Tags

Type your tag names separated by a space and hit enter

Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group.
Am J Trop Med Hyg. 1999 Apr; 60(4):533-41.AJ

Abstract

The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was > 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria.

Authors+Show Affiliations

Department of Clinical Tropical Medicine, Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Thailand.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

10348225

Citation

Looareesuwan, S, et al. "Malarone (atovaquone and Proguanil Hydrochloride): a Review of Its Clinical Development for Treatment of Malaria. Malarone Clinical Trials Study Group." The American Journal of Tropical Medicine and Hygiene, vol. 60, no. 4, 1999, pp. 533-41.
Looareesuwan S, Chulay JD, Canfield CJ, et al. Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. Am J Trop Med Hyg. 1999;60(4):533-41.
Looareesuwan, S., Chulay, J. D., Canfield, C. J., & Hutchinson, D. B. (1999). Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. The American Journal of Tropical Medicine and Hygiene, 60(4), 533-41.
Looareesuwan S, et al. Malarone (atovaquone and Proguanil Hydrochloride): a Review of Its Clinical Development for Treatment of Malaria. Malarone Clinical Trials Study Group. Am J Trop Med Hyg. 1999;60(4):533-41. PubMed PMID: 10348225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group. AU - Looareesuwan,S, AU - Chulay,J D, AU - Canfield,C J, AU - Hutchinson,D B, PY - 1999/5/29/pubmed PY - 1999/5/29/medline PY - 1999/5/29/entrez SP - 533 EP - 41 JF - The American journal of tropical medicine and hygiene JO - Am J Trop Med Hyg VL - 60 IS - 4 N2 - The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was > 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria. SN - 0002-9637 UR - https://www.unboundmedicine.com/medline/citation/10348225/Malarone__atovaquone_and_proguanil_hydrochloride_:_a_review_of_its_clinical_development_for_treatment_of_malaria__Malarone_Clinical_Trials_Study_Group_ L2 - https://ajtmh.org/doi/10.4269/ajtmh.1999.60.533 DB - PRIME DP - Unbound Medicine ER -