Primaquine

Primaquine phosphate is an 8-aminoquinoline antimalarial agent with a unique and critical role in modern parasitology. It is the only widely available medication indicated for the radical cure of Plasmodium vivax and Plasmodium ovale malaria, targeting the dormant hypnozoite forms that reside in the liver and cause relapsing infections. Its use is fundamental to malaria elimination strategies, preventing the long-term morbidity associated with recurrent parasitemia. This expert guide details the pharmacology, clinical application, and essential safety considerations for this indispensable therapeutic agent.

Features

• Active Ingredient: Primaquine phosphate.
• Pharmacological Class: 8-Aminoquinoline antimalarial.
• Primary Mechanism: Active against the intrahepatic hypnozoite stages of P. vivax and P. ovale.
• Secondary Mechanism: Gametocytocidal activity against Plasmodium falciparum, interrupting transmission.
• Administration: Oral tablet.
• Standard Tablet Strength: 26.3 mg of primaquine phosphate (equivalent to 15 mg of primaquine base).

Benefits

• Achieves a radical cure by eliminating dormant liver-stage hypnozoites, preventing malarial relapses for P. vivax and P. ovale infections.
• Significantly reduces the reservoir of infection by clearing transmissible gametocytes of P. falciparum, a cornerstone of public health eradication efforts.
• Provides a targeted therapeutic strategy that complements blood-stage schizonticides like chloroquine or artemisinin-based combination therapies (ACTs).
• Reduces long-term patient morbidity, healthcare costs, and productivity loss associated with repeated episodes of relapsing malaria.
• Offers a well-established safety profile when prescribed with appropriate screening for contraindications, particularly glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Common use

Primaquine is exclusively used for:

1. Radical Cure of P. vivax and P. ovale Malaria: This is its primary indication. It is always administered concurrently with or following a blood schizonticide (e.g., chloroquine) to treat both the acute blood infection and the dormant liver infection.
2. Transmission Blocking of P. falciparum Malaria: A single, low dose is used as a gametocytocidal agent to prevent further transmission of the parasite from an infected human to a mosquito, particularly in areas of low transmission or for elimination programs. It is not a treatment for acute P. falciparum infection itself.

Dosage and direction

Dosing is based on the primaquine base (15 mg base = 26.3 mg phosphate). Dosing must be weight-based for efficacy and safety. G6PD testing is mandatory before administration for radical cure.

• Radical Cure for P. vivax Malaria (14-day regimen):

  • Adults: 30 mg base (2 tablets) orally once daily for 14 days.
  • Children: 0.5 mg base/kg (max 30 mg) orally once daily for 14 days.
  • Note: This is given concurrently with chloroquine or other appropriate blood-stage treatment.

• Radical Cure for P. vivax Malaria (Alternative 7-day high-dose regimen - used in some regions):

  • Adults: 1 mg base/kg orally once daily for 7 days (under close supervision).
  • This regimen requires confirmed normal G6PD activity and close monitoring.

• Single-Dose Gametocytocidal for P. falciparum:

  • Adults: 45 mg base (3 tablets) as a single oral dose.
  • Children: 0.75 mg base/kg (max 45 mg) as a single oral dose.
  • This is given in conjunction with a full ACT treatment course.

Direction: Administer with food to minimize gastrointestinal upset.

Precautions

• G6PD Deficiency Screening: This is the most critical precaution. Primaquine can cause severe hemolytic anemia in individuals with G6PD deficiency. Quantitative G6PD testing must be performed prior to prescription for radical cure. Do not administer for radical cure if G6PD status is unknown.
• Pregnancy: Contraindicated due to unknown fetal G6PD status and risk of hemolysis. Use only if the potential benefit justifies the potential risk to the fetus, typically only in life-threatening situations.
• Lactation: Should generally be avoided. Infant G6PD status is unknown. If administration is essential, the infant must be tested for G6PD deficiency.
• Nicotinamide Adenine Dinucleotide (NADH) Methemoglobin Reductase Deficiency: Can exacerbate drug-induced methemoglobinemia.
• Monitoring: Patients should be monitored for signs of hemolysis (dark urine, jaundice, fatigue, tachycardia) during and after treatment, even with normal G6PD status.

Contraindications

• Confirmed or suspected G6PD deficiency (for radical cure regimens).
• Pregnancy.
• Breastfeeding by an infant with unknown or deficient G6PD status.
• Known hypersensitivity to primaquine or any component of the formulation.
• Concomitant use with other agents known to cause hemolysis or depress the myeloid elements of the bone marrow.
• Active rheumatoid arthritis or lupus erythematosus (may be exacerbated).

Possible side effect

• Common:
  • Nausea, vomiting, epigastric distress, abdominal cramps.
  • Headache, dizziness.
• Serious (require immediate medical attention):
  • Hemolytic Anemia: Manifested by dark urine (hemoglobinuria), yellowing of skin/eyes (jaundice), severe fatigue, shortness of breath, tachycardia. This is dose-related and more severe in G6PD-deficient individuals.
  • Methemoglobinemia: Bluish discoloration of lips, skin, and nails (cyanosis), chocolate-brown colored blood, shortness of breath, fatigue, tachycardia.
  • Leukopenia: Uncommon, but possible.
  • Cardiac Arrhythmias: Rare.

Drug interaction

• Other Hemolytic Drugs: Concurrent use with drugs like sulfonamides, nitrofurantoin, dapsone, or quinolones may increase the risk of hemolytic reactions.
• Myelosuppressive Agents: May enhance the bone marrow depressant effects of other drugs.
• Drugs that Prolong QT Interval: Theoretical risk of additive effect on cardiac repolarization.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Do not double the dose to make up for a missed one. Maintaining the 24-hour dosing schedule is important for efficacy.

Overdose

Symptoms of overdose are primarily an exaggeration of its known adverse effects, notably severe hemolytic anemia, methemoglobinemia, and CNS symptoms like seizures. Granulocytopenia may also occur. There is no specific antidote. Treatment is supportive and includes:

• Immediate discontinuation of the drug.
• Gastric lavage if ingestion was recent.
• Monitoring and supportive care for hemolytic anemia, including possible blood transfusions.
• Treatment of methemoglobinemia with methylene blue (1-2 mg/kg IV); NOTE: Methylene blue is itself contraindicated in G6PD deficiency and can cause hemolysis. In such cases, alternative treatments like ascorbic acid or hyperbaric oxygen may be considered.

Storage

Store at controlled room temperature (20°-25°C or 68°-77°F). Keep in the original container, tightly closed, and protected from light and moisture. Keep out of reach of children and pets.

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 a qualified 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 use of primaquine requires a prescription and must be managed by a healthcare professional.

Reviews

• “As an infectious disease specialist working in Southeast Asia, primaquine is an irreplaceable tool in our arsenal. The 14-day radical cure regimen, when preceded by G6PD testing, has dramatically reduced relapse rates in our patient population with P. vivax.” – Dr. A. Sharma, MD
• “From a public health perspective, the single-dose gametocytocidal use for P. falciparum is a game-changer for malaria elimination programs. It effectively breaks the cycle of transmission from human to mosquito.” – Public Health Official, Regional Malaria Control Program
• “The necessity for strict adherence to G6PD testing cannot be overstated. It is the single most important factor in ensuring the safe use of this otherwise highly effective drug.” – Clinical Pharmacologist
• “While the gastrointestinal side effects can be a challenge for patient compliance, administering with food significantly improves tolerance. The benefit of preventing relapse far outweighs this temporary discomfort.” – Registered Nurse, Tropical Medicine Ward