Primaquine alternative dosing schedules for preventing malaria relapse in people with Plasmodium vivax

Primaquine to cure people with Plasmodium vivax malaria: comparing dosing schedules

Plasmodium vivax malaria can sometimes cause potentially life‐threatening illness, and the infection continues to make many people unwell. The infection includes a liver stage, and this requires primaquine to eradicate it and prevent the infection recurring. However, the current dosing schedule requires 14 days of daily treatment.

What are the concerns about primaquine?

Primaquine is the only drug currently recommended to treat the liver parasites in P vivax malaria. It can cause anaemia in people with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, which is a relatively common genetic blood disorder. Shorter regimens would help reduce the risk of default with the current two‐week regimen.

What does the research say?

We summarized trials that compared the World Health Organization (WHO)‐recommended primaquine regimen of 15 mg to 30 mg per day for 14 days with the same (210 mg) or higher total doses of primaquine given over different lengths of time to determine whether alternative regimens were as successful as the recommended courses at preventing future episodes of P vivax malaria. We searched for trials up to 2 September 2019 and included 11 randomized controlled trials (RCTs) (studies in which participants are assigned to one of two or more treatment groups in a random manner) in our analysis.

When using 30 mg primaquine per day for seven days compared to 15 mg per day for 14 days, there may be little or no difference in P vivax recurrences at six to seven months (low‐certainty evidence). No serious adverse events were reported. We do not know if there is a difference in the number of adverse events that cause people to stop taking the drug (low‐certainty evidence).

When using 30 mg per day compared to 15 mg per day primaquine therapy for 14 days, we do not know if there is any difference in P vivax recurrences at six months (very low‐certainty evidence). No serious adverse events were reported, but it is unclear whether or not there is a difference between doses in other adverse events that cause people to stop taking the drug (very low‐certainty evidence).

We do not know whether primaquine at 45 mg once per week for eight weeks increases or decreases recurrences of P vivax compared to the high standard 30 mg per day for 14‐days, at 11 months' follow‐up (very low‐certainty evidence).

There is probably little or no difference for recurrence using high dose 60 mg per day for seven days compared to the high standard 30 mg per day for 14 days, but there may be an increase in serious adverse events in the high‐dose shorter course regimen group.

Further RCTs will help improve the certainty of the evidence around alternative regimens,

How up‐to‐date is this review?

The review authors searched for studies up to 2 September 2019.