Malarone

• GlaxoSmithKline LLC

Malarone is part of the drug class:

• Antimalarial biguanides

You should not use this medication if you are allergic to atovaquone or proguanil. You should not use this medication to prevent malaria if you have severe kidney disease.

Before using this medication, tell your doctor if you have liver or kidney disease, severe complications from infection with malaria, or uncontrolled vomiting or diarrhea.

Take atovaquone and proguanil at the same time each day with food or a milky drink.

If you vomit within 1 hour after taking this medication, take another dose. If your vomiting continues, call your doctor.

If you are taking this medicine to prevent malaria, start taking it 1 or 2 days before entering an area where malaria is common. Take the medication every day during your stay and for at least 7 days after you leave. If you stop taking the medicine early for any reason, contact a healthcare professional about another form of malaria prevention.

If you are taking this medicine to treat malaria, take the medication every day for 3 days in a row.

Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.

In addition to taking atovaquone and proguanil, use protective clothing, insect repellents, and mosquito netting around your bed to further prevent mosquito bites that could cause malaria.

Contact your doctor as soon as possible if you have been exposed to malaria, or if you have a fever or other symptoms of illness during or after a stay in an area where malaria is common.

No medication is 100% effective in treating or preventing malaria. For best results, keep using the medication as directed. Talk with your doctor if you have fever, vomiting, or diarrhea during your treatment.

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Use atovaquone and proguanil regularly to best prevent malaria. If you stop using the medication early for any reason, talk to your doctor about other forms of malaria prevention.

Take atovaquone and proguanil at the same time each day with food or a milky drink.

If you vomit within 1 hour after taking this medication, take another dose. If your vomiting continues, call your doctor.

If you are taking this medicine to prevent malaria:

• Start taking the medicine 1 or 2 days before entering an area where malaria is common. Continue taking the medicine every day during your stay and for at least 7 days after you leave the area.

• If you stop taking the medicine early for any reason, contact a healthcare professional about another form of malaria prevention.

If you are taking this medicine to treat malaria:

• Take the medicine every day for 3 days in a row.

• Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared.

In addition to taking atovaquone and proguanil, use protective clothing, insect repellents, and mosquito netting around your bed to further prevent mosquito bites that could cause malaria.

To be sure this medication is not causing harmful effects, your liver function will need to be checked with frequent blood tests. Visit your doctor regularly.

Contact your doctor as soon as possible if you have been exposed to malaria, or if you have fever or other symptoms of illness during or after a stay in an area where malaria is common.

No medication is 100% effective in treating or preventing malaria. For best results, keep using the medication as directed. Talk with your doctor if you have fever, vomiting, or diarrhea during your treatment.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include stomach discomfort, vomiting, mouth sores, hair loss, easy bruising or bleeding, and peeling of the skin on your hands or feet.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Belly pain.
• Cough.
• Upset stomach or throwing up.
• Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Each Malarone Tablet (adult strength) contains 250 mg atovaquone and 100 mg proguanil hydrochloride. Malarone Tablets are pink, film‑coated, round, biconvex tablets engraved with “GX CM3” on one side.

Each Malarone Pediatric Tablet contains 62.5 mg atovaquone and 25 mg proguanil hydrochloride. Malarone Pediatric Tablets are pink, film‑coated, round, biconvex tablets engraved with “GX CG7” on one side.

There is no information on overdoses of Malarone substantially higher than the doses recommended for treatment.

There is no known antidote for atovaquone, and it is currently unknown if atovaquone is dialyzable. Overdoses up to 31,500 mg of atovaquone have been reported. In one such patient who also took an unspecified dose of dapsone, methemoglobinemia occurred. Rash has also been reported after overdose.

Overdoses of proguanil hydrochloride as large as 1,500 mg have been followed by complete recovery, and doses as high as 700 mg twice daily have been taken for over 2 weeks without serious toxicity. Adverse experiences occasionally associated with proguanil hydrochloride doses of 100 to 200 mg/day, such as epigastric discomfort and vomiting, would be likely to occur with overdose. There are also reports of reversible hair loss and scaling of the skin on the palms and/or soles, reversible aphthous ulceration, and hematologic side effects.

Malarone Tablets, containing 250 mg atovaquone and 100 mg proguanil hydrochloride.

Malarone Pediatric Tablets, containing 62.5 mg atovaquone and 25 mg proguanil hydrochloride.

Storage Conditions

Store at 25°C (77°F). Temperature excursions are permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature).

Absorption

Bioavailability

Oral bioavailability of atovaquone shows considerable interindividual variation;1 absorption of atovaquone may be reduced in patients with diarrhea and vomiting.1

Proguanil hydrochloride extensively absorbed from GI tract.1

Food

Administration with dietary fat increases rate and extent of GI absorption of atovaquone;1 absolute bioavailability is 23% when taken with food.1

Distribution

Extent

Atovaquone distributed into milk in rats; not known whether distributed into human milk.1

Small amounts of proguanil distributed into milk.1

Plasma Protein Binding

Atovaquone >99% bound to plasma proteins; proguanil 75% bound to plasma proteins.1

Elimination

Metabolism

There is indirect evidence that atovaquone may undergo limited metabolism; however, a specific metabolite(s) has not been identified.1 Proguanil metabolized principally by CYP2C19 to the active metabolite cycloguanil and to 4-chlorophenylbiguanide.1

Elimination Route

Following oral administration in healthy individuals, >94% of a dose of atovaquone excreted unchanged in feces; 40–60% of a dose of proguanil excreted in urine.1

Half-life

Atovaquone: Elimination half-life about 2–3 days in adults and 1–2 days in pediatric patients.1

Proguanil: Elimination half-life 12–21 hours in adult and pediatric patients;1 may be longer in slow metabolizers.1

Special Populations

In patients with mild to moderate hepatic impairment, there were no marked differences in rate or extent of systemic exposure to atovaquone, although elimination half-life of atovaquone was prolonged in individuals with moderate hepatic impairment.1 In patients with mild to moderate hepatic impairment, extent of systemic exposure to proguanil was increased and elimination half-life prolonged, with resultant decrease in systemic exposure to cycloguanil and increase in elimination half-life of this metabolite.1

Pharmacokinetics of atovaquone and proguanil in patients with mild renal impairment (Clcr 50–80 mL/minute) similar to that in those with normal renal function.1 In patients with moderate renal impairment (Clcr 30–50 mL/minute), oral clearance of atovaquone unaffected but proguanil oral clearance reduced approximately 35%.1

In patients with severe renal impairment (Clcr <30 mL/minute), systemic exposure to atovaquone was decreased and elimination half-lives of proguanil and cycloguanil were increased, resulting in potential for drug accumulation and toxicity with repeated dosing.1

In geriatric individuals (65–79 years of age), extent of systemic exposure to cycloguanil (active metabolite of proguanil) was increased, and average elimination half-life prolonged (mean: 14.9 hours) compared with younger adults (mean: 8.3 hours).1