Atovaquone is a medication primarily used to prevent and treat malaria and to treat a type of pneumonia called Pneumocystis pneumonia (PCP). It works by interfering with the reproduction of parasites and microorganisms.

In malaria treatment, atovaquone is often used in combination with proguanil (sold under the brand name Malarone) and is effective against both Plasmodium falciparum and Plasmodium vivax strains of the malaria parasite.

For Pneumocystis pneumonia, atovaquone is used as an alternative treatment, particularly in patients who cannot tolerate the standard therapy with trimethoprim-sulfamethoxazole.

Atovaquone inhibits the reproduction of protozoal infections. It is used to treat the following conditions: 

• Adults and adolescents 13 years of age and older who are unable to take trimethoprim-sulfamethoxazole 
• Adults and adolescents 13 years of age and older who are unable to tolerate TMP-SMZ can receive an acute oral treatment for mild to moderate PCP infection.
• Off Label Uses of Atovaquone in Adults include:
  • Babesiosis
  • HIV patients' prevention, care, and long-term maintenance therapy for toxoplasma gondii encephalitis

Atovaquone Dose in Adults

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

• Take 1,500 mg once a day with food by mouth.

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Atovaquone Dose in the treatment of mild to moderate PCP:  

• Take 750 mg twice a day with food by mouth for 21 days.

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

• Take atovaquone orally at 750 mg twice daily along with azithromycin for at least 7 to 10 days.
• If the infection comes back, treatment may need to continue for at least 6 weeks.

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

Prophylaxis:

• Take 1,500 mg once daily with food.
• This can be used alone or with pyrimethamine plus leucovorin.
• Prophylaxis is recommended for patients who are Toxoplasma IgG-positive with a CD4 count less than 100 cells/mm³.
• Continue prophylaxis until CD4 count is over 200 cells/mm³ for more than 3 months after starting ART.

Treatment:

• Take 1,500 mg twice daily with food.
• This can be with pyrimethamine plus leucovorin, sulfadiazine, or as monotherapy.
• Treatment should continue for at least 6 weeks, longer if the disease is extensive or there's an incomplete response.

Secondary prophylaxis (chronic maintenance):

• Take 750 to 1,500 mg twice daily with food.
• This can be with pyrimethamine plus leucovorin, sulfadiazine, or as monotherapy.
• This can be discontinued when asymptomatic and the CD4 count is over 200 cells/mm³ for more than 6 months while on antiretrovirals.

Atovaquone Dose in Children

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

Prophylaxis:

• Infants and Children:
  • 1 to 3 months: Take 30 mg/kg/day once daily
  • 4 to 24 months: Take 45 mg/kg/day once daily
  • Over 24 months: Take 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day
• Adolescents: Take 1,500 mg once daily

Treatment for mild to moderate infection (duration: 21 days):

• Infants and Children:
  • 1 to 3 months: Take 30 to 40 mg/kg/day divided once or twice daily
  • 4 to 24 months: Take 45 mg/kg/day divided once or twice daily
  • Over 24 months: Take 30 to 40 mg/kg/day divided once or twice daily; maximum daily dose: 1,500 mg/day
• Adolescents: Take 750 mg twice daily

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Atovaquone 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: Take 30 mg/kg/day once daily
  • 4 to 24 months: Take 45 mg/kg/day once daily; with or without pyrimethamine/leucovorin
  • Over 24 months: Take 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day
• Adolescents: Take 1,500 mg once daily; with or without pyrimethamine/leucovorin

Treatment (encephalitis):

• Adolescents: Take 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:
  • 1 to 3 months: Take 30 mg/kg/day once daily with leucovorin
  • 4 to 24 months: Take 45 mg/kg/day once daily; with or without pyrimethamine/leucovorin
  • Over 24 months: Take 30 mg/kg/day once daily; maximum daily dose: 1,500 mg/day; with leucovorin
• Adolescents: Take 750 to 1,500 mg twice daily; use in combination with pyrimethamine/leucovorin or sulfadiazine is preferred

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Atovaquone Dose in the treatment of Babesiosis:

For treating Babesiosis in infants and children, the atovaquone dose is:

• Oral: 40 mg/kg/day divided twice daily; maximum daily dose: 1,500 mg/day with azithromycin for 7 to 10 days.

For adolescents, the dose is:

• Oral: 750 mg twice daily for 7 to 10 days with azithromycin.

Pregnancy Risk Factor: C

• There's not much information about using atovaquone during pregnancy.
• But when it comes to diagnosing and treating Pneumocystis jirovecii pneumonia (PCP) in pregnant women, it's pretty much the same as in women who aren't pregnant.
• Sometimes, if necessary, atovaquone can be used as a different option for treating PCP and Toxoplasma gondii infections during pregnancy, according to guidelines from the U.S.
• Department of Health and Human Services in 2017.

Atovaquone use during breastfeeding:

• It's uncertain if atovaquone passes into breast milk.
• Women with HIV should avoid breastfeeding entirely to lower the risk of passing HIV to their infants.

Atovaquone Dose in Renal Disease:

• The manufacturer's instructions don't include dosage adjustments because there haven't been studies on this.
• However, it's known that atovaquone is not significantly eliminated through the kidneys.

Atovaquone Dose in Liver Disease:

• The manufacturer's instructions don't include dosage adjustments because there haven't been studies on this.
• Atovaquone goes through a process called enterohepatic cycling and is mainly removed by the liver.
• If a patient has severe liver problems, it's essential to be cautious and closely monitor their condition when using atovaquone.

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• Not always specified is frequency. Statistics on adverse reactions have been gathered from trials that included participants with advanced HIV illness.
• As a result, it is challenging to discern between side effects linked to atovaquone and those brought on by the underlying illness or a mix of both.

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:

• If someone has a hypersensitivity reaction to atovaquone or any ingredient in the medication, it's crucial to avoid using it.

Warnings and Precautions

Diarrhea, vomiting and other symptoms:

• If a patient experiences diarrhea or vomiting, their body might not absorb atovaquone properly.
• It's important to monitor them closely and think about using an antiemetic (a medication to prevent vomiting).
• If the symptoms are severe, it might be necessary to consider using a different antiprotozoal medication.

Hypersensitivity

• Hypersensitivity reactions, such as angioedema, bronchospasm, throat tightness, and urticaria (hives), have been reported with atovaquone use.

Gastrointestinal disorders:

• In patients who struggle to take atovaquone with food due to gastrointestinal issues, consider using alternative agents administered through injection.
• Gastrointestinal disorders can affect the absorption of oral medications, potentially leading to inadequate levels of atovaquone in the bloodstream.

Hepatic impairment

• In individuals with severe liver problems, it's important to be cautious when using atovaquone.
• Close monitoring is necessary because there have been rare instances of cholestatic hepatitis, elevated liver function tests, and even fatal liver failure reported with its use.

Pneumocystis jirovecii pneumonia (PCP):

• Atovaquone has been indicated for treating mild to moderate Pneumocystis jirovecii pneumonia (PCP), but it hasn't been studied for severe cases.
• Compared to the treatment of choice, trimethoprim-sulfamethoxazole (TMP-SMZ), atovaquone tends to have fewer adverse effects.
• However, it's worth noting that TMP-SMZ is more effective than atovaquone in treating mild to moderate PCP.

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

Risk Factor C (Monitor therapy).
Etoposide	Etoposide may be increased by atovaquone. Management: It is worth separating atovaquone from etoposide for at least one to two days.
Etoposide Phosphate	Etoposide Phosphate may be increased by atovaquone. Management: It is worth separating atovaquone administration from etoposide for at least one to two days.
Indinavir	Indinavir serum concentration may be decreased by Atovaquone
Ritonavir	May lower the serum level of Atovaquone.
Tetracycline (Systemic)	May lower the serum level of Atovaquone.
Risk Factor D (Regard therapy modification)
Efavirenz	It may cause a decrease in serum Atovaquone concentration. Management: If possible, consider alternatives to atovaquone and efavirenz. Monitor for evidence of decreased atovaquone clinical efficacy if this combination is necessary.
Metoclopramide	It may cause a decrease in serum Atovaquone concentration. Management: If metoclopramide is not available, consider other options. Atovaquone should be used only with metoclopramide.
Risk Factor X (Avoid Combination)
Rifamycin Derivatives	May lower the serum level of Atovaquone.

Monitor: 

Hepatic Function:

• Monitor closely during treatment, especially in patients with severe liver problems.

Hypersensitivity Reactions:

• Watch out for signs like angioedema, bronchospasm, throat tightness, or hives.

CD4 Count:

• Important for deciding on ongoing treatment for toxoplasmosis.

Patient's Food Tolerance:

• Consider if the patient can take atovaquone with food; if not, explore alternatives.

Post-dose Vomiting:

• Keep an eye on patients who vomit after taking atovaquone; it might affect how much is absorbed.

Diarrhea:

• Be aware that diarrhea could impact absorption; monitor closely and consider using anti-diarrheal medication if needed.

How to administer Atovaquone?

Administration for Adults:

• Oral: Always give with food.
• Shake the suspension gently before using it.
• After opening, you can pour the contents of a foil pouch onto a dosing spoon, into a cup, or directly into the mouth.

Administration for Children:

• Oral: Should be given with food or a high-fat meal.
• Shake the suspension gently before using it.
• After opening, you can pour the contents of a foil pouch onto a dosing spoon, into a cup, or directly into the mouth.

Mechanism of action of Atovaquone:

• Atovaquone works by slowing down the flow of electrons in mitochondria, which are like energy factories in cells.
• This slowdown stops certain important enzymes from doing their job in making DNA and ATP, which are essential for cell function and growth.

Absorption:

• Absorption is about twice as effective when taken with food.

Distribution:

• Volume of distribution (V) is around 0.6 ± 0.17 liters per kilogram.
• Atovaquone concentration in cerebrospinal fluid (CSF) is less than 1% of its concentration in the blood plasma.

Protein Binding:

• More than 99% of atovaquone binds to proteins in the blood.

Metabolism:

• The process of metabolism for atovaquone is not fully understood.

Bioavailability:

• When taken as a suspension with food, about 47% ± 15% of atovaquone is available in the bloodstream.

Half-life Elimination:

• Atovaquone's elimination half-life ranges from 67 ± 33.4 hours to 77.6 ± 23.1 hours.

Excretion:

• Over 94% of atovaquone is eliminated from the body unchanged, primarily through the feces.
• Less than 1% is excreted in urine.

International Brands of Atovaquone:

• Mepron
• Samtirel
• Wellvone

Atovaquone brands in Pakistan:

Atovaquone [Tabs 250 Mg]
Proqon	Hilton Pharma (Pvt) Limited
Proqon	Hilton Pharma (Pvt) Limited

 

Atovaquone [Tabs 62.5 Mg]
Proqon	Hilton Pharma (Pvt) Limited
Proqon	Hilton Pharma (Pvt) Limited