Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India

• Published in: Journal of vector borne diseases Vol. 50; no. 4; pp. 258 - 264
• Main Authors: Valecha, Neena, Srivastava, Bina, Dubhashi, N G, Rao, B H Krishnamoorthy, Kumar, Ashwani, Ghosh, S K, Singh, Jai Prakash Narayan, Kiechel, J R, Sharma, Bhawna, Jullien, V, Dash, A P, Taylor, W R J, Anvikar, Anupkumar R
• Format: Journal Article
• Language: English
• Published: India Medknow Publications & Media Pvt. Ltd 01-12-2013; Wolters Kluwer Medknow Publications
• Subjects: Adult; Antimalarials - administration & dosage; Antimalarials - adverse effects; Antimalarials - pharmacokinetics; Artemisinins - administration & dosage; Artemisinins - adverse effects; Artemisinins - pharmacokinetics; Artesunate; India; malaria; mefloquine; P. falciparum; pharmacokinetics; Blister packs; Demography; Drug dosages; Drug therapy; Drug Therapy, Combination; Endemic Diseases; Failure; Female; Fever; Humans; India - epidemiology; Kaplan-Meier Estimate; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Male; Mefloquine - administration & dosage; Mefloquine - adverse effects; Mefloquine - pharmacokinetics; Parasitemia; Parasites; Plasmodium falciparum - drug effects; Treatment Outcome; Young Adult; India
• ISSN: 0972-9062; 0972-9062
• DOI: 10.4103/0972-9062.126232

India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs.
This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008.
A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported.
The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.