Chloroquine + Primaquine = Precautionary

Effect on Concentration

Chloroquine
No change
Applies within class?
No
Primaquine
Increase
Applies within class?
No

Pharmacologic Effects

Chloroquine
Effect
N/A
Applies within class?
No
Primaquine
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 15-May-2020

Summary

Both peak concentration and overall primaquine exposure was increased while no changes were observed in chloroquine. Enhanced cardiovascular toxicity should be considered in individuals with predispositions.

Sources

Pharmacokinetic interactions between primaquine and chloroquine ^

Study Design

In an open-label crossover pharmacokinetic study, 16 healthy volunteers (4 males and 12 females) aged 20 to 47 years were randomized into two groups of three sequential hospital admissions to receive a single oral dose of 30 mg (base) primaquine, 600 mg (base) chloroquine, and the two drugs together.

Study Results

The coadministration of the two drugs did not affect chloroquine or desethylchloroquine pharmacokinetics but increased plasma primaquine concentrations significantly (P &8804; 0.005); the geometric mean (90 confidence interval CI) increases were 63 (47 to 81) in maximum concentration and 24 (13 to 35) in total exposure. There were also corresponding increases in plasma carboxyprimaquine concentrations (P &8804; 0.020). There were no significant electrocardiographic changes following primaquine administration, but there was slight corrected QT (QTc) (Fridericia) interval lengthening following chloroquine administration (median range 6.32 -1.45 to 12.3 ms; P 0.001), which was not affected by the addition of primaquine (5.58 1.74 to 11.4 ms; P 0.642).

Study Conclusions

This pharmacokinetic interaction may explain previous observations of synergy in preventing P. vivax relapse.

References

Pukrittayakamee, S. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother. 2014; 6: 3354-9.