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Pharmacogenomics Oct 2008Amodiaquine is a central drug in the new global strategy of combination therapies for the control of malaria. Amodiaquine is mainly metabolized hepatically towards its... (Review)
Review
Amodiaquine is a central drug in the new global strategy of combination therapies for the control of malaria. Amodiaquine is mainly metabolized hepatically towards its major active metabolite desethylamodiaquine, by the polymorphic P450 isoform CYP2C8. Amodiaquine is associated with rare but serious side effects, as well as with relatively frequent mild ones. These are expected to be at least partially related to CYP2C8 alleles. Pharmacogenetic knowledge of amodiaquine exposed populations is important for pharmacovigilance issues and in being a first step for future realistic applications from a personal medicine perspective.
Topics: Alleles; Amodiaquine; Animals; Antimalarials; Cytochrome P-450 Enzyme System; Endemic Diseases; Forecasting; Half-Life; Humans; Malaria, Falciparum; Models, Biological; Pharmacogenetics; Plasmodium falciparum; Polymorphism, Genetic
PubMed: 18855526
DOI: 10.2217/14622416.9.10.1385 -
The Cochrane Database of Systematic... 2000Amodiaquine has been widely used to treat malaria. Due to reports of fatal adverse drug reactions, discontinuation or modification of its use has been suggested. (Review)
Review
BACKGROUND
Amodiaquine has been widely used to treat malaria. Due to reports of fatal adverse drug reactions, discontinuation or modification of its use has been suggested.
OBJECTIVES
The objective of this review was to assess the effects of amodiaquine for treating malaria.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group trials register and Medline. We also contacted researchers in the field and drug companies.
SELECTION CRITERIA
Randomised and quasi-randomised trials comparing amodiaquine with other treatment for uncomplicated malarial infections in adults and children.
DATA COLLECTION AND ANALYSIS
Both reviewers independently extracted data and assessed trial quality.
MAIN RESULTS
Forty trials were included. Allocation was adequately concealed in three trials. Amodiaquine was more effective than chloroquine for parasite clearance. The combined results of parasite clearance at seven days from 24 trials was 83% for amodiaquine and 56% for chloroquine (odds ratio 4.29, 95% confidence interval 3.51 to 5.24). The odds ratio for parasite clearance at 14 days was 6.00, 95% confidence interval 4.38 to 8.21. Amodiaquine and sulfadoxine/pyrimethamine showed similar results for parasite clearance on day seven, but sulfadoxine/pyrimethamine appeared to be more effective on day 14 and 28. No significant difference for adverse events was observed between amodiaquine and chloroquine and sulfadoxine/pyrimethamine. Reported adverse effects were minor or moderate, not life threatening.
REVIEWER'S CONCLUSIONS
There is some evidence to support the continued use of amodiaquine in the treatment of uncomplicated malaria, although drug resistance should be considered. Monitoring for toxicity should also continue.
Topics: Amodiaquine; Antimalarials; Humans; Malaria
PubMed: 10796468
DOI: 10.1002/14651858.CD000016 -
Lancet (London, England) Dec 1996
Topics: Africa South of the Sahara; Amodiaquine; Antimalarials; Chloroquine; Drug Resistance; Health Policy; Humans; Malaria
PubMed: 8962005
DOI: 10.1016/S0140-6736(05)65723-6 -
Lancet (London, England) Nov 1996Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse... (Comparative Study)
Comparative Study Review
BACKGROUND
Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse events have been reported in travellers taking it as prophylaxis. It is not recommended as first-line treatment. In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria.
METHODS
This is a systematic review of published and unpublished randomised or pseudorandomised trials of amodiaquine. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events.
FINDINGS
40 trials met the inclusion criteria. Symptomatic patients were enrolled in 24 studies in comparisons of amodiaquine (n = 1071) with chloroquine (n = 1097). Amodiaquine was significantly more effective than chloroquine, with odds ratios and 99% confidence intervals (OR [99% CI]) of 4.29 (3.30-5.58) on day 7 and 6.00 (3.97-9.06) on day 14. Time to parasite clearance was significantly shorter with amodiaquine and fever clearance times were marginally faster. Eight studies compared amodiaquine with chloroquine in asymptomatic parasitaemia, with effects on parasitological outcomes similar to those for symptomatic malaria. At twelve sites, 692 amodiaquine and 679 sulfadoxine/pyrimethamine (S/P) recipients were enrolled. The two drugs did not differ significantly on day 7 (OR 0.74 [0.48-1.15]) but the odds ratios favoured S/P on day 14 (OR 0.51 [0.28-0.93]) and on day 28 (OR 0.30 [0.16-0.55]). The time to parasitological clearance was similar in the two groups; fever clearance times were significantly shorter with amodiaquine. Tolerability was assessed for both comparative and non-comparative trials. The rates of adverse events in controlled trials were 10.7%, 8.8%, and 14.3% with amodiaquine, chloroquine, and S/P, respectively. No life-threatening adverse events and no significant shifts in laboratory indices were reported.
INTERPRETATION
This systematic review of published and unpublished trials supports the use of amodiaquine in the treatment of uncomplicated malaria. However, there is partial cross-resistance between chloroquine and amodiaquine, and monitoring of the effectiveness of this drug and surveillance for evidence of toxicity must continue.
Topics: Amodiaquine; Antimalarials; Chloroquine; Humans; Malaria, Falciparum; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 8898036
DOI: 10.1016/S0140-6736(96)06217-4 -
The Lancet. Infectious Diseases Dec 2004
Topics: Adult; Amodiaquine; Antimalarials; Artemisinins; Drug Therapy, Combination; Female; Humans; Malaria; Pregnancy; Pregnancy Complications, Parasitic; Safety; Sesquiterpenes; Treatment Outcome
PubMed: 15567117
DOI: 10.1016/S1473-3099(04)01198-3 -
The Medical Journal of Australia Feb 1977A case of profound neutropenia and severe infection after the administration of amodiaquine is presented. The recommended dose for malaria prophylaxis was administered.
A case of profound neutropenia and severe infection after the administration of amodiaquine is presented. The recommended dose for malaria prophylaxis was administered.
Topics: Adult; Agranulocytosis; Amodiaquine; Female; Humans; Neutropenia
PubMed: 859490
DOI: 10.5694/j.1326-5377.1977.tb130706.x -
Expert Opinion on Drug Safety Nov 2007Few antimalarial drugs have been evaluated extensively in pregnancy because of fears over toxicity. However, increasing Plasmodium falciparum resistance to chloroquine... (Review)
Review
Few antimalarial drugs have been evaluated extensively in pregnancy because of fears over toxicity. However, increasing Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine makes finding alternative antimalarials that are safe and effective in pregnancy a priority. There is a renewed interest in amodiaquine as a potential candidate, particularly as a partner drug in artemisinin-based combination therapy. The available data suggest that, at standard dosages, amodiaquine is not teratogenic and that the adverse events associated with taking amodiaquine in pregnancy are not greater than those associated with falciparum malaria in pregnancy. Thus, amodiaquine in combination with other antimalarial drugs may be useful for malaria treatment in pregnancy, but inadequate data on its safety and pharmacokinetics in pregnancy limits its deployment for intermittent preventive treatment in pregnancy.
Topics: Amodiaquine; Animals; Antimalarials; Female; Humans; Malaria, Falciparum; Pregnancy; Pregnancy Complications, Parasitic
PubMed: 17967151
DOI: 10.1517/14740338.6.6.631 -
Expert Opinion on Investigational Drugs Jul 2007Without an effective vaccine for the prevention of malaria, a fundamental component of the strategy for the control of this disease is based on prompt and effective... (Review)
Review
Without an effective vaccine for the prevention of malaria, a fundamental component of the strategy for the control of this disease is based on prompt and effective treatment. Due to the high resistance level of Plasmodium falciparum to the most affordable drugs such as chloroquine and sulfadoxine-pyrimethamine, artemisinin-based combination therapies are presently used in many countries or are being developed for registration. One artemisinin combination therapy that is drawing a certain degree of interest is the combination of artesunate (a short half-life drug) plus amodiaquine (a long half-life drug that is presently used in loose combination in many countries). The short half-life drug achieves substantial and rapid parasite killing, while a high concentration of the long half-life drug kills off the remaining malaria parasites. In addition to the effectiveness of 3 days of treatment (rapid clearance of fever and malaria parasites) in western and central Africa, where resistance to amodiaquine is low, the combination of artesunate plus amodiaquine may delay or prevent the emergence of resistance to both drugs. An important step is the recent registration in Morocco (the country where the drug is manufactured) of a fixed combination of artesunate plus amodiaquine by the Drugs for Neglected Diseases initiative with sanofi-aventis as the industrial partner. A prequalification dossier of this fixed combination has been submitted to the WHO. This new co-formulation will almost certainly increase its effectiveness by improving drug compliance.
Topics: Amodiaquine; Animals; Artemisinins; Artesunate; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Drugs, Investigational; Female; Follow-Up Studies; Humans; Malaria, Falciparum; Male; Maximum Tolerated Dose; Plasmodium falciparum; Randomized Controlled Trials as Topic; Sesquiterpenes; Severity of Illness Index; Treatment Outcome
PubMed: 17594191
DOI: 10.1517/13543784.16.7.1079 -
Antiviral Research Feb 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral infection caused by a bandavirus in the family of Phenuiviridae, commonly known as...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral infection caused by a bandavirus in the family of Phenuiviridae, commonly known as SFTS virus (SFTSV). We have previously isolated SFTSV from blood samples of SFTS patients and established an antiviral assay system to identify selective inhibitors of SFTSV in vitro. Using the assay system, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. However, due to its insufficient antiviral activity, 98 amodiaquine derivatives were newly synthesized and examined for their anti-SFTSV activity. Among the derivatives, some compounds showed selective inhibitory effect on SFTSV replication in vitro. The 50% effective concentration (EC) and cytotoxic concentration (CC) of the most active compound (C-90) were 2.6 ± 0.6 and >50 μM, respectively. This EC value was comparable to or slightly better than that of favipiravir (4.1 ± 0.6 μM). On the other hand, pharmacokinetic studies in vivo revealed that C-90 was poor in its oral bioavailability in mice. Therefore, we further designed and synthesized derivatives and obtained 2 compounds with selective anti-SFTSV activity in vitro and improved pharmacokinetics in vivo.
Topics: Animals; Mice; Severe Fever with Thrombocytopenia Syndrome; Amodiaquine; Phlebovirus; Antiviral Agents; Tick-Borne Diseases
PubMed: 36566117
DOI: 10.1016/j.antiviral.2022.105479 -
Journal of Hepatology Feb 1988Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the...
Three patients suffered from fulminant hepatitis within 23, 59 and 22 weeks after having ingested a total dose of 16, 26 and 15 g, respectively, of amodiaquine for the prophylaxis of malaria. Amodiaquine administration was continued for 44, 21 and 25 days after the onset of jaundice, respectively. One patient underwent emergency orthotopic liver transplantation and survived. The other two died. Fulminant hepatitis threatens patients in whom amodiaquine administration is protracted for several months and not interrupted when jaundice occurs.
Topics: Adolescent; Adult; Amodiaquine; Chemical and Drug Induced Liver Injury; Female; Humans; Malaria; Male; Middle Aged
PubMed: 3346531
DOI: 10.1016/s0168-8278(88)80469-0