A Cochrane review included 15 trials with a total of 4377 participants. Trials compared various regimens of primaquine with the standard primaquine regimen, or with placebo or no treatment. All trials treated blood stage infection with chloroquine.
Alternative primaquine regimens compared to 14-day primaquine: Relapse rates were higher over six months with the five-day primaquine regimen than the standard 14-day regimen (RR 10.05, 95% CI 2.82 to 35.86; two trials, 186 participants). Similarly, relapse over six months was higher with three days of primaquine than the standard 14-day regimen (RR 3.18, 95% CI 2.1 to 4.81; two trials, 262 participants; six months follow-up); and with primaquine for seven days followed up over two months, compared to 14-day primaquine (RR 2.24, 95% CI 1.24 to 4.03; one trial, 126 participants). Relapse with once-weekly supervised primaquine for eight weeks was little different over nine months follow-up compared to 14-day self-administered primaquine in one small study (RR 2.97, 95% CI 0.34 to 25.87; one trial, 129 participants).
Primaquine regimens compared to no primaquine: The number of people that relapsed was similar between people given five days of primaquine or given placebo or no primaquine (four trials, 2213 participants; follow-up six to 15 months); but lower with 14 days of primaquine (RR 0.6; 95% CI 0.48 to 0.75; ten trials, 1740 participants; follow-up seven weeks to 15 months). No serious adverse events were reported. Treatment-limiting adverse events were rare and non-serious adverse events were mild and transient.
Compared with chloroquine alone, five-day primaquine plus chloroquine was no better at preventing relapses (OR 1.04, 95% CI 0.64 to 1.69, random-effects model; 3 trials, n=2104), while 14-day primaquine plus chloroquine was significantly better (OR 0.24, 95% CI 0.12 to 0.45, random-effects model; 6 trials, n=1071). Limited data suggest the advantage for the 14-day primaquine regimen persisted for over six months (OR 0.41, 95% CI 0.29 to 0.60; 2 trials, n=585). Direct comparisons of the 14-day and five-day primaquine plus chloroquine regimens also confirm the superiority of the longer course (OR 13.33, 95% CI 3.45 to 51.44; 2 trials, n=186). Adverse effects were poorly reported, with three trials reporting skin rash, vertigo, headache, abdominal pain and/or nausea, and two trials reporting that primaquine was well tolerated.