Tekturna contains aliskiren hemifumarate, adirect renin inhibitor. Aliskiren hemifumarate is chemically described as (2S,4S,5S,7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4-hydroxy- 2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamide hemifumarate and its structural formula is: Molecular formula: C 30 H 53 N 3 O 6 • 0.5 C 4 H 4 O 4 Aliskiren hemifumarate is a white to slightly yellowish crystalline powder with a molecular weight of 609.8 (free base- 551.8). It is soluble in phosphate buffer, n-octanol, and highly soluble in water. Tekturna is available as film-coated tablets, which contains 165.75 mg or 331.5 mg aliskiren hemifumerate (equivalent to 150 mg or 300 mg aliskiren) and the following excipients: crospovidone; magnesium stearate; microcrystalline cellulose; povidone; silica, colloidal anhydrous; hypromellose; macrogol; talc; iron oxide, black (E 172); iron oxide, red (E 172); titanium dioxide (E 171). Structural Formula

Tekturna is a renin inhibitor (RI) indicated for the treatment of hypertension in adults and in pediatric patients weighing 50 kg or greater who are at least 6 years of age, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions

Hypertension Tekturna is indicated for the treatment of hypertension in adults and in pediatric patients weighing 50 kg or greater who are at least 6 years of age and older 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 Tekturna. 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.

150 mg light pink biconvex round tablet, imprinted NVR/IL (Side 1/Side 2). 300 mg light red biconvex ovaloid round tablet, imprinted NVR/IU (Side 1/Side 2). Tablets: 150 mg, 300 mg

Starting dose (adults and pediatric patients): 150 mg once daily with a routine pattern with regard to meals. If blood pressure remains uncontrolled titrate up to 300 mg daily. Majority of effect of given dose attained in 2 weeks

Recommended Dosage In adult patients and in pediatric patients weighing 50 kg or greater who are at least 6 years of age, the recommended starting dose of Tekturna is 150 mg once daily. In patients whose blood pressure is not adequately controlled, the daily dose may be increased to 300 mg once daily. 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 dosage is substantially attained (85% to 90%) by 2 weeks

Relationship to Meals Patients should establish a routine pattern for taking Tekturna with regard to meals. High-fat meals decrease absorption substantially .

Avoid concomitant use with ARBs or ACEIs particularly in patients with renal impairment [creatinine clearance (CrCl) <60 mL/min]. Anaphylactic Reactions and Head and Neck Angioedema. Hypotension: Correct imbalances in volume and/or salt depleted patients. Impaired Renal Function: Monitor serum creatinine periodically. Hyperkalemia: Monitor potassium levels periodically. 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 Tekturna as soon as possible

Renal Impairment/Hyperkalemia/Hypotension when Tekturna is Given in Combination with ARBs or ACEIs Tekturna is 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 Tekturna with ACE inhibitors or ARBs, particularly in patients with creatinine clearance (CrCl) less than 60 mL/min

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 Tekturna 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 Tekturna immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister

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

Impaired Renal Function Monitor renal function periodically in patients treated with Tekturna. 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 Tekturna . Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function

Hyperkalemia Monitor serum potassium periodically in patients receiving Tekturna. Drugs that affect the RAAS can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes, combination use with ARBs or ACEIs , NSAIDs, or potassium supplements or potassium sparing diuretics

Cyclosporine or Itraconazole When Tekturna was given with cyclosporine or itraconazole, the blood concentrations of aliskiren were significantly increased. Avoid concomitant use of Tekturna with cyclosporine or itraconazole .

Cyclosporine: Avoid coadministration of cyclosporine with aliskiren . Itraconazole: Avoid coadministration of itraconazole with aliskiren . Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors with agents that affect the RAAS, including aliskiren, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving aliskiren and NSAID therapy. The antihypertensive effect of aliskiren may be attenuated by NSAIDs. Dual Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): The concomitant use of aliskiren with other agents acting on the RAAS such as ACEIs or ARBs is associated with an increased risk of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two drugs that inhibit the renin-angiotensin system do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with CrCl less than 60 mL/min. Monitor blood pressure, renal function, and electrolytes in patients taking aliskiren and other agents that affect the RAAS . The concomitant use of aliskiren with an ARB or an ACEI in diabetic patients is contraindicated . Furosemide: Oral coadministration of aliskiren and furosemide reduced exposure to furosemide. Monitor diuretic effects when furosemide is coadministered with aliskiren. Cyclosporine or Itraconazole: Avoid concomitant use. ( 5.7 , 7 , 12.3 ) Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Increased risk of renal impairment and loss of antihypertensive effect.