Primaquine

PRIMAQUINE

In contrast to other antimalarial drugs, primaquine is a poor erythrocytic schizontocide: has weak action on P. vivax, but blood forms of P. falciparum are totally insensitive. On the other hand, it is more active against the preerythrocytic stage of P. falciparum than that of P. vivax. Primaquine differs from all other available antimalarials in having a marked effect on primary as well as secondary tissue phases of the malarial parasite. It is highly active against gametocytes and hypnozoites.

The mechanism of action of primaquine is not known. However, it is different from that of chloroquine. Though, resistance among P. vivax against primaquine can be induced, it is not a clinical problem.

Pharmacokinetics Primaquine is readily absorbed after oral ingestion. It is oxidized in liver with a plasma t½ of 3–6 hrs and excreted in urine within 24 hours. It is not a cumulative drug.

Adverse Effects The usual doses of primaquine produce only abdominal pain, g.i. upset, weakness or uneasiness in chest as side effect. These can be minimized by taking the drug with meals. CNS and cardiovascular symptoms are infrequent. Leucopenia occurs rarely with larger doses.

The most important toxic potential is dose related haemolysis, methaemoglobinaemia, tachypnoea and cyanosis. These are due to the oxidant property of primaquine. Its metabolites are more potent in this regard. However, in normal individuals doses < 60 mg (base) produce little haemolysis. Those with G6PD deficiency are highly sensitive and haemolytic anaemia can occur with 15–30 mg/day. The incidence of G6PD deficiency is low among Indians, except in some tribal people of Jharkhand, Andhra Pradesh, Madhya Pradesh and Assam. It is high among black races and Mediterranean people. Spot tests are available for detecting G6PD deficiency. Passage of dark urine is an indication of haemolysis; primaquine should be promptly stopped if it occurs. The risk of haemolysis and leucopenia is increased in patients of rheumatoid arthritis, SLE and in those acutely ill.

Primaquine should be avoided during pregnancy, because foetus is G6PD deficient.

Use

The primary indication of primaquine is for radical cure of relapsing (vivax) malaria: 15 mg (children 0.25 mg/kg) daily for 2 weeks is given with full curative dose of chloroquine (to cover the erythrocytic phase). Relapse rate with 5 day primaquine treatment employed earlier by NAMP (India) has been found similar to no treatment; therefore not recommended now. The G6PD status of the patient should be tested before giving 14 day primaquine course.

An alternative regimen is primaquine 45 mg (0.75 mg/kg) + chloroquine 300 mg once a week for 8–10 weeks. This does not require G6PD testing; has been found to effect radical cure without inducing significant haemolysis.

Falciparum malaria: A single 45 mg dose of primaquine is given with the curative dose of chloroquine to kill the gametes and cut down transmission to mosquito. This use is restricted to low transmission areas or where effective vector control is implimented.

PRIMALINE (as phosphate 26 mg = 15 mg base) 7.5, 15 mg tab., PRIMALEX, MALIRID 7.5, 15 mg tabs.

Primaquine 15 mg/day given with clindamycin 600 mg TDS is an alternative drug for Pneumocystis jiroveci pneumonia in AIDS patients.

Bulaquine

This congener of primaquine, developed in India, has shown comparable antirelapse activity in vivax malaria when administered for 5 days along with a course of chloroquine. It is partly metabolized in the body to primaquine. Whether the activity is due to bulaquine itself or due to primaquine produced from it is not clear. Bulaquine is claimed to be better tolerated, especially by G6PD deficient individuals, but without any convincing evidence. Precautions and contraindications are the same as for primaquine. Since 5 day antirelapse treatment has been discontinued, the status of bulaquine is uncertain. Dose: 25 mg/day for 5 days starting on 2nd day of chloroquine therapy.

AABLAQUINE 25 mg cap + chloroquine tablets.