Proguanil dosing

Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Since 2000 atovaquone is available as a fixed dose preparation (Malarone) with proguanil for the oral treatment of falciperum malaria. Its activity probably is based on a selective inhibiton of mitochondrial electron transport with consequent inhibition of pyrimidin synthesis. Malarone should not be used to treat severe malaria, when an injectable drug is needed. 

PROGUANIL ANTACIDS l proguanil levels i absorption Separate doses by at least 4 hours... 

PROGUANIL CNS STIMULANTS -MODAFINIL May cause moderate t plasma concentrations of these substrates Modafinil is a reversible inhibitor of CYP2C19 when used in therapeutic doses Be aware... 

Adverse effects. In prophylactic doses it is well tolerated. Mouth ulcers and stomatitis have been reported. Proguanil should be avoided or used in reduced dose for patients with impaired renal function. 

The adverse effects of mefloquine have been extensively reviewed both for prophylaxis (when rare neuropsychiatric adverse effects make its use controversial) and in treatment doses, when it has been linked to an increased incidence of the postmalaria neurological syndrome. A retrospective review of 5120 Itahan soldiers showed an overall chemoprophylaxis curtailment rate of less than 1%, which was not significantly different from the combination of chloroquine and proguanil (11). A semi-systematic review also suggested no significant difference in tolerabihty compared with other antimalarial drugs (12). 

Proguanil is one of the antimalarial drugs most widely used for prophylactic purposes, usually in combination with chloroquine or atovaquone in malaria prophylaxis, and with atovaquone in malaria treatment (SEDA-21, 297). A biguanide, it is rapidly absorbed in standard doses and mainly excreted by the kidneys. Its antimalarial effect is due to its metabolite cycloguanU. However, its metabolism varies individually, and this is reflected in a variable degree of efficacy (SEDA-17, 328). 

In P. falciparum (chloroquine-resistant) infections, a dose of 750 mg mefloquine followed by 500 mg 12 hours later is recommended. The pediatric dose of mefloquine is 15 mg/kg (<45 kg) followed by 10 mg/kg 8 to 12 hours later.Intravenous quinidine gluconate followed by oral quinine should be administered for severe illness, as already indicated.A second drug needs to be administered in chloroquine-resistant P. falciparum, and this second drug should follow the oral quinidine regimen either a single dose of three tablets of pyrimethamine-sulfadoxine (Fansidar) on the last day of intravenous quinidine or clindamycin 900 mg three times daily for 3 to 5 days. An alternative oral treatment for chloroquine-resistant P falciparum infection in adults, especially in those with a history of seizures or psychiatric disorders, is the combination of atovaquone 250 mg and proguanil 100 mg (Malarone) (4 tablets daily... 

In rat-foot oedema tests, chloroquine sulphate in intraperitoneal doses of 10 mg/kg twice daily two days before and immediately prior to a formalin injection was found to be ineffective , whereas other workers have found chloroquine inhibitory in oral doses of 50 mg/kg . In these latter tests mepacrine, proguanil and primaquine, in oral doses of 50 mg/kg, were also effective. Chloroquine sulphate in doses of 10 mg/kg twice daily intraperitoneally for short or long term administration does not affect the development of generalized oedema produced by intraperitoneal dextran or egg-white . When administered chronically it reduces skin inflammation produced locally by chloroform, but is less effective than salicylates . ... 

In lactating mothers, atovaquone-proguanil is not recommended. Also, the infant must be shown to have a normal G6PD level before using primaquine. For prophylaxis in long-term travelers, chloroquine is safe at the doses used, but may necessitate yearly retinal examinations. Mefloquine and doxycycline are well tolerated. Atovaquone-proguanil has been studied for up to 20 weeks but probably is acceptable for years based on experience with the individual components. 

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