TEKTURNA- aliskiren hemifumarate tablet, film coated
Novartis Pharmaceuticals Corporation
WARNING: FETAL TOXICITY
When pregnancy is detected, discontinue Tekturna as soon as possible. (5.1)
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)
1 INDICATIONS AND USAGE
1.1 Hypertension
Tekturna is 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. There are no controlled trials demonstrating risk reduction with Tekturna.
DOSAGE AND ADMINISTRATION
2.1 Hypertension
The usual 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. 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.
2.2 Relationship to Meals
Patients should establish a routine pattern for taking Tekturna with regard to meals. High fat meals decrease absorption substantially [see Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
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)
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)].
Tekturna is 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
Pregnancy Category D
DESCRIPTION
Tekturna contains aliskiren hemifumarate, direct renin inhibitor, that is provided as tablets for oral administration. 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
Molecular formula: C30 H53 N3 O6 � 0.5 C4 H4 O4
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.
12 CLINICAL PHARMACOLOGY
Figure 1: The impact of co-administered drugs on the pharmacokinetics of aliskiren.Figure 2: The impact of aliskiren on the pharmacokinetics of co-administered drugs.
12.1 Mechanism of Action
Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by ACE and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known.
Information for Patients
Pregnancy: Advise female patients of child bearing age about the consequences of exposure to Tekturna during pregnancy. Discuss treatment options with women planning to become pregnant. Advise patients to report pregnancies to their physicians as soon as possible.
Anaphylactic Reactions and Angioedema: Advise patients to immediately report any signs or symptoms suggesting a severe allergic reaction (difficulty breathing or swallowing, tightness of the chest, hives, general rash, swelling, itching, dizziness, vomiting, or abdominal pain) or angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physicians. Angioedema, including laryngeal edema, may occur at any time during treatment with Tekturna.
Symptomatic Hypotension: Advise patients that lightheadedness can occur, especially during the first days of Tekturna therapy, and that it should be reported to the prescribing physician. Advise patients that if syncope occurs, Tekturna should be discontinued until the physician has been consulted.
Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.
Potassium Supplements: Advise patients receiving Tekturna not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.
Relationship to Meals: Advise patients to establish a routine pattern for taking Tekturna with regard to meals. High-fat meals decrease absorption substantially.
