine can cause severe hemolysis in patients with G6PD deficiency. Quantitative G6PD testing is required prior to initiation to determine eligibility and, if applicable, a modified dosing schedule.
• Pregnancy and Lactation: Contraindicated in pregnancy due to unknown fetal G6PD status and risk of hemolysis. Use with extreme caution during lactation; the infant must be tested for G6PD deficiency.
• Monitoring: Patients should be advised to monitor for signs of hemolysis (dark urine, jaundice, severe fatigue, shortness of breath) and seek immediate medical attention if they occur.
• NADH Methemoglobin Reductase Deficiency: Use with caution in individuals with this deficiency, as primaquine can induce methemoglobinemia.
• Corticosteroids: Concomitant use may increase the risk of toxicity.

Contraindications

• Known G6PD deficiency (absolute contraindication for standard dosing).
• Pregnancy.
• Breastfeeding an infant with unknown or known G6PD-deficient status.
• History of granulocytopenia or methemoglobinemia.
• Concomitant use of other hemolytic drugs or agents that suppress bone marrow function.
• Known hypersensitivity to primaquine or other 8-aminoquinolines (e.g., tafenoquine).

Possible side effect

• Hemolytic Anemia: The most serious adverse effect, ranging from mild to severe and potentially fatal, primarily in G6PD-deficient individuals.
• Methemoglobinemia: Can cause cyanosis (bluish discoloration of skin) and symptoms of hypoxia (shortness of breath, fatigue, headache).
• Gastrointestinal Disturbances: Nausea, vomiting, epigastric distress, and abdominal cramps are common, especially if taken on an empty stomach.
• Leukopenia: A less common side effect involving a decrease in white blood cell count.
• Cardiovascular Effects: High doses may depress cardiac conductivity and lead to arrhythmias.

Drug interaction

• Other Hemolytic Drugs: Concurrent use with drugs like dapsone, sulfonamides, nitrofurantoin, or quinidine increases the risk of hemolytic anemia.
• Bone Marrow Suppressants: May compound the risk of leukopenia or agranulocytosis.
• Drugs inducing Methemoglobinemia: (e.g., nitrates, local anesthetics like benzocaine) can have additive effects.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered on the same day. If the missed dose is not remembered until the next day, the patient should not double the dose. They should simply resume the normal dosing schedule. Maintaining the 14-day course is paramount; therefore, the treatment period may need to be extended by one day to ensure a full 14 doses are taken, if a dose was completely skipped. Patients should be instructed to never take two doses at once.

Overdose

Symptoms of overdose are an exaggerated presentation of its adverse effects: severe abdominal cramps, vomiting, burning epigastric distress, central nervous system and cardiovascular disturbances including cardiac arrhythmia and circulatory collapse, cyanosis due to methemoglobinemia, and profound hemolytic anemia with granulocytosis. There is no specific antidote. Management is strictly supportive and symptomatic, including gastric lavage if presented early, monitoring of electrolytes and hematologic parameters, and treatment of methemoglobinemia with methylene blue (contraindicated in G6PD deficiency). In cases of severe hemolysis, blood transfusions may be necessary.

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 prescribing physician is responsible for determining the appropriate diagnosis, dosage, and monitoring for each individual patient, including mandatory G6PD testing.

Reviews

“Primaquine remains the gold standard and an indispensable tool for the radical cure of relapsing malaria. While its safety profile demands rigorous pre-screening, its efficacy in preventing relapses is unmatched. The 14-day adherence challenge is real, but the clinical outcome justifies the effort.” – Infectious Disease Specialist, Southeast Asia

“From a public health perspective, the gametocytocidal activity of primaquine is a cornerstone of our malaria elimination strategy. A single dose significantly reduces the infectious reservoir and is a powerful intervention for blocking transmission.” – Medical Epidemiologist, Sub-Saharan Africa

“The necessity of G6PD testing cannot be overstated. It transforms primaquine from a potentially dangerous drug into a safe and life-saving one. Access to point-of-care quantitative G6PD tests is as important as access to the drug itself.” – Tropical Medicine Pharmacologist