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U.S. Department of Health and Human Services

Safety

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Lotrel (amlodipine besylate and benazepril hydrochloride) tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) – June 2011 and October 2012

 

October 2012

Summary View

 

CONTRAINDICATIONS

  • Do not co-administer aliskiren with angiotensin receptor blockers, ACE inhibitors, including Lotrel in patients with diabetes.
 

WARNINGS AND PRECAUTIONS

Patients with Aortic and Mitral Valve Stenosis, Obstructive Hypertrophic Cardiomyopathy

  • As with all other vasodilators, special caution is required when using amlodipine in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

Hepatitis and Hepatic Failure

  • There have been rare reports of predominantly cholestatic hepatitis and isolated cases of acute liver failure, some of them fatal, in patients on ACE inhibitors. The mechanism is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevation of hepatic enzymes should discontinue the ACE inhibitor and be kept under medical surveillance.

Impaired Renal Function

  • Monitor renal function periodically in patients treated with Lotrel. Changes in renal function, including acute renal failure, can be caused by drugs that affect the renin-angiotensin system. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, severe heart failure, post-myocardial infarction or volume depletion) or who are on NSAIDS or angiotensin receptor blockers may be at particular risk of developing acute renal failure on Lotrel. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Lotrel.

Hyperkalemia

  • Monitor serum potassium periodically in patients receiving Lotrel. Drugs that affect the renin-angiotensin system can cause hyperkalemia.
 

ADVERSE REACTIONS

Postmarketing-Experience
  • Paresthesia, dysgeusia, orthostatic symptoms and hypotension, angina pectoris and arrhythmia, pruritus, photosensitivity reaction, arthralgia, arthritis, myalgia, BUN increase, serum creatinine increased, renal impairment, impaired vision, agranulocytosis, neutropenia.
  • Rare reports in association with use of amlodipine: gingival hyperplasia, tachycardia, jaundice, and hepatic enzyme elevations (mostly consistent with cholestasis severe enough to require hospitalization) leucocytopenia, allergic reaction, hyperglycemia, dysgeusia, hypoestheia, paresthesia, syncope, peripheral neuropathy, hypertonia, visual impairment, diplopia, hypotension, vasculitis, rhinitis, gastritis, hyperhidrosis, pruritis, skin discoloration, urticaria, erythema multiform, muscle spasms, arthralgia, micturition disorder, nocturia, erectile dysfunction, malaise, weight decrease or gain.
 

DRUG INTERACTIONS

Amlodipine
  • Simvastatin: Co-administration 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: Co-administration 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 co-administered 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 co-administered with CYP3A4 inducers.
Benazapril
Dual Blockade of the Renin-Angiotensin System (RAS):
  • Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on Lotrel and other agents that block the RAS.
  • Do not co-administer aliskiren with Lotrel in patients with diabetes. Avoid use of aliskiren with Lotrel in patients with renal impairment (GFR <60 ml/min).
 

USE IN SPECIFIC POPULATIONS

Geriatric Use
  • In geriatrics, exposure to amlodipine is increased, thus consider lower initial doses of Lotrel
Hepatic Impairment
  • Exposure to amlodipine is increased in patients with hepatic insufficiency, thus consider using lower doses of Lotrel
Renal Impairment
  • In patients with severe renal impairment systemic exposure to benazepril is increased. The recommended dose of benazepril in this subgroup is 5 mg which is not an available strength with Lotrel. Lotrel is not recommended in patients with severe renal impairment. No dose adjustment of Lotrel is needed in patients with mild or moderate impairment of renal function.
 

OVERDOSAGE

Treatment:
  • Patients should be admitted to hospital and, generally, should be managed in an intensive care setting, with continuous monitoring of cardiac function, blood gases, and blood biochemistry. Emergency supportive measures such as artificial ventilation or cardiac pacing should be instituted if appropriate.
  • In the event of a potentially life-threatening oral overdose, use induction of vomiting or gastric lavage and/or activated charcoal to remove the drug from the gastrointestinal tract (only if presented within 1 hour after ingestion of Lotrel).
  • Other clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care.

 

June 2011

Summary View

 

*NSAID interaction

 

DRUG INTERACTIONS

Non-Steroidal Anti-Inflammatory Agents 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, co-administration 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.