Dosing and uses of Tekturna HCT (hydrochlorothiazide-aliskiren)
Adult dosage forms and strengths
hydrochlorothiazide/aliskiren
tablet
- 12.5mg/150mg
- 12.5mg/300mg
- 25mg/150mg
- 25mg/300mg
Hypertension
Add-on or initial therapy: Initiate with 12.5 mg/150 mg PO qDay; after 2-4 weeks, may increase dose if needed; not to exceed 25 mg/300 mg
Add-on therapy: Initiate by adding lowest available dose of alternative component (hydrochlorothiazide 12.5 mg or aliskiren 150 mg)
Replacement therapy: May be substituted for individually titrated components
Renal Impairment
CrCl <30 mL/min: Use caution; hydrochlorothiazide usually ineffective when CrCl <30 mL/min and contraindicated in anuric patients; hyperkalemia and progressive renal dysfunction may occur with aliskiren
CrCl ≥30 mL/min: Dose adjustment not necessary
Hepatic Impairment
Dose adjustment not necessary
Pediatric dosage forms and strengths
Safety and efficacy not established
Tekturna HCT (hydrochlorothiazide-aliskiren) adverse (side) effects
Adverse reactions reported with combination product and individual agents
>10%
Increased BUn
1-10%
Dizziness (2%)
Vertigo (1%)
Hypokalemia (2%)
Increased uric acid level (2%)
Hyperkalemia (1%)
Diarrhea (2%)
Increased ALT (1%)
Flu-like syndrome (2%)
Cough (1%)
Weakness (1%)
Arthralgia (1%)
Aliskiren
- Diarrhea (2.3%)
- Cough (1.1%)
- Rash (1%)
- Increased creatinine kinase (1%)
- Increased BUN (≤ 7%)
- Hyperkalemia (≤1%)
<1%
Decreased hematocrit
Decreased hemoglobin
Aliskiren
- Gastroesophageal reflux
- Periorbital edema
- Toxic epiderma necrolysis
- Increased uric acid
- Severe hypotension
- Stevens Johnson syndrome
Frequency not defined
Hydrochlorothiazide
- AnorexiaEpigastric distress
- Hypotension
- Orthostatic hypotension
- Photosensitivity
- Anaphylaxis
- Anemia
- Confusion
- Erythema multiforme
- Stevens-Johnson syndrome
- Exfoliative dermatitis including toxic epidermal necrolysis
- Dizziness
- Hypokalemia and/or hypomagnesemia
- Hyperuricemia
- Headache
Postmarketing Reports
Aliskiren: 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 to aliskiren, hydrochlorothiazide, or sulfonamides
Anuria
Concomitant use with ACEIs or ARBs in patients with diabetes
Cautions
Caution in volume- or salt-depleted patients
Not for initial treatment
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported with aliskiren, necessitating hospitalization and intubation; may occur at any time during treatment and has occurred with and without a history of angioedema with ACE inhibitors or angiotensin receptor antagonist; 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
Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)
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
Hydrochlorothiazide can cause hypokalemia and hyponatremia; hypomagnesemia can also result in hypokalemia
Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients
If patient becomes pregnant, discontinue therapy; patient should inform doctor right away; therapy is not for patients who plan to become pregnant
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
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%)
Pregnancy and lactation
Pregnancy category: d
Lactation: enters breast milk; 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 HCT (hydrochlorothiazide-aliskiren)
Mechanism of action
Hydrochlorothiazide: Thiazide diuretic; affects renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride
Aliskiren: Direct renin inhibitor; decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I
Pharmacokinetics
Hydrochlorothiazide
- Half-Life: 6-15 hr
- Bioavailability: 70%
- Onset: 2 hr (diuresis); 4-6 hr (peak effect)
- Duration: 6-12 hr (diuresis); 1 wk (HTN)
- Vd: 3.6-7.8 L/kg
- Peak Plasma:1.5-2.5 hr
- Protein Bound: 68%
- Metabolism: Minimally metabolized
- Clearance: 335 mL/min
- Excretion: Urine 50-70%
- Dialyzable: No
- Aliskiren: 1 hr
Aliskiren
- Onset: Within 2 weeks
- Bioavailability: 3%
- Peak Plasma Time: 1-3 hr
- Metabolism: Metabolized by CYP3A4
- Half-Life: 24 hr
- Excretion: Urine (25% as parent compound in urine)
