The preparation method comprises the following the steps. Costeffectiveness of dihydroartemisininpiperaquine. Eurartesim dihydroartemisininpiperaquine medicines. Also, tracii aims to investigate the safety, pharmacokinetic characteristics and efficacy of a novel combination of an artemisininderivative and two long acting partner drugs, piperaquine and mefloquine. The safety and efficacy of a novel combination of dihydroartemisinin dha and piperaquine, artekin holleykin pharmaceuticals, were assessed in 106 patients 76 children and 30 adults with uncomplicated falciparum malaria from 2 remote areas in cambodia. It has come back into use in combination with the artemisinin derivative db11638 as part of the combination product eurartesim. Table 2 pharmacokinetic variables of dihydroartemisinin dha, piperaquine pq, artemether, lumefantrine, desbuthyllumefantrine and moxifloxacin on treatment day.
Failure of dihydroartemisininpiperaquine treatment of. A randomized trial of dihydroartemisininpiperaquine. Enrolled children were randomized to dihydroartemisinin piperaquine dp given once a month iptm, dp given once a school term 4 treatments over 12 months, iptst, or placebo and followed for 12 months. Intravenous artesunate and its follow on full course dihydroartemisininpiperaquine are the standard treatment for severe malaria in indonesia. Wellcome trust southeast asian tropical medicine research programmes pdf, 177kb. Jan 28, 2019 effects of dihydroartemisininpiperaquine phosphate and artemetherlumefantrine on qtc interval prolongation. Piperaquine dihydroartemisinin combination therapy has established efficacy for the treatment of malaria. The efficacy of dihydroartemisininpiperaquine and artemetherlumefantrine with and without primaquine on plasmodium vivax recurrence. Dihydroartemisininpiperaquine for the prevention of. Current trends in malaria and tuberculosis chemotherapy three of the regimes had excellent and similar efficacy in treating the malaria attack, but of those, treatment with combination dihydroartemisininpiperaquine the combination most recent recommended by the. Aug 10, 2011 dihydroartemisininpiperaquine phosphate in a fixeddose preparation of dihydroartemisinin 40 mg and piperaquine phosphate 320 mg has been shown to be highly effective in treating falciparum malaria with an efficacy of over 90% in china, vietnam, and cambodia 1012. Dihydroartemisininpiperaquine for the prevention of malaria. Dihydroartemisininpiperaquine dhapq is also recommended by the who for uncomplicated malaria in africa but, few data are available on its clinical efficacy and safety 6, 7 but little is know on dhapq combination.
Treatment failures in cases with pfpm2 amplificationpositive parasites and adequate piperaquine exposure support the presence of piperaquine resistance in vietnam. Dihydroartemisinin an overview sciencedirect topics. Dihydroartemisininpiperaquine study drugs were provided free of charge by holleypharm, china. Artemetherlumefantrine versus dihydroartemisininpiperaquine. Artemisininpiperaquine ap, dihydroartemisininpiperaquine phosphate. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Dec 24, 2014 also, tracii aims to investigate the safety, pharmacokinetic characteristics and efficacy of a novel combination of an artemisininderivative and two long acting partner drugs, piperaquine and mefloquine. Delayed haemolytic anaemia has been observed up to one month following use of iv artesunate and oral artemisininbased. Dihydroartemisininpiperaquine is not treating malaria effectively across the eastern greater mekong subregion. Artemisininbased combination regimens are recommended by who for the treatment of uncomplicated plasmodium falciparum malaria. Dihydroartemisininpiperaquine dhappq oral essential drugs. Recommended artekin dihydroartemisinin dhapiperaquine dosing schedule, by. Eurartesim dihydroartemisininpiperaquine medicines for. It is a fixeddose coformulation, which improves adherence, it is better tolerated, and it is around three times less expensive.
Artemisinin combination therapy act is used world wide as the firstline treatment against uncomplicated falciparum malaria 1. Dihydroartemisinin 40 mg and piperaquine phosphate 320 mg capsules. A randomized trial of dihydroartemisininpiperaquine versus. Dihydroartemisininpiperaquine has been shown to be effective for the treatment of malaria in pregnant and nonpregnant populations 29,30 and for the prevention of malaria in children and nonpregnant adults. Pdf effects of dihydroartemisininpiperaquine phosphate. The parent drug is considered to best reflect the biopharmaceutical quality of the proposed product. View the article pdf and any associated supplements and figures for a period of 48 hours.
Does the use of dihydroartemisininpiperaquine in treating. Strict regulation and monitoring of antimalarial use, along. The reaction is stopped and the dha is precipitated with water and acid. Reduced exposure to piperaquine, compared to adults, in. Drug resistance of falciparum malaria is a global problem. Dihydroartemisininpiperaquine is a combination of dihydroartemisinin and piperaquine which is highly effective in the treatment of. Dhapq is a potential alternative for the treatment of uncomplicated malaria in mali. One such combination comprises the artemisinin derivative dihydroartemisinin and the bisquinolone piperaquine. Efficacy and safety of dihydroartemisininpiperaquine artekin in. Dihydroartemisinin blocks the nuclear translocation of relap65 from the cytosol rather than suppressing relap65 protein synthesis. The combination dihydroartemisininpiperaquine is an effective antimalarial that is used widely around the world. Its pragmatic use of both treatment combinations in a field hospital is evaluated.
Effects of dihydroartemisininpiperaquine phosphate and. Dihydroartemisinin dihydroqinghaosu parasite inhibitor. It is necessary that the potential drugdrug interactions of mefloquine and dihydroartemisinin piperaquine dhapqp are characterized. Mar 10, 2016 dihydroartemisininpiperaquine has been shown to be effective for the treatment of malaria in pregnant and nonpregnant populations 29,30 and for the prevention of malaria in children and nonpregnant adults. Optimal dosing of dihydroartemisininpiperaquine for seasonal. Ibasunate dihydroartemisinin and piperaquine phosphate. The efficacy of dihydroartemisininpiperaquine and artemether. Databases including central, medline, and ictrp were searched until august 2018. In a randomized controlled trial, prasanna jagannathan and colleagues compare the impact of intermittent preventive treatment of malaria in pregnancy using dihydroartemisinin piperaquine versus sulfadoxinepyrimethamine on malaria risk during childhood. Dihydroartemisininpiperaquine dhp is the first line therapy. Jul 12, 2011 for dhp, treatment was as for arm dihydroartemisinin piperaquine. The first human studies of piperaquine were carried out in the 1970s and involved its prophylactic use in several thousand adults and children. Evidence of plasmodium falciparum malaria multidrug resistance to artemisinin and piperaquine in western cambodia. Dihydroartemisininpiperaquine also became one of the few antimalarials to be formally registered by a stringent regulatory authority when the european medicines agency.
Support letter from medicines for malaria venture pdf, 317kb. Choreoathetosis an unusual adverse effect of dihydroartemisinin. The dramatic decline in efficacy of dihydroartemisininpiperaquine compared with what was observed in a study at the same location in 2010 was strongly associated with a new triple mutation including the kelch cys580tyr substitution. The funders had no involvement in the study design, data collection, data analysis, data interpretation, in the writing of the paper, or in the decision to submit it for publication. Cn101954090a dihydroartemisinin betacyclodextrin inclusion. Its use declined in the 1980s as piperaquine resistant strains of plasmodium falciparum appeared and artemisinin derivatives became available. Major article malaria transmission after artemetherlumefantrine and dihydroartemisinin piperaquine.
Treatment failure of dihydroartemisininpiperaquine for. Dihydroartemisinin piperaquine has several advantages over artesunatemefloquine. The world health organization who recommends artemisinin. The invention discloses a dihydroartemisinin betacyclodextrin inclusion compound, a preparation method thereof and an antimalarialdrug with the inclusion compound. The dihydroartemisinin would, for certain individuals bring effects of greater or lesser severity for example, a reversible reduction in reticulocyte counts. Glyceraldehyde 3phosphate dehydrogenase gapdh served as a loading control.
Artemetherlumefantrine 20 mg of artemether and 120 mg of lumefantrine is. Dihydroartemisininpiperaquine is an especially attractive combination therapy, given its prolonged posttreatment prophylactic effect. The current policy suggests that intravenous and oral quinine could be used when standard therapy is not available. A randomized controlled noninferiority trial was conducted to compare the safety and efficacy of dihydroartemisinin piperaquine and artesunateamodiaquine versus artemetherlumefantrine in children less than 10 years of age for acute uncomplicated plasmodium falciparum infection. Dihydroartemisininpiperaquine, a fixeddose combination antimalarial, is an inexpensive, safe and highly effective. Dihydroartemisininpiperaquine dhappq oral essential. Data sources include ibm watson micromedex updated 28 feb 2020, cerner multum updated 2 mar 2020, wolters kluwer updated. Hmdb is offered to the public as a freely available resource. A fixed oral combination of the bisquinolone piperaquine and dihydroartemisinin dhp is a new and promising artemisininbased combination therapy.
Low piperaquine blood levels, irrespective of the presence of pfpm2 amplifications, might play a role in some treatment failures. The primary outcome was the incidence of malaria over 12 months. Dihydroartemisininpiperaquine and azithromycinbased combinations are showing great promise as potential candidates for iptp but pharmacokinetic data suggest that dose. This combination has retained excellent cure rates. Dihydroartemisinin is used to treat malaria, generally as a combination drug with piperaquine. Dihydroartemisininpiperaquine against multidrugresistant. Application of dihydroartemisinin plus piperaquine for inclusion in the model list of essential medicines pdf, 285kb. Cn103263418a dihydroartemisinin piperaquine phosphate. Optimal dosing of dihydroartemisininpiperaquine for. An indonesian observational study detected a higher rate of abortion after first trimester exposure to dihydroartemisininpiperaquine poespoprodjo 2014.
Conclusions and recommendations of sixth biannual meeting september 2014. Piperaquine is an antimalarial agent first synthesized in the 1960s and used throughout china. Dihydroartemisininpiperaquine has been shown to be effective for the treatment of malaria in pregnant and nonpregnant populations 29,30 and for the prevention of malaria in children and. The inclusion compound is composed of dihydroartemisinin and betacyclodextrin based on the weight ratio of 1. Pdf the efficacy of dihydroartemisininpiperaquine and. Immunoblot analysis of the expression levels of bcl2 and bax after treatment of hct116 tp53cells with 20.
However, dihydroartemisinin piperaquine cures slightly more. Pdf formulation of dihydroartemisininpiperaquine dhp. Enrolled children were randomized to dihydroartemisininpiperaquine dp given once a month iptm, dp given once a school term 4 treatments over 12 months, iptst, or placebo and followed for 12 months. Malaria transmission after artemether lumefantrine and. Efficacy and safety of dihydroartemisininpiperaquine. In southeast asia, where resistance has emerged towards both artemisinin and piperaquine, the combination is being trialed with a third drug, namely mefloquine. Therapeutic efficacy and safety of dihydroartemisininpiperaquine. The invention discloses dihydroartemisinin piperaquine phosphate tablets and a preparation method thereof. Stability of dihydroartemisininpiperaquine tablet halves during. It is a semisynthetic derivative of artemisinin and is widely used as an intermediate in the preparation of other artemisininderived.
Frequently asked questions about eurartesim dihydroartemisininpiperaquine eurartesim is a novel combination therapy based on an artemisinin derivative extracted from artemisia annua, a traditional chinese medicinal treatment for fever, and an antimalarial drug, piperaquine, which remains in the body for up to 60 days. A fifth combination has recently been added dihydroartemisininpiperaquine 74. Efficacy and safety of dihydroartemisininpiperaquine sciencedirect. Eurartesim is a fixeddose combination of dihydroartemisininpiperaquine dhapqp, developed by alfasigma s. Dihydroartemisininpiperaquine phosphate in a fixeddose preparation of dihydroartemisinin 40 mg and piperaquine phosphate 320 mg has been shown to be highly effective in treating falciparum malaria with an efficacy of over 90% in china, vietnam, and cambodia 1012. Dihydroartemisinin piperaquine and azithromycinbased combinations are showing great promise as potential candidates for iptp but pharmacokinetic data suggest that dose. As a result of increasing resistance to sulfadoxinepyrimethamine, new treatments are necessary to prevent malaria in pregnant women in africa. Frequently asked questions about eurartesim medicines for.
The declining efficacy of dihydroartemisininpiperaquine against plasmodium falciparum in cambodia. The world health organization recommended the use of artemisininbased combination therapies acts for treatment of uncomplicated falciparum malaria a decade ago in response to problems of drug resistance. Compared with the prior art, in the invention, the inclusion compound is prepared from the dihydroartemisinin and the betacyclodextrin, thereby increasing the solubility of the dihydroartemisinin in water greatly, improving the stability of the dihydroartemisinin, and being beneficial for the followup operation of the dihydroartemisinin in. Dihydroartemisinin is the active metabolite of all artemisinin compounds artemisinin, artesunate, artemether, etc. Use and redistribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material hmdb and the original publication see the hmdb citing page. Secondary outcomes included parasite prevalence and anemia over 12 months.
Intravenous artesunate plus oral dihydroartemisinin. Although dihydroartemisinin piperaquine dp treatment is a welltolerated, effective therapy for uncomplicated malarial infections, this drug combination is known to interfere with cardiac repolarization by prolonging qt intervals on electrocardiograms. In a randomized controlled trial, prasanna jagannathan and colleagues compare the impact of intermittent preventive treatment of malaria in pregnancy using dihydroartemisininpiperaquine versus sulfadoxinepyrimethamine on malaria risk during childhood. Resistance in plasmodium falciparum to commonly used antimalarial drugs, especially chloroquine, is being increasingly documented in india.
Malaria contributes significantly to the global disease burden. Dec 30, 2019 intravenous artesunate and its follow on full course dihydroartemisininpiperaquine are the standard treatment for severe malaria in indonesia. For piperaquine, only in the case of a crossover study, the analytical. Coformulated tablets of dihydroartemisinin dhapiperaquine ppq, in blister pack, for a complete treatment for one individual there are 5 different blister packs. The combination dihydroartemisinin piperaquine is an effective antimalarial that is used widely around the world. Recommended artekin dihydroartemisinin dhapiperaquine dosing schedule, by patient age. The tablets are prepared from dihydroartemisinin, piperaquine phosphate, hydroxypropyl methyl cellulose e5, hydrophilic accessory and lubricating agent, wherein the weight ratio of the dihydroartemisinin to the hydroxypropyl methyl cellulose e5 is 1. Use of the information, documents and data from the echa website is subject to the terms and conditions of this legal notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the echa website may be reproduced, distributed andor used, totally or in part, for noncommercial purposes provided that echa is. May 18, 2007 dihydroartemisinin piperaquine study drugs were provided free of charge by holleypharm, china. Researchers tested the efficacy of threedose and monthlydose dihydroartemisininpiperaquine and compared the results with sulfadoxinepyrimethamine. Dihydroartemisinin what does dihydroartemisinin stand. Dihydroartemisininpiperaquine phosphate in a fixed. Determinants of dihydroartemisininpiperaquine treatment failure in. The funding source had no involvement in the authors work.
This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Plasmodium falciparum dihydroartemisininpiperaquine failures in. The dramatic decline in efficacy of dihydroartemisinin piperaquine compared with what was observed in a study at the same location in 2010 was strongly associated with a new triple mutation including the kelch cys580tyr substitution. Dihydroartemisinin treatment effectively upregulates the cytosolic relap65 protein level and downregulates the nuclear relap65 protein level. Eurartesim has proved effective in the treatment of uncomplicated plasmodium falciparum malaria. Dihydroartemisininpiperaquine dp is recommended for the treatment of uncomplicated malaria. Dihydroartemisininpiperaquine dhp is highly recommended for the treatment of. Mar 29, 2018 2 no noticeable side effect of dihydroartemisinin is reported. Dihydroartemisininpiperaquine failure associated with a. Studies have shown that eurartesims long halflife affords patients a useful period of protection from new malaria infections. Dihydroartemisinin also known as dihydroqinghaosu, artenimol or dha is a drug used to treat malaria. Dihydroartemisininpiperaquine resistance in plasmodium. The efficacy of dihydroartemisininpiperaquine was equivalent to that of artesunatemefloquine, the current treatment of choice for multidrugresistant falciparum malaria in southeast asia.
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