Drug Interactions between atovaquone / proguanil and quinapril

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

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ADJUST DOSING INTERVAL: Food, particularly high-fat food, significantly enhances the oral absorption and bioavailability of atovaquone. In 16 healthy volunteers, administration of a single 750 mg dose of atovaquone suspension following a standard breakfast (23 g fat: 610 kCal) resulted in an approximately 3.4-fold increase in the mean peak plasma concentration (Cmax) and a 2.5-fold increase in the mean area under the plasma concentration-time curve (AUC) of atovaquone compared to administration following an overnight fast. In a study consisting of 19 HIV-infected volunteers receiving atovaquone suspension 500 mg/day, Cmax and AUC of atovaquone increased by 72% and 66%, respectively, in the fed state relative to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atovaquone products (suspension, tablet, or in combination with proguanil) should be administered with a meal or milky drink, or enteral nutrition at the same time(s) each day. Because plasma atovaquone concentrations have been shown to correlate with the likelihood of successful treatment and in some cases, survival, alternative therapies may be appropriate for patients who have difficulty taking atovaquone with food.

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MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

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