Primaquine: Effects, Uses & Risks

Primaquine is a prescription drug with anti-parasitic properties. It is used for the prevention, treatment, and follow-up of malaria. In its guidelines for the treatment of malaria, the German Society for Tropical Medicine and International Health (DTG) recommends primaquine as an adjunctive therapy to chloroquine in the treatment of malaria tertiana. In Germany, primaquine is manufactured and marketed by Bayer AG under the trade name Primaquine.

What is primaquine?

Primaquine or N4-(6-methoxyquinolin-8-yl)pentan-1,4-diamine is a racemic mixture with the molecular formula C15 H21 N3 O. It is an 8-aminoquinoline derivative. The underlying substance (primaquine bisphosphonate) is a crystalline, red-orange and water-soluble powder with neutral odor and bitter taste.

Pharmacological action

After oral administration, primaquine is readily absorbed through the digestive tract and rapidly metabolized by the liver to a carboxyl derivative. Peak plasma concentration of primaquine is reached in approximately 2 to 3 hours. Primaquine has a half-life of 5 to 6 hours. The carboxyl derivative (carboxyprimaquine) has a half-life of 24 to 30 hours. Only a small fraction of primaquine (approximately 1%) is excreted in the original form. Excretion occurs through the urine. As a therapeutic agent, primaquine is taken for 14 days. The daily dose is calculated according to the patient’s body weight and depends on the overall treatment regimen or other medications used. For the purpose of prophylaxis, it is recommended to take the drug for 1 to 2 days. The dose for adults is 30 mg, for children 0.3 mg per kilo of body weight per day. The prophylactic measure must be taken within the period from 1 day before to 1 week after staying in the malaria area. Primaquine is not approved as a drug for malaria prophylaxis in Germany. For this purpose, the drug must be obtained abroad.

Medical use and application

Primaquine has been manufactured since the 1940s and used as an antimalarial in several countries. However, its exact mechanism of action is still unknown despite intensive research. It is believed that an interaction of the substance with the DNA of plasmodia inhibits the biosynthesis of proteins, leading to the death of the pathogen. Mitochondrial dysfunction is also being considered. Primaquine is very effective against the exoerythrocytic stages of Plasmodium vivax and Plasmodium ovale, and at the beginning of the exoerythrocytic phase of Plasmodium falciparum. The preparation also shows great efficacy against the gametocytes of Plasmodia, especially Plasmodium falciparum. However, primaquine has been shown to be ineffective on erythrocytic stages of plasmodia. Although not approved for this purpose in Germany, primaquine finds use in the prophylase of all types of malaria. Studies in Central African countries, Colombia, Iran and Indonesia show a preventive effect of primaquine of up to 85% against the pathogen Plasmodium falciparum, which is responsible for malaria tropica. In contrast, use of primaquine for therapeutic treatment of malaria quartana and malaria tropica is not considered useful. As a therapeutic agent and for the purpose of preventing recurrence, primaquine is used for malaria tertiana, which is caused by Plasmodium vivax and Plamodium ovale.

Risks and side effects

Primaquine is contraindicated for people with glucose-6-phosphate dehydrogenase deficiency and for people who have lupus erythematosus or rheumatoid arthritis. Another contraindication is taking potentially hemolytic medications or having a personal sensitivity to the drug. While taking primaquine, it is advisable to monitor blood counts. The safety of primaquine use during pregnancy has not been established, so potential risks to the unborn child must be considered as part of the risk-benefit ratio when establishing the therapeutic plan. Side effects of primaquine include anemia and headache, fatigue and drowsiness, indigestion and stomach cramps, and itchy skin. If the urine becomes dark, treatment with primaquine must be discontinued immediately, as this may indicate liver overload, kidney disease or hemolysis.