Safety of primaquine given to people with G6PD deficiency: systematic review of prospective studies

Abstract

BackgroundHaemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people.MethodsMajor electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data.ResultsFive randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] −1.45 g/dl, 95% CI −2.17 to −0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD −10.31%, 95% CI −17.69 to −2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD −1.19 g/dl, 95% CI −1.94 to −0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD −9.10%, 95% CI −12.55 to −5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4–0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD −4.99%, 95% CI −9.96 to −0.02). For low-dose PQ (0.1–0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI −1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (−0.57 g (95% CI −0.97 to −0.17, 1 trial)); although change from baseline was similar (MD −1.45%, 95% CI −5.69 to 2.78, 3 trials).ConclusionsFalls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1989-3) contains supplementary material, which is available to authorized users.

The prevalence of glucose-6-phosphate dehydrogenase deficiency in the Cape Verdean population in the context of malaria elimination

“…These results are consistent with results from a preliminary study in the country in 2010 [36], and similary to the reports from other studies conducted in other African countries, as Mauritania [37], Uganda [38], Mozambique [39] Senegal [40,41] and Gambia [42]. The high G6PDd prevalence in the African or Afro-descendant population as shown by several studies [39][40][41][42][43] may reflect the population's exposure to malaria endemicity or ethnicity related [8][9][10][11][12][13][14][15][16]. However, our results do not allow drawing any conclusions of this nature since almost all the participants of this study were of Cape Verdean citizenship and no ethnic classification was made.…”

“…The schizontocidal treatment for non-falciparum malaria is done with the AL or Artesunate + Amodiaquine, following the WHO guidelines [7]. Nevertheless, this use of primaquine is carried out regardless the knowledge of the frequency of the Glucose-6-phosphate-dehydrogenase (G6PD) deficiency among the target population, which endangers all the patients harbouring this deficiency with the risk of haemolysis [8][9][10][11][12].…”

Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission

“…In terms of safety, adverse effects of PQ in people with G6PD deficiency are less common with lower doses of PQ ( Olalekan 2017 ), although direct comparisons are few and sample sizes small. Most trials included in this review excluded individuals with G6PD deficiency, but some included them, did not test for it or did not state whether they tested; thus some trials included some G6PD deficient participants.…”

“…These occasional, but clearly serious, adverse effects have led to a reputation of being "unsafe" ( Ashley 2014 ). Although the haemolysis appears less likely at lower dose, there have been few studies in G6PD‐deficient people at low doses of PQ ( Olalekan 2017 ).…”

Efficacy and safety of artemisinin-based combination therapy and chloroquine with concomitant primaquine to treat Plasmodium vivax malaria in Brazil: an open label randomized clinical trial

“…4 ). The median difference in haemoglobin at day 14 (Hb at day 14 − Hb at baseline/Hb at baseline) [ 22 ] in ASMQ + Pq, AL + Pq, and CQ + Pq were − 0.74 (95% CI − 1.13; − 0.36), − 0.49 (95% CI − 0.87; − 0.09), and − 0.58 (95% CI − 0.91; − 0.24), respectively. These were not statistically different.…”