Proguanil prophylaxis

Lundgren, J.D., Gragsted, U.B. Atovaquone / proguanil. Prophylaxis and treatment of malaria. Ugesker. Laeger. 2000 162 4177-4181... 

VI.a.2.2. Biguanides. Proguanil is a dihydrofolate reductase inhibitor. It is a slow acting blood schizonticide and not effective on its own. It has also a marked effect on the primary tissue stages of Plasmodium falciparum. It is used in combination with chloroquine for the prophylaxis of chloroquine-resistant Plasmodium falciparum. 

Several drugs (for example amiodarone, androgens, glucocorticoids, phenytoin, and salicylates) interfere with the transport or metabolism of thyroid hormones and thereby alter thyroid function tests. These have been reviewed (90). In patients taking levothyroxine serum TSH rises after treatment with sertraline (91) and antimalarial prophylaxis with chloroquine and proguanil... 

Patel SN, Kain KC. Atovaquone/proguanil for the prophylaxis and treatment of malaria. Expert Rev Anti Infect Ther. 2005 3 849-861. 

PROGUANIL H2 RECEPTOR BLOCKERS-CIMETIDINE 1 efficacy of proguanil L absorption and l formation of active metabolite Avoid concomitant use. Clinical significance is not established effectiveness of malarial prophylaxis may be 1... 

Preventing the initial hepatic cycle. This is also called causal prophylaxis. Primaquine has long been regarded as too toxic for prolonged use but evidence now suggests it may be used safely, and it is inexpensive proguanil is weakly effective. Doxycycline may be used short-term. 

Mefloquine, chloroquine, proguanil, and pyrimethamine plus dapsone (Maloprim), alone or in combination are most commonly advised for prophylaxis regimens and doxycycline for special cases (drug resistance or intolerance) primaquine is being re-evaluated. 

Atovaquone acts synergistically with proguanil, and the combination of these two drugs (Malarone ) is highly efficacious in the treatment of uncomplicated malaria (8), including that against multidrug resistant forms, and in prophylaxis (9). It has not yet been widely marketed, so data on rare adverse effects are currently sparse. 

Lell B, Luckner D, Ndjave M, Scott T, Kremsner PG. Randomised placebo-controlled study of atovaquone plus proguanil for malaria prophylaxis in children. Lancet 1998 351(9104) 709-13. 

Anonymous. Atovaquone -f proguanil for malaria prophylaxis. Drug Ther Bull 2001 39(10) 73-5. 

A marked increase in serum TSH occurred in the same patient on two occasions after several weeks of anti-malarial prophylaxis with chloroquine and proguanil, the likely mechanism being enzyme induction and increased thyroxine catabolism (SEDA-22, 469). 

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). 

Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, Toovey S, Knobloch J, Nothdurft HD, Shaw D, Roskell NS, Chulay JD Malarone International Study Team. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers results from a randomized, double-blind study. Clin Infect Dis 200I 33(7) 1015-21. 

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). 

Drugs used in prophylaxis. These block a stage in the life cycle, e.g. chloroquine, dapsone, doxycycline, mefloquine, proguanil and pyrimethamine, and often in combinations. 

Another alternative regimen for chemoprophylaxis is the combination of atovaquone and proguanil (Malarone) 1 tablet daily beginning 1 to 2 days prior to travel and continuing for the duration of stay and 1 week after leaving the area. Daily primaquine 15 mg (base) also has been recommended for prophylaxis for both P. vivax and P falciparum malaria. ... 

Drugs for clinical cure Drugs for radical cure Drugs for prophylaxis Quinine, halofantrine Primaquine Chloroquine, proguanil... 

Chloroquine or proguanil can be used for prophylaxis, although choice of drug will depend on whether the plasmodium is resistant in the area that is being visited. 

Atovaquone is an antimalarial preparation. It inhibits mitochondrial electron transport in parasites, causing inhibition of nucleic acid synthesis. Proguanil exerts its effect by means of the metabolite cycloguanil, which inhibits dihydrofolate reductase in the malarial parasite, disrupting deox-ythymidylate synthesis. It is indicated in prophylaxis of P. falciparum in patients with severe renal impairment (Ccr less than 30 mL/min) hypersensitivity to any component of the product. 

Atovaquone (mepron) has potent activity against Plasmodium species and the opportunistic pathogens Pneumocystis jirovici arul Toxoplasma gondii it is FDA approved for treatment of P. jirovici pneumonia in patients intolerant of trimethoprim-sulfamethoxazole. In patients with uncomplicated P. falciparum malaria, combination therapy with proguanil and atovaquone evoked high cure rates with few relapses and minimal toxicity. A fixed combination of atovaquone with proguanil (maiarone) is available in the U.S.for malaria prophylaxis and treatment. 

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. 

Prophylaxis mefloquine backup drugs doxycycline, atovaquone-proguanil Treatment quinine +/- either doxycycline or clindamycin or pyrimethamine... 

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