Overview
11 DESCRIPTION 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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 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.
Indications
- 1 INDICATIONS AND USAGE 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. ( 1.1 ) 1.1 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.
Common Doses
- 150 mg
- 300 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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. ( 2.1 ) Majority of effect of given dose attained in 2 weeks. ( 2.1 ) 2.1 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.
Black Box Warning
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue Tekturna 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 ) WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. When pregnancy is detected, discontinue Tekturna 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 )
Contraindications
- 4 CONTRAINDICATIONS Do not use Tekturna 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 )]. Tekturna is contraindicated in pediatric patients less than 2 years of age because of the risk of high aliskiren exposures identified in juvenile animals due to immaturity of transporters and metabolic enzymes [see Use in Specific Populations ( 8.4 )].
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reaction: diarrhea (incidence 2.3%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LXO US Inc. at 1-844-800-8007 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Most common adverse reaction: diarrhea (incidence 2.3%) ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact LXO US Inc. at 1-844-800-8007 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The following serious adverse reactions are discussed in greater detail in other sections of the label: Fetal Toxicity [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Cyclosporine: Avoid coadministration of cyclosporine with aliskiren [see Warnings and Precautions ( 5.7 ) and Clinical Pharmacology ( 12.3 )] . Itraconazole: Avoid coadministration of itraconazole with aliskiren [see Warnings and Precautions ( 5.7 ) and Clinical Pharmacology ( 12.3 )]. 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...