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Generic Name: Atovaquone
Class: Antiprotozoals, Miscellaneous
VA Class: AM900
Chemical Name: trans2-[4-(4-Chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione
Molecular Formula: C22H19ClO3
CAS Number: 95233-18-4

Introduction

Antiprotozoal; hydroxynaphthoquinone derivative.1 7 8 10 15 17

Uses for Mepron

Pneumocystis jirovecii Pneumonia

Alternative for treatment and prevention of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) in adults, adolescents, or children 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 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

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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 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 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 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

Mepron 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 Mepron

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 Mepron

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

Mepron 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 (Clcr <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 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

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.

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

Atovaquone

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

750 mg/5 mL*

Atovaquone Suspension

Mepron

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mepron 750MG/5ML Suspension (GLAXO SMITH KLINE): 210/$1,124.69 or 630/$3,277.90

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 29, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. GlaxoSmithKline. Mepron (atovaquone) oral suspension prescribing information. Research Triangle Park, NC; 2013 Mar.

2. Nightingale SL. From the Food and Drug Administration. JAMA. 1992; 267:339. [PubMed 1727943]

3. Falloon J, Kovacs J, Hughes W et al. A preliminary evaluation of 566C80 for the treatment of pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome. New Engl J Med. 1991; 325:1534-8. [IDIS 289180] [PubMed 1944437]

4. Hughes WT. A new drug (566C80) for the treatment of pneumocystis carinii pneumonia. Ann Intern Med. 1992; 116:953-4. [IDIS 296797] [PubMed 1580456]

5. Hughes WT, Kennedy W, Shenep JL et al. Safety and pharmacokinetics of 566C80, a hydroxynaphthoquinone with anti-pneumocystis carinii activity: a phase I study in human immunodeficiency virus (HIV)-infected men. J Infect Dis. 1991; 163:843-8. [IDIS 279851] [PubMed 2010637]

6. Anon. FDA authorizes wider use of new oral medication for AIDS. Oncology. 1991; 5:59.

7. Dohn MN, Frame PT, Baughman RP et al. Open-label efficacy and safety trial of 42 days of 566C80 for Pneumocystis carinii pneumonia in AIDS patients. J Protozool. 1991; 38:220-1S.

8. Hudson AT, Randall AW, Fry M et al. Novel anti-malarial hydroxynaphthoquinones with potent broad spectrum anti-protozoal activity. Parasitology. 1985; 90:45-55. [PubMed 3920634]

9. Wong RJ. Highlights of the Seventh International Conference on AIDS. Clin Pharm. 1991; 10:809-22. [IDIS 286982] [PubMed 1686580]

10. Gutteridge WE. Antimalarial drugs currently in development. J R Soc Med. 1989; 17:63-6.

11. Araujo FG, Huskinson J, Remington JS. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother. 1991; 35: 293-9.

12. Hughes WT, Gray VL, Gutteridge WE et al. Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis. Antimicrob Agents Chemother. 1990; 34:225-8. [PubMed 2327770]

13. Hammond DJ, Burchell JR, Pudney M. Inhibition of pyrimidine biosynthesis de novo in Plasmodium falciparum by 2-(4-t-butylcyclohexyl)-3-hydroxy-1, 4-naphthoquinone in vitro. Mol Biochem Parasitol. 1985; 14:97-109. [PubMed 3885032]

14. Davies CS, Pudney M, Matthews PJ et al. The causal prophylactic activity of the novel hydroxynaphthoquinone 566C80 against Plasmodium berghei infections in rats. Acta Leiden. 1989; 58:115-28. [PubMed 2489391]

15. Burroughs Wellcome, Research Triangle Park, NC: Personal communication.

16. Sattler FR, Feinberg J. New developments in the treatment of Pneumocystis carinii pneumonia. Chest. 1992; 101:451-7. [IDIS 291546] [PubMed 1531191]

17. Gutteridge WE. 566C80, an antimalarial hydroxynaphthoquinone with broad spectrum: experimental activity against opportunistic parasitic infections of AIDS patients. J Protozool. 1991; 38:141-3S.

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