Proguanil

MECHANISM OF ACTION

Proguanil works by stopping the growth of malaria parasites in the body. After entering the body, it is converted into an active form called cycloguanil, which blocks an important enzyme (dihydrofolate reductase) needed by the parasite to make DNA and multiply. Without this process, the parasite cannot grow or reproduce, helping to prevent and treat malaria.

PHARMACOKINETICS

Absorption

Proguanil is well absorbed from the stomach after oral administration. It enters the bloodstream easily, and food does not significantly affect its absorption. The drug reaches effective levels in the blood within a few hours.

Distribution

Proguanil is widely distributed throughout the body after absorption. It can enter body tissues, including the liver and red blood cells, where malaria parasites live. This wide distribution helps the drug act effectively against the parasite.

Metabolism

Proguanil is metabolized in the liver, where it is converted into its active form called cycloguanil by liver enzymes (mainly CYP2C19). This active form is responsible for killing the malaria parasite, while some unchanged drug also remains in the body.

Elimination

Proguanil is mainly eliminated from the body through the kidneys in urine. A small amount is also excreted in feces. Both the unchanged drug and its metabolites are removed over time.

PHARMACODYNAMICS

Proguanil works by interfering with the malaria parasite’s ability to make DNA and grow. Its active metabolite (cycloguanil) blocks the enzyme dihydrofolate reductase (DHFR), which is essential for folate metabolism in the parasite. Without this enzyme, the parasite cannot multiply, so the infection is controlled or prevented.

ADMINISTRATION

Proguanil is given by mouth in tablet form. It is usually taken once daily, often at the same time each day. For malaria prevention, it is started before travel to malaria-endemic areas and continued during exposure and for a short period after leaving the area. It is also commonly used in combination with other antimalarial drugs.

DOSAGE AND STRENGTH

For malaria prevention, Proguanil is usually taken orally once daily. The adult dose is commonly 200 mg daily, started 1–2 days before entering a malaria-endemic area, continued throughout exposure, and for about 7 days after leaving the area. In children, the dose is adjusted based on body weight, typically around 3 mg/kg daily, up to the adult dose limit. It is also used in combination with other antimalarial drugs such as atovaquone in fixed-dose regimens.

DRUG INTERACTIONS

Proguanil can interact with drugs that affect liver enzymes, especially those involving CYP2C19 metabolism, which may alter its effectiveness. However, clinically significant interactions are generally limited compared to many other antimalarial drugs.

FOOD INTERACTIONS

Proguanil can be taken with or without food. Taking it with food may help reduce stomach upset in some patients, but food does not significantly affect its absorption or effectiveness.

CONTRAINDICATIONS

Proguanil should not be used in individuals with known hypersensitivity to the drug. Caution is advised in patients with severe kidney or liver impairment, as drug elimination may be affected.

SIDE EFFECTS

• Nausea 

• Vomiting 

• Stomach pain or discomfort 

• Headache 

• Diarrhea 

• Usually mild and temporary

OVER DOSAGE

Overdosage of Proguanil is uncommon but may lead to symptoms such as nausea, vomiting, dizziness, abdominal discomfort, and general weakness. In most cases, treatment is supportive, focusing on relieving symptoms and maintaining hydration, as serious toxicity is rare at recommended doses.

TOXICITY

Proguanil is generally well tolerated, but very high doses may cause gastrointestinal symptoms and liver strain. Serious toxicity is rare when used at recommended doses.