Azor (Amlodipine/olmesartan) is indicated for the treatment of hypertension, alone or with other antihypertensive agents  , to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Azor (Amlodipine/olmesartan) .

 Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

 Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

 Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

 Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Azor (Amlodipine/olmesartan) may also be used as initial therapy in patients who are likely to need multiple antihypertensive agents to achieve their blood pressure goals.

Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. The decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. Individual blood pressure goals may vary based upon the patient’s risk.

Data from an 8-week, placebo-controlled, parallel-group factorial study [see ] provide estimates of the probability of reaching a blood pressure goal with Azor (Amlodipine/olmesartan) compared to amlodipine or olmesartan medoxomil monotherapy. The figures below provide estimates of the likelihood of achieving the targeted systolic or diastolic blood pressure goals with Azor (Amlodipine/olmesartan) 10/40 mg compared with amlodipine or olmesartan medoxomil monotherapy, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling from all available data of that treatment group. The right tail of each curve is less reliable because of small numbers of subjects with high baseline blood pressures.

The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal (e.g., Week 8 SBP

 For example, a patient with a baseline blood pressure of 160/100 mmHg has about a 48% likelihood of achieving a goal of

The side effects of olmesartan medoxomil are generally rare and apparently independent of dose. Those of amlodipine are generally dose-dependent (mostly edema).

Maximum antihypertensive effects are attained within 2 weeks after a change in dose.

Azor (Amlodipine/olmesartan) may be taken with or without food.

Azor (Amlodipine/olmesartan) may be administered with other antihypertensive agents.

Dosage may be increased after 2 weeks. The maximum recommended dose of Azor (Amlodipine/olmesartan) is 10/40 mg.

Azor (Amlodipine/olmesartan) may be substituted for its individually titrated components.

When substituting for individual components, the dose of one or both of the components can be increased if blood pressure control has not been satisfactory.

Azor (Amlodipine/olmesartan) may be used to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with olmesartan medoxomil (or another angiotensin receptor blocker) alone.

Azor (Amlodipine/olmesartan) tablets are formulated for oral administration in the following strength combinations:

None.

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Olmesartan medoxomil
During the second and third trimesters of pregnancy, these drugs have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.

These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should have the patient discontinue the use of Azor (Amlodipine/olmesartan) as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to a drug acting on the renin-angiotensin system will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses and serial ultrasound examinations should be performed to assess the intra-amniotic environment.

If oligohydramnios is observed, discontinue Azor (Amlodipine/olmesartan) unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.

No teratogenic effects were observed when olmesartan medoxomil was administered to pregnant rats at oral doses up to 1000 mg/kg/day (240 times the maximum recommended human dose (MRHD) on a mg/m basis) or pregnant rabbits at oral doses up to 1 mg/kg/day (half the MRHD on a mg/m basis; higher doses could not be evaluated for effects on fetal development as they were lethal to the does). In rats, significant decreases in pup birth weight and weight gain were observed at doses ≥1.6 mg/kg/day, and delays in developmental milestones (delayed separation of ear auricular, eruption of lower incisors, appearance of abdominal hair, descent of testes, and separation of eyelids) and dose-dependent increases in the incidence of dilation of the renal pelvis were observed at doses ≥8 mg/kg/day. The no observed effect dose for developmental toxicity in rats is 0.3 mg/kg/day, about one-tenth the MRHD of 40 mg/day.

Olmesartan medoxomil

Amlodipine

Amlodipine

Azor (Amlodipine/olmesartan) .
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar effects would be expected with olmesartan medoxomil and Azor (Amlodipine/olmesartan) .

Amlodipine
1/2
Azor (Amlodipine/olmesartan)
Amlodipine
(6.2)
Olmesartan medoxomil

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Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to Azor (Amlodipine/olmesartan) in more than 1600 patients including more than 1000 exposed for at least 6 months and more than 700 exposed for 1 year. Azor (Amlodipine/olmesartan) was studied in one placebo-controlled factorial trial (see ). The population had a mean age of 54 years and included approximately 55% males. Seventy-one percent were Caucasian and 25% were Black. Patients received doses ranging from 5/20 mg to 10/40 mg orally once daily.

The overall incidence of adverse reactions on therapy with Azor (Amlodipine/olmesartan) was similar to that seen with corresponding doses of the individual components of Azor (Amlodipine/olmesartan) , and to placebo. The reported adverse reactions were generally mild and seldom led to discontinuation of treatment (2.6% for Azor (Amlodipine/olmesartan) and 6.8% for placebo).

Edema is a known, dose-dependent adverse effect of amlodipine but not of olmesartan medoxomil.

The placebo-subtracted incidence of edema during the 8-week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was significantly reduced when 20 mg or 40 mg of olmesartan medoxomil was added to the 10 mg amlodipine dose.

*12.3% = actual placebo incidence

Across all treatment groups, the frequency of edema was generally higher in women than men, as has been observed in previous studies of amlodipine.

Adverse reactions seen at lower rates during the double-blind period also occurred in the patients treated with Azor (Amlodipine/olmesartan) at about the same or greater incidence as in patients receiving placebo. These included hypotension, orthostatic hypotension, rash, pruritus, palpitation, urinary frequency, and nocturia.

The adverse event profile obtained from 44 weeks of open-label combination therapy with amlodipine plus olmesartan medoxomil was similar to that observed during the 8-week, double-blind, placebo-controlled period.

Initial Therapy
Analyzing the data described above specifically for initial therapy, it was observed that higher doses of Azor (Amlodipine/olmesartan) caused slightly more hypotension and orthostatic symptoms, but not at the recommended starting dose of Azor (Amlodipine/olmesartan) 5/20 mg. No increase in the incidence of syncope or near syncope was observed. The incidences of discontinuation because of any treatment emergent adverse events in the double blind phase are summarized in the table below.

Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1730) in doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine due to adverse reactions was required in only about 1.5% of amlodipine-treated patients and about 1% of placebo-treated patients. The most common side effects were headache and edema. The incidence (%) of dose-related side effects was as follows:

For several adverse experiences that appear to be drug- and dose-related, there was a greater incidence in women than men associated with amlodipine treatment as shown in the following table;

Olmesartan medoxomil has been evaluated for safety in more than 3825 patients/subjects, including more than 3275 patients treated for hypertension in controlled trials. This experience included about 900 patients treated for at least 6 months and more than 525 for at least 1 year. Treatment with olmesartan medoxomil was well tolerated, with an incidence of adverse events similar to that seen with placebo. Events were generally mild, transient, and without relationship to the dose of olmesartan medoxomil.

The overall frequency of adverse events was not dose-related. Analysis of gender, age, and race groups demonstrated no differences between olmesartan medoxomil- and placebo-treated patients. The rate of withdrawals due to adverse events in all trials of hypertensive patients was 2.4% (i.e., 79/3278) of patients treated with olmesartan medoxomil and 2.7% (i.e., 32/1179) of control patients. In placebo-controlled trials, the only adverse event that occurred in more than 1% of patients treated with olmesartan medoxomil and at a higher incidence in olmesartan medoxomil treated patients vs. placebo was dizziness (3% vs 1%).

The following adverse reactions have been identified during post-approval use of the individual components of Azor (Amlodipine/olmesartan) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Amlodipine.
Olmesartan medoxomil.
        asthenia, angioedema        vomiting        rhabdomyolysis        acute renal failure        alopecia, pruritus, urticaria

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The pharmacokinetics of amlodipine and olmesartan medoxomil are not altered when the drugs are co-administered.

No drug interaction studies have been conducted with Azor (Amlodipine/olmesartan) and other drugs, although studies have been conducted with the individual amlodipine and olmesartan medoxomil components of Azor (Amlodipine/olmesartan) , as described below, and no significant drug interactions have been observed.

In vitro
Effect of Other Agents on Amlodipine
    Co-administration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine.    Co-administration of 240 mL of grapefruit juice with a single oral dose of amlodipine 10 mg in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.    Co-administration of the antacid Maalox with a single dose of amlodipine had no significant effect on the pharmacokinetics of amlodipine.    A single 100 mg dose of sildenafil in subjects with essential hypertension had no effect on the pharmacokinetic parameters of amlodipine. When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect.

Effect of Amlodipine on Other Agents
   Co-administration of multiple 10 mg doses of amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady state pharmacokinetic parameters of atorvastatin.   Co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.   Single and multiple 10 mg doses of amlodipine had no significant effect on the pharmacokinetics of ethanol.   Co-administration of amlodipine with warfarin did not change the warfarin prothrombin response time.

In clinical trials, amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.

No significant drug interactions were reported in studies in which olmesartan medoxomil was co-administered with digoxin or warfarin in healthy volunteers.

The bioavailability of olmesartan medoxomil was not significantly altered by the co-administration of antacids [Al(OH)/Mg(OH)].

Olmesartan medoxomil is not metabolized by the cytochrome P450 system and has no effects on P450 enzymes; thus, interactions with drugs that inhibit, induce, or are metabolized by those enzymes are not expected.

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Amlodipine.
2
The safety and effectiveness of Azor (Amlodipine/olmesartan) in pediatric patients have not been established.

Amlodipine.
Olmesartan medoxomil.
Of the total number of subjects in the double-blind clinical study of Azor (Amlodipine/olmesartan) , 20% (384/1940) were 65 years of age or older and 3% (62/1940) were 75 years or older. No overall differences in safety or effectiveness were observed between subjects 65 years of age or older and younger subjects.

Elderly patients have decreased clearance of amlodipine. Starting amlodipine or adding amlodipine at 2.5 mg in patients ≥75 years old is recommended. The lowest dose of Azor (Amlodipine/olmesartan) is 5/20 mg; therefore, initial therapy with Azor (Amlodipine/olmesartan) is not recommended in patients ≥75 years old.

Amlodipine.
Olmesartan medoxomil.
There are no studies of Azor (Amlodipine/olmesartan) in patients with hepatic insufficiency, but both amlodipine and olmesartan medoxomil show moderate increases in exposure in patients with hepatic impairment. Use caution when administering Azor (Amlodipine/olmesartan) to patients with severe hepatic impairment.

Patients with hepatic impairment have decreased clearance of amlodipine. Starting amlodipine or adding amlodipine at 2.5 mg in patients with hepatic impairment is recommended. The lowest dose of Azor (Amlodipine/olmesartan) is 5/20 mg; therefore, initial therapy with Azor (Amlodipine/olmesartan) is not recommended in hepatically impaired patients.

There are no studies of Azor (Amlodipine/olmesartan) in patients with renal impairment.

Amlodipine.
Olmesartan medoxomil.

There is no information on overdosage with Azor (Amlodipine/olmesartan) in humans.

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited.

If massive overdose should occur, active cardiac and respiratory monitoring should be instituted. Frequent blood pressure measurements are essential. Should hypotension occur, cardiovascular support including elevation of the extremities and the judicious administration of fluids should be initiated. If hypotension remains unresponsive to these conservative measures, administration of vasopressors (such as phenylephrine) should be considered with attention to circulating volume and urine output. Intravenous calcium gluconate may help to reverse the effects of calcium entry blockade. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Azor (Amlodipine/olmesartan) is a combination of the calcium channel receptor blocker (CCB) amlodipine besylate and the angiotensin II receptor blocker (ARB) olmesartan medoxomil.

The amlodipine besylate component of Azor (Amlodipine/olmesartan) is chemically described as 3-ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. Its empirical formula is CHCINO•CHOS.

Olmesartan medoxomil, a prodrug, is hydrolyzed to olmesartan during absorption from the gastrointestinal tract.

The olmesartan medoxomil component of Azor (Amlodipine/olmesartan) is chemically described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(1-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate. Its empirical formula is CHNO.

The structural formula for amlodipine besylate is:

The structural formula for olmesartan medoxomil is:

Azor (Amlodipine/olmesartan) contains amlodipine besylate, a white to off-white crystalline powder, and olmesartan medoxomil, a white to light yellowish-white powder or crystalline powder. The molecular weights of amlodipine besylate and olmesartan medoxomil are 567.1 and 558.59, respectively. Amlodipine besylate is slightly soluble in water and sparingly soluble in ethanol. Olmesartan medoxomil is practically insoluble in water and sparingly soluble in methanol.

Each tablet of Azor (Amlodipine/olmesartan) also contains the following inactive ingredients: silicified microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, and magnesium stearate. The color coatings contain polyvinyl alcohol, macrogol/polyethylene glycol 3350, titanium dioxide, talc, iron oxide yellow (5/40 mg, 10/20 mg, 10/40 mg tablets), iron oxide red (10/20 mg and 10/40 mg tablets), and iron oxide black (10/20 mg tablets).

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

Olmesartan medoxomil.
1
An AT receptor is found also in many tissues, but this receptor is not known to be associated with cardiovascular homeostasis. Olmesartan has more than a 12,500-fold greater affinity for the AT receptor than for the AT receptor.

Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is a mechanism of many drugs used to treat hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because olmesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known.

Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II levels do not overcome the effect of olmesartan on blood pressure.

Amlodipine.
With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105-114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90-104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/-2 mmHg).

In hypertensive patients with normal renal function, therapeutic doses of amlodipine resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria.

As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In hemodynamic studies, amlodipine has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered with beta-blockers to man. Similar findings, however, have been observed in normals or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.

Amlodipine does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In clinical studies in which amlodipine was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed.

Olmesartan medoxomil.
Plasma concentrations of angiotensin I and angiotensin II and plasma renin activity (PRA) increase after single and repeated administration of olmesartan medoxomil to healthy subjects and hypertensive patients. Repeated administration of up to 80 mg olmesartan medoxomil had minimal influence on aldosterone levels and no effect on serum potassium.

The pharmacokinetics of amlodipine and olmesartan medoxomil from Azor (Amlodipine/olmesartan) are equivalent to the pharmacokinetics of amlodipine and olmesartan medoxomil when administered separately. The bioavailability of both components is well below 100%, but neither component is affected by food. The effective half-lives of amlodipine (45±11 hours) and olmesartan (7±1 hours) result in a 2- to 3- fold accumulation for amlodipine and negligible accumulation for olmesartan with once-daily dosing.

Amlodipine.
Olmesartan medoxomil.
max
Distribution
Olmesartan medoxomil.
In rats, olmesartan crossed the blood-brain barrier poorly, if at all. Olmesartan passed across the placental barrier in rats and was distributed to the fetus. Olmesartan was distributed to milk at low levels in rats.

Metabolism and Excretion
Amlodipine.
Olmesartan medoxomil.
Olmesartan appears to be eliminated in a biphasic manner with a terminal elimination half-life of approximately 13 hours. Olmesartan shows linear pharmacokinetics following single oral doses of up to 320 mg and multiple oral doses of up to 80 mg. Steady-state levels of olmesartan are achieved within 3 to 5 days and no accumulation in plasma occurs with once-daily dosing.

Geriatric
The pharmacokinetic properties of Azor (Amlodipine/olmesartan) in the elderly are similar to those of the individual components.

Amlodipine.
Pediatric
Amlodipine.
Olmesartan medoxomil.
Gender
Population pharmacokinetic analysis indicated that female patients had approximately 15% smaller clearances of olmesartan than male patients. Gender had no effect on the clearance of amlodipine.

Olmesartan medoxomil.
max
Renal Insufficiency
Amlodipine.
Olmesartan medoxomil.
Hepatic Insufficiency
Amlodipine.
Olmesartan medoxomil.
Heart Failure
Amlodipine.

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An 8-week multicenter, randomized, double-blind, placebo controlled, parallel group factorial study in patients with mild to severe hypertension was conducted to determine if treatment with Azor (Amlodipine/olmesartan) was associated with clinically significant reduction in blood pressure compared to the respective monotherapies. The study randomized 1940 patients equally to one of the following 12 treatment arms: placebo, monotherapy treatment with amlodipine 5 mg or 10 mg, monotherapy treatment with olmesartan medoxomil 10 mg, 20 mg, or 40 mg, or combination therapy with amlodipine/olmesartan medoxomil at doses of 5/10 mg, 5/20 mg, 5/40 mg, 10/10 mg, 10/20 mg, and 10/40 mg. Patients discontinued their prior antihypertensive treatment. The mean baseline blood pressure of the study population was 164/102 mmHg. Of the total cohort, 970 patients were treated with the combination as initial therapy.

Treatment with Azor (Amlodipine/olmesartan) resulted in statistically significant greater reductions in diastolic and systolic blood pressure compared to the respective monotherapy components.

The following table presents the results for mean reduction in seated systolic and diastolic blood pressure following 8 weeks of treatment with Azor (Amlodipine/olmesartan) . Placebo-adjusted reductions from baseline in blood pressure were progressively greater with increases in dose of both amlodipine and olmesartan medoxomil components of Azor (Amlodipine/olmesartan) .

The antihypertensive effect of Azor (Amlodipine/olmesartan) was similar in patients with and without prior antihypertensive medication use, in patients with and without diabetes, in patients 65 years of age and
Azor (Amlodipine/olmesartan) was effective in treating black patients (usually a low-renin population), and the magnitude of blood pressure reduction in black patients approached that observed for non-Black patients. This effect in black patients has been seen with ACE inhibitors, angiotensin receptor blockers, and beta-blockers.

The blood pressure lowering effect was maintained throughout the 24-hour period with Azor (Amlodipine/olmesartan) once daily, with trough-to-peak ratios for systolic and diastolic response between 71% and 82%.

Upon completing the 8-week, double-blind, placebo-controlled study, 1684 patients entered a 44-week open-label extension and received combination therapy with amlodipine 5 mg plus olmesartan medoxomil 40 mg. During the open-label extension, patients whose blood pressure was not adequately controlled (i.e., did not achieve a blood pressure goal of

Azor (Amlodipine/olmesartan) tablets contain amlodipine besylate at a dose equivalent to 5 or 10 mg amlodipine and olmesartan medoxomil in the strengths described below.

Azor (Amlodipine/olmesartan) tablets are differentiated by tablet color/size and are debossed with an individual product tablet code on one side. Azor (Amlodipine/olmesartan) tablets are supplied for oral administration in the following strength and package configurations:

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Physicians should instruct female patients of childbearing age about the consequences of second and third trimester exposure to drugs that act on the renin-angiotensin system and they should be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. These patients should be informed to report pregnancies to their physicians as soon as possible. [See and ].

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