MALARONE ® is a drug based on Atovaquone + Proguanile hydrochloride
THERAPEUTIC GROUP: AntimalarialsIndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects
Indications MALARONE ® - Atovaquone + Proguanile hydrochloride
MALARONE ® is indicated, in accordance with the guidelines of the World Health Organization, in the prophylaxis and treatment of episodes of malaria sustained by Plasmodium Falciparum.
Mechanism of action MALARONE ® - Atovaquone + Proguanile hydrochloride
MALARONE ® is a drug widely used in the prevention and treatment of Malaria sustained by Plasmodium Falciparum, thanks to the important schizonticidal activity supported by the association of two different active ingredients with complementary mechanisms of action.
More precisely :
- Proguanil is a prodrug that taken orally and absorbed at the gastro-enteric level, is converted into cycloguanil by cytochrome p450, thus being effective in blocking the enzyme dihydrofolate reductase, compromising nucleotide synthesis and inhibiting the proliferation of elements with a high proliferation rate. hepatocyte schizonts.
- The atovaquonte is a naphthoquinone, with a structure similar to the ubiquinone of the protozoa and therefore able to block the transport of electrons along the mitochondrial membrane, blocking the biosynthetic activities of the parasite.
Furthermore, the association between the two drugs seems to determine the emergence of emergent properties, which make prophylaxis even more effective by preventing hepatocyte schizonts from reaching the erythrocyte cycle.
At the end of its biological activity, following a half-life of more than 10 hours, proguanil and atovaquone are eliminated respectively predominantly via the kidneys and the intestine.
Studies carried out and clinical efficacy
CAUSES OF INSUCCESSES OF THE ATOVAQUONE THERAPY - PROGUANIL
Malar J. 2012 May 2; 11: 146.
Work which, while reiterating the high antimalarial efficacy of the combination of atovaquone-proguanil, attributes the potential failures of therapy and prophylaxis with these drugs to the onset of new resistance mechanisms rather than to a wrong dosage.
ATOVAQUONE - PROGUANIL IN THAILAND
Malar J. 2008 Jan 28; 7: 23. doi: 10.1186 / 1475-2875-7-23.
Study that after evaluating the pharmacogenomic profile of various Plasmodia, reaffirms the efficacy of the association atovaquone / proguanil in the treatment of multi-resistant malaria in Thailand.
ATOVAQUONE / PROGUANIL IN JAPAN
Parasitol Int. 2012 Sep; 61 (3): 466-9. doi: 10.1016 / j.parint.2012.03.004. Epub 2012 Mar 29.
Study that evaluates the effectiveness of several therapeutic protocols in the treatment of imported malaria, defining that based on atovaquone and proguanil as the most effective and safe at least in the Japanese territory.
Method of use and dosage
Atovaquone 200 mg tablets and 100 mg Proguanile hydrochloride
The doctor should define the preventive and therapeutic protocols based on MALARONE ® in accordance with international guidelines drawn up by the World Health Organization and taking into account the physiopathological conditions of the patient.
It is clear that the dosing schedule will vary considerably depending on the age of the patient, on the possible presence of liver and kidney diseases and on the basis of different purposes, preventive or therapeutic.
Given the absorption profile of Atovaquone, it would be preferable to take MALARONE ® during meals, in order to guarantee maximum systemic absorption.
Warnings MALARONE ® - Atovaquone + Proguanile hydrochloride
The therapeutic or preventive protocol with MALARONE ® should be defined by the physician, in line with the WHO, based on the patient's physiopathological characteristics, the patient's geographical area and any conditions that compromise the safety of the patient. use of the drug.
More precisely, patients suffering from hepatic and renal diseases, in light of the pharmacokinetic characteristics of both active ingredients, should take MALARONE ® under strict medical supervision in order to limit the appearance of unpleasant side effects.
At the same time as chemoprophylaxis it would be advisable to implement all the hygienic rules necessary to limit the risk of puncture, thus the penetration of the protozoan into the host organism.
The use of MALARONE ® for therapeutic purposes, must necessarily be supervised by the doctor, evaluating the degree of parasitemia and the progressive improvement of the patient's clinical conditions.
If the current therapy is ineffective it would be advisable to evaluate different strategies.
PREGNANCY AND BREASTFEEDING
Considering the biological activity of the active ingredients of MALARONE ® and given the absence of particularly significant clinical trials, designed to evaluate the safety of the drug for fetal health, it would be preferable to avoid the use of this specialty during pregnancy and lactation unless it is strictly necessary.
In this case, continuous specialist medical supervision is required.
Patients taking MALARONE ® therapy should pay particular attention, by requesting medical advice, to the simultaneous recruitment of:
- Trisilicate magnesium-based drugs, given the reduced systemic absorption induced by Proguanile;
- Oral anticoagulants, for the enhancement of drug-induced anticoagulant activity;
- Metaclopramide, tetracycline, rifampicin and rifabutin able to reduce the systemic absorption of Atovaquone.
Contraindications MALARONE ® - Atovaquone + Proguanile hydrochloride
The use of MALARONE ® is contraindicated in patients who are hypersensitive to the active ingredient or to any of its excipients and in patients with severe impairment of liver and kidney function.
Undesirable effects - Side effects
The use of MALARONE ® could cause the appearance of headache, nausea, vomiting, diarrhea, abdominal pain, insomnia, fever, increased transaminases, stomatitis and mouth ulcers and only in the most serious cases adverse reactions from hypersensitivity such as angioedema, bronchospasm, vasculitis and anaphylaxis.
MALARONE ® is a drug subject to mandatory medical prescription.