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Drug overview for MEPRON (atovaquone):
Generic name: ATOVAQUONE (a-TOE-va-kwone)
Drug class: Antiprotozoal Agents
Therapeutic class: Anti-Infective Agents
Atovaquone, a synthetic hydroxynaphthoquinone derivative, is an antiprotozoal agent.
No enhanced Uses information available for this drug.
Generic name: ATOVAQUONE (a-TOE-va-kwone)
Drug class: Antiprotozoal Agents
Therapeutic class: Anti-Infective Agents
Atovaquone, a synthetic hydroxynaphthoquinone derivative, is an antiprotozoal agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
MEPRON 750 MG/5 ML SUSPENSION
The following indications for MEPRON (atovaquone) have been approved by the FDA:
Indications:
Pneumocystis jirovecii pneumonia prevention
Pneumocystis jirovecii pneumonia
Professional Synonyms:
PCP prophylaxis
Pneumocystis carinii pneumonia prevention
Pneumocystis carinii pneumonia prophylaxis
Pneumocystis jiroveci pneumonia prevention
Pneumocystis jirovecii (carinii) pneumonia
Pneumocystis pneumonia
Pneumocystosis jirovecii pneumonia
Pulmonary pneumocystosis
Indications:
Pneumocystis jirovecii pneumonia prevention
Pneumocystis jirovecii pneumonia
Professional Synonyms:
PCP prophylaxis
Pneumocystis carinii pneumonia prevention
Pneumocystis carinii pneumonia prophylaxis
Pneumocystis jiroveci pneumonia prevention
Pneumocystis jirovecii (carinii) pneumonia
Pneumocystis pneumonia
Pneumocystosis jirovecii pneumonia
Pulmonary pneumocystosis
The following dosing information is available for MEPRON (atovaquone):
The pharmacokinetics of atovaquone in individuals with renal or hepatic impairment and the possible need for caution and/or dosage adjustment remain to be fully determined. The manufacturer states that atovaquone should be used with caution and close monitoring in patients with severe hepatic impairment.
Atovaquone is administered orally. Atovaquone must be taken with food to optimize GI absorption. (See Pharmacokinetics: Absorption.) Alternative therapy should be considered in patients who have difficulty taking atovaquone with food.
The multiple-dose bottle containing atovaquone oral suspension should be shaken gently before removing a dose. If a single-dose foil pouch containing atovaquone oral suspension is used, the pouch should be opened by removing the perforated tab and the entire contents of the pouch ingested; the dose can be discharged from the pouch into a dosing spoon or cup or directly into the mouth.
The multiple-dose bottle containing atovaquone oral suspension should be shaken gently before removing a dose. If a single-dose foil pouch containing atovaquone oral suspension is used, the pouch should be opened by removing the perforated tab and the entire contents of the pouch ingested; the dose can be discharged from the pouch into a dosing spoon or cup or directly into the mouth.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| MEPRON 750 MG/5 ML SUSPENSION | Maintenance | Adults take 5 milliliters (750 mg) by oral route 2 times per day with meals |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ATOVAQUONE 750 MG/5 ML SUSP | Maintenance | Adults take 5 milliliters (750 mg) by oral route 2 times per day with meals |
| ATOVAQUONE 750 MG/5ML SUSP CUP | Maintenance | Adults take 5 milliliters (750 mg) by oral route 2 times per day with meals |
The following drug interaction information is available for MEPRON (atovaquone):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Artemether; Lumefantrine/Antimalarials SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Halofantrine and quinine may inhibit the metabolism of lumefantrine by CYP2D6.(1) The combination of artemether-lumefantrine and antimalarials may result in additive effects on the QT interval.(1) CLINICAL EFFECTS: Concurrent use may result in toxicity and/or prolongation of the QT interval, which may result in life-threatening arrhythmias.(1,2) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(3) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(3) PATIENT MANAGEMENT: The UK manufacturer of artemether-lumefantrine states that the concurrent use of artemether-lumefantrine with other antimalarials is contraindicated.(1) The US manufacturer of artemether-lumefantrine states that artemether-lumefantrine should not be given concurrently with antimalarials.(2) If a patient deteriorates during artemether-lumefantrine therapy and requires another antimalarial agent, it may be started immediately, but the UK manufacturer of artemether-lumefantrine recommends ECG and potassium monitoring.(1) In patients who have previously received halofantrine, both the UK and US manufacturers of artemether-lumefantrine recommends that one month elapse between the last dose of halofantrine and the initiation of artemether-lumefantrine.(1) If concurrent therapy is deemed medically necessary, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study in 14 healthy subjects, administration of a single intravenous dose of quinine (10 mg/kg) 2 hours after the sixth dose of artemether-lumefantrine had no effect on lumefantrine or dihydroartemisinin levels. Artemether levels were decreased; however, this was not believed to be clinically significant.(1,2) Concurrent quinine and artemether-lumefantrine produced a slight, but significant increase on the QTc interval.(1) |
COARTEM |
There are 5 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Atovaquone/Rifabutin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown but likely involves rifabutin-induced increase in the metabolism of atovaquone.(1,2) CLINICAL EFFECTS: Concurrent administration of atovaquone with rifabutin may result in decreased levels and clinical effects of atovaquone(1,2). PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The administration of rifabutin during atovaquone therapy is not recommended.(1,2) Consider alternative agents to rifabutin during atovaquone therapy.(1) If coadministration is necessary, the National Institute of Health Opportunistic Infections guidelines recommend patients take atovaquone with a fatty meal and monitor for decreased atovaquone efficacy.(3) DISCUSSION: In a study of 13 HIV-positive patients, rifampin (600 mg every 24 hours) and atovaquone (750 mg every 12 hours) resulted in a decrease in average atovaquone steady-state plasma concentration by 52% and an increase in average rifampin steady-state plasma concentration by 37%.(1) In a trial of 24 healthy volunteers, rifabutin 300 mg once daily with atovaquone oral suspension 750 mg twice daily resulted in a 34% decrease in the mean steady-state plasma atovaquone concentration and a 19% decrease in the mean steady-state plasma rifabutin concentration.(1) |
RIFABUTIN, TALICIA |
| Atovaquone/Tetracycline SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: The concurrent administration of tetracycline may result in decreased levels and effectiveness of atovaquone.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The CDC states that tetracycline should not be administered with atovaquone.(1) If concurrent use of tetracycline and atovaquone is warranted, parasitemia should be closely monitored.(2) DISCUSSION: Concurrent tetracycline has been associated with a 40% decrease in atovaquone plasma concentrations.(1) |
BISMUTH-METRONIDAZOLE-TETRACYC, PYLERA, TETRACYCLINE HCL |
| Atovaquone/Metoclopramide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Metoclopramide decreases the absorption of atovaquone.(1-3) CLINICAL EFFECTS: The concurrent use of metoclopramide may result in decreased levels and effectiveness of atovaquone.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Metoclopramide should only be used in patients receiving atovaquone if no other antiemetic is available.(1-3) DISCUSSION: Concurrent metoclopramide has been associated with a 50% decrease in atovaquone plasma concentrations.(1) |
GIMOTI, METOCLOPRAMIDE HCL, REGLAN |
| Atovaquone; Proguanil/Efavirenz SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The mechanism of interaction between atovaquone and efavirenz is unknown. Efavirenz, an inducer of CYP2C19, may induce the metabolism of proguanil.(1,2) CLINICAL EFFECTS: Concurrent use of CYP2C19 inducers with atovaquone and proguanil may result in decreased levels and effectiveness of the antimalarial agents and treatment failure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concomitant administration of atovaquone/proguanil with efavirenz is not recommended and may result in decreased levels of atovaquone and proguanil.(1) Monitor patients for signs of treatment failure. DISCUSSION: In a study of 30 human immunodeficiency virus (HIV)-infected subjects enrolled in three treatment arms (10 taking no antiretroviral therapy, 10 taking combination antiretroviral therapy including efavirenz, and 10 taking combination antiretroviral therapy with atazanavir/ritonavir) received atovaquone 750 mg BID for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with a washout period in between. The subjects on a combination antiretroviral regimen including efavirenz had a 47% and 44% lower atovaquone area-under-curve (AUC) on both dosing regimens, 750 mg BID and 1500 mg BID, respectively (p<0.01). Concentrations of atovaquone required to successfully treat Pneumocystis jiroveci pneumonia (average Concentration > 15 mcg/ml) were achieved in 50% of the subjects receiving an efavirenz based regimen. Concentrations of atovaquone required to successfully treat Toxoplasma encephalitis (average Concentration > 18.5 mcg/ml) were achieved in 20% of the subjects receiving an efavirenz based regimen with atovaquone 750 mg BID.(3) In a study of 76 HIV-infected patients, 18 healthy volunteers, 20 patients with efavirenz, 19 patients with lopinavir/ritonavir, or 19 patients with atazanavir/ritonavir received a single dose of atovaquone/proguanil 250/100 mg dose. The geometric mean ration (GMR) [95% confidence interval] AUC and maximum concentration (Cmax) for atovaquone, respectively, were 0.25 and 0.56 for patients on efavirenz, 0.26 and 0.56 for patients on lopinavir/ritonavir, and 0.54 and 0.51 for patients on atazanavir/ritonavir. Proguanil concentrations after adjustment for confounders including CYP2C19 genotype resulted in the GMR AUC of 0.57 for patients on efavirenz, 0.62 for patients on lopinavir/ritonavir, and 0.59 for patients on atazanavir/ritonavir. The Cmax for proguanil was unchanged in all three groups compared to healthy controls.(4) |
EFAVIRENZ, EFAVIRENZ-EMTRIC-TENOFOV DISOP, EFAVIRENZ-LAMIVU-TENOFOV DISOP, SYMFI, SYMFI LO |
| Atovaquone/Rifampin; Rifapentine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown.(1,2) CLINICAL EFFECTS: Concurrent use may lead to decreased levels and clinical effects of atovaquone and increased levels of and side effects from the rifamycin.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concomitant administration with rifampin or rifapentine is not recommended by the US manufacturer of atovaquone and the National Institute of Health HIV guidelines.(1-3) DISCUSSION: In a study of 13 HIV-positive patients, rifampin (600 mg every 24 hours) and atovaquone (750 mg every 12 hours) resulted in a decrease in average atovaquone steady-state plasma concentration by 52% and an increase in average rifampin steady-state plasma concentration by 37%.(1) |
PRIFTIN, RIFADIN, RIFAMPIN |
There are 0 moderate interactions.
The following contraindication information is available for MEPRON (atovaquone):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 0 contraindications.
There are 1 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Malabsorption states |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Severe hepatic disease |
The following adverse reaction information is available for MEPRON (atovaquone):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 13 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Acute renal failure Angioedema Bronchospastic pulmonary disease Disorder of cornea Erythema multiforme Hepatic failure Hepatitis Methemoglobinemia Pancreatitis Stevens-johnson syndrome Throat constriction Thrombocytopenic disorder Urticaria |
There are 16 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Cough Diarrhea Fever Headache disorder Insomnia Nausea Skin rash Vomiting |
Acute abdominal pain Dizziness Hyperhidrosis |
| Rare/Very Rare |
|---|
|
Depression General weakness Myalgia Pruritus of skin Sinusitis |
The following precautions are available for MEPRON (atovaquone):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Reproduction studies in rats using atovaquone dosages resulting in plasma concentrations up to 2-3 times the estimated human exposure have not revealed evidence of teratogenicity. However, maternal and fetal toxicity (decreased mean fetal body lengths and weights and increased early fetal resorption and postimplantation fetal loss) did occur in rabbits receiving oral atovaquone dosages resulting in plasma concentrations approximately one-half the estimated human exposure. It is not clear whether these effects were caused by atovaquone or resulted from maternal toxicity.
Atovaquone concentrations in rabbit fetuses averaged 30% of concurrent maternal plasma concentrations. In another study, atovaquone concentrations in rat fetuses following single 14C-radiolabeled doses were 18% (middle gestation) and 60% (late gestation) of concurrent maternal plasma concentrations. There are no adequate and controlled studies to date using atovaquone in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Atovaquone concentrations in rabbit fetuses averaged 30% of concurrent maternal plasma concentrations. In another study, atovaquone concentrations in rat fetuses following single 14C-radiolabeled doses were 18% (middle gestation) and 60% (late gestation) of concurrent maternal plasma concentrations. There are no adequate and controlled studies to date using atovaquone in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
It is not known whether atovaquone is distributed into human milk. The drug is distributed into breast milk of rats in concentrations 30% of concurrent maternal plasma concentrations. Atovaquone should be used with caution in nursing women.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for MEPRON (atovaquone):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for MEPRON (atovaquone)'s list of indications:
| Pneumocystis jirovecii pneumonia | |
| B59 | Pneumocystosis |
| Pneumocystis jirovecii pneumonia prevention | |
| B20 | Human immunodeficiency virus [HIv] disease |
| Z94.0 | Kidney transplant status |
| Z94.1 | Heart transplant status |
| Z94.2 | Lung transplant status |
| Z94.3 | Heart and lungs transplant status |
| Z94.4 | Liver transplant status |
| Z94.81 | Bone marrow transplant status |
| Z94.82 | Intestine transplant status |
| Z94.84 | Stem cells transplant status |
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