Atovaquone inhibits the reproduction of protozoal infections. [select-faq faq_id='7360'] It is used to treat the following conditions: 

• Prevention of PCP in adults and adolescents 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole

• Acute oral treatment of mild to moderate PCP infection in adults and adolescents 13 years and older who cannot tolerate TMP-SMZ

• Off Label Uses of Atovaquone in Adults include:

  • Babesiosis

  • Prophylaxis, treatment, and chronic maintenance therapy for Toxoplasma gondii encephalitis in HIV Patients

Atovaquone Dose in Adults

Dose in the prevention of Pneumocystis jirovecii pneumonia (PCP):

• 1,500 mg orally OD daily with food

Dose in the treatment of mild to moderate PCP:

• 750 mg orally BID daily with food for 3 weeks

Dose in the treatment of Babesiosis (off-label):

• 750 mg orally BID daily with azithromycin for at least 7-10 days;

Dose in the treatment of Toxoplasma gondii encephalitis in HIV-infected patients: 

• Prophylaxis:

  • 1,500 mg orally once daily is given with food either as monotherapy or with pyrimethamine plus leucovorin.
  • Primary prophylaxis is used for Toxoplasma IgG-positive patients with CD4 count less than 100 cells/mm³.
  • Primary prophylaxis should be continued following initiation of ART until CD4 count >200 cells/mm³ for more than 3 months.
  • Some experts recommend discontinuing primary prophylaxis in patients with a CD4 count between 100 to 200 cells/mm who are using ART and have had an undetectable viral load for 3 - 6 months

• Treatment:

  • 1,500 mg orally twice a day 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)

• Secondary prophylaxis:

  • 750 - 1,500 mg orally two times a day with food either with pyrimethamine plus leucovorin, or with sulfadiazine, or as monotherapy)
  • Can be discontinued when asymptomatic and CD4 count >200 cells/mm for >6 months in response to antiretrovirals.

Atovaquone Dose in Childrens

Dose in the treatment of Pneumocystis jirovecii pneumonia (PCP) in HIV-exposed/-positive patients:

• Primary or secondary Prophylaxis :

  • Infants and Children:
    • In age 1 to 3 months:
      • 30 mg/kg/day orally once daily is recommended.
    • In age 4 to 24 months:
      • 45 mg/kg/day orally once daily is recommended.
    • In age greater than 24 months:
      • 30 mg/kg/day orally once daily to a maximum daily dose of 1,500 mg/day is given
  • Adolescents:
    • Oral: 1,500 mg OD daily

Treatment of mild to moderate infection:

Treatment duration:3 Weeks

• Infants and Children:
  • 1 to 3 months:
    • 30 to 40 mg/kg/day orally divided dose given once or twice daily
  • 4 to 24 months:
    • 45 mg/kg/day orally divided dose given once or twice daily
  • older than 24 months:
    • 30 - 40 mg/kg/day orally divided dose given once or twice daily to a maximum daily dose of 1,500 mg/day
• Adolescent:
  • 750 mg orally twice daily

Dose in the treatment of Toxoplasmosis (Toxoplasma gondii) and encephalitis caused by Toxoplasma gondii in HIV-exposed/-positive patients:

• Primary prophylaxis:

  • Infants and Children:
    • 1 to 3 months:
      • 30 mg/kg/day orally is used once daily
    • 4 to 24 months:
      • 45 mg/kg/day orally is used once a day; with or without pyrimethamine/leucovorin
    • older than 24 months:
      • 30 mg/kg/day orally used once daily to a maximum daily dose of 1,500 mg/day
  • Adolescents:
    • 1,500 mg orally used once a day with or without pyrimethamine/ leucovorin

• Treatment of encephalitis:

  • Adolescents:
    • 1,500 mg orally twice daily is recommended for at least 6 weeks (longer treatment is recommended if an extensive disease or incomplete response)
    • Use in combination with pyrimethamine/ leucovorin or sulfadiazine is advised

• Secondary prophylaxis and chronic maintenance suppressive therapy:

  • Infants and Children:
    • 1 to 3 months:
      • 30 mg/kg/day once daily along with leucovorin
    • 4 to 24 months:
      • 45 mg/kg/day once a day with or without pyrimethamine/ leucovorin
    • older than 24 months:
      • 30 mg/kg/day once daily to a maximum daily dose of 1,500 mg/day with leucovorin
  • Adolescents:
    • 750 - 1,500 mg orally twice daily
    • Use in combination with pyrimethamine/ leucovorin or sulfadiazine is given priority

Dose in the treatment of Babesiosis:

• Infants and Children:
  • 40 mg/kg/day orally in two divided doses daily to a maximum daily dose of 1,500 mg/day with azithromycin for 7 - 10 days
• Adolescents:
  • 750 mg orally in two divided doses daily for 7 to 10 days with azithromycin

Pregnancy Risk Factor: C

• It is not possible to provide information specific to atovaquone use during pregnancy.
• The treatment and diagnosis of Pneumocystis Jirovecii Pneumonia (PCP), in pregnant women are the same as for nonpregnant patients.
• When necessary, Atovaquone may be used in lieu of Toxoplasma gondii and PCP infections during pregnancy.

Atovaquone use during breastfeeding:

• It is unknown if atovaquone can be found in breast milk.
• To reduce the risk of HIV transmission, pregnant women with HIV should not breastfeed.

Atovaquone Dose in Renal Disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.
• However, atovaquone is not appreciably renally excreted.

Atovaquone Dose in Liver Disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.
• Atovaquone undergoes enterohepatic cycling and primarily hepatic excretion.
• Use caution in patients with severe impairment and monitor closely.

• 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.

Common Side Effects of Atovaquone Include:

• Central Nervous System:
  • Headache
  • Insomnia
  • Depression
  • Pain
• Dermatologic:
  • Skin Rash
  • Pruritus
  • Diaphoresis
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal Pain
• Infection:
  • Infection
• Neuromuscular & Skeletal:
  • Weakness
  • Myalgia
• Respiratory:
  • Cough
  • Rhinitis
  • Dyspnea
  • Sinusitis
  • Flu-Like Symptoms
• Miscellaneous:
  • Fever

Less Common Side Effects of Atovaquone Include:

• Cardiovascular:
  • Hypotension
• Central Nervous System:
  • Dizziness
  • Anxiety
• Endocrine & Metabolic:
  • Hyponatremia
  • Hyperglycemia
  • Increased Amylase
  • Hypoglycemia
• Gastrointestinal:
  • Oral Candidiasis
  • Anorexia
  • Dyspepsia
  • Constipation
  • Dysgeusia
• Hematologic & Oncologic:
  • Anemia
  • Neutropenia
• Hepatic:
  • Increased Liver Enzymes
• Renal:
  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine
• Respiratory:
  • Bronchospasm

Contraindication to Atovaquone Include:

• Allergic reactions to atovaquone or any component of the formulation

Warnings and Precautions

• Diarrhea, vomiting and other symptoms:
  • Patients with diarrhea or vomiting may have less absorption
  • Take care and be aware of the possibility of using an antiemetic.
  • Consider using an antiprotozoal alternative if the symptoms are severe.
• Hypersensitivity
  • Hypersensitivity reactions such as angioedema and bronchospasm or throat tightness, urticaria, and bronchospasm may occur.
• Gastrointestinal disorders:
  • Patients who are unable to take atovaquone with their food should consider parenteral therapy using alternative agents.
  • Gastrointestinal conditions can limit the absorption of oral medication and cause low plasma levels.
• Hepatic impairment
  • Patients with severe hepatic impairment should be cautious and closely monitored.
  • Reports of rare cases of cholestatic liver disease, liver function tests that are elevated, and even fatal liver failure have been made.
• Pneumocystis jirovecii pneumonia (PCP):
  • It is not indicated for use in treatment.
  • It is not recommended for 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.

Atovaquone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor: 

• 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

How to administer Atovaquone?

• It must be administered orally with food.
• Shake the suspension gently before use.
• Once opened, a foil pouch can be emptied on a dosing spoon, in a cup, or directly into the mouth.

Mechanism of action of Atovaquone:

It blocks electron transport in mitochondria, resulting in inhibition of key metabolic enzymes that are responsible for the synthesis nucleic acid and ATP.

Absorption:

• Enhanced about 2-fold with food

Protein binding:

• >99%

Metabolism:

• Unknown

Bioavailability:

• When the suspension is administered with food: 47% ± 15%

Half-life elimination:

• Range: 67 ± 33.4 hours to 77.6 ± 23.1 hours

Excretion:

• Feces (greater than 94% as unchanged drug); urine (<1%)

International Brands of Atovaquone:

• Mepron
• Samtirel
• Wellvone

Atovaquone brands in Pakistan: