Atovaquone is a medication used against malaria, a serious disease caused by parasites spread through mosquito bites. It offers a valuable option for prevention and treatment, especially for travelers to malaria-prone regions. Understanding its mechanism and uses highlights its importance in global health efforts.
Understanding Atovaquone
Atovaquone is an antimalarial drug that targets malaria parasites. It eliminates parasites within the body and prevents illness. For improved effectiveness, atovaquone is combined with proguanil, known by the brand name Malarone.
This combination medication is available as a fixed-dose tablet. An adult strength typically contains 250 mg of atovaquone and 100 mg of proguanil hydrochloride. A pediatric formulation is also available with lower doses. The combination provides a synergistic effect, working together for a stronger impact on the malaria parasite than either drug could achieve alone.
How Atovaquone Combats Malaria
Atovaquone disrupts the malaria parasite’s life cycle by interfering with its metabolic processes. It targets the parasite’s mitochondrial electron transport chain, a complex series of reactions within the parasite’s mitochondria. By binding to the cytochrome bc1 complex (Complex III) within this chain, atovaquone prevents the normal flow of electrons, which collapses the parasite’s mitochondrial membrane potential.
This disruption halts the production of adenosine triphosphate (ATP), the primary energy source for the parasite’s survival and replication. Atovaquone also indirectly inhibits dihydroorotate dehydrogenase (DHOD), an enzyme crucial for pyrimidine synthesis, which are building blocks for the parasite’s DNA and RNA. The proguanil component, through its active metabolite cycloguanil, also contributes by inhibiting dihydrofolate reductase, another enzyme involved in pyrimidine synthesis. This dual mechanism ensures a comprehensive attack on the parasite’s ability to grow and reproduce, helping prevent rapid drug resistance that can occur if atovaquone is used alone.
When Atovaquone is Used
Atovaquone, usually combined with proguanil, is prescribed for malaria prevention (prophylaxis) and treating active disease. For travelers visiting malaria-common areas, especially those with drug-resistant Plasmodium falciparum, it serves as a preventive measure. The medication is typically started one to two days before entering a malaria-risk area, taken once daily throughout the stay, and continued for seven days after leaving.
For active malaria infections, atovaquone/proguanil is generally used for uncomplicated Plasmodium falciparum malaria. It is also effective against other Plasmodium species, such as P. vivax, particularly where other medications like chloroquine may be less effective due to resistance. This combination is not typically recommended for severe or complicated forms of malaria, which may require different treatments. The medication can be prescribed to adults and children weighing at least 11 pounds (5 kg).
What to Know About Side Effects and Precautions
Atovaquone can cause side effects, though they are generally mild. Common side effects include nausea, vomiting, abdominal pain, headache, and diarrhea. Taking atovaquone with food or a milky drink can significantly improve its absorption and help reduce gastrointestinal upset. If vomiting occurs within one hour of taking a dose, it is generally advised to take another full dose to ensure adequate absorption.
Precautions and contraindications are associated with atovaquone use. Individuals with severe kidney impairment (creatinine clearance below 30 mL/min) should not use atovaquone for malaria prevention. Serious allergic reactions, including anaphylaxis, angioedema, or severe skin conditions like Stevens-Johnson syndrome, are rare but have been reported. Patients should also be aware of potential liver problems, as elevated liver enzymes and, rarely, liver failure have been reported.
Using atovaquone during pregnancy or breastfeeding requires careful consideration, as data on its effects are not extensive, and potential risks versus benefits must be weighed. Proguanil is known to be excreted in small amounts into breast milk, while atovaquone’s excretion into milk is less understood. Atovaquone can interact with other medications. For example, drugs like rifampin, rifabutin, and tetracycline can reduce atovaquone levels in the blood, potentially decreasing its effectiveness. Metoclopramide may also decrease atovaquone absorption, and close monitoring is advised for individuals taking warfarin.