Version May 2024
Babesiosis (off-label use): Oral: 750 mg twice daily in combination with azithromycin for 7 to 10 days; a longer duration of ≥6 weeks, including 2 weeks after resolution of parasitemia, may be necessary for patients at high risk of relapse (eg, patients who are highly immunocompromised) (Ref).
Pneumocystis jirovecii pneumonia:
Prophylaxis, patients without HIV (alternative agent): Oral: 1.5 g once daily.
Prophylaxis (primary and secondary), patients with HIV (alternative agent): Oral: 1.5 g once daily (as monotherapy or with pyrimethamine and leucovorin). Continue prophylaxis following initiation of antiretroviral therapy (ART) until CD4 count >200 cells/mm3 for >3 months; some experts discontinue prophylaxis in patients with a CD4 count between 100 to 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).
Treatment, mild to moderate disease (alternative agent): Oral: 750 mg twice daily for 21 days (Ref).
Toxoplasmosis encephalitis (alternative agent) (off-label use):
Primary prophylaxis in patients with HIV: Oral: 1.5 g once daily (either as monotherapy or with pyrimethamine plus leucovorin); primary prophylaxis is indicated for Toxoplasma IgG-positive patients with CD4 count <100 cells/mm3. Continue primary prophylaxis following initiation of ART until CD4 count >200 cells/mm3 for >3 months; some experts discontinue primary prophylaxis in patients with a CD4 count between 100 to 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).
Treatment: Oral: 1.5 g twice daily (either with pyrimethamine plus leucovorin or with sulfadiazine); for patients with HIV, monotherapy may be considered if patients are intolerant to combination agents. Duration is for ≥6 weeks (longer if extensive disease or incomplete response) followed by chronic maintenance therapy (Ref).
Secondary prophylaxis (chronic maintenance):
Patients with HIV: Oral: 750 mg to 1.5 g twice daily (either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy); may discontinue when asymptomatic and CD4 count >200 cells/mm3 for >6 months in response to ART (Ref).
Solid organ transplant recipients: Oral: 750 mg every 6 to 12 hours (either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy); continue lifelong (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (<1% excreted in the urine) (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use caution in patients with severe impairment.
Refer to adult dosing.
(For additional information see "Atovaquone: Pediatric drug information")
Pneumocystis jirovecii pneumonia (PCP), HIV-exposed/-infected (Ref): Limited data available in ages <13 years:
Prophylaxis; primary or secondary:
Infants and Children: Oral:
1 to 3 months: 30 mg/kg/day once daily
4 to 24 months: 45 mg/kg/day once daily
>24 months: 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day
Adolescents: Oral: 1,500 mg once daily
Treatment; mild to moderate infection: Treatment duration: 21 days
Infants and Children: Oral:
1 to 3 months: 30 to 40 mg/kg/day divided once or twice daily
4 to 24 months: 45 mg/kg/day divided once or twice daily
>24 months: 30 to 40 mg/kg/day divided once or twice daily; maximum daily dose: 1,500 mg/day
Adolescent: Oral: 750 mg twice daily
Toxoplasmosis (toxoplasma gondii); encephalitis, HIV-exposed/-infected (Ref) : Limited data available:
Primary prophylaxis:
Infants and Children: Oral:
1 to 3 months: 30 mg/kg/day once daily
4 to 24 months: 45 mg/kg/day once daily; with or without pyrimethamine/leucovorin
>24 months: 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day
Adolescents: Oral: 1,500 mg once daily; with or without pyrimethamine/leucovorin
Treatment (encephalitis): Adolescents: Oral: 1,500 mg twice daily for at least 6 weeks (longer if extensive disease or incomplete response); use in combination with pyrimethamine/leucovorin or sulfadiazine is preferred
Secondary prophylaxis/chronic maintenance therapy (suppressive):
Infants and Children: Oral:
1 to 3 months: 30 mg/kg/day once daily with leucovorin
4 to 24 months: 45 mg/kg/day once daily; with or without pyrimethamine/leucovorin
>24 months: 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day; with leucovorin
Adolescents: Oral: 750 to 1,500 mg twice daily; use in combination with pyrimethamine/leucovorin or sulfadiazine is preferred
Babesiosis: Limited data available (Ref):
Infants and Children: Oral: 40 mg/kg/day divided twice daily; maximum daily dose: 1,500 mg/day with azithromycin for 7 to 10 days
Adolescents: Oral: 750 mg twice daily for 7 to 10 days with azithromycin
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Adolescents ≥13 years: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, atovaquone is not appreciably renally excreted.
Adolescents ≥13 years: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Atovaquone undergoes enterohepatic cycling and primarily hepatic excretion. Use caution in patients with severe impairment; monitor closely.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%, postmarketing, and/or case reports: 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
Hypersensitivity to atovaquone or any component of the formulation.
Concerns related to adverse effects:
• Diarrhea/vomiting: Absorption may be decreased in patients who have diarrhea or vomiting.
• 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; 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-SMX) (the treatment of choice for mild to moderate PCP), although atovaquone is less effective than TMP-SMX (HHS [OI adult 2023]).
Special populations:
• Older adult: Use with caution in older adults.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Oral:
Mepron: 750 mg/5 mL (5 mL, 210 mL) [contains benzyl alcohol; citrus flavor]
Generic: 750 mg/5 mL (5 mL, 10 mL [DSC], 210 mL)
Yes
Suspension (Atovaquone Oral)
750 mg/5 mL (per mL): $6.56 - $7.51
Suspension (Mepron Oral)
750 mg/5 mL (per mL): $7.96
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Mepron: 750 mg/5 mL (210 mL) [contains benzyl alcohol, saccharin sodium]
Generic: 750 mg/5 mL (210 mL)
Oral: Must administer with food. Shake suspension gently before use. Once opened, a foil pouch can be emptied on a dosing spoon, in a cup, or directly into the mouth.
Oral: Must administer with food or a high-fat meal. Shake suspension gently before use. Once opened, a foil pouch can be emptied on a dosing spoon, in a cup, or directly into the mouth.
Pneumocystis jirovecii pneumonia (PCP), prophylaxis: Prevention of PCP in adults and adolescents 13 years and older who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX).
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-SMX.
Limitations of use: Clinical experience with atovaquone for the treatment of PCP has been limited to subjects with mild to moderate PCP (alveolar-arterial oxygen diffusion gradient [(A-a)DO2] ≤45 mm Hg). Treatment of more severe episodes of PCP with atovaquone has not been studied. The efficacy of atovaquone in subjects who are failing TMP-SMX therapy has not been studied.
Babesiosis; Toxoplasmosis encephalitis
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amodiaquine: May enhance the adverse/toxic effect of Atovaquone. Specifically, the risk for extrapyramidal side effects may be increased. Risk C: Monitor therapy
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. Risk D: 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. Risk C: 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. Risk C: Monitor therapy
Indinavir: Atovaquone may decrease the serum concentration of Indinavir. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Atovaquone. Risk C: 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. Risk D: Consider therapy modification
Nirmatrelvir and Ritonavir: May decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Rifabutin: Atovaquone may decrease the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Atovaquone. Risk X: Avoid combination
RifAMPin: Atovaquone may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Atovaquone. Risk X: Avoid combination
Ritonavir: May decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Tetracycline (Systemic): May decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
Ingestion with a fatty meal increases absorption. Management: Administer with food, preferably high-fat meals (peanuts or ice cream).
Data specific to the use of atovaquone in pregnancy are limited.
Diagnosis and treatment of Pneumocystis jirovecii pneumonia (PCP) in pregnant patients is the same as in nonpregnant patients. Atovaquone may be used as an alternative agent for PCP and Toxoplasma gondii infections when needed in pregnancy (HHS [OI adult 2023]).
It is not known if atovaquone is present in breast milk.
Breastfeeding is not recommended by the manufacturer when used for the prevention of Pneumocystis jirovecii pneumonia in patients with HIV.
Must be taken with food.
Hepatic function at baseline (monitor closely during treatment in patients with severe hepatic impairment), hypersensitivity reactions, CD4 count (for chronic maintenance treatment in patients with HIV who have toxoplasmosis), patient's food tolerance/ability to take atovaquone, post-dose vomiting, diarrhea.
Inhibits electron transport in mitochondria resulting in the inhibition of key metabolic enzymes responsible for the synthesis of nucleic acids and ATP
Absorption: Enhanced ~2-fold with food
Distribution: Vdss: 0.6 ± 0.17 L/kg; CSF concentration is <1% of the plasma concentration
Protein binding: >99%
Metabolism: Unknown
Bioavailability: Suspension (administered with food): 47% ± 15%
Half-life elimination: Range: 67 ± 33.4 hours to 77.6 ± 23.1 hours
Excretion: Feces (>94% as unchanged drug); urine (<1%)
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