Drug Interaction Report

MONITOR: Pregabalin has been associated with the development of angioedema, and coadministration with other drugs that are also known to cause angioedema (e.g., ACE inhibitors, angiotensin II receptor antagonists, renin inhibitors) may theoretically increase the risk. There have been postmarketing reports of angioedema in patients during initial and chronic treatment with pregabalin, some without a prior history of angioedema. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). In some cases, the angioedema led to life-threatening respiratory compromise that required emergency treatment.

MANAGEMENT: Clinicians and patients should be aware of the potential for increased risk of angioedema when pregabalin is prescribed with other drugs that are also known to cause angioedema. Patients should be advised to promptly discontinue these medications and seek medical attention if they develop signs or symptoms suggestive of angioedema such as swelling of the face, extremities, eyes, lips, or tongue, and difficulty swallowing or breathing.

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.