Brand name: Mepron
Drug class: Antiprotozoals, Pneumocystis jirovecii Pneumonia
- Antiprotozoal Agents
Chemical name: trans2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione
Molecular formula: C₂₂H₁₉ClO₃
CAS number: 95233-18-4

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antiprotozoal; hydroxynaphthoquinone derivative.^{1 7 8 10 15 17}

Uses for Atovaquone

Pneumocystis jirovecii Pneumonia

Alternative for treatment and prevention of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) in adults, adolescents, or children^{† [off-label]} who cannot tolerate co-trimoxazole.^{1 24 33 34 38 134 155 156} Designated an orphan drug by FDA for treatment of PCP associated with acquired immunodeficiency syndrome (AIDS) and prevention of PCP in high-risk HIV-infected patients (i.e., history of ≥1 episode of PCP and/or CD4⁺ T-cell counts ≤200/mm²).²²

Co-trimoxazole is drug of choice for treatment of mild, moderate, or severe PCP in adults, adolescents, and children, including HIV-infected individuals.^{134 155 156}

Atovaquone used alone is one of several alternatives recommended by CDC, NIH, and IDSA for treatment of mild to moderate PCP in HIV-infected adults and adolescents when co-trimoxazole cannot be used.¹⁵⁵ Although efficacy and safety not established in pediatric patients¹ and data limited regarding use in children, CDC, NIH, IDSA, and AAP state atovaquone also can be considered an alternative for treatment of mild to moderate PCP in HIV-infected children^{† [off-label]} when co-trimoxazole cannot be used.¹⁵⁶ Not systematically studied for treatment of severe PCP;¹ not included in recommendations for treatment of severe PCP.^{134 155 156}

Recommended by CDC, NIH, and IDSA as alternative for prevention of initial episode of PCP (primary prophylaxis) in HIV-infected adults and adolescents who cannot tolerate drug of choice (co-trimoxazole);¹⁵⁵ used alone or in conjunction with pyrimethamine (and leucovorin) for primary PCP prophylaxis in HIV-infected adults and adolescents.¹⁵⁵

Recommended by CDC, NIH, and IDSA as alternative for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) of PCP in HIV-infected adults and adolescents who cannot tolerate drug of choice (co-trimoxazole);¹⁵⁵ used alone or in conjunction with pyrimethamine (and leucovorin) for secondary PCP prophylaxis in HIV-infected adults and adolescents.¹⁵⁵

Recommended by CDC, NIH, IDSA, and AAP as alternative for primary and secondary PCP prophylaxis in HIV-infected children and infants ≥1 month of age^{† [off-label]} who cannot tolerate drug of choice (co-trimoxazole);¹⁵⁶ used alone for primary and secondary PCP prophylaxis in HIV-infected pediatric patients.¹⁵⁶

Toxoplasmosis

Alternative for treatment or prevention of toxoplasmosis^{† [off-label]} caused by Toxoplasma gondii.^{42 43 134 155 156} Designated an orphan drug by FDA for primary prophylaxis in HIV-infected individuals at high risk for developing T. gondii encephalitis and for treatment and suppression of T. gondii encephalitis.²²

Pyrimethamine (and leucovorin) in conjunction with sulfadiazine is regimen of choice for treatment of toxoplasmosis, including toxoplasmosis in HIV-infected adults, adolescents, and children;^{134 155 156} pyrimethamine (and leucovorin) in conjunction with clindamycin is preferred alternative in those who cannot tolerate or do not respond to regimen of choice.^{155 156}

Atovaquone in conjunction with pyrimethamine (and leucovorin), atovaquone in conjunction with sulfadiazine, or atovaquone alone are alternative regimens for treatment of toxoplasmosis^{† [off-label]} in HIV-infected adults and adolescents when regimen of choice and preferred alternative cannot be used.^{134 155} Atovaquone regimens not adequately studied for treatment of toxoplasmosis in children^†.¹⁵⁶

Recommended by CDC, NIH, and IDSA as alternative for prevention of initial episode of T. gondii encephalitis (primary prophylaxis)^† in HIV-infected adults and adolescents when regimen of choice (co-trimoxazole) and preferred alternative (dapsone in conjunction with pyrimethamine [and leucovorin]) cannot be used;¹⁵⁵ used alone or in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in HIV-infected adults and adolescents.¹⁵⁵

Recommended by CDC, NIH, and IDSA as alternative for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent relapse of toxoplasmosis^† in HIV-infected adults and adolescents when regimen of choice (pyrimethamine [and leucovorin] in conjunction with sulfadiazine) cannot be used;¹⁵⁵ used in conjunction with pyrimethamine (and leucovorin), in conjunction with sulfadiazine, or alone for secondary toxoplasmosis prophylaxis in HIV-infected adults and adolescents.¹⁵⁵

Recommended by CDC, NIH, IDSA, and AAP as alternative for primary toxoplasmosis prophylaxis in HIV-infected infants and children ≥1 month of age^† when regimen of choice (co-trimoxazole) and preferred alternative (dapsone in conjunction with pyrimethamine [and leucovorin]) cannot be used;¹⁵⁶ used alone for primary toxoplasmosis prophylaxis in those ≥1 month of age, but can be used alone or in conjunction with pyrimethamine (and leucovorin) for primary toxoplasmosis prophylaxis in those 4–24 months of age.¹⁵⁶

Recommended by CDC, NIH, IDSA, and AAP as alternative for secondary toxoplasmosis prophylaxis in HIV-infected infants and children ≥1 month of age^† when regimen of choice (sulfadiazine in conjunction with pyrimethamine [and leucovorin]) and recommended alternative (pyrimethamine [and leucovorin] in conjunction with clindamycin) cannot be used;¹⁵⁶ used alone for secondary toxoplasmosis prophylaxis in those ≥1 month of age, but can be used alone or in conjunction with pyrimethamine (and leucovorin) for secondary toxoplasmosis prophylaxis in those 4–24 months of age.¹⁵⁶

Babesiosis

Treatment of babesiosis^† caused by Babesia microti.^{105 134 178 181}

When anti-infectives indicated, regimens of choice for treatment of babesiosis are clindamycin in conjunction with quinine or atovaquone in conjunction with azithromycin;^{105 134 178 181} the clindamycin and quinine regimen may be preferred for severe babesiosis.¹⁷⁸ Exchange transfusions have been used as an adjunct in severely ill patients with high levels of parasitemia (>10%), significant hemolysis, or compromised renal, hepatic, or pulmonary function.^{105 134 178}

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

Drug Interactions

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

Atovaquone Pharmacokinetics

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 (Cl_cr <30 mL/minute).⁴¹

Stability

Storage

Oral

Suspension

15–25°C. Do not freeze.¹

Actions and Spectrum

• 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 gondii^{11 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

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.)

Preparations

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

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