Primaquine

BRAND NAMES

• Primaquine Phosphate – Most widely used form in many countries 

• Primacip – Available in some regions 

• Primaquine Tablets – Common labeled product form

MECHANISM OF ACTION

Primaquine acts against malaria parasites by generating reactive oxygen species (oxidative stress) that damage parasite mitochondria and cellular structures. It is particularly effective against liver hypnozoites of Plasmodium vivax and Plasmodium ovale, preventing relapse, and also acts on gametocytes, reducing transmission of malaria.

PHARMACOKINETICS

Absorption 

Primaquine is rapidly and well absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are usually reached within 1–3 hours. Food may slightly delay absorption but does not significantly reduce overall bioavailability.

Distribution

Primaquine has a large volume of distribution (approximately 2–3 L/kg), indicating extensive tissue distribution beyond the plasma.

Metabolism 
Primaquine is extensively metabolized in the liver, mainly by CYP2D6 enzymes, into active and inactive metabolites. These metabolites are responsible for its antimalarial activity as well as some of its toxic effects, including hemolysis in susceptible individuals.

Elimination 

Primaquine is eliminated mainly through urinary excretion as metabolites, with a small amount excreted in feces. It has a short plasma half-life, but its metabolites may persist and contribute to both therapeutic and adverse effects.

PHARMACODYNAMICS

Primaquine exerts its antimalarial effect by generating reactive oxygen species that disrupt parasite mitochondrial function and cellular integrity. It is active against liver-stage hypnozoites of Plasmodium vivax and Plasmodium ovale, enabling radical cure and preventing relapse. It also acts on gametocytes, reducing transmission of malaria.

ADMINISTRATION

Primaquine is given orally in tablet form, usually once daily with food to reduce gastrointestinal upset. The duration and dose depend on the indication (radical cure or transmission blocking) and are adjusted based on patient factors such as weight and G6PD status due to risk of hemolysis.

DOSAGE AND STRENGTH

Primaquine is commonly available as 7.5 mg and 15 mg tablets. For radical cure of Plasmodium vivax and Plasmodium ovale, the usual adult dose is 15 mg base once daily for 14 days (dose may be adjusted by weight and guidelines). For transmission blocking, a single dose is sometimes used. Dose must be modified in G6PD-deficient patients to avoid hemolysis.

DRUG INTERACTIONS

Primaquine may cause increased hemolysis with oxidant drugs like sulfonamides and dapsone. CYP2D6 inhibitors or inducers can also affect its activity.

FOOD INTERACTIONS DRUG INTERACTIONS

Food has minimal effect on absorption, but taking primaquine with food can reduce stomach upset and improve tolerance.

CONTRAINDICATIONS

Primaquine is contraindicated in patients with G6PD deficiency due to risk of severe hemolytic anemia. It is also contraindicated in pregnancy, breastfeeding (if infant G6PD status is unknown), and in patients with a history of severe hypersensitivity to the drug. It should be avoided in severe hemolytic disorders or significant anemia.

SIDE EFFECTS

• Nausea

• Vomiting

• Abdominal pain

• Loss of appetite

• Headache

• Dizziness

• Hemolytic anemia (serious, especially in G6PD deficiency)

• Cyanosis (rare)

• Methemoglobinemia (rare)

• Fatigue

OVERDOSE 

Overdose may cause hemolytic anemia, nausea, vomiting, dizziness, and in severe cases methemoglobinemia. Treatment is supportive.

TOXICITY

Primaquine toxicity is mainly due to oxidative damage to red blood cells, leading to hemolysis, especially in G6PD-deficient individuals. It may also cause methemoglobinemia, resulting in cyanosis, fatigue, and shortness of breath. Severe toxicity can lead to anemia, jaundice, and hypoxia. Management is supportive, with drug discontinuation and blood transfusion if needed.