Primaquine 45 mg · Tablets

Primaquine phosphate is an 8-aminoquinoline antimalarial drug. The mechanism of action has not been fully established. The major assumptions are an inhibition of the mitochondrial system of dormant parasites, and an oxidative stress generated through reactive metabolites in infected cells. In humans, primaquine phosphate activity is probably related to hydroxylated metabolites generated intrahepatically by CYP2D6.

Following single oral dosing, the Cmax and AUC of primaquine increase approximately dose-proportionally over a primaquine base dose range of 15 mg to 45 mg (3 times the approved dose).

The pharmacokinetic parameters and properties of primaquine and carboxyprimaquine (main circulating metabolite not expected to be active) in patients with P. vivax malaria following Oral Administration of Primaquine phosphate Tablets are provided in TABLE 1.

Published clinical reports indicate that primaquine is a CYP2D6 substrate. Experiments in mice indicate primaquine activity likely depends on the formation of CYP2D6 metabolite(s). CYP2D6 has variants that affect CYP2D6 metabolic function. CYP2D6 poor metabolizers are individuals with two nonfunctional alleles (e.g., CYP2D6*5/*5), and as a result have no CYP2D6 activity. CYP2D6 intermediate metabolizers are individuals with a combination of nonfunctional, reduced, or normal function alleles, and as a result have reduced CYP2D6 activity (e.g., CYP2D6*1/*5, CYP2D6*4/*10).

Individuals who are CYP2D6 intermediate or poor metabolizers exhibit a prolonged primaquine half-life and increased primaquine plasma concentrations when compared to individuals who are CYP2D6 normal metabolizers. CYP2D6 metabolizer status may be associated with variability in clinical response to Primaquine phosphate Tablets (see PRECAUTIONS).