Inovum HCT

Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), Hydrochlorothiazide (Inovum HCT) 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 (Inovum HCT), Amlodipine (Inovum HCT), Hydrochlorothiazide (Inovum HCT) tablets.

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.

This fixed combination drug is not indicated for the initial therapy of hypertension.

General Considerations

Dose once daily.

Dosage may be increased after 2 weeks. The full blood pressure lowering effects are attained within 2 weeks after a change in dose. The maximum recommended dose of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets is 40 mg/10 mg/25 mg. Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets may be taken with or without food.

Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), Hydrochlorothiazide (Inovum HCT) tablets may be administered with other antihypertensive agents.

Renal Impairment

The usual regimens of therapy with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets may be followed if the patient’s creatinine clearance is > 30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so avoid use of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets.

Elderly

Patients ≥ 75 years of age should start Amlodipine (Inovum HCT) at 2.5 mg, which is not available with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets.

Hepatic Impairment

Patients with severe hepatic impairment should start Amlodipine (Inovum HCT) at 2.5 mg, which is not available with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets.

Replacement Therapy

Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets may be substituted for their individually titrated components.

Add-on/Switch Therapy

Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets may be used to provide additional blood pressure lowering for patients not adequately controlled on maximally tolerated, labeled, or usual doses of any two of the following antihypertensive classes: angiotensin receptor blockers (ARB), calcium channel blockers (CCB), and diuretics.

A patient who experiences dose-limiting adverse reactions to an individual component while on any dual combination of the components of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets may be switched to Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets containing a lower dose of that component to achieve similar blood pressure reductions.

Because of the Hydrochlorothiazide (Inovum HCT) component, Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets are contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Do not coadminister aliskiren with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets in patients with diabetes.

Reduced effects w/ NSAIDs. Potentiation of orthostatic hypotension may occur w/ alcohol, barbiturates or narcotics. Antidiabetic drugs. Additive effect or potentiation w/ other antihypertensive drugs. Reduced absorption of Hydrochlorothiazide (Inovum HCT) w/ cholestyramine & colestipol resins. Intensified electrolyte depletion particularly hypokalemia w/ corticosteroids, ACTH. Increased responsiveness to nondepolarizing skeletal muscle relaxants (eg tubocurarine). Reduced renal clearance of lithium by diuretics.

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.

Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets

In the controlled trial of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets, patients were randomized to Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets 40 mg/10 mg/25 mg, Olmesartan Medoxomil (Inovum HCT)/Amlodipine (Inovum HCT) 40 mg/10 mg, Olmesartan Medoxomil (Inovum HCT)/Hydrochlorothiazide (Inovum HCT) 40 mg/25 mg, or Amlodipine (Inovum HCT)/Hydrochlorothiazide (Inovum HCT) 10 mg/25 mg. Subjects who received triple combination therapy were treated between two and four weeks with one of the three dual combination therapies. Safety data from this study were obtained in 574 patients with hypertension who received Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets for 8 weeks.

The frequency of adverse reactions was similar between men and women, patients < 65 years of age and patients ≥ 65 years of age, patients with and without diabetes, and Black and non-Black patients. Discontinuations because of adverse events occurred in 4% of patients treated with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets, 40 mg/10 mg/25 mg compared to 1% of patients treated with Olmesartan Medoxomil (Inovum HCT)/Amlodipine (Inovum HCT) 40 mg/10 mg, 2% of patients treated with Olmesartan Medoxomil (Inovum HCT)/Hydrochlorothiazide (Inovum HCT) 40 mg/25 mg, and 2% of patients treated with Amlodipine (Inovum HCT)/Hydrochlorothiazide (Inovum HCT) 10 mg/25 mg. The most common reason for discontinuation with Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets was dizziness (1%).

Dizziness was one of the most frequently reported adverse reactions with incidence of 1.4% to 3.6% in subjects continuing on dual combination therapy compared to 5.8% to 8.9% in subjects who switched to Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets.

The other most frequent adverse reactions that occurred in at least 2% of subjects are presented in the table below:

Syncope was reported by 1% of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablet subjects compared to 0.5% or less for the other treatment groups.

Olmesartan Medoxomil (Inovum HCT)

Olmesartan Medoxomil (Inovum HCT) 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 treated for at least 1 year. Treatment with Olmesartan Medoxomil (Inovum HCT) was well tolerated, with an incidence of adverse reactions similar to that seen with placebo. Adverse reactions were generally mild, transient, and without relationship to the dose of Olmesartan Medoxomil (Inovum HCT).

Amlodipine (Inovum HCT)

Amlodipine (Inovum HCT) has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials.

The following adverse reactions occurred in < 1% but > 0.1% of patients in controlled clinical trials under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert physicians to a possible relationship:

The following adverse reactions occurred in < 0.1% of patients: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, coughing, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia.

Hydrochlorothiazide (Inovum HCT)

Other adverse reactions that have been reported with Hydrochlorothiazide (Inovum HCT), without regard to causality, are listed below:

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of the individual components of Olmesartan Medoxomil (Inovum HCT), Amlodipine (Inovum HCT), and Hydrochlorothiazide (Inovum HCT) tablets. 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.

Olmesartan Medoxomil (Inovum HCT). The following adverse reactions have been reported in postmarketing experience:

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.

Amlodipine (Inovum HCT). The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of Amlodipine (Inovum HCT).