Amlodipine Mechanism of Action

Review the mechanism of action of amlodipine—a component of TWYNSTA, a fixed-dose ARB/CCB combining telmisartan and amlodipine for the treatment of hypertension

Review the mechanism of action of amlodipine—a component of TWYNSTA, the only ARB/CCB combining telmisartan and amlodipine for the treatment of hypertension
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels.

Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and a reduction in blood pressure.

References
1. Twynsta PI. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2009.
2. Data on file. Study 1235.1. Boehringer Ingelheim Pharmaceuticals, Inc.

Reductions that help patients reach their blood pressure target.1, 2

Review study results

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INDICATION

Twynsta® (telmisartan/amlodipine) tablets is an angiotensin II receptor blocker (ARB) and a dihydropyridine calcium channel blocker (DHP-CCB) combination product indicated for the treatment of hypertension, alone or with other antihypertensive agents. It may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Base the choice of TWYNSTA tablets as initial therapy for hypertension on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of TWYNSTA tablets. Consider the patient's baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy when deciding whether to use TWYNSTA tablets as initial therapy.

IMPORTANT SAFETY INFORMATION

WARNING: AVOID USE IN PREGNANCY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue TWYNSTA as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.

TWYNSTA is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan or amlodipine or any other components of this product.

Symptomatic hypotension may occur in patients with an activated renin-angiotensin system. Correct volume and/or salt depletion in patients before initiating TWYNSTA or start treatment under close supervision with a reduced dose.

Patients taking TWYNSTA should be told not to use potassium supplements or salt substitutes that contain potassium without consulting their physician. Consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances.

Titrate slowly in patients with hepatic or severe renal impairment and closely monitor. Initial therapy with TWYNSTA is not recommended in hepatically impaired patients.

In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system such as patients with severe congestive heart failure or renal dysfunction, treatment with ACE inhibitors and an ARB such as TWYNSTA has been associated with oliguria and/or progressive azotemia and, rarely, with acute renal failure and/or death. In patients with renal artery stenosis, increases in serum creatinine or blood urea nitrogen may occur. When adding an ACE inhibitor to an ARB, monitor renal function closely. Use of TWYNSTA with ramipril is not recommended.

Uncommonly, patients starting or increasing their dose of a CCB have developed increased frequency, duration, or severity of angina or acute myocardial infarction.

Monitor patients with heart failure for worsening of their condition.

In clinical trials, the most common reasons for discontinuation of therapy with TWYNSTA were peripheral edema, dizziness, and hypotension. Adverse events that occurred at a ≥2% higher incidence with TWYNSTA than with placebo were peripheral edema, dizziness, and back pain.

Please see full Prescribing Information, including boxed WARNING, for TWYNSTA.



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