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, highly immunocompromised patients) (IDSA [Krause 2021]; Krause 2000; Krause 2008; Sanchez 2016).
Pneumocystis jirovecii pneumonia:
Prophylaxis, HIV-uninfected (alternative agent): Oral: 1.5 g once daily.
Prophylaxis (primary and secondary), patients with HIV: 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 (HHS [OI adult 2020]).
Treatment, mild to moderate disease (alternative agent): Oral: 750 mg twice daily for 21 days.
Toxoplasma gondii encephalitis in patients with HIV (off-label use; alternative agent): Oral:
Primary prophylaxis: 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 (HHS [OI adult 2020]).
Treatment: 1.5 g twice daily (either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy) for at least 6 weeks (longer if extensive disease or incomplete response) (HHS [OI adult 2020]).
Secondary prophylaxis (chronic maintenance): 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 antiretrovirals (HHS [OI adult 2020]).
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) (expert opinion).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): No supplemental dose or dosage adjustment necessary (expert opinion).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
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.
(For additional information see "Atovaquone: Pediatric drug information")
Pneumocystis jirovecii pneumonia (PCP), HIV-exposed/-infected (HHS [adult OI 2017, pediatric OI 2016]): 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 (HHS [adult OI 2017, pediatric OI 2016]): 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 (IDSA [Wormser 2006]):
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.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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, 210 mL)
Yes
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-SMZ)
Pneumocystis jirovecii pneumonia (PCP), treatment: Acute oral treatment of mild to moderate PCP in adults and adolescents 13 years and older who are intolerant to TMP-SMZ
Babesiosis; Toxoplasma gondii encephalitis (prophylaxis/treatment/chronic maintenance) in patients with HIV
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; 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 2020]).
Special populations:
• Older adult: 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.
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).
Information specific to the use of atovaquone in pregnancy is limited.
Diagnosis and treatment of Pneumocystis jirovecii pneumonia (PCP) in pregnant women is the same as in nonpregnant women. Atovaquone may be used as an alternative agent for PCP and Toxoplasma gondii infections when needed in pregnancy (HHS [OI adult 2020]).
It is not known if atovaquone is present in breast milk.
Females with HIV infection should completely avoid breastfeeding to decrease the potential transmission of 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 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%)
Suspension (Atovaquone Oral)
750 mg/5 mL (per mL): $3.87 - $10.06
Suspension (Mepron Oral)
750 mg/5 mL (per mL): $7.96
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