Atovaquone

Unless your doctor tells you otherwise, continue your normal diet.

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

>10%

Abdominal pain (4-21%)

Cough (14-25%)

Depression (undefined)

Diarrhea (19-42%)

Dyspnea (15-21%)

Fever (14-40%)

Headache (16-31%)

Infection (18-22%)

Insomnia (10-19%)

Myalgia (undefined)

Nausea (21-32%)

Rash (22-46%)

Rhinitis (5-24%)

Vomiting (14-22%)

Weakness (8-31%)

1-10%

Amylase increased (7-8%)

Anemia (4-6%)

Anorexia (<7%)

Anxiety (<7%)

BUN/creatinine increased (<1%)

Constipation (<3%)

Dyspepsia (<5%)

Dizziness (3-8%)

Hyperglycemia (<9%)

Hypoglycemia (<1%)

Hyponatremia (7-10%)

Liver enzymes elevated (4-8%)

Neutropenia (3-5%)

Pruritus (5-10%)

Oral moniliasis (5-10%)

Taste perversion (<3%)

Antiprotozoal; hydroxynaphthoquinone derivative.1 7 8 10 15 17

Absorption

Bioavailability

Following oral administration, bioavailability highly dependent on formulation and diet.1

Bioavailability of oral suspension in fasting or fed state is about twice that of previously available tablet formulation.1

In HIV-infected adults, absolute bioavailability is approximately 47% when 750-mg dose given as the oral suspension under fed conditions compared with approximately 23% when dose given as previously available tablets.1

Food

Food increases absorption approximately twofold;1 should be taken with food to ensure adequate plasma concentrations.1

In HIV-infected adults receiving 500 mg as the oral suspension, peak plasma concentrations were 15.1 mcg/mL when administered with food (400 kcal, 23 g fat) compared with 8.8. mcg/mL when given in fasting state.1

Special Populations

Absorption may be limited in patients with GI disorders.1

Distribution

Plasma Protein Binding

Extensively bound to plasma proteins (99.9%).1

Crosses placenta in animals.1

Distributed into milk in rats in concentrations approximately 30% of concurrent maternal plasma concentrations.1 Not known whether distributed into human milk.1

Elimination

Metabolism

Minimally metabolized; no metabolite identified. 1

Elimination Route

Enterohepatic recirculation and eventual elimination in feces;1 >94% of dose excreted unchanged in feces over 21 days.1 Minimal excretion in urine (<0.6%).1

Half-life

67–78 hours.1

Special Populations

Hepatic impairment: Studies using atovaquone/proguanil indicate no marked differences in rate or extent of systemic exposure to atovaquone in patients with mild to moderate hepatic impairment, but atovaquone elimination half-life prolonged in those with moderate hepatic impairment.41

Renal impairment: Studies using atovaquone/proguanil indicate atovaquone clearance in patients with mild to moderate renal impairment similar to that in those with normal renal function,41 but atovaquone plasma concentrations and AUC decreased in those with severe renal impairment (Clcr <30 mL/minute).41

• Synthetic hydroxynaphthoquinone-derivative antiprotozoal agent.1 7 8 10 15 17

• Selectively inhibits mitochondrial electron transport with consequent inhibition of de novo pyrimidine synthesis.3 5 7 8 10 11 12 13 15 17 24

• Active in vitro and/or in vivo against a variety of protozoa,3 5 11 12 14 15 16 17 including Toxoplasma gondii11 15 and Plasmodium.14 15 41

• Also active against the fungus Pneumocystis jirovecii (formerly Pneumocystis carinii);3 5 7 12 15 16 17 mechanism of action against P. jirovecii not fully elucidated.1

• Although clinical importance unknown, P. jirovecii with amino acid substitutions in cytochrome b (a likely target for atovaquone) have been obtained from several patients who developed PCP after receiving atovaquone prophylaxis.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atovaquone is used to prevent and treat Pneumocystis jiroveci pneumonia (PCP) in adults and children 13 years of age and older who cannot tolerate other medicines, such as trimethoprim-sulfamethoxazole. PCP is a very serious type of pneumonia which occurs usually in patients with poor immune systems, (such as cancer, AIDS, and organ transplanted patients).

atovaquone is available only with your doctor's prescription.

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.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Muscle pain.
• Not able to sleep.
• Sweating a lot.
• Runny nose.
• Stuffy nose.

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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about atovaquone, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about atovaquone. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using atovaquone.

Review Date: October 4, 2017

Inhibits electron transport in mitochondria resulting in the inhibition of key metabolic enzymes responsible for the synthesis of nucleic acids and ATP

Absorption

Oral:

Infants and Children <2 years of age: Decreased absorption

Adults: Oral suspension: Absorption is enhanced 1.4-fold with food; decreased absorption with single doses exceeding 750 mg

Distribution

Vdss: 0.6 ± 0.17 L/kg; CSF concentration is <1% of the plasma concentration

Metabolism

Undergoes enterohepatic recirculation

Excretion

Feces (>94% as unchanged drug); urine (<1%)

Time to Peak

Dual peak serum concentrations at 1 to 8 hours and at 24 to 96 hours after dose due to enterohepatic cycling

Half-Life Elimination

Children (4 months to 12 years): 60 hours (range: 31-163 hours); Adults: 2.9 days; Adults with AIDS: 2.2 days

Protein Binding

>99%

Pneumocystis jirovecii pneumonia (PCP), prophylaxis: Prevention of PCP in adults and adolescents 13 years and older who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMZ)

Pneumocystis jirovecii pneumonia (PCP), treatment: Acute oral treatment of mild-to-moderate PCP in adults and adolescents 13 years and older who are intolerant to TMP-SMZ

Must be taken with food.

750 mg orally every 6 hours for 2 to 6 months
Similar doses given every 6 to 8 hours are used for toxoplasmosis maintenance therapy.

Atovaquone is considered second-line therapy for toxoplasmosis. It should be administered in combination with pyrimethamine and leucovorin, with sulfadiazine, or as a single agent in patients intolerant of pyrimethamine with sulfadiazine.

No data available

Caution and monitoring are advised in patients with severe hepatic insufficiency.

No data available

Summary of Use during Lactation

No information is available on the use of atovaquone during breastfeeding. However, the quantity of drug in breast milk is assumed too low to provide adequate protection against malaria for the breastfed infant.[1] A dosage has been established for infants weighing as little as 5 kg, so it is unlikely to adversely affect breastfed infants weighing 5 kg or more.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Chloroquine, Mefloquine

References

1. Centers for Disease Control and Prevention. CDC Health Information for International Travel 2016. New York: Oxford University Press. 2016. wwwnc.cdc.gov/travel/page/yellowbook-home-2014