Dosing and uses of Tekturna (aliskiren)
Adult dosage forms and strengths
tablet
- 150mg
- 300mg
Hypertension
150 mg PO qDay, may increase to 300 mg PO qDay
Administration: Use standard routine with regards to meals to ensure dosing consistency
Dosage modification
Hepatic impairment: No dose adjustment required
Renal impairment
- CrCl ≥30 mL/min: No dose adjustment required
- CrCl <30 mL/min: No dose adjustment required, but risk of hyperkalemia and renal dysfunction may occur; use caution
Pediatric dosage forms and strengths
Safety and efficacy not established
Tekturna (aliskiren) adverse (side) effects
1-10%
Diarrhea (2.3%)
Cough (1.1%)
Rash (1%)
Increase in serum creatinine (<7%)
Hyperkalemia (<1%)
<1%
Angioedema
Headache
Gout
Renal stones
Seizure
Severe hypotension
Rhabomyolysis
Toxic epidermal necrolysis
Increase in uric acid
Angina
Postmarketing Reports
Peripheral edema
Increased serum creatinine
Nausea/vomiting
Warnings
Black box warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity
Coadministration with ARBs or ACE inhibitors in patients with diabetes mellitus
Cautions
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 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; patients who experience these effects, even without respiratory distress, require prolonged observation and appropriate monitoring measures; 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 therapy immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister
Patients whose renal function may depend in part on activity of renin-angiotensin‐ aldosterone system (RAAS; e.g., patients with renal artery stenosis, severe heart failure, postmyocardial infarction or volume depletion) or patients receiving ARB, ACE inhibitors or nonsteroidal anti-inflammatory drug (NSAID), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors), therapy may be at particular risk of developing acute renal failure; monitor renal function periodically; consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function
High fat meal significantly reduces absorption
Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients
Symptomatic hypotension may occur after initiation of treatment 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); volume or salt depletion should be corrected prior to administration of therapy, or 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 blood pressure has stabilized
Cyclosporine or itraconazole increase aliskiren levels; avoid concomitant use
Coadministration with ACE inhibitors or ARBs
- When aliskiren was prescribed with ACE inhibitors or angiotensin receptor blockers (ARBs) in the ALTITUDE study, an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension was observed after 18-24 months
- The ALTITUDE trial included patients with hypertension plus type 2 diabetes and renal impairment who were at high risk of cardiovascular and renal events
- Coadministration of aliskiren with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment; their use is contraindicated in patients with diabetes
- Avoid use of aliskiren with ARBs or ACEIs in moderate to severe renal impairment (ie, GFR <60 mL/min)
- Hyperkalemia: Increases in serum potassium >5.5 mEq/L were infrequent with aliskiren (0.9% compared to 0.6% with placebo); however, when used in combination with an ACE inhibitor in a diabetic population, increases in serum potassium were more frequent (5.5%); monitor potassium levels periodically
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimesters), see Boxed Warning
Lactation: Excretion in milk unknown/not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tekturna (aliskiren)
Mechanism of action
Renin inhibitor that inhibits the conversion of angiotensinogen to angiotensin I. The decrease in antiotensin I causes a decrease in angiotensin II, a potent blood pressure elevating peptide
Pharmacokinetics
Bioavailability: ~3%
Peak Plasma Time: 1-3 hr
Metabolism: CYP3A4
Half-Life elimination: 24 hr
Excretion: Urine (~25%)
Onset of action: Optimum effect achieved within 2 weeks
