Primaquine is the drug of choice for the eradication of dormant liver forms of P vivax and P ovale and can also be used for chemoprophylaxis against all malarial species.
Primaquine phosphate is a synthetic 8-aminoquinoline (Figure 52–2). The drug is well absorbed orally, reaching peak plasma levels in 1–2 hours. The plasma half-life is 3–8 hours. Primaquine is widely distributed to the tissues, but only a small amount is bound there. It is rapidly metabolized and excreted in the urine.
Primaquine is active against hepatic stages of all human malaria parasites. It is the only available agent active against the dormant hypnozoite stages of P vivax and P ovale. The drug is also gametocidal against the four human malaria species and it has weak activity against erythrocytic stage parasites. The mechanism of antimalarial action is unknown.
Some strains of P vivax in New Guinea, Southeast Asia, Central and South America, and other areas are relatively resistant to primaquine. Liver forms of these strains may not be eradicated by a single standard treatment and may require repeated therapy.
1.
Therapy (radical cure) of acute vivax and ovale malaria—Standard therapy for these infections includes chloroquine to eradicate erythrocytic forms and primaquine to eradicate liver hypnozoites and prevent a subsequent relapse. Chloroquine is given acutely, and therapy with primaquine is withheld until the G6PD status of the patient is known. If the G6PD level is normal, a 14-day course of primaquine is given. Prompt evaluation of the G6PD level is helpful, since primaquine appears to be most effective when instituted before completion of dosing with chloroquine.
2.
Terminal prophylaxis of vivax and ovale malaria—
Standard chemoprophylaxis does not prevent a relapse of vivax or ovale malaria, because the hypnozoite forms of these parasites are not eradicated by available blood schizonticides. To diminish the likelihood of relapse, some authorities advocate the use of primaquine after the completion of travel to an endemic area.
3.
Chemoprophylaxis of malaria—Daily treatment with 30 mg (0.5 mg/kg) of primaquine base provided good protection against falciparum and vivax malaria, and the drug is now listed as an alternative chemoprophylactic regimen by the CDC.
4.
Gametocidal action—Primaquine renders P falciparum gametocytes noninfective to mosquitoes. Including primaquine with treatment for falciparum malaria is used in some areas to decrease transmission, and routine inclusion of single low doses of primaquine (which may be safe without testing for G6PD deficiency) is under study.
5.
Pneumocystis jiroveci infection—The combination of clindamycin and primaquine is an alternative regimen in the treatment of pneumocystosis, particularly mild to moderate disease. This regimen offers improved tolerance compared with high-dose trimethoprim-sulfamethoxazole or pentamidine, although its efficacy against severe pneumocystis pneumonia is not well studied.
Primaquine in recommended doses is generally well tolerated. It infrequently causes nausea, epigastric pain, abdominal cramps, and headache, and these symptoms are more common with higher dosages and when the drug is taken on an empty stomach. More serious but rare adverse effects are leukopenia, agranulocytosis, leukocytosis, and cardiac arrhythmias. Standard doses of primaquine may cause hemolysis or methemoglobinemia (manifested by cyanosis), especially in persons with G6PD deficiency or other hereditary metabolic defects.
Primaquine should be avoided in patients with a history of granulocytopenia or methemoglobinemia, in those receiving potentially myelosuppressive drugs (eg, quinidine), and in those with disorders that commonly include myelosuppression.