Primaquine: The Definitive Antimalarial for Radical Cure
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Primaquine phosphate is an 8-aminoquinoline antimalarial agent with a distinct and critical role in modern parasitology. Unlike suppressive therapies, its primary function is to achieve a radical cure, specifically targeting the dormant hypnozoite stages of Plasmodium vivax and Plasmodium ovale parasites that reside in the liver. This action prevents relapse, a hallmark of these malaria species, which can occur weeks or even months after the initial infection. Its use is a cornerstone of public health strategies in endemic regions and is essential for travelers returning from these areas. This comprehensive monograph details the pharmacology, clinical application, and essential safety considerations for this potent therapeutic.
Features
- Active Ingredient: Primaquine phosphate
- Drug Class: 8-Aminoquinoline antimalarial
- Primary Mechanism: Tissue schizonticide; targets exo-erythrocytic (liver) hypnozoites
- Secondary Mechanism: Gametocytocide; interrupts transmission of P. falciparum
- Available Formulations: Oral tablets (typically 26.3 mg primaquine phosphate, equivalent to 15 mg primaquine base)
- Pharmacokinetics: Rapidly absorbed; extensive tissue distribution; metabolized hepatically
Benefits
- Eradicates Dormant Parasites: Achieves a radical cure by eliminating the hypnozoite forms of P. vivax and P. ovale, preventing relapses of malaria.
- Breaks the Transmission Cycle: Acts as a potent gametocytocide for P. falciparum, rendering patients non-infectious to mosquitoes and reducing community transmission.
- Oral Administration: Convenient tablet form facilitates outpatient treatment and improves adherence to the full course of therapy.
- Proven Efficacy: Decades of clinical use and study have confirmed its critical role as the only widely available medication for radical cure.
- Synergistic Use: Effectively paired with a blood schizonticide (e.g., chloroquine) to treat both the acute blood-stage infection and the dormant liver reservoir simultaneously.
Common use
Primaquine is exclusively indicated for the radical cure (prevention of relapse) of malaria caused by Plasmodium vivax and Plasmodium ovale. It is always administered concurrently with or following a blood schizonticide to treat the acute asexual erythrocytic infection. A second, critical use is as a gametocytocidal agent to eliminate the sexual stages of Plasmodium falciparum gametocytes. This use does not treat the clinical infection but is a public health measure to reduce the transmissibility of the parasite from an infected human to a mosquito, thereby helping to control the spread of malaria in endemic areas. It is not used for prophylaxis.
Dosage and direction
Dosing is based on the primaquine base (15 mg). The standard adult dose for radical cure of P. vivax or P. ovale malaria is 30 mg base (52.6 mg phosphate) orally once daily for 14 days, taken with food to minimize gastrointestinal upset. This is co-administered with chloroquine or, in chloroquine-resistant areas, an appropriate alternative blood schizonticide. Pediatric dosing is 0.5 mg base/kg (maximum 30 mg base) once daily for 14 days. For terminal prophylaxis, a dose of 30 mg base daily for 14 days is used after departure from a malaria-endemic area. As a single-dose gametocytocide for P. falciparum, the dose is 45 mg base as a single dose. Adherence to the full 14-day course is absolutely paramount for efficacy.
Precautions
The most significant precaution is the risk of hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD quantitative testing is mandatory prior to initiation of therapy. Primaquine is contraindicated in patients with severe G6PD deficiency and must be used with extreme caution and possibly an alternative regimen in those with mild to moderate deficiency. Use with caution in patients with a history of granulocytopenia, methemoglobinemia, or rheumatoid arthritis. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and generally avoided during breastfeeding unless the infant has been tested for G6PD deficiency. Nicotinamide adenine dinucleotide (NADH) methemoglobin reductase deficiency is also a contraindication.
Contraindications
- Known G6PD deficiency (severe variants).
- Pregnancy (due to unknown G6PD status of the fetus and risk of hemolysis).
- Concomitant use with other drugs known to cause hemolysis or depress the myeloid elements of the bone marrow.
- Known hypersensitivity to primaquine or other 8-aminoquinolines.
- Active rheumatoid arthritis or lupus erythematosus (may be exacerbated).
- NADH methemoglobin reductase deficiency.
Possible side effect
The most serious adverse reaction is dose-related hemolytic anemia in individuals with G6PD deficiency. Other common side effects are generally gastrointestinal and include: abdominal cramps, nausea, vomiting, and epigastric distress. These can often be mitigated by taking the drug with food. Less common effects include leukopenia (low white blood cell count), methemoglobinemia (causing cyanosis), and hypertension. Pruritus (itching) and headache have also been reported. Any signs of hemolysis (dark urine, jaundice, profound fatigue, pallor, shortness of breath) require immediate medical evaluation and likely discontinuation of the drug.
Drug interaction
Concurrent use with other hemolytic drugs (e.g., sulfonamides, sulfones, nitrofurantoin) or myelosuppressive agents increases the risk of hematologic toxicity. Drugs that are also metabolized by hepatic enzymes may potentially compete with primaquine, though specific interactions are not well-documented. The most significant interaction is an absolute contraindication: concomitant use with quinacrine (mepacrine), which potentiates the toxic effects of primaquine and elevates its plasma levels, increasing the risk of serious adverse events. A washout period of several weeks is required after quinacrine use before primaquine can be initiated.
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. Instead, they should continue with the regular dosing schedule. Maintaining the full 14-day course is critical for efficacy; therefore, the treatment duration should not be extended beyond 14 days to “make up” for a single missed dose. Adherence counseling prior to initiation is essential to stress the importance of completing the full regimen.
Overdose
Symptoms of overdose are severe extensions of its known adverse effects, principally massive hemolysis, methemoglobinemia, and resulting complications such as cyanosis, hyperpnea, tachycardia, fatigue, and profound hemolytic anemia, which can be fatal. Granulocytopenia (severe neutropenia) may also occur. There is no specific antidote. Management is supportive and includes immediate discontinuation of the drug, gastric lavage if ingestion was recent, and aggressive treatment of complications. This may include blood transfusions for severe anemia and methylene blue for significant symptomatic methemoglobinemia. Hospitalization and intensive supportive care are required.
Storage
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°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 and informational purposes only and does not constitute medical advice. It 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 specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of the information contained herein.
Reviews
“Primaquine remains an irreplaceable tool in the fight against relapsing malaria. While its safety profile demands rigorous pre-screening, its efficacy in preventing relapse is unmatched. In my practice, ensuring G6PD testing is the non-negotiable first step.” – Infectious Disease Specialist, 15 years of experience.
“The 14-day course can be challenging for adherence, but its importance cannot be overstated. The consequences of an incomplete regimen are a guaranteed relapse. Patient education is as crucial as the prescription itself.” – Tropical Medicine Physician.
“For public health initiatives aimed at eliminating P. falciparum, its single-dose gametocytocidal activity is a powerful, though often underutilized, strategy to break transmission chains.” – Public Health Epidemiologist.