Atovaquone

Name: Atovaquone

What side effects can this medication cause?

Atovaquone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • nausea
  • vomiting
  • diarrhea
  • headache
  • dizziness
  • anxiety
  • difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

  • rash
  • fever
  • swelling of the eyes, face, lips, tongue, mouth, or throat
  • hives
  • difficulty breathing or swallowing
  • hoarseness or throat tightness

Atovaquone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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What is atovaquone?

Atovaquone is a medication that interferes with the reproduction of protozoa (single-cell organisms) that can cause disease in the body.

Atovaquone is used to treat or prevent pneumonia caused by a fungal infection called Pneumocystitis carinii (also called Pneumocystis jiroveci).

Atovaquone may also be used for other purposes not listed in this medication guide.

Atovaquone Dosage and Administration

Administration

Administer orally.1

Must be taken with food to optimize GI absorption.1 Consider alternative in patients who have difficulty taking atovaquone with food.1

If using multiple-dose bottle containing oral suspension, shake gently before removing a dose.1

If using single-dose foil pouch containing oral suspension, open pouch by removing perforated tab and ingest entire contents; dose can be discharged from pouch into a dosing spoon or cup or directly into mouth.1

Dosage

Pediatric Patients

Pneumocystis jirovecii Pneumonia (PCP) Treatment of Mild to Moderate PCP Oral

Infants 1–3 months of age†: 30–40 mg/kg once daily for 21 days.134 156 Alternatively, 15–20 mg/kg twice daily for 21 days.156

Infants and children 4–24 months of age†: 45 mg/kg once daily for 21 days.134 156 Alternatively, 22.5 mg/kg twice daily for 21 days.156

Children >24 months to 12 years of age†: 30–40 mg/kg once daily for 21 days.134 156

Adolescents ≥13 years of age: 750 mg twice daily for 21 days.1 134 155

Prevention of Initial Episode (Primary Prophylaxis) of PCP Oral

Infants 1–3 months of age†: 30–40 mg/kg once daily.134 156

Infants and children 4–24 months of age†: 45 mg/kg once daily.134 156

Children >24 months to 12 years of age†: 30–40 mg/kg once daily.134 156

Adolescents ≥13 years of age: 1.5 g once daily.1 134 155 156 Alternatively, 1.5 g once daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Infants born to HIV-infected mothers: Initiate primary PCP prophylaxis at 4–6 weeks of age and continue until infant found to be non-HIV-infected or presumptively non-HIV-infected.156

HIV-infected infants <1 year of age: Initiate primary PCP prophylaxis regardless of CD4+ T-cell count or CD4+ percentage;156 at minimum, continue throughout first year of life.156

HIV-infected children 1 to <6 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <500/mm3 or CD4+ percentage <15%.156

HIV-infected children 6–12 years of age: Initiate primary PCP prophylaxis if CD4+ T-cell count <200/mm3 or CD4+ percentage <15%.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing primary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing primary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Prevention of Recurrence (Secondary Prophylaxis) of PCP Oral

Infants 1–3 months of age†: 30–40 mg/kg once daily.134 156

Infants and children 4–24 months of age†: 45 mg/kg once daily.134 156

Children >24 months to 12 years of age†: 30–40 mg/kg once daily.134 156

Adolescents ≥13 years of age: 1.5 g once daily.1 134 155 156 Alternatively, 1.5 g once daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Initiate secondary PCP prophylaxis in all HIV-infected infants and children with a history of PCP.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥500/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Consider discontinuing secondary PCP prophylaxis in HIV-infected children 6–12 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained ≥200/mm3 or CD4+ percentages that have remained ≥15% for >3 months.156 Assess CD4+ T-cell count and CD4+ percentage every 3 months; reinitiate if indicated based on age-specific thresholds.156

Criteria for initiating or discontinuing secondary PCP prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Toxoplasmosis† Treatment of Toxoplasmosis† Oral

Adolescents: 1.5 g twice daily in conjunction with oral pyrimethamine (200-mg loading dose, then 50 mg once daily in those weighing <60 kg or 75 mg once daily in those weighing ≥60 kg) and oral leucovorin (10–25 mg once daily, may be increased to 50 mg once or twice daily).155

Alternatively, 1.5 g twice daily in conjunction with oral sulfadiazine (1 g every 6 hours in those weighing <60 kg or 1.5 g every 6 hours in those weighing ≥60 kg).155

Alternatively, 1.5 g twice daily alone.155

Treatment duration at least 6 weeks; longer duration may be appropriate if clinical or radiologic disease is extensive or response incomplete at 6 weeks.155

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis† Oral

Infants 1–3 months of age†: 30 mg/kg once daily.156

Infants and children 4–24 months of age†: 45 mg/kg once daily.156 Alternatively, 45 mg/kg once daily in conjunction with oral pyrimethamine (1 mg/kg or 15 mg/m2 [up to 25 mg] once daily) and oral leucovorin (5 mg once every 3 days).156

Children >24 months of age†: 30 mg/kg once daily.156

Adolescents: 1.5 g once daily.155 Alternatively, 1.5 g once daily in conjunction with pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

HIV-infected children seropositive for T. gondii: Initiate primary toxoplasmosis prophylaxis in those <6 years of age if CD4+ T-cell percentage <15% and in those ≥6 years of age if CD4+ T-cell count <100/mm3.156

Consider discontinuing primary toxoplasmosis prophylaxis in HIV-infected children 1 to <6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell percentages that have remained ≥15% for >3 months.156 Reinitiate if CD4+ T-cell percentage decreases to <15%.156

Consider discontinuing primary toxoplasmosis prophylaxis in HIV-infected children ≥6 years of age who have received ≥6 months of antiretroviral therapy and have CD4+ T-cell counts that have remained >200/mm3 for >3 months.156 Reinitiate if CD4+ T-cell count decreases to <100–200/mm3.156

Criteria for initiating or discontinuing primary toxoplasmosis prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Prevention of Recurrence (Secondary Prophylaxis) of Toxoplasmosis† Oral

Infants 1–3 months of age†: 30 mg/kg once daily.156

Infants and children 4–24 months of age†: 45 mg/kg once daily.156 Alternatively, 45 mg/kg once daily in conjunction with oral pyrimethamine (1 mg/kg or 15 mg/m2 [up to 25 mg] once daily) and oral leucovorin (5 mg once every 3 days).156

Children >24 months of age†: 30 mg/kg once daily.156

Adolescents: 750–1500 mg twice daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155 Alternatively, 750–1500 mg twice daily in conjunction with oral sulfadiazine (2–4 g daily in 2–4 divided doses).155 Alternatively, 750–1500 mg twice daily used alone.155

Initiate secondary toxoplasmosis prophylaxis in all HIV-infected infants and children who have been treated for T. gondii encephalitis.156

Consider discontinuing secondary toxoplasmosis prophylaxis in HIV-infected children 1 to <6 years of age who completed toxoplasmosis treatment, are asymptomatic with respect to toxoplasmic encephalitis, have received ≥6 months of antiretroviral therapy, and have CD4+ T-cell percentages that have remained ≥15% for >6 consecutive months.156 Reinitiate if CD4+ T-cell percentage decreases to <15%.156

Consider discontinuing secondary toxoplasmosis prophylaxis in HIV-infected children ≥6 years of age who completed toxoplasmosis treatment, are asymptomatic with respect to toxoplasmic encephalitis, have received ≥6 months of antiretroviral therapy, and have CD4+ T-cell counts that have remained >200/mm3 for >6 consecutive months.156 Reinitiate if CD4+ T-cell count decreases to <200/mm3.156

Criteria for initiating or discontinuing secondary toxoplasmosis prophylaxis in HIV-infected adolescents are the same as those recommended for adults.155 (See Adult Dosage under Dosage and Administration.)

Babesiosis† Oral

20 mg/kg (up to 750 mg) twice daily for 7–10 days recommended by IDSA and others;134 178 used in conjunction with oral azithromycin (10 mg/kg [up to 500 mg] once on day 1, then 5 mg/kg [up to 250 mg] once daily for total of 7–10 days).134 178

Adults

Pneumocystis jirovecii Pneumonia Treatment of Mild to Moderate PCP Oral

750 mg twice daily for 21 days.1 134 155

Prevention of Initial Episode (Primary Prophylaxis) of PCP Oral

1.5 g once daily.1 134 155 Alternatively, 1.5 g once daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Initiate primary PCP prophylaxis in HIV-infected adults with CD4+ T-cell counts <200/mm3 or a history of oropharyngeal candidiasis.155 Also consider primary PCP prophylaxis if CD4+ T-cell percentage <14% or there is a history of an AIDS-defining illness.155 Also consider in those with CD4+ T-cell counts >200/mm3 but <250/mm3 if frequent monitoring (e.g., every 3 months) not possible.155

Discontinue primary PCP prophylaxis in HIV-infected adults responding to antiretroviral therapy who have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155

Reinitiate primary PCP prophylaxis if CD4+ T-cell count decreases to <200/mm3.155

Prevention of Recurrence (Secondary Prophylaxis) of PCP Oral

1.5 g once daily.1 134 155 Alternatively, 1.5 g once daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Initiate secondary PCP prophylaxis in all HIV-infected adults with a history of PCP.155

Consider discontinuing secondary PCP prophylaxis in HIV-infected adults who have responded to antiretroviral therapy and have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155 Reinitiate if CD4+ T-cell count decreases to <200/mm3 or PCP recurs when CD4+ T-cell count >200/mm3.155

Consider continuing secondary PCP prophylaxis for life (regardless of CD4+ T-cell count) if PCP occurred or recurred when CD4+ T-cell count >200/mm3.155

Toxoplasmosis† Treatment of Toxoplasmosis† Oral

1.5 g twice daily in conjunction with oral pyrimethamine (200-mg loading dose, then 50 mg once daily in those weighing <60 kg or 75 mg once daily in those weighing ≥60 kg) and oral leucovorin (10–25 mg once daily, may be increased to 50 mg once or twice daily).155

Alternatively, 1.5 g twice daily in conjunction with oral sulfadiazine (1 g every 6 hours in those weighing <60 kg or 1.5 g every 6 hours in those weighing ≥60 kg).155

Alternatively, 1.5 g twice daily alone.155

Treatment duration at least 6 weeks; longer duration may be appropriate if clinical or radiologic disease is extensive or response incomplete at 6 weeks.155

Prevention of Initial Episode (Primary Prophylaxis) of Toxoplasmosis† Oral

1.5 g once daily.155 Alternatively, 1.5 g once daily in conjunction with pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Initiate primary toxoplasmosis prophylaxis in all HIV-infected adults seropositive for Toxoplasma IgG antibody who have CD4+ T-cell counts <100/mm3.155

Discontinue primary toxoplasmosis prophylaxis in HIV-infected adults responding to antiretroviral therapy who have CD4+ T-cell counts that have remained >200/mm3 for >3 months.155

Reinitiate primary toxoplasmosis prophylaxis if CD4+ T-cell count decreases to <100–200/mm3.155

Prevention of Recurrence (Secondary Prophylaxis) of Toxoplasmosis† Oral

750–1500 mg twice daily in conjunction with oral pyrimethamine (25 mg once daily) and oral leucovorin (10 mg once daily).155

Alternatively, 750–1500 mg twice daily in conjunction with oral sulfadiazine (2–4 g daily in 2–4 divided doses).155

Alternatively, 750–1500 mg twice daily alone.155

Initiate secondary toxoplasmosis prophylaxis in all HIV-infected adults who have been treated for T. gondii encephalitis.155

Consider discontinuing secondary toxoplasmosis prophylaxis in adults who completed toxoplasmosis treatment, are asymptomatic with respect to toxoplasmic encephalitis,and have responded to antiretroviral therapy with CD4+ T-cell counts that have remained >200/mm3 for >6 months.155

Reinitiate secondary toxoplasmosis prophylaxis if CD4+ T-cell count decreases to <200/mm3.155

Babesiosis† Oral

750 mg twice daily for 7–10 days recommended by IDSA and others;134 178 used in conjunction with oral azithromycin (0.5–1 g on day 1, then 250 mg once daily for total of 7–10 days; 0.6–1 g daily in immunocompromised patients).178

Prescribing Limits

Pediatric Patients

Babesiosis† Oral

Maximum 750 mg twice daily.178

Special Populations

No special population dosage recommendation at this time.1

Cautions for Atovaquone

Contraindications

  • Hypersensitivity to atovaquone or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Precautions Related to PCP

Clinical experience with atovaquone for treatment of PCP limited to patients with mild to moderate infections.1 Treatment of more severe episodes and efficacy following failure of co-trimoxazole treatment not systematically studied.1

Not effective therapy for concurrent pulmonary conditions such as bacterial, viral, or fungal pneumonia or mycobacterial diseases.1 Clinical deterioration during atovaquone treatment could represent secondary infection with nonsusceptible pathogen and/or progression of PCP.1 Evaluate all patients with acute PCP for other possible causes of pulmonary disease and treat with additional agents as appropriate.1

General Precautions

Administration Precautions

Must be administered with food to enhance GI absorption of the drug and provide adequate plasma concentrations.1 Plasma atovaquone concentrations correlate with treatment response and survival.1

Consider alternative in patients unable to take atovaquone with food.1

Use with caution in patients with GI disorders that may impair absorption (e.g., chronic diarrhea, malabsorption syndrome).1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Caution advised.1

Pediatric Use

Safety and efficacy not established in children.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine if they respond differently than younger adults; clinical experience has not identified differences.1

Select dosage with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Use caution and close monitoring in patients with severe hepatic impairment.1

Common Adverse Effects

Rash, diarrhea, nausea, headache, vomiting, fever, asthenia.1

Interactions for Atovaquone

Protein-bound Drugs

Highly bound to plasma proteins; use with caution in patients receiving highly protein-bound drugs with narrow therapeutic indices since competition for binding sites may occur.1

Specific Drugs

Drug

Interaction

Comments

Antimycobacterials, rifamycins

Rifampin: Decreased atovaquone concentrations and half-life; increased rifampin concentrations1

Rifabutin: Specific studies not available; pharmacokinetic interactions similar to those reported with rifampin may occur1

Rifampin: Concomitant use not recommended1

Co-trimoxazole

Slightly decreased concentrations of trimethoprim and sulfamethoxazole; no clinically important effect on atovaquone concentrations1

Metoclopramide

Decreased bioavailability of atovaquone reported with the fixed combination of atovaquone and proguanil hydrochloride (atovaquone/proguanil)41

Use concomitantly only if other antiemetics not available41

Phenytoin

No effect on protein binding of either drug1

Tetracycline

Decreased atovaquone concentrations reported with atovaquone/proguanil41

Zidovudine

Increased zidovudine AUC; no change in atovaquone pharmacokinetics1

Not considered clinically important

Stability

Storage

Oral

Suspension

15–25°C. Do not freeze.1

Advice to Patients

  • Importance of taking atovaquone concomitantly with food.1

  • Advise patients using the multiple-dose bottle of oral suspension to shake it gently before removing a dose.1 Advise those using single-dose foil pouch of oral suspension to ingest entire contents by mouth by discharging the dose into a dosing spoon or cup or directly into the mouth.1

  • Importance of completing full course of therapy, even if feeling better after a few days.1

  • Importance of recognizing pulmonary manifestations of possibly concurrent bacterial, viral, fungal, or mycobacterial infections associated with HIV infection and/or progression of the underlying PCP and contacting a clinician if pulmonary symptomatology develops or worsens during atovaquone therapy.1 20

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

What do I need to tell my doctor BEFORE I take Atovaquone?

  • If you have an allergy to atovaquone or any other part of atovaquone.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Rifabutin or rifampin.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take atovaquone with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Atovaquone?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Do not use longer than you have been told. A second infection may happen.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using atovaquone while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Off Label Uses

Babesiosis

Data from a prospective, nonblinded, randomized trial in patients with non-life-threatening babesiosis, supports the use of atovaquone (in combination with azithromycin) for the treatment of this condition [Krause 2000]. Clinical experience also suggests the utility of atovaquone (in combination with azithromycin) for the treatment of immunocompetent patients with mild-to-moderate babesiosis [Vannier 2012]. Additional trials may be necessary to further define the role of atovaquone in the treatment of this condition.

Based on the Infectious Diseases Society of America (IDSA) guidelines for the clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis, atovaquone (in combination with azithromycin) is effective and recommended for the treatment of babesiosis.

Toxoplasma gondii encephalitis (prophylaxis/treatment/chronic maintenance) in HIV-infected patients (adolescents and adults)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, atovaquone is an effective and recommended agent for prophylaxis, treatment, or as chronic maintenance therapy for T. gondii encephalitis in adolescent and adult HIV-infected patients.

Toxoplasma gondii encephalitis (prophylaxis) in HIV-exposed/infected patients (children)

Based on the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics (AAP) guidelines for the prevention and treatment of opportunistic infections among HIV-exposed and HIV-Infected children, atovaquone is effective and recommended for the prophylaxis of T. gondii encephalitis in HIV-exposed/-infected children.

Contraindications

Hypersensitivity to atovaquone or any component of the formulation

Dosing Adult

Pneumocystis jirovecii pneumonia (PCP), prevention: Oral: 1,500 mg once daily with food

PCP, mild-to-moderate, treatment: Oral: 750 mg twice daily with food for 21 days

Babesiosis (off-label use): Oral: 750 mg twice daily with azithromycin for 7 to 10 days; Note: Relapsing infection may require at least 6 weeks of therapy (Krauss 2000; Vannier 2012).

Toxoplasma gondii encephalitis in HIV-infected patients (off-label use) (HHS [OI adult 2015]): Oral:

Prophylaxis: 1,500 mg once daily with food (either as monotherapy or with pyrimethamine plus leucovorin)

Treatment: 1,500 mg twice daily with food (either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy) for at least 6 weeks (longer if extensive disease or incomplete response)

Chronic maintenance: 750 to 1,500 mg twice daily with food (either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy); may discontinue when asymptomatic and CD4 count >200 cells/mm3 for 6 months

Dosing Geriatric

Refer to adult dosing.

Drug Interactions

Efavirenz: May decrease the serum concentration of Atovaquone. Management: Consider alternatives to the use of atovaquone with efavirenz when possible. If this combination must be used, monitor for evidence of reduced atovaquone clinical effectiveness. Consider therapy modification

Etoposide: Atovaquone may increase the serum concentration of Etoposide. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Monitor therapy

Etoposide Phosphate: Atovaquone may increase the serum concentration of Etoposide Phosphate. Management: Consider separating the administration of atovaquone and etoposide by at least 1 to 2 days. Monitor therapy

Indinavir: Atovaquone may decrease the serum concentration of Indinavir. Monitor therapy

Metoclopramide: May decrease the serum concentration of Atovaquone. Management: Consider alternatives to metoclopramide when possible; atovaquone should only be used with metoclopramide if no other antiemetics are available. Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Atovaquone. Avoid combination

Ritonavir: May decrease the serum concentration of Atovaquone. Avoid combination

Tetracycline: May decrease the serum concentration of Atovaquone. Monitor therapy

Adverse Reactions

Frequency not always defined. Adverse reaction statistics have been compiled from studies including patients with advanced HIV disease. Consequently, it is difficult to distinguish reactions attributed to atovaquone from those caused by the underlying disease or a combination thereof.

>10%:

Central nervous system: Headache (16% to 31%), insomnia (10% to 19%), depression, pain

Dermatologic: Skin rash (22% to 46%), pruritus (5% to ≥10%), diaphoresis

Gastrointestinal: Diarrhea (19% to 42%), nausea (21% to 32%), vomiting (14% to 22%), abdominal pain (4% to 21%)

Infection: Infection (18% to 22%)

Neuromuscular & skeletal: Weakness (8% to 31%), myalgia

Respiratory: Cough (14% to 25%), rhinitis (5% to 24%), dyspnea (15% to 21%), sinusitis (7% to ≥10%), flu-like symptoms

Miscellaneous: Fever (14% to 40%)

1% to 10%:

Cardiovascular: Hypotension (≤1%)

Central nervous system: Dizziness (3% to 8%), anxiety (≤7%)

Endocrine & metabolic: Hyponatremia (7% to 10%), hyperglycemia (≤9%), increased amylase (7% to 8%), hypoglycemia (≤1%)

Gastrointestinal: Oral candidiasis (5% to 10%), anorexia (≤7%), dyspepsia (≤5%), constipation (≤3%), dysgeusia (≤3%)

Hematologic & oncologic: Anemia (4% to 6%), neutropenia (3% to 5%)

Hepatic: Increased liver enzymes (4% to 8%)

Renal: Increased blood urea nitrogen (≤1%), increased serum creatinine (≤1%)

Respiratory: Bronchospasm (2% to 4%)

<1% (Limited to important or life-threatening): Acute renal failure, angioedema, constriction of the pharynx, corneal disease (vortex keratopathy), desquamation, erythema multiforme, hepatic failure (rare), hepatitis (rare), hypersensitivity reaction, methemoglobinemia, pancreatitis, Stevens-Johnson syndrome, thrombocytopenia, urticaria

Warnings/Precautions

Concerns related to adverse effects:

• Diarrhea/vomiting: Absorption may be decreased in patients who have diarrhea or vomiting; monitor closely and consider use of an antiemetic. If severe, consider use of an alternative antiprotozoal.

• Hypersensitivity: Hypersensitivity reactions (eg, angioedema, bronchospasm, throat tightness, urticaria) have occurred.

Disease-related concerns:

• Gastrointestinal disorders: Consider parenteral therapy with alternative agents in patients who have difficulty taking atovaquone with food. Gastrointestinal disorders may limit absorption of oral medications; may not achieve adequate plasma levels.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment; monitor closely; rare cases of cholestatic hepatitis, elevated liver function tests, and fatal liver failure have been reported.

Pneumocystis jirovecii pneumonia (PCP): Appropriate use: When used for treatment, has only been indicated in mild-to-moderate PCP; not studied for use in severe PCP; atovaquone has less adverse effects than trimethoprim-sulfamethoxazole (TMP-SMZ) (the treatment of choice for mild-to-moderate PCP), although atovaquone is less effective than TMP-SMZ (HHS [OI adult 2015]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in elderly patients.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Where can i get more information?

Your pharmacist can provide more information about atovaquone.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Usual Adult Dose for Pneumocystis Pneumonia Prophylaxis

1500 mg orally once a day

Usual Pediatric Dose for Babesiosis

1 to 12 years: 20 mg/kg orally twice a day with azithromycin (12 mg/kg once a day) for 7 to 10 days
13 years or older: 750 mg orally twice a day with azithromycin (500 to 600 mg on day 1, followed by 250 to 600 mg once a day thereafter or 1000 mg once a day for 3 days, followed by 500 mg once a day thereafter) for 7 to 10 days

Maximum dose: 1500 mg/day

Precautions

Atovaquone treatment failures, due to decreased absorption and inadequate serum levels, have occurred when patients take the drug on an empty stomach. If the patient cannot take atovaquone with meals, it is suggested that alternate treatment be initiated if possible. For similar reasons, atovaquone should be avoided in patients with diarrhea or malabsorption syndrome.

The efficacy of atovaquone has not been established in patients with severe Pneumocystis pneumonia or in patients who are not responding to sulfamethoxazole-trimethoprim therapy.

Rarely, hepatitis, elevated liver function tests, and at least one case of fatal liver failure have been reported with the use of atovaquone. However, causality could not be established due to many confounding medical conditions and concurrent drug treatments.

Caution and monitoring is advised in patients with severe hepatic impairment.

Safety and efficacy have not been established in pediatric patients.

Other Comments

Atovaquone should be administered with food or a high-fat meal.

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