Amodiaquine-induced fulminant hepatitis

Bernuau, Jacques; Larrey, Dominique; Campillo, Bernard; Degott, Claude; Verdier, F.; Rueff, B; Pessayre, Dominique; Benhamou, Jean‐Pierre

doi:10.1016/s0168-8278(88)80469-0

Cited by 27 publications

(12 citation statements)

References 2 publications

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“…No clinically significant hepatic toxicity, agranulocytosis [29-32] or serious other side-effects were seen. No significant increase in alanine or aspartate aminotransaminase activity was observed between day 0 and day 3.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Djallé

Njuimo

Manirakiza

et al. 2014

Malar J

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BackgroundThe efficacy of artemisinin-based combination therapy (ACT) has been established. The objective of the present study was to compare the efficacy and safety in the Central African Republic (CAR) of three commercially available artemisinin-based combinations, artemether + lumefantrine (AL), artesunate + sulphamethoxypyrazine–pyrimethamine (AS-SMP) and artesunate + amodiaquine (AS-AQ), with those of sulphadoxine–pyrimethamine + amodiaquine (SP-AQ), which was the first-line reference treatment in the country from 2004, until it was replaced by ACT in 2006 in accordance with changes in international recommendations based on resistance identified in other regions.MethodsChildren aged six to 59 months with uncomplicated Plasmodium falciparum malaria were recruited in Bangui, the capital of the CAR. The 251 patients selected were randomly assigned to receive AL (n = 60), AS-SMP (n = 58), AS-AQ (n = 68) or SP-AQ (n = 65) and were followed up for 28 days. Clinical outcome was classified according to the standard 2003 World Health Organization protocol.ResultsAt day 28, the cure rates in a per-protocol analysis were 92% (48/52) with AL, 93% (50/54) with AS-SMP, 93% (55/59) with AS-AQ and 100% (57/57) with SP-AQ, with no statistically significant difference between the four treatments. Defervescence was significantly faster with AS-AQ than with AL (p <0.035). Fatigue was reported significantly more frequently by patients receiving AQ than by those treated with AS-SMP or AL (p = 0.006). All the other adverse events reported were mild, and no significant difference was noted by treatment.ConclusionThe three artemisinin-bsed combinations show similar, satisfactory results, comparable to that with SP-AQ. This evaluation is the first conducted in CAR since the official introduction of ACT. It should guide the National Malaria Control Programme in choosing the appropriate ACT for treatment of uncomplicated P. falciparum malaria in the future.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Djallé

Njuimo

Manirakiza

et al. 2014

Malar J

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“…55 Fatal acute hepatitis due to amodiaquine has been reported. 56,57 Combination antimalarial therapy is being explored to delay development of resistance to falciparum malaria. Orrell et al reported acute asymptomatic hepatitis in a healthy normal volunteer exposed to two oral doses of amodiaquine and artesunate.…”

Section: Jaundice Due To Drugsmentioning

confidence: 99%

Jaundice in malaria

Anand

Puri

2005

J of Gastro and Hepatol

110

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Jaundice is not an unusual accompaniment of malaria. It can occur due to intravascular hemolysis, disseminated intravascular coagulation, and, rarely, 'malarial hepatitis'. Although the primary schizogony of the malarial parasite always leads to the rupture of the infected hepatocyte, alteration of the hepatic functions is uncommonly recorded due to this event. Histologically, the hepatitis or the actual inflammation in the liver has never been demonstrated. Nonetheless, the term 'malarial hepatitis' (MH) has been used in the literature to describe the occurrence of hepatocellular jaundice in patients with Plasmodium falciparum infection. The authors' own data and review of the literature indicate that it is not an uncommon entity. In endemic areas, jaundice is seen in approximately 2.5% of patients with falciparum malaria. It also appears to be a heterogeneous syndrome and one can recognize two clinical subsets. In one group there was an acute, virulent presentation with coma, renal failure and in some cases even hemorrhagic manifestations. It is only in this setting that jaundice signified a 'severe' disease as noted by the World Health Organization action program. This presentation is often confused with acute viral hepatitis and acute hepatic failure in non-endemic areas, but can be clinically differentiated.

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“…1986), hepatitis (Larrey et al. 1986; Bernuau et al. 1988), and increases in serum aspartate aminotransferase (AST) levels (Sturchler et al.…”

Section: Drugs With Questionable Safety During Pregnancy or With Insumentioning

confidence: 99%

“…Amodiaquine (AQ), a 4-aminoquinoline related to CQ, falls under the category of antimalarials about which there are insufficient data to be certain about their use in pregnancy. In non-pregnant women taking AQ for chemoprophylaxis, there have been reports of agranulocytosis and granulocytopenia (Hatton et al 1986;Neftel et al 1986), hepatitis (Larrey et al 1986;Bernuau et al 1988), and increases in serum aspartate aminotransferase (AST) levels (Sturchler et al 1987). A study comparing AQ with atovaquone + proguanil found no serious adverse events, but found that pruritis, weakness, insomnia and dizziness were more common in the AQ group (Radloff et al 1996).…”

Section: Drugs With Questionable Safety During Pregnancy or With Insumentioning

confidence: 99%

Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum‐endemic sub‐Saharan Africa

Newman

Parise

Slutsker

et al. 2003

Tropical Med Int Health

104

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SummaryPlasmodium falciparum malaria in pregnancy poses substantial risk to a pregnant woman and her neonate through anaemia and low birth weight (LBW), respectively, and is responsible for up to 35% of preventable LBW in malaria-endemic areas. Chemoprophylaxis or intermittent preventive treatment (IPT) with an effective antimalarial can ameliorate the adverse effects of malaria during pregnancy. Current guidelines from the WHO recommend that women in highly malarious areas receive IPT with an effective antimalarial. Two central considerations in evaluating drugs for use during pregnancy are safety for the mother and her foetus and effectiveness, which is determined by efficacy, cost, availability, deliverability and acceptability of the drug. These factors may be scored and potential drugs or drug combinations ranked in order of potential effectiveness for use in prevention programmes. The seven most promising regimens are all IPT, primarily because they are more easily delivered and less expensive than chemoprophylaxis. Currently, IPT with sulphadoxine-pyrimethamine (SP) is more likely to have the best overall effectiveness in preventing adverse outcomes associated with malaria in pregnancy. Its low cost, wide availability, easy deliverability and acceptability make it the clear choice in countries where efficacy of the drug remains good. For countries where resistance to SP is rising or already high, amodiaquine (alone or in combination with SP or artesunate) artesunate + SP, chlorproguanil-dapsone (with and without artesunate) and artemether-lumefantrine require urgent evaluation for use in pregnancy.

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Amodiaquine-induced fulminant hepatitis

Cited by 27 publications

References 2 publications

Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Efficacy and safety of artemether + lumefantrine, artesunate + sulphamethoxypyrazine-pyrimethamine and artesunate + amodiaquine and sulphadoxine-pyrimethamine + amodiaquine in the treatment of uncomplicated falciparum malaria in Bangui, Central African Republic: a randomized trial

Jaundice in malaria

Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum‐endemic sub‐Saharan Africa

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