Malarone® (Atovaquone/Proguanil)

Malarone® is a combination product of atovaquone and proguanil that is used for the prevention (prophylaxis) and treatment of uncomplicated falciparum malaria (Plasmodium falciparum).

The major advantage of Malarone® is the short duration of intake before and after the trip: start only 1–2 days before entering the malaria area and stop as early as 7 days after leaving it.

Mechanism of action: Both active ingredients attack the malaria parasite at different points:

• Atovaquone: Inhibits the parasite's mitochondrial electron transport (complex III, cytochrome bc1)
• Proguanil: Is converted to cycloguanil, which inhibits the parasite's dihydrofolate reductase

Dual action:

• Acts against liver schizonts (prevents infection of the liver)
• Acts against blood schizonts (kills parasites in the blood)
• Thanks to causal prophylaxis at the liver stage: short intake period after travel

Why only 7 days after travel? Because Malarone® already acts in the liver, there is no need to "intercept" parasites coming out of the liver. Other prophylactic agents (e.g., doxycycline) act only in the blood and must be taken for 4 weeks after travel.

Malarone® is suitable for:

• Travelers to malaria areas (tropics and subtropics)
• Short- and long-term prophylaxis (ideal for trips of up to approx. 4 weeks)
• Emergency self-treatment (stand-by therapy)
• Children with a body weight of 11 kg or more

Especially recommended for:

• Short trips (short intake period before/after travel)
• Areas where Plasmodium falciparum is resistant to other agents
• Intolerance of mefloquine or doxycycline

Not suitable:

• Severe renal impairment (GFR < 30 ml/min)
• In case of known hypersensitivity

Malaria prophylaxis, adults:

• 1 tablet (250/100 mg) daily
• Start: 1–2 days before entering the malaria area
• Throughout the entire stay: daily
• After leaving: for another 7 days

Emergency self-treatment (stand-by):

• 4 tablets as a single dose on 3 consecutive days (= 12 tablets in total)

Children (prophylaxis):

• 11–20 kg: 1 Malarone® Junior daily (62.5/25 mg)
• 21–30 kg: 2 Malarone® Junior daily
• 31–40 kg: 3 Malarone® Junior daily
• > 40 kg: 1 Malarone® adult tablet daily

Duration of prophylaxis: Safety and efficacy have been demonstrated in studies lasting up to 12 weeks in residents of malaria areas with partial immunity. In non-immune persons, the average duration of use in studies was 27 days. Longer use is possible after individual consultation.

Intake:

• Once daily, always at the same time of day
• With a high-fat meal or a milk-based drink (improves the absorption of atovaquone!)
• If you vomit within 1 hour: repeat the dose

Prophylaxis plan: 1. Start 1–2 days before entering the area 2. Daily during the stay 3. Continue taking it for 7 days after leaving

Important notes:

• Don't forget to take it while traveling! (set a phone alarm)
• Protection against mosquitoes remains important in addition (repellent, mosquito net, long clothing)
• If you have a fever after a trip to the tropics, ALWAYS see a doctor (even if you took prophylaxis)

Malarone® must not be taken in cases of:

• Hypersensitivity to atovaquone or proguanil
• Severe renal impairment (GFR < 30 ml/min) – contraindicated for prophylaxis only

Caution in cases of:

• Mild to moderate renal impairment
• Pregnancy (no experience regarding the safety of use)
• Breastfeeding (proguanil passes into breast milk)
• Diarrheal illnesses (reduced absorption)

Pregnancy: There is no experience regarding the safety of use during pregnancy, and the possible risk is unknown. Malarone® should only be used during pregnancy if the expected benefit for the mother outweighs any possible risk to the unborn child.

Very common (10% or more):

• Abdominal pain
• Nausea
• Headache
• Diarrhea
• Vomiting

Common (1–10%):

• Sleep disturbances, unusual dreams
• Dizziness
• Loss of appetite
• Skin rash
• Allergic reactions
• Elevated liver enzymes

Uncommon (0.1–1%):

• Hair loss

Frequency not known:

• Mouth ulcers
• Severe allergic reactions (anaphylaxis, angioedema)
• Severe skin reactions (Stevens-Johnson syndrome, DRESS, erythema multiforme)

General: Malarone® is one of the best-tolerated antimalarials. The side effects are usually mild and temporary.

Reduced atovaquone levels due to:

• Metoclopramide (reduced absorption)
• Tetracyclines (serum levels of atovaquone decrease)
• Rifampicin/rifabutin (marked reduction in atovaquone levels)

Proguanil + warfarin:

• May increase the INR → close INR monitoring

Important:

• A high-fat meal significantly improves atovaquone absorption
• With concurrent diarrhea, effectiveness may be reduced