Aliskiren/amlodipine Disease Interactions

The use of aliskiren is contraindicated in patients with diabetes who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), as there is an increased risk of renal impairment, hyperkalemia, and hypotension.

In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

Increased frequency, duration, and/or severity of angina, as well as acute myocardial infarction, have rarely developed during initiation or dosage increase of calcium channel blockers (CCBs), particularly in patients with severe obstructive coronary artery disease and those treated with immediate-release formulations. The mechanism of this effect is not established. Therapy with CCBs should be administered cautiously in patients with significant coronary artery disease.

Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, some patients have developed cholestasis or hepatocellular injury. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function is advised.

Symptomatic hypotension may occur after treatment initiation with aliskiren in patients with marked volume depletion, salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system. It is recommended to correct the volume or salt depletion before administering aliskiren. Close monitoring is recommended.

Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.

Calcium channel blockers (CCBs) may have varying degrees of negative inotropic effect. Congestive heart failure (CHF), worsening of CHF, and pulmonary edema have occurred in some patients treated with a CCB, primarily verapamil. Some CCBs have also caused mild to moderate peripheral edema due to localized vasodilation of dependent arterioles and small blood vessels, which can be confused with the effects of increasing left ventricular dysfunction. Although some CCBs have been used in the treatment of CHF, therapy with CCBs should be administered cautiously in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, caution is advised in patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened by administration of a CCB.