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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
Hypersensitivity to atovaquone or any component of the formulation
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
Refer to adult dosing.
Pneumocystis jirovecii pneumonia (PCP), prevention:
Infants and Children <13 years (off-label use) (CDC 2009): Oral:
1 to 3 months: 30 mg/kg once daily with food
4 to 24 months: 45 mg/kg once daily with food
>24 months: 30 mg/kg once daily with food
Adolescents ≥13 years: Refer to adult dosing.
PCP, mild-to-moderate, treatment:
Infants and Children <13 years (off-label use) (CDC 2009): Oral:
Birth to 3 months: 30 to 40 mg/kg/day in 2 divided doses with food (maximum: 1,500 mg daily)
3 to 24 months: 45 mg/kg/day in 2 divided doses with food (maximum: 1,500 mg daily)
≥24 months: 30 to 40 mg/kg/day in 2 divided doses with food (maximum: 1,500 mg daily)
Adolescents ≥13 years: Refer to adult dosing
Toxoplasma gondii encephalitis in HIV-exposed/infected patients (off-label use):
Infants and Children <13 years: Prophylaxis (either as monotherapy or with pyrimethamine plus leucovorin) (CDC 2009): Oral:
1 to 3 months: 30 mg/kg once daily with food
4 to 24 months: 45 mg/kg once daily with food
>24 months: 30 mg/kg once daily with food
Adolescents: Prophylaxis, treatment, and chronic maintenance (HHS [OI adult 2015]): Refer to adult dosing.
Babesiosis (off-label use): Children: Oral: 40 mg/kg/day in 2 divided doses with azithromycin for 7 to 10 days (maximum: 1,500 mg daily). Note: Relapsing infection may require at least 6 weeks of therapy (Vannier 2012).
There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied). However, atovaquone is not appreciably renally excreted.
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.
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.
Must be taken with food.
Store at 15 � �C to 25 � �C (59 � �F to 77 � �F). Do not freeze.
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 (210 mL)
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
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
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
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.
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Adverse events were observed in animal reproduction studies. Diagnosis and treatment of Pneumocystis jirovecii pneumonia (PCP) in pregnant women is the same as in nonpregnant women; however, information specific to the use of atovaquone in pregnancy is limited (HHS [OI adult 2015]).
Inhibits electron transport in mitochondria resulting in the inhibition of key metabolic enzymes responsible for the synthesis of nucleic acids and ATP
Oral:
Infants and Children <2 years of age: Decreased absorption
Adults: Oral suspension: Absorption is enhanced 1.4-fold with food; decreased absorption with single doses exceeding 750 mg
Vdss: 0.6 � � 0.17 L/kg; CSF concentration is <1% of the plasma concentration
Undergoes enterohepatic recirculation
Feces (>94% as unchanged drug); urine (<1%)
Dual peak serum concentrations at 1 to 8 hours and at 24 to 96 hours after dose due to enterohepatic cycling
Children (4 months to 12 years): 60 hours (range: 31-163 hours); Adults: 2.9 days; Adults with AIDS: 2.2 days
>99%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, nausea, vomiting, muscle pain, insomnia, sweating a lot, rhinitis, or rhinorrhea. Have patient report immediately to prescriber depression, white patches in mouth, cough, flu-like symptoms, or signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.