ATOVAQUONE Drug Interactions: What You Need to Know

INTERACTIONS 7 DRUG INTERACTIONS

7.1 Rifampin/Rifabutin Concomitant administration of rifampin or rifabutin and atovaquone oral suspension is known to reduce atovaquone concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology (Section 12.3)]</span>. Concomitant administration of atovaquone oral suspension and rifampin or rifabutin is not recommended.

7.2 Tetracycline Concomitant administration of tetracycline and atovaquone oral suspension has been associated with a reduction in plasma concen- trations of atovaquone <span class="opacity-50 text-xs">[see Clinical Pharmacology (Section 12.3)]</span> . Caution should be used when prescribing tetracycline concomitant- ly with atovaquone oral suspension. Monitor patients for potential loss of efficacy of atovaquone if coadministration is necessary.

7.3 Metoclopramide Metoclopramide may reduce the bioavailability of atovaquone and should be used only if other antiemetics are not available <span class="opacity-50 text-xs">[see Clinical Pharmacology (Section 12.3)]</span>.

7.4 Indinavir Concomitant administration of atovaquone and indinavir did not result in any change in the steady-state AUC and C max of indinavir but resulted in a decrease in the C trough of indinavir <span class="opacity-50 text-xs">[see Clinical Pharmacology (Section 12.3)]</span>. Caution should be exercised when prescribing atovaquone oral 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 oral suspension is necessary. -------------------- DRUG INTERACTIONS ------------------------ Concomitant administration of rifampin or rifabutin reduces atovaquone concentrations; concomitant use with atovaquone oral suspension is not recommended. (7.1) Concomitant administration of tetracycline reduces atovaquone concentrations; use caution when co-administering. Monitor patients for potential loss of efficacy of atovaquone if co-administration of tetracycline is necessary. (7.2) Concomitant administration with metoclopramide reduces atovaquone concentrations; administer concomitantly only if other antiemetics are not available. (7.3) Concomitant administration of indinavir reduces indinavir trough concentrations; use caution when co-administering. Monitor patients for potential loss of efficacy of indinavir if co-administration is necessary. (7.4)

7.1 Rifampin/Rifabutin Concomitant administration of rifampin or rifabutin and atovaquone oral suspension is known to reduce atovaquone concentrations <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>. Concomitant administration of atovaquone oral suspension and rifampin or rifabutin is not recommended.

7.2 Tetracycline Concomitant administration of tetracycline and atovaquone oral suspension has been associated with a reduction in plasma concentrations of atovaquone <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>. Caution should be used when prescribing tetracycline concomitantly with atovaquone oral suspension. Monitor patients for potential loss of efficacy of atovaquone if co-administration is necessary.

7.3 Metoclopramide Metoclopramide may reduce the bioavailability of atovaquone and should be used only if other antiemetics are not available <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3)]</span>.

7.4 Indinavir Concomitant administration of atovaquone and indinavir did not result in any change in the steady-state AUC and C max of indinavir but resulted in a decrease in the C trough of indinavir <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3)]</span>. Caution should be exercised when prescribing atovaquone oral suspension with indinavir due to the decrease in trough concentrations of indinavir. Monitor patients for potential loss of efficacy of indinavir if co-administration with atovaquone oral suspension is necessary.

4 CONTRAINDICATIONS

• Known serious hypersensitivity reactions to atovaquone or proguanil hydrochloride or any component of the formulation. ( 4.1 )
• Prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min). ( 4.2 )

4.1 Hypersensitivity Atovaquone and proguanil hydrochloride is contraindicated in individuals with known hypersensitivity reactions (e.g., anaphylaxis, erythema multiforme or Stevens-Johnson syndrome, angioedema, vasculitis) to atovaquone or proguanil hydrochloride or any component of the formulation.

4.2 Severe Renal Impairment Atovaquone and proguanil hydrochloride is contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance &lt;30 mL/min) because of pancytopenia in patients with severe renal impairment treated with proguanil <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )]</span>

AND PRECAUTIONS

• Atovaquone absorption may be reduced in patients with diarrhea or vomiting. If used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required. ( 5.1 )
• In mixed P. falciparum and Plasmodium vivax infection, P. vivax relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride tablets alone. ( 5.2 )
• In the event of recrudescent P. falciparum infections after treatment or prophylaxis failure, patients should be treated with a different blood schizonticide. ( 5.2 )
• Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use. ( 5.3 )
• Atovaquone and proguanil hydrochloride tablets have not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria. Patients with severe malaria are not candidates for oral therapy. ( 5.4 )

5.1 Vomiting and Diarrhea Absorption of atovaquone may be reduced in patients with diarrhea or vomiting. If atovaquone and proguanil hydrochloride tablets are used in patients who are vomiting, parasitemia should be closely monitored and the use of an antiemetic considered <span class="opacity-50 text-xs">[see Dosage and Administration (2) ]</span>. Vomiting occurred in up to 19% of pediatric patients given treatment doses of atovaquone and proguanil hydrochloride tablets. In the controlled clinical trials, 15.3% of adults received an antiemetic when they received atovaquone/proguanil and 98.3% of these patients were successfully treated. In patients with severe or persistent diarrhea or vomiting, alternative antimalarial therapy may be required.

5.2 Relapse of Infection In mixed P. falciparum and Plasmodium vivax infections, P. vivax parasite relapse occurred commonly when patients were treated with atovaquone and proguanil hydrochloride tablets alone. In the event of recrudescent P. falciparum infections after treatment with atovaquone and proguanil hydrochloride tablets or failure of chemoprophylaxis with atovaquone and proguanil hydrochloride tablets, patients should be treated with a different blood schizonticide.

5.3 Hepatotoxicity Elevated liver laboratory tests and cases of hepatitis and hepatic failure requiring liver transplantation have been reported with prophylactic use of atovaquone and proguanil hydrochloride tablets.

5.4 Severe or Complicated Malaria Atovaquone and proguanil hydrochloride tablets have not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria, including hyperparasitemia, pulmonary edema, or renal failure. Patients with severe malaria are not candidates for oral therapy.