Amlodipine and benazepril

Potassium supplements/potassium-sparing diuretics: hyperkalemia (7.1) Lithium: Increased serum lithium levels; toxicity symptoms (7.1) Injectable gold: facial flushing, nausea, vomiting, hypotension (7.1) Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Risk of renal dysfunction, loss of antihypertensive effect (7.1) Do not exceed doses greater than 20 mg daily of simvastatin (7.1) mTOR inhibitors: increased risk of angioedema (7.1) Dual inhibition of the RAS: Increased risk of renal impairment, hypotension, and hyperkalemia (7.1) Neprilysin inhibitors: increased risk of angioedema (7.1)

7.1 Drug/Drug Interactions Amlodipine Simvastatin : Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. CYP3A4 Inhibitors: Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A4 inhibitors to determine the need for dose adjustment. CYP3A4 Inducers : No information is available on the quantitative effects of CYP3A4 inducers on amlodipine.

Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers (e.g. rifampicin, St. John’s Wort). Benazepril Potassium Supplements and Potassium-Sparing Diuretics: Benazepril can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. If concomitant use of such agents is indicated, the patient’s serum potassium should be monitored frequently. Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium.

When coadministering amlodipine and benazepril hydrochloride and lithium, frequent monitoring of serum lithium levels is recommended. Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including benazepril, may be attenuated by NSAIDs.

Antidiabetic Agents: In rare cases, diabetic patients receiving an ACE inhibitor (including benazepril) concomitantly with insulin or oral antidiabetics may develop hypoglycemia. Such patients should therefore be advised about the possibility of hypoglycemic reactions and should be monitored accordingly. Mammalian Target of Rapamycin (mTOR) Inhibitors : The risk of angioedema may be increased in patients receiving coadministration of ACE inhibitors and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus).

Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on amlodipine and benazepril hydrochloride and other agents that block the RAS.

Do not coadminister aliskiren with amlodipine and benazepril hydrochloride in patients with diabetes. Avoid use of aliskiren with amlodipine and benazepril hydrochloride in patients with renal impairment [glomerular filtration rate (GFR) < 60 mL/min]. Neprilysin Inhibitor: Patients taking concomitant neprilysin inhibitors may be at increased risk for angioedema [see Warnings and Precautions (5.1)] .