OLMESARTAN MEDOXOMIL
Generic: OLMESARTAN MEDOXOMIL
Basic Information
Manufacturer
direct rx
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
b57e47a5-43e0-d1c5-e053-2a95a90a2b07
Indications & Usage
Olmesartan medoxomil tablets are indicated for the treatment of hypertension, 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 olmesartan medoxomil.
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.
It may be used alone or in combination with other antihypertensive agents.
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 olmesartan medoxomil.
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.
It may be used alone or in combination with other antihypertensive agents.
Adverse Reactions
6.1 Clinical Trials Experience 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.
Adult Hypertension 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 reactions similar to placebo.
Events generally were mild, transient and had no relationship to the dose of olmesartan medoxomil.
The overall frequency of adverse reactions 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 reactions 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 reaction that occurred in more than 1% of patients treated with olmesartan medoxomil and at a higher incidence versus placebo was dizziness (3% vs.
1%).
The following adverse reactions occurred in placebo-controlled clinical trials at an incidence of more than 1% of patients treated with olmesartan medoxomil, but also occurred at about the same or greater incidence in patients receiving placebo: back pain, bronchitis, creatine phosphokinase increased, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, influenza-like symptoms, pharyngitis, rhinitis and sinusitis.
The incidence of cough was similar in placebo (0.7%) and olmesartan medoxomil (0.9%) patients.
Other potentially important adverse reactions that have been reported with an incidence of greater than 0.5%, whether or not attributed to treatment, in the more than 3100 hypertensive patients treated with olmesartan medoxomil monotherapy in controlled or open-label trials are listed below.
Body as a Whole: chest pain, peripheral edema Central and Peripheral Nervous System: vertigo Gastrointestinal: abdominal pain, dyspepsia, gastroenteritis, nausea Heart Rate and Rhythm Disorders: tachycardia Metabolic and Nutritional Disorders: hypercholesterolemia, hyperlipemia, hyperuricemia Musculoskeletal: arthralgia, arthritis, myalgia Skin and Appendages: rash Facial edema was reported in five patients receiving olmesartan medoxomil.
Angioedema has been reported with angiotensin II antagonists.
Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of olmesartan medoxomil.
Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g/dL and 0.3 volume percent, respectively) were observed.
Liver Function Tests: Elevations of liver enzymes and/or serum bilirubin were observed infrequently.
Five patients (0.1%) assigned to olmesartan medoxomil and one patient (0.2%) assigned to placebo in clinical trials were withdrawn because of abnormal liver chemistries (transaminases or total bilirubin).
Of the five olmesartan medoxomil patients, three had elevated transaminases, which were attributed to alcohol use, and one had a single elevated bilirubin value, which normalized while treatment continued.
Pediatric Hypertension No relevant differences were identified between the adverse experience profile for pediatric patients aged 1 to 16 years and that previously reported for adult patients.
6.2 Post-Marketing Experience The following adverse reactions have been reported in post-marketing experience.
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.
Body as a Whole: Asthenia, angioedema, anaphylactic reactions Gastrointestinal: Vomiting, sprue-like enteropathy [see WARNINGS AND PRECAUTIONS (5.5)] Metabolic and Nutritional Disorders: Hyperkalemia Musculoskeletal: Rhabdomyolysis Urogenital System: Acute renal failure, increased blood creatinine levels Skin and Appendages: Alopecia, pruritus, urticaria Data from one controlled trial and an epidemiologic study have suggested that high-dose olmesartan may increase cardiovascular (CV) risk in diabetic patients, but the overall data are not conclusive.
The randomized, placebo-controlled, double-blind ROADMAP trial (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention trial, n=4447) examined the use of olmesartan, 40 mg daily, vs.
placebo in patients with type 2 diabetes mellitus, normoalbuminuria, and at least one additional risk factor for CV disease.
The trial met its primary endpoint, delayed onset of microalbuminuria, but olmesartan had no beneficial effect on decline in glomerular filtration rate (GFR).
There was a finding of increased CV mortality (adjudicated sudden cardiac death, fatal myocardial infarction, fatal stroke, revascularization death) in the olmesartan group compared to the placebo group (15 olmesartan vs.
3 placebo, HR 4.9, 95% confidence interval [CI], 1.4, 17), but the risk of non-fatal myocardial infarction was lower with olmesartan (HR 0.64, 95% CI 0.35, 1.18).
The epidemiologic study included patients 65 years and older with overall exposure of > 300,000 patient-years.
In the sub-group of diabetic patients receiving high-dose olmesartan (40 mg/d) for > 6 months, there appeared to be an increased risk of death (HR 2.0, 95% CI 1.1, 3.8) compared to similar patients taking other angiotensin receptor blockers.
In contrast, high-dose olmesartan use in non-diabetic patients appeared to be associated with a decreased risk of death (HR 0.46, 95% CI 0.24, 0.86) compared to similar patients taking other angiotensin receptor blockers.
No differences were observed between the groups receiving lower doses of olmesartan compared to other angiotensin blockers or those receiving therapy for < 6 months.
Overall, these data raise a concern of a possible increased CV risk associated with the use of high-dose olmesartan in diabetic patients.
There are, however, concerns with the credibility of the finding of increased CV risk, notably the observation in the large epidemiologic study for a survival benefit in non-diabetics of a magnitude similar to the adverse finding in diabetics.
Adult Hypertension 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 reactions similar to placebo.
Events generally were mild, transient and had no relationship to the dose of olmesartan medoxomil.
The overall frequency of adverse reactions 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 reactions 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 reaction that occurred in more than 1% of patients treated with olmesartan medoxomil and at a higher incidence versus placebo was dizziness (3% vs.
1%).
The following adverse reactions occurred in placebo-controlled clinical trials at an incidence of more than 1% of patients treated with olmesartan medoxomil, but also occurred at about the same or greater incidence in patients receiving placebo: back pain, bronchitis, creatine phosphokinase increased, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, influenza-like symptoms, pharyngitis, rhinitis and sinusitis.
The incidence of cough was similar in placebo (0.7%) and olmesartan medoxomil (0.9%) patients.
Other potentially important adverse reactions that have been reported with an incidence of greater than 0.5%, whether or not attributed to treatment, in the more than 3100 hypertensive patients treated with olmesartan medoxomil monotherapy in controlled or open-label trials are listed below.
Body as a Whole: chest pain, peripheral edema Central and Peripheral Nervous System: vertigo Gastrointestinal: abdominal pain, dyspepsia, gastroenteritis, nausea Heart Rate and Rhythm Disorders: tachycardia Metabolic and Nutritional Disorders: hypercholesterolemia, hyperlipemia, hyperuricemia Musculoskeletal: arthralgia, arthritis, myalgia Skin and Appendages: rash Facial edema was reported in five patients receiving olmesartan medoxomil.
Angioedema has been reported with angiotensin II antagonists.
Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of olmesartan medoxomil.
Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g/dL and 0.3 volume percent, respectively) were observed.
Liver Function Tests: Elevations of liver enzymes and/or serum bilirubin were observed infrequently.
Five patients (0.1%) assigned to olmesartan medoxomil and one patient (0.2%) assigned to placebo in clinical trials were withdrawn because of abnormal liver chemistries (transaminases or total bilirubin).
Of the five olmesartan medoxomil patients, three had elevated transaminases, which were attributed to alcohol use, and one had a single elevated bilirubin value, which normalized while treatment continued.
Pediatric Hypertension No relevant differences were identified between the adverse experience profile for pediatric patients aged 1 to 16 years and that previously reported for adult patients.
6.2 Post-Marketing Experience The following adverse reactions have been reported in post-marketing experience.
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.
Body as a Whole: Asthenia, angioedema, anaphylactic reactions Gastrointestinal: Vomiting, sprue-like enteropathy [see WARNINGS AND PRECAUTIONS (5.5)] Metabolic and Nutritional Disorders: Hyperkalemia Musculoskeletal: Rhabdomyolysis Urogenital System: Acute renal failure, increased blood creatinine levels Skin and Appendages: Alopecia, pruritus, urticaria Data from one controlled trial and an epidemiologic study have suggested that high-dose olmesartan may increase cardiovascular (CV) risk in diabetic patients, but the overall data are not conclusive.
The randomized, placebo-controlled, double-blind ROADMAP trial (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention trial, n=4447) examined the use of olmesartan, 40 mg daily, vs.
placebo in patients with type 2 diabetes mellitus, normoalbuminuria, and at least one additional risk factor for CV disease.
The trial met its primary endpoint, delayed onset of microalbuminuria, but olmesartan had no beneficial effect on decline in glomerular filtration rate (GFR).
There was a finding of increased CV mortality (adjudicated sudden cardiac death, fatal myocardial infarction, fatal stroke, revascularization death) in the olmesartan group compared to the placebo group (15 olmesartan vs.
3 placebo, HR 4.9, 95% confidence interval [CI], 1.4, 17), but the risk of non-fatal myocardial infarction was lower with olmesartan (HR 0.64, 95% CI 0.35, 1.18).
The epidemiologic study included patients 65 years and older with overall exposure of > 300,000 patient-years.
In the sub-group of diabetic patients receiving high-dose olmesartan (40 mg/d) for > 6 months, there appeared to be an increased risk of death (HR 2.0, 95% CI 1.1, 3.8) compared to similar patients taking other angiotensin receptor blockers.
In contrast, high-dose olmesartan use in non-diabetic patients appeared to be associated with a decreased risk of death (HR 0.46, 95% CI 0.24, 0.86) compared to similar patients taking other angiotensin receptor blockers.
No differences were observed between the groups receiving lower doses of olmesartan compared to other angiotensin blockers or those receiving therapy for < 6 months.
Overall, these data raise a concern of a possible increased CV risk associated with the use of high-dose olmesartan in diabetic patients.
There are, however, concerns with the credibility of the finding of increased CV risk, notably the observation in the large epidemiologic study for a survival benefit in non-diabetics of a magnitude similar to the adverse finding in diabetics.