Action And Clinical Pharmacology: Proguanil is metabolized in the body to the antimalarial drug cycloguanil, a triazine derivative, which inhibits plasmodial dihydrofolate reductase thus indirectly inhibiting synthesis of nucleic acids in the parasite. Proguanil, like pyrimethamine, is active against pre-erythrocytic forms and is a slow blood schizontocide. It also has some sporonticidal activity, rendering the gametocytes noninfective to the mosquito vector.
Pharmacokinetics: Proguanil is well absorbed from the gastrointestinal tract and peak plasma concentrations are attained in 3 hours after a single oral dose; about 75% of proguanil in the plasma is bound to proteins and the concentrations of the drug in erythrocytes is approximately 6 times that of plasma. About 50% of the administered dose is excreted in the urine, 60% as unchanged drug and 30% as the active metabolite cycloquanil.
Indications And Clinical Uses: Causal prophylaxis of falciparum (P. falciparum) malaria; proguanil also supresses other forms of malaria, and it is used to reduce transmission of infection. Proguanil should not be used alone in countries where chloroquine-resistant malaria has been confirmed (see Dosage).
Contra-Indications: Known or suspected hypersensitivity to proguanil.
A high degree of resistance appears to develop in all species of Plasmodium and in some geographical areas this has limited the usefulness of proguanil. Proguanil alone should not be used if resistance to other antimalarials has been confirmed. Cross-resistance occurs with other antimalarials.
Precautions: It is generaly accepted that all drug treatment should be avoided if possible during the first trimester of pregnancy. A causal connection between the use of proguanil and any adverse effect on mother and fetus has never been established, but the attending physician should carefully weigh the expected benefits against the potential risks.
Use proguanil with caution in patients with severe renal impairment.
Adverse Reactions: At normal therapeutic doses, the side effect most commonly encountered is mild gastric intolerance. This usually subsides as treatment is continued. Mouth ulceration has occasionally been reported. Large doses (1 g daily) may cause vomiting, abdominal pain, hematuria and renal irritation. Blood dyscrasias have been reported in patients with renal failure given proguanil.
Selected cases of skin reactions and reversible hair loss have been reported in association with the use of proguanil.
Symptoms And Treatment Of Overdose: Symptoms: The following effects have been reported in cases of overdosage: hematuria, renal irritation, epigastric discomfort and vomiting. tag_Treatment
Treatment: There is no specific antidote; symptoms should be treated as they arise. Treatment should be symptomatic and supportive.
Dosage And Administration: For prophylaxis of malaria: Adults: Usual dose is 100 mg daily. In highly endemic areas this dose may be safely increased to 200 mg daily. The daily dose is best taken with water after food.
Nonimmune subjects entering a malarious region are advised to begin treatment with proguanil at least 24 hours before arrival. A daily dose of proguanil should be continued for 6 weeks after leaving the area.
Elderly: There are no special dosage recommendations for the elderly, but it may be advisable to monitor elderly patients so that optimum dosage can be individually determined.
Children: Under 1 year: 25 mg daily; 1 to 4 years: 50 mg daily; 5 to 8 years: 75 mg daily; 9 to 12 years: 100 mg daily; over 12 years: adult dose daily.
For a young child, the dose may be administered crushed and mixed with milk, honey or jam.
For all countries with chloroquine-resistant malaria: The dose of proguanil is increased to 200 mg daily with chloroquine (base) given 300 mg once a week, i.e., approximately equivalent to 500 mg chloroquine phosphate.
Note: Although widely used, the safety of this therapeutic regimen has not been formally established.
In Southeast Asia and the Pacific where chloroquine resistance is commonplace, the above regimen is apparently ineffective.
Availability And Storage: Each white, biconvex tablet, embossed P/P on one side with a score line, contains: proguanil HCl 100 mg. Nonmedicinal ingredients: lactose powdered, magnesium stearate, starch corn and starch paste. Energy: 0.6 kJ (0.15 kcal)/tablet. Alcohol-, gluten-, parabens-, sugar-, sulfites- and tartrazine-free. Bottles of 100. Store at temperatures around 25°C. (Shown in Product Recognition Section)
PALUDRINE® Wyeth-Ayerst Proguanil HCl Antimalarial