Atovaquone (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Antiprotozoal
Ubiquinone

DOSING:

Adult Dose

:
Important Note
Orphan drug designation:
Treatment of AIDS-associated Pneumocystis carinii pneumonia
Prevention of Pneumocystis carinii pneumonia (PCP) in high-risk, HIV-infected patients defined by a history of one or more episodes of PCP and/or a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm(3)

Babesiosis:

750 mg

ORALLY every 12 hours plus Azithromycin 500 to

1000 mg

ORALLY on day 1 followed by 250 mg/day thereafter for 7 to 10 days

HIV infection - Toxoplasma encephalitis:
Alternative therapy,

1500 mg

ORALLY twice daily with food (or nutritional supplement), alone or in combination with either sulfadiazine 1000 to

1500 mg orally

every 6 hours
Pyrimethamine

200 mg

ORALLY for 1 dose, then 50 mg (less than 60 kg) to 75 mg (60 kg or greater) ORALLY daily plus leucovorin 10 to

25 mg ORALLY daily

(can increase to 50 mg) for at least 6 week

HIV infection - Toxoplasma encephalitis; Prophylaxis:
Primary prophylaxis (alternative regimen):
1500 mg ORALLY daily with or without pyrimethamine 25 mg ORALLY plus leucovorin 10 mg ORALLY daily

Secondary prophylaxis (alternative regimen):
750 mg ORALLY every 6 to 12 hr with or without either sulfadiazine 2000 to

4000 mg

ORALLY daily or pyrimethamine 25 mg ORALLY daily plus leucovorin 10 mg ORALLY daily

Pneumocystis pneumonia, In patients who cannot tolerate trimethoprim-sulfamethoxazole; Prophylaxis:
1500 mg orally once daily with food (

manufacturer dosage

)
(Patients with HIV) Primary and secondary prophylaxis: 1500 mg orally daily, alone or in combination with pyrimethamine 25 mg orally and leucovorin 10 mg orally daily (

Guideline dosage

)

Pneumocystis pneumonia (Mild to Moderate), In patients who cannot tolerate trimethoprim-sulfamethoxazole:
750 mg orally twice daily with food for 21 days

Pediatric Dose

:
Important Note
Orphan drug designation:
Treatment of AIDS-associated Pneumocystis carinii pneumonia:
Prevention of Pneumocystis carinii pneumonia (PCP) in high-risk, HIV-infected patients defined by a history of one or more episodes of PCP and/or a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm(3)

Babesiosis:
20 mg/kg ORALLY every 12 hours (maximum 750 mg/dose) plus azithromycin 10 mg/kg ORALLY on day 1 (maximum 500 mg/dose) followed by 5 mg/kg/day (maximum 250 mg/dose) thereafter for 7 to 10 days

Pneumocystis pneumonia, In patients who cannot tolerate trimethoprim-sulfamethoxazole; Prophylaxis:
(13 years or older)
1500 mg orally once daily with food (manufacturer dosage)

(Adolescents with HIV) Primary and secondary prophylaxis:
1500 mg orally daily, alone or in combination with pyrimethamine 25 mg orally and leucovorin 10 mg orally daily (guideline dosage)

(1 to 3 months, and older than 24 months, with HIV) Primary and secondary prophylaxis:
30 mg/kg orally daily (guideline dosage)

(4 to 24 months, with HIV) Primary and secondary prophylaxis:
45 mg/kg orally daily (guideline dosage)

Pneumocystis pneumonia (Mild to Moderate), In patients who cannot tolerate trimethoprim-sulfamethoxazole:
(13 years or older) 750 mg orally twice daily with food for 21 days

(Younger than 3 months, or 24 months or older) Patients with HIV:
30 to 40 mg/kg/day orally in 2 divided

doses with food

for 21 days; Maximum 1500 mg/day (guideline dosage)

(3 to 24 months) Patients with HIV:
45 mg/kg/day orally in 2 divided doses with food for 21 days; Maximum 1500 mg/day (guideline dosage)

MECHANISM OF ACTION:
Systemic:

Atovaquone

has possible cidal activity against susceptible organisms. The action against Pneumocystis carinii is not fully understood.

Atovaquone is

structurally similar to ubiquinone, which inhibits the mitochondrial electron-transport chain at the site of the cytochrome bc 1 complex (complex III) in Plasmodium species. This may ultimately inhibit the synthesis of nucleic acid and ATP. Atovaquone also has been shown to have good in vitro activity against Toxoplasma gondii.

ADVERSE EFFECT:
Common:
Dermatologic:
Rash (6.3% to 39%)

Gastrointestinal:
Diarrhea (3.2% to 42%)
Nausea (4.1% to 26%)
Vomiting (2.2% or greater)

Neurologic:
Headache (16% to 28%)
Insomnia (10% or greater)

Respiratory:
Cough (14%)
Rhinitis (24%)

Other:
Fever (14% to 40%)

Serious:
Dermatologic:
Erythema multiforme
Stevens-Johnson syndrome

Hematologic:
Methemoglobinemia

Hepatic:
Hepatitis
Increased liver function test
Liver failure

CONTRAINDICATION:
Known allergic or hypersensitivity

reaction to atovaquone

or any of its components

INTERACTION:
Rifampin/Rifabutin:
Concomitant administration of rifampin or rifabutin and

atovaquone suspension

is known to reduce atovaquone concentrations. Concomitant administration of atovaquone suspension and rifampin or rifabutin is not recommended.

Tetracycline :
Concomitant administration of tetracycline and atovaquone suspension has been associated with a reduction in plasma concentrations of atovaquone .Caution should be

used

when prescribing tetracycline concomitantly with atovaquone suspension. Monitor patients for potential loss of efficacy of atovaquone if coadministration is necessary.

Metoclopramide:
Metoclopramide may reduce the

bioavailability of atovaquone

and should be used only if other antiemetics are not available

Indinavir:
Concomitant

administration of atovaquone

and indinavir did not result in any change in the steady-state AUC and Cmax of indinavir but resulted in a decrease in the Ctrough of indinavir .Caution should be exercised when

prescribing atovaquone

suspension with indinavir due to the decrease in trough concentrations of indinavir. Monitor patients for potential loss of efficacy of indinavir if coadministration with atovaquone suspension is necessary.

Major:
Efavirenz (theoretical)
Rifabutin (probable)
Rifampin (probable)
Ritonavir (probable)

Moderate:
Tetracycline (probable)
Warfarin (probable)

PHARMACOKINETICS:
Absorption:
Bioavailability:
Oral tablets: 23%
Oral suspension: 47% ± 15%

Effect of Food:
Oral Tablets: Increase 3-fold with food
Oral suspension: Increase 2-fold with food

Distribution:
Volume of distribution (Vd): 0.6 L/kg
Plasma Protein Binding of oral suspension: 99.9%

Excretion:
Systemic: Fecal: 94%; Renal 0.6%

Elimination:
Systemic: 2.2 to 3.2 days

PRECAUTION:
Concomitant

use of

rifampin or rifabutin is not recommended.
Concomitant use of metoclopramide should be avoided.

Gastrointestinal:
Optimum atovaquone concentrations may not be achieved in patients with an inability to take atovaquone with food; consider alternative agent. Optimum atovaquone concentrations may not be achieved in patients with gastrointestinal disorders which may limit drug absorption; consider alternative agent.

Hepatic:
Risk of hepatotoxicity in patients with sever hepatic impairment; monitoring recommended
Hepatotoxicity (liver failure, cholestatic hepatitis, and elevated liver function tests) has been reported.

PREGNANCY CATEGORY:
C (FDA)
B2 (AUS)

BREAST FEEDING:
Infant risk cannot be ruled out.
MONITORING:
Arterial blood gases, chest films, respiratory function, sputum staining and microscopy
Liver function in patients with preexisting severe hepatic impairment

HOW TO TAKE OR ADMINISTRATION:
Oral:
(Suspension)
Shake bottle well before each use.
For 5-mL

unit dose

, take entire contents of 1 foil pouch either by dispensing into a dosing spoon or cup or by placing directly into the mouth. For 10-mL unit dose, take entire contents of 2 foil pouches.
Take with food.

DOSAGE FORM:
Oral Suspension:
750 MG/5 ML

TOXICOLOGY:
TOXICITY: A minimum

toxic dose

has not been established.

Overdoses

of up to 31.5 grams have been well tolerated. atovaquone

PATIENT COUNSELING OR CLINICAL TEACHING:
Drug may cause rash, sweating, diarrhea, nausea, asthenia, dizziness, headache, dyspnea, cough, or fever.
Patient should take drug with meals as reduced absorption may result if taken on an empty stomach.




Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.