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Primaquine

Introduction


Primaquine should generally be reserved for travelers unable to take first line malaria medication regimens recommended for the region of travel ( Malarone – Mefloquine) . The traveler must have a documented level of G6PD in the normal range prior to being prescribed primaquine.

P. vivax and P. ovale parasites can persist in the liver and cause relapses for as long as 4 years or more after routine preventative treatment is discontinued. Please be aware to this risk.

Indications


Primaquine has long been used for the treatment of relapsing malaria (terminal treatment) , because of it’s capability to kill the male and female forms of the parasite that are the cause of the relapse. But in the last decade it has been reexamined for malaria prevention. When adults take a daily dose of 30 mg (or 0.6 mg/kg per day for children), an effectiveness of 88-95% against P. falciparum (as well as P. vivax and P. ovale) has been demonstrated. It is often used as a second line drug when medications such as Mefloquine, Malarone, Doxycycline, cannot be tolerated.

Administration


Primaquine should be started 1 day before exposure, taken daily at the same time of day, during exposure, and for 7 days postexposure.

Caution

  • Because primaquine is capable of causing severe blood disorder called hemolytic anemia, a G-6-PD enzyme-screening test is required before using this drug. (see below)
  • Primaquine is contraindicated in pregnant women because the child may have G3PD deficiency.
  • Primaquine can cause some stomach irritation and nausea. It should be taken with food

Direction - Dose for malaria prevention:

  • Adult dose: 30 mg daily ( Taken as 2 tablets of 15mg each)
  • Children dose: 0.6 mg/kg per day


Medication is started 1-2 days prior to malaria zone, daily during and daily for 7 days after leaving malaria zone.

Terminal Treatment

Because most malarious areas of the world (except Haiti and the Dominican Republic) have at least one species of relapsing malaria, travelers to these areas have some risk for acquiring either P. vivax or P. ovale, although the actual risk for an individual traveler is difficult to define. Terminal prophylaxis with primaquine for prevention of relapses is generally indicated only for persons who have had prolonged exposure in malaria-endemic areas (e.g., missionaries and NGO volunteers).

Primaquine terminal treatment decreases the risk of relapses by acting against the liver stages of P. vivax or P. ovale. Travelers to high risk zones of relapsing malaria may be given a supply of primaquine in order to perform a terminal treatment at the end of their exposure. They may use primaquine, in a dosage of 2 x 15mg tablets per day for 14 days (children 0.6 mg/kg), in order to eliminate the P. vivax or P. ovale male and female forms from the liver.

NOTE: When chloroquine, doxycycline, or mefloquine is used for primary prophylaxis, primaquine is usually taken during the last 2 weeks of postexposure prophylaxis. When atovaquone/proguanil is used for primary prophylaxis, primaquine may be taken either during the final 7 days of atovaquone/ proguanil and then for an additional 7 days, or for 14 days after atovaquone/proguanil is completed.

Glucose-6-phosphate dehydrogenase deficiency

This enzyme defect increases the sensitivity of red blood cells to become destroyed after certain stress. It is an inherited disorder.

Distribution

  • Type A- G6PD deficiency: Especially in West and Central Africa, and in 11% of Afro-Americans
  • Mediterranean type G6PD deficiency: Kurdish Jews, Sephardic Jews, Italians and Greeks.

Symptomatology

Although the life-span of red blood cells may be slightly diminished, there is often no anemia. Generally, most individuals are asymptomatic only have episodic hemolytic crises. Red cell breakdown occurs only under certain conditions: e.g. viral or bacterial infections, medication, or increase acidity of the blood.

Antimalarial drugs in patients with G6PD deficiency

  • Approved for malaria prevention or considered safe: mefloquine (Lariam), chloroquine (Aralen), sulfadoxine + pyrimethamine (Fansidar), doxycycline (Vibramycin and generic), atovaquone-proguanil (Malarone).
  • Contraindicated: primaquine. (A normal G6PD level MUST be documented before prescribing primaquine.)

Substances that must be avoided in all cases of G6PD deficiency

  • Diaphenylsulfone (Dapsone).
  • Nitrofurans Nitrofurantoin (Furadantin).
  • Analgesics Acetanilide, phenazopyridine.
  • Misc. Nalidixic acid (Negram), furazolidone, niridazole (Ambilhar), phenylhydrazine, probenecid (Benemid), procainamide, thiazolsulfone,methylene blue, naphthalene (moth repellent), toluidine blue; trinitrotoluene.