ALISKIREN

ALISKIREN- aliskiren hemifumarate tablet, film coated
Par Pharmaceutical, Inc.

WARNING: FETAL TOXICITY

When pregnancy is detected, discontinue aliskiren tablets as soon as possible. (5.1,8.1)

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1,8.1)

1 INDICATIONS AND USAGE

1.1 Hypertension

Aliskiren tablets are indicated for the treatment of hypertension in adults 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. There are no controlled trials demonstrating risk reduction with aliskiren 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 1 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 have also 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 (e.g., 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.

2 DOSAGE AND ADMINISTRATION

2.1 Adult Hypertension

The usual recommended starting dose of aliskiren tablets is 150 mg once daily. In patients whose blood pressure is not adequately controlled, the daily dose may be increased to 300 mg. Doses above 300 mg did not give an increased blood pressure response but resulted in an increased rate of diarrhea. The antihypertensive effect of a given dose is substantially attained (85% to 90%) by 2 weeks.

2.4 Relationship to Meals

Patients should establish a routine pattern for taking aliskiren tablets with regard to meals. High-fat meals decrease absorption substantially [see Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

150 mg Pink colored, film-coated, biconvex round tablets debossed with “E” on one side and “590” on the other side.

300 mg Brown colored, film-coated, ovaloid shaped biconvex tablets debossed with “E” on one side and “591” on the other side.

4 CONTRAINDICATIONS

Do not use aliskiren with ARBs or ACEIs in patients with diabetes [see Warnings and Precautions (5.2) and Clinical Studies (14.3)].

Aliskiren tablets are contraindicated in patients with known hypersensitivity to any of the components [see Warnings and Precautions (5.3)].

5 WARNINGS AND PRECAUTIONS

5.1 Fetal Toxicity

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue aliskiren tablets as soon as possible [see Use in Specific Populations (8.1)].

5.2 Renal Impairment/Hyperkalemia/Hypotension when Aliskiren Tablets are Given in Combination with ARBs or ACEIs

Aliskiren tablets are contraindicated in patients with diabetes who are receiving ARBs or ACEIs because of the increased risk of renal impairment, hyperkalemia, and hypotension. In general, avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with creatinine clearance (CrCl) less than 60 mL/min [see Contraindications (4), Drug Interactions (7) and Clinical Studies (14.3)].

5.3 Anaphylactic Reactions and Head and Neck Angioedema

Hypersensitivity reactions such as anaphylactic reactions and angioedema of the face, extremities, lips, tongue, glottis and/or larynx have been reported in patients treated with aliskiren tablets and has necessitated hospitalization and intubation. This may occur at any time during treatment and has occurred in patients with and without a history of angioedema with ACEIs or angiotensin receptor antagonists. Anaphylactic reactions have been reported from postmarketing experience with unknown frequency. If angioedema involves the throat, tongue, glottis or larynx, or if the patient has a history of upper respiratory surgery, airway obstruction may occur and be fatal. Patients who experience these effects, even without respiratory distress, require prolonged observation and appropriate monitoring measures since treatment with antihistamines and corticosteroids may not be sufficient to prevent respiratory involvement. Prompt administration of subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and measures to ensure a patent airway may be necessary.

Discontinue aliskiren tablets immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister [see Dosage and Administration (2.1) and Contraindications (4)].

5.4 Hypotension

Symptomatic hypotension may occur after initiation of treatment with aliskiren tablets in patients with marked volume depletion, patients with salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system (RAAS). The volume or salt depletion should be corrected prior to administration of aliskiren tablets, or the treatment should start under close medical supervision.

A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

5.5 Impaired Renal Function

Monitor renal function periodically in patients treated with aliskiren tablets. Changes in renal function, including acute renal failure, can be caused by drugs that affect the RAAS. Patients whose renal function may depend in part on the activity of the RAAS (e.g., patients with renal artery stenosis, severe heart failure, post-myocardial infarction or volume depletion) or patients receiving ARB, ACEI or nonsteroidal anti-inflammatory drug (NSAID), including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors), therapy may be at particular risk for developing acute renal failure on aliskiren tablets [see Warnings and Precautions (5.2), Drug Interactions (7), Use in Specific Populations (8.6), and Clinical Studies (14.3)]. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function.

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