Pharmaceutical Approval Update

Pharmaceutical Approval Update

Amlodipine/Olmesartan Medoxomil (Azor)

Manufacturer: Daiichi Sankyo, Parsippany, NJ

Indication: besylate plus olmesartan medoxomil is indicated for the treatment of hypertension, alone or with other antihypertensive agents. It is not indicated for the initial therapy of hypertension.

Drug Class: This product combines the complementary actions of the calcium-channel blocker generic amlodipine, which inhibits the entrance of calcium into the blood vessel walls, and of those of olmesartan, which blocks angiotensin II receptors. Angiotensin II is a hormone that causes blood vessels to constrict.

Uniqueness of Drug: Azor relaxes the blood vessels so that blood can flow more easily. The two agents have been found to produce significant mean reductions in systolic and diastolic blood pressure in patients with hypertension.

Black-Box Warning: When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, Azor should be discontinued as soon as possible.

Warnings and Precautions: In volume-depleted or salt-depleted patients, symptomatic hypotension resulting from the olmesartan component in particular may occur after the drug is initiated. Treatment should start with patients under close medical supervision.

Patients, particularly those with severe obstructive coronary artery disease, may experience an increased frequency, duration, or severity of angina or acute myocardial infarction (MI) when beginning calcium-channel blocker therapy.

In studies of angiotensin-converting enzyme (ACE)-inhib-itors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. No data are available for the long-term use of olmesartan in patients with unilateral or bilateral renal artery stenosis, but similar effects would be expected with amlodipine/olmesartan because of the olmesartan component.

Because amlodipine drug is extensively metabolized by the liver and the plasma elimination half-life is 56 hours in patients with severely impaired hepatic function, caution should be exercised in patients with severe hepatic impairment.

The only adverse event that occurred in more than 3% of treated patients, and more frequently than with placebo, was edema (22.2°% with Azor vs. 12.3°% with placebo).

Safety Information about Olmesartan:

Use in Pregnancy: Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus when they are used in pregnancy during the second and third trimesters. When pregnancy is confirmed, should be discontinued as soon as possible.

Hypotension in Volume- or Salt-Depleted Patients: In patients with an activated renin-angiotensin system, such as those with volume or salt depletion (e.g., if they are receiving high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Azor. Treatment should be initiated with patients under close medical supervision. If hypotension occurs, the patient should be placed in the supine position and, if necessary, should be given an intravenous (IV) infusion of normal saline solution. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty after the blood pressure has stabilized.

Impaired Renal Function: In studies of ACE-inhibitors in patients with unilateral or bilateral renal artery stenosis, elevated serum creatinine or BUN levels have been reported. There are no data on the long-term use of olmesartan in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.

Dosage and Administration: Azor may be substituted for its individually titrated components for patients receiving amlodipine and olmesartan. Azor may also be used as add-on therapy for patients whose hypertension is not adequately controlled with or olmesartan therapy.

The dosage may be increased after two weeks to a maximum dose of 10/40 mg once daily, usually, with one component increased at a time. The amounts of both components may be raised to achieve more rapid control. Maximum anti-hypertensive effects are attained within two weeks after a change in the dose.

Azor tablets are formulated for oral administration as shown in Table 1. The dosage may be increased after two weeks. The maximum recommended dose of the combination product is 10/40 mg.

Table 1 Amlodipine/Olmesartan Medoxomil (Azor) Formulations

5/20

5/40

10/20

10/40

mg

mg

mg

mg

Amlodipine equivalent

5

5

10

10

Olmesartan medoxomil
equivalent

20

40

20

40

Commentary: Hypertension is one of the most prevalent conditions in the U.S. It affects almost one in three American adults and about one billion people worldwide. It is often difficult to control. Only about 35% of patients with a diagnosis of high blood pressure have the condition under control.

Both components of Azor have established clinical efficacy and a favorable side-effect profile. The product provides two complementary mechanisms of action to lower blood pressure. Together the two medications relax the blood vessels so that blood can flow more effectively. The combination should give physicians a new option for treating blood pressure that remains too high with currently prescribed drugs.

Category: Main

Tags: Amlodipine, Medoxomil

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