Mepron

Agents for Toxoplasmosis

Atovaquone should be administered with food to enhance oral absorption. Failure to administer atovaquone with food in this manner may limit treatment efficacy.

Unit-dose oral suspension in foil pouch (5 mL): No further reconstitution or dilution is necessary. Each pouch contains 750 mg atovaquone. Open pouch by folding along the dotted line and tearing open at horizontal slit as directed by arrow on pouch. Contents may be poured into a dosing spoon or cup or directly into the mouth.
Bulk suspension (210 mL): No further reconstitution or dilution is necessary. The concentration of atovaquone is 750 mg/5 mL. Shake the suspension gently before use, and measure dose with a calibrated oral syringe or device.

bronchospasm / Rapid / 2.0-4.0
erythema multiforme / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
pancreatitis / Delayed / 0-1.0
hepatic failure / Delayed / 0-1.0
methemoglobinemia / Early / 0-1.0

dyspnea / Early / 15.0-21.0
candidiasis / Delayed / 5.0-10.0
hyponatremia / Delayed / 7.0-10.0
hyperglycemia / Delayed / 9.0-9.0
elevated hepatic enzymes / Delayed / 4.0-8.0
hyperamylasemia / Delayed / 7.0-7.0
anemia / Delayed / 4.0-6.0
neutropenia / Delayed / 3.0-5.0
constipation / Delayed / 3.0-3.0
hepatitis / Delayed / 0-1.0
hypoglycemia / Early / 1.0-1.0
thrombocytopenia / Delayed / 0-1.0
keratopathy / Delayed / 0-1.0
hypotension / Rapid / 1.0-1.0

rash / Early / 6.3-46.0
diarrhea / Early / 3.2-42.0
fever / Early / 0.6-40.0
nausea / Early / 4.1-32.0
asthenia / Delayed / 8.0-31.0
headache / Early / 16.0-31.0
cough / Delayed / 14.0-25.0
rhinitis / Early / 5.0-24.0
maculopapular rash / Early / 23.0-23.0
vomiting / Early / 2.2-22.0
infection / Delayed / 18.0-22.0
abdominal pain / Early / 4.0-21.0
insomnia / Early / 0-19.0
dizziness / Early / 3.0-8.0
anorexia / Delayed / 7.0-7.0
anxiety / Delayed / 7.0-7.0
dyspepsia / Early / 5.0-5.0
dysgeusia / Early / 3.0-3.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 10.0
influenza / Delayed / 10.0
sinusitis / Delayed / 10.0
myalgia / Early / 10.0
hyperhidrosis / Delayed / 10.0

Mepron

Rx

Oral antiprotozoal agent; active against both Toxoplasma gondii and Pneumocystis jiroveci (formerly Pneumocystis carinii); structurally and pharmacologically related to lapinone and parvaquone (antimalarials); effective for malaria when used with proguanil.

750 mg PO twice daily for 21 days as alternative therapy for mild to moderate infection then chronic suppressive therapy.

750 mg PO twice daily for 21 days as alternative therapy for mild to moderate infection then chronic suppressive therapy. 

30 to 40 mg/kg/dose (Max: 1,500 mg/dose) PO once daily for 21 days as alternative therapy then chronic suppressive therapy.

45 mg/kg/dose PO once daily for 21 days as alternative therapy then chronic suppressive therapy.

30 to 40 mg/kg/dose PO once daily for 21 days as alternative therapy then chronic suppressive therapy.

750 to 1,500 mg PO twice daily for 14 to 21 days as alternative therapy for mild to moderate infection.

750 to 1,500 mg PO twice daily for 14 to 21 days as alternative therapy for mild to moderate infection.

30 to 40 mg/kg/day PO in 1 or 2 divided doses (Max: 1,500 mg/day) for 14 to 21 days as alternative therapy for mild to moderate infection.

45 mg/kg/day PO in 1 or 2 divided doses for 14 to 21 days as alternative therapy for mild to moderate infection.

30 to 40 mg/kg/day PO in 1 or 2 divided doses for 14 to 21 days as alternative therapy for mild to moderate infection.

750 mg PO 2 or 3 times daily for 14 to 21 days as alternative therapy for mild to moderate infection.

750 mg PO twice daily for 14 to 21 days as alternative therapy for mild to moderate infection.

30 to 40 mg/kg/dose (Max: 1,500 mg/dose) PO once daily for 14 to 21 days as alternative therapy for mild to moderate infection.

45 mg/kg/dose PO once daily for 14 to 21 days as alternative therapy for mild to moderate infection.

30 to 40 mg/kg/dose PO once daily for 14 to 21 days as alternative therapy for mild to moderate infection.

1,500 mg PO once daily alone or in combination with daily pyrimethamine and leucovorin as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.

1,500 mg PO once daily alone or in combination with daily pyrimethamine and leucovorin as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.

30 to 40 mg/kg/dose (Max: 1,500 mg/dose) PO once daily as alternative therapy. Recommended for patients with CD4 count less than 200 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.

30 to 40 mg/kg/dose PO once daily as alternative therapy. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

45 mg/kg/dose PO once daily as alternative therapy. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

45 mg/kg/dose PO once daily as alternative therapy. Recommended for all HIV-infected or HIV-indeterminate infants younger than 12 months regardless of CD4 count or percentage. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.

30 to 40 mg/kg/dose PO once daily as alternative therapy. Recommended for all HIV-infected or HIV-indeterminate infants younger than 12 months regardless of CD4 count or percentage. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.

1,500 mg PO once daily alone or in combination with daily pyrimethamine and leucovorin as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.

1,500 mg PO once daily alone or in combination with daily pyrimethamine and leucovorin as alternative therapy. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary. 

30 to 40 mg/kg/dose (Max: 1,500 mg/dose) PO once daily as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.

30 to 40 mg/kg/dose PO once daily as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

45 mg/kg/dose PO once daily as alternative therapy. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.

45 mg/kg/dose PO once daily as alternative therapy. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.

30 to 40 mg/kg/dose PO once daily as alternative therapy. Do not discontinue prophylaxis in HIV-infected infants younger than 12 months.

750 mg PO twice daily or 1,500 mg PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

750 mg PO twice daily or 1,500 mg PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.

30 mg/kg/dose (Max: 1,500 mg/dose) PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.  

45 mg/kg/dose PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT as alternative therapy. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.   

1,500 mg PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

1,500 mg PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

30 to 40 mg/kg/dose (Max: 1,500 mg/dose) PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

45 mg/kg/dose PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

30 to 40 mg/kg/dose PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients, as alternative therapy. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.

1,500 mg PO once daily alone or in combination with weekly pyrimethamine and leucovorin as alternative therapy. Recommended for patients receiving alemtuzumab, fludarabine/cyclophosphamide/rituximab, corticosteroids at doses equivalent to more than 20 mg/day of prednisone for 4 weeks, nucleoside or purine analogs, radiotherapy for brain tumors/metastasis plus high-dose steroids as well as for patients with acute lymphoblastic leukemia (ALL) and lymphoma treated with R-CHOP14 or escalated BEACOPP. Duration of prophylaxis for ALL is from induction to the end of maintenance. Prophylaxis for alemtuzumab-associated treatment and fludarabine/cyclophosphamide/rituximab treatment is suggested for at least 6 months after treatment completion.

1,500 mg PO once daily as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.

30 mg/kg/dose (Max: 1,500 mg/dose) PO once daily as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.

45 mg/kg/dose PO once daily as alternative therapy. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.

1,500 mg PO once daily as alternative therapy. Recommended for patients receiving corticosteroids at doses equivalent to 20 mg/day or more of prednisone for 4 weeks or more, particularly if an additional risk factor is present.

As an alternative, the HIV guidelines recommend 1,500 mg PO twice daily either alone or in combination with either pyrimethamine plus leucovorin or sulfadiazine. Treatment duration should be at least 6 weeks; however a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however they should not be used prophylactically.

1,500 mg PO once daily, with or without pyrimethamine and leucovorin, in patients with CD4 count less than 100 cells/mm3 and IgG antibody to toxoplasma is recommended as an alternative therapy by the HIV guidelines. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral therapy with an increase in CD4 counts to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be restarted if the CD4 counts decrease to less than 100 to 200 cells/mm3.

30 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. For children 1 to 5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 percentage of 15% or more for more than 3 consecutive months. For children 6 years of age and older, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 count greater than 200 cells/mm3 for more than 3 consecutive months.

45 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1 to 5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 percentage of 15% or more for more than 3 consecutive months.

30 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life.

750 to 1,500 mg PO every 12 hours with either sulfadiazine or pyrimethamine plus leucovorin is recommended as an alternative therapy by the HIV guidelines. Secondary prophylaxis may be discontinued in asymptomatic patients who have a sustained increase in their CD4 counts greater than 200 cells/mm3 after highly active antiretroviral therapy for 6 months or more; however, limited number of patients have been evaluated and recurrences have been observed. Secondary prophylaxis should be reintroduced if the CD4 count decreases to less than 200 cells/mm3.

30 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. For children 1 to 5 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 percentage of 15% or more for more than 6 consecutive months. For children 6 years of age and older, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 count greater than 200 cells/mm3 for more than 6 consecutive months. Additionally, in order to safely discontinue secondary prophylaxis, children must also have completed initial therapy for toxoplasmic encephalitis and be asymptomatic.

45 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1 to 5 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy in patients with a CD4 percentage of 15% or more for more than 6 consecutive months. Additionally, in order to safely discontinue secondary prophylaxis, children must also have completed initial therapy for toxoplasmic encephalitis and be asymptomatic.

30 mg/kg PO once daily, with or without pyrimethamine and leucovorin, is recommended as an alternative therapy by the HIV guidelines. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. Additionally, in order to safely discontinue secondary prophylaxis, children must also have completed initial therapy for toxoplasmic encephalitis and be asymptomatic.

750 mg PO every 12 hours for 7 to 10 days.

20 mg/kg/dose (Max: 750 mg/dose) PO every 12 hours for 7 to 10 days.

750 mg PO every 12 hours for at least 7 to 10 days; duration may need to be extended in these patients.

20 mg/kg/dose (Max: 750 mg/dose) PO every 12 hours for at least 7 to 10 days; duration may need to be extended in these patients.

750 mg PO every 12 hours for at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

20 mg/kg/dose (Max: 750 mg/dose) PO every 12 hours for at least 6 weeks, including 2 final weeks during which parasites are no longer detected on peripheral blood smear.

750 mg PO every 12 hours as part of combination therapy which may include clindamycin, azithromycin plus clindamycin, or azithromycin plus clindamycin plus quinine.

20 mg/kg/dose (Max: 750 mg/dose) PO every 12 hours as part of combination therapy which may include clindamycin, azithromycin plus clindamycin, or azithromycin plus clindamycin plus quinine.

†Indicates off-label use

No dosage adjustments are necessary in patients with mild to moderate hepatic impairment (manufacturer data). Studies have not been conducted in patients with severe hepatic impairment.

Dosing in patients with renal impairment has not been studied; but no dosage adjustment appears to be needed.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Atazanavir: (Major) Concurrent administration of atazanavir plus ritonavir with atovaquone; proguanil has shown to decrease the atovaquone AUC by 46% and the proguanil AUC by 41%. Consider alternative malaria prophylaxis.
Atazanavir; Cobicistat: (Major) Concurrent administration of atazanavir plus ritonavir with atovaquone; proguanil has shown to decrease the atovaquone AUC by 46% and the proguanil AUC by 41%. Consider alternative malaria prophylaxis.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline.
Efavirenz: (Major) Avoid concurrent administration of efavirenz and atovaquone; proguanil. Use of these drugs together results in a 75% decreased in atovaquone AUC and a 43% decrease in proguanil AUC. Consider use of an alternative malaria prophylaxis.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent administration of efavirenz and atovaquone; proguanil. Use of these drugs together results in a 75% decreased in atovaquone AUC and a 43% decrease in proguanil AUC. Consider use of an alternative malaria prophylaxis.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concurrent administration of efavirenz and atovaquone; proguanil. Use of these drugs together results in a 75% decreased in atovaquone AUC and a 43% decrease in proguanil AUC. Consider use of an alternative malaria prophylaxis.
Indinavir: (Major) The use of atovaquone with food plus indinavir without food led to a decrease in the trough concentration of indinavir; changes in the AUC or maximum concentration of indinavir did not occur. Caution is advised if these drugs are coadministered.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
Isoniazid, INH; Rifampin: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
Lamivudine, 3TC; Zidovudine, ZDV: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of lopinavir; ritonavir with atovaquone; proguanil has shown to decrease the atovaquone AUC by 74% and the proguanil AUC by 38%. Consider alternative malaria prophylaxis or antiretroviral therapy. If used together, an increase in the atovaquone dose may be needed. The clinical significance and mechanism of this potential interaction are unknown. (Minor) The concurrent administration of ritonavir with atovaquone may result in decreased plasma levels of atovaquone. The clinical significance and mechanism of this potential interaction are unknown; the manufacturer states that an increase in atovaquone doses may be needed.
Metoclopramide: (Major) Avoid the concomitant use of metoclopramide and atovaquone. Metoclopramide may reduce the bioavailability of atovaquone. Use metoclopramide with atovaquone only if other antiemetics are not available.
Nirmatrelvir; Ritonavir: (Minor) The concurrent administration of ritonavir with atovaquone may result in decreased plasma levels of atovaquone. The clinical significance and mechanism of this potential interaction are unknown; the manufacturer states that an increase in atovaquone doses may be needed.
Omeprazole; Amoxicillin; Rifabutin: (Major) The administration of rifabutin with atovaquone is not recommended. Taking these drugs together reduces the average steady-state plasma concentrations of atovaquone and rifabutin by 34% and 19%, respectively. Dose adjustments have not been established. If these drugs are given together, instruct patient to take atovaquone with a fatty meal and monitor for decreased atovaquone efficacy.
Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Rifabutin: (Major) The administration of rifabutin with atovaquone is not recommended. Taking these drugs together reduces the average steady-state plasma concentrations of atovaquone and rifabutin by 34% and 19%, respectively. Dose adjustments have not been established. If these drugs are given together, instruct patient to take atovaquone with a fatty meal and monitor for decreased atovaquone efficacy.
Rifampin: (Major) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration. Other rifamycins, (e.g.; rifapentine) may exert similar effects on atovaquone pharmacokinetics, but data are not available.
Rifapentine: (Moderate) The administration of rifampin with atovaquone is not recommended, as rifampin is known to reduce atovaquone levels by 52%. Rifapentine may exert similar effects on atovaquone pharmacokinetics, but data are not available. In a small study of HIV-positive subjects, concomitant administration of oral rifampin with atovaquone suspension lead to a substantial decrease in average steady-state plasma atovaquone concentrations and a simultaneous increase in average steady-state plasma rifampin concentrations. The half-life of atovaquone decreased from 82 hours (without rifampin) to 50 hours during rifampin administration.
Ritonavir: (Minor) The concurrent administration of ritonavir with atovaquone may result in decreased plasma levels of atovaquone. The clinical significance and mechanism of this potential interaction are unknown; the manufacturer states that an increase in atovaquone doses may be needed.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance. (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs in a small number of HIV-positive subjects. This may not be of any clinical significance but should be used with caution.
Tetracycline: (Moderate) Concomitant use of tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline.
Trimethoprim: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance.
Zidovudine, ZDV: (Minor) Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine. Inhibition of zidovudine metabolism by atovaquone could result in an increase in zidovudine-induced adverse effects.

Atovaquone/Mepron Oral Susp: 5mL, 750mg

Doses of up to 3 g/day PO have been used.

Doses of up to 3 g/day PO have been used.

Doses of up to 3 g/day PO have been used.

> 2 years: Safety and efficacy have not been established; doses of up to 40 mg/kg/day (maximum 1.5 g/day) PO have been used for the treatment of Pneumocystis pneumonia infections.
<= 24 months: Safety and efficacy have not been established; doses of up to 45 mg/kg/day PO have been recommended for the treatment of Pneumocystis pneumonia infections.

>= 4 months: Safety and efficacy have not been established; doses of up to 45 mg/kg/day PO have been recommended for the treatment of Pneumocystis pneumonia infections.
1—3 months: Safety and efficacy have not been established; doses of up to 40 mg/kg/day PO have been recommended for the treatment of Pneumocystis pneumonia infections.

Safety and efficacy have not been established; doses of up to 40 mg/kg/day PO have been recommended for the treatment of Pneumocystis pneumonia infections.

Unlike other drugs currently used to treat PCP, atovaquone does not work by antagonizing folate. The antiprotozoal activity of atovaquone is probably related to its ability to selectively inhibit mitochondrial electron transport, leading to inhibition of pyrimidine synthesis. The site of action appears to be the cytochrome bc1 complex (complex III). This is the proposed site of action for Pneumocystis jiroveci (formerly Pneumocystis carinii), however the exact site of action in Toxoplasma gondii has not been investigated. The effect on pyrimidines is selective for protozoa, since these organisms cannot utilize preformed pyrimidines as can mammalian cells. A unique characteristic of atovaquone is that atovaquone can kill Pneumocystis organisms directly as opposed to inhibiting their growth as do other treatments.
 
Besides Pneumocystis, atovaquone is active against other protozoans including Plasmodium species, Toxoplasma gondii, Entamoeba histolytica, Trichomonas vaginalis, Leishmania species, and microsporidia. Although atovaquone has been successful for the treatment of falciparum malaria, recrudescence has occurred due to atovaquone-resistant organisms several weeks after therapy concluded.

Atovaquone is administered orally. Atovaquone is extensively bound to plasma proteins (99.9%) over the concentration range of 1 to 90 mcg/mL. After IV administration, the mean volume of distribution at steady-state was 0.6 +/- 0.17 L/kg. In 3 HIV-infected children, the CSF concentrations of atovaquone were less than 1% of plasma concentrations after 2 weeks of treatment. The metabolism of atovaquone is unknown. The mean plasma clearance of atovaquone after IV administration in 9 HIV-infected patients was 10.4 +/-5.5 mL/minute. More than 94% of the atovaquone dose was recovered in the feces unchanged over 21 days. The mean half-life of atovaquone ranged from 67 +/- 33.4 to 77.6 +/- 23.1 hours after oral administration. The half-life of atovaquone is due to presumed enterohepatic cycling and eventual fecal elimination.[28830]
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Atovaquone is a highly lipophilic compound with low aqueous solubility. Under fed conditions, the bioavailability of atovaquone suspension is 47% +/- 15%. Plasma concentrations do not increase proportionally with dose after ascending repeat-dose administration of atovaquone oral suspension. Administering atovaquone oral suspension with food enhances its bioavailability. The mean atovaquone AUC increased by 2.6-fold under fed conditions (n = 16). When atovaquone oral suspension was administered to 5 HIV-infected patients at a dose of 750 mg PO twice daily, the mean steady-state plasma atovaquone concentration was 21 +/- 4.9 mcg/mL, and the mean Cmax was 24 +/- 5.7 mcg/mL. Another study of 18 HIV-infected patients administered atovaquone oral suspension 750 mg PO twice daily with meals resulted in a mean steady-state plasma concentration of 22 +/- 10.1 mcg/mL. In a comparative clinical trial with atovaquone tablets 750 mg PO 3 times daily for 21 days for the treatment of mild-to-moderate Pneumocystis pneumonitis in HIV-infected patients, the relationship between successful treatment outcome and atovaquone plasma concentrations (n = 113) is 0% for 0 to less than 5 mcg/mL, 69% for 5 to less than 10 mcg/mL, 79% for 10 to less than 15 mcg/mL, 95% for 15 to less than 20 mcg/mL, and 100% for more than 20 mcg/mL.[28830]

Available data from postmarketing experience with atovaquone use during pregnancy are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women with HIV who are infected with Pneumocystis pneumonia (PCP) are at increased risk of adverse pregnancy outcomes, such as severe illness and maternal death associated with PCP, compared with non-pregnant women.[28830] Although data are limited, guidelines suggest that atovaquone may be considered in pregnant patients for PCP infection prophylaxis or treatment as preclinical studies have not demonstrated toxicity.[34362] In animal studies, fetal malformations were not observed when atovaquone was given during organogenesis at plasma concentrations up to 0.5 to 3 times the estimated human exposure based on steady-state plasma concentrations.[28830]

There are no data on the presence of atovaquone in human breast milk, the effects on the breast-fed child, or the effects on milk production. Atovaquone was detected in rat milk when lactating rats were given oral atovaquone. Because of the potential for HIV transmission to HIV-negative infants, advise HIV-infected mothers against breast-feeding if they are taking atovaquone for the prevention or treatment of Pneumocystis pneumonia (PCP).[28830] [46675]