Tekturna HCT aliskiren hemifumarate and hydrochlorothiazide 300; 25 mg; mg Tablet, Film Coated, 30-count — NDC 70839-325-30 (Billing 70839-0325-30)
This is a package of 30 tablets of Tekturna HCT aliskiren hemifumarate and hydrochlorothiazide 300; 25 mg; mg Tablet, Film Coated from Noden Pharma USA, Inc., no longer marketed, no longer in the FDA NDC Directory; retail pharmacies pay about $10.74 per tablet (NADAC). It is this product's only package size.
NDC database record
One package, one record: these facts belong to NDC 70839-325-30 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 70839 labeler · 325 product · 30 package
- Billing quantity
- 30 EA per package
- Barcode (UPC-A, from the NDC)
- 3 7083932530 9
- FDA record last changed
- Jul 15, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 063592
- GCN: 99313
- HICL (First Databank): 035338
- AHFS class code: 24:32.40.00
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 8, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 8, 2026
Clinical
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 8, 2026
- FDA label on DailyMed · label index refreshed Oct 8, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $10.738 | $322.13 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
- CMS NADAC weekly file · file of Nov 23, 2022
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · refreshed Oct 9, 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Marketing end | Status |
|---|---|---|---|---|
| 70839-0325-30 You're viewing this Main listing | 30 TABLET, FILM COATED in 1 BOTTLE | 2017-01-01 | — | Discontinued by firm |
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tekturna HCT 300; 25 mg/1; mgthis 70839-0325-30 | Noden | 30 tablets | $10.738 | — | Discontinued | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- FDA Orange Book · refreshed Oct 9, 2026
- CMS NADAC weekly file · file of Nov 23, 2022
Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
Our estimate: July 2028 about 2 years away
How sure: Toss-up. Still unsettled. Just as likely to slip as to hold.
Why then: A patent that protects the brand runs out. After that, approved generics can be sold.
See the full forecast for generic Tekturna HCT →🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 8618172 ↗ | Drug product | — | Jul 13, 2028 |
| US 8618172 ↗ | Drug product | — | Jul 13, 2028 |
| US 8618172 ↗ | Drug product | — | Jul 13, 2028 |
| US 8618172 ↗ | Drug product | — | Jul 13, 2028 |
Is there a generic version of TEKTURNA HCT 300-25 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
- FDA Orange Book · refreshed Oct 9, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
Where does this data come from?
IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.- FDA label on DailyMed · label index refreshed Oct 8, 2026
- FDA openFDA NDC Directory · synced Oct 8, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Noden Pharma USA, Inc. labeler code 70839
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 8, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue Tekturna HCT 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 HCT 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 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Tekturna HCT 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 including hydrochlorothiazide (HCTZ).
There are no controlled trials demonstrating risk reduction with Tekturna HCT. 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. Tekturna HCT is a combination of aliskiren, a renin inhibitor, and hydrochlorothiazide (HCTZ), a thiazide diuretic, indicated for the treatment of hypertension, to lower blood pressure: In patients not adequately controlled with monotherapy.
( 1 ) As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. ( 1 ) Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction. Add-On Therapy A patient whose blood pressure is not adequately controlled with aliskiren alone or HCTZ alone may be switched to combination therapy with Tekturna HCT.
A patient whose blood pressure is controlled with HCTZ alone but who experiences hypokalemia may be switched to combination therapy with Tekturna HCT. A patient who experiences dose-limiting adverse reactions on either component alone may be switched to Tekturna HCT containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. Replacement Therapy Tekturna HCT may be substituted for the titrated components.
Initial Therapy Tekturna HCT may be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. The choice of Tekturna HCT as initial therapy should be based on an assessment of potential benefits and risks. Patients with Stage 2 hypertension are at a relatively high risk for cardiova… [Excerpted — this section continues on DailyMed.]
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Initiate with 150/12.5mg daily. Titrate as needed up to a maximum of 300/25 mg ( 2.2 ) Order of increasing mean effect: 150/12.5 mg, 150/25 mg or 300/12.5 mg, and 300/25 mg ( 2.1 ) Replacement therapy: May be substituted for titrated components ( 2.4 )
2.1Dose Selection The recommended once-daily doses of Tekturna HCT in order of increasing mean effect are 150/12.5 mg, 150/25 mg or 300/12.5 mg, and 300/25 mg.
2.2Dose Titration The antihypertensive effect of Tekturna HCT is largely manifested within 1 week, with maximal effects generally seen at around 4 weeks. If blood pressure remains uncontrolled after 2 to 4 weeks of therapy, the dose may be titrated up to a maximum of aliskiren 300 mg/HCTZ 25 mg.
2.3Add-On Therapy A patient whose blood pressure is not adequately controlled with aliskiren alone or hydrochlorothiazide alone may be switched to combination therapy with Tekturna HCT. The usual recommended starting dose is 150/12.5 mg once daily as needed to control blood pressure. The dose may be titrated up to a maximum of aliskiren 300 mg/hydrochlorothiazide 25 mg once daily.
2.4Replacement Therapy Tekturna HCT may be substituted for the individually titrated components.
2.5Initial Therapy The usual recommended starting dose is 150/12.5 mg once daily as needed to control blood pressure. The dose may be titrated up to a maximum of aliskiren 300 mg/HCTZ 25 mg once daily. Tekturna HCT is not recommended for use as initial therapy in patients with intravascular volume depletion [ see Warnings and Precautions ( 5.4 ) ].
2.6Relationship to Meals Patients should establish a routine pattern for taking Tekturna HCT with regard to meals. High-fat meals decrease absorption substantially [see Clinical Pharmacology ( 12.3 )].
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 150 mg/12.5 mg tablets: white, biconvex ovaloid, film-coated tablets imprinted with NVR/LCI 150 mg/25 mg tablets: pale yellow, biconvex ovaloid, film-coated tablets imprinted with NVR/CLL 300 mg/12.5 mg tablets: violet white, biconvex ovaloid, film-coated tablets imprinted with NVR/CVI 300 mg/25 mg tablets: light yellow, biconvex ovaloid, film-coated tablets imprinted with NVR/CVV Tablets (mg aliskiren/mg HCTZ): 150/12.5, 150/25, 300/12.5, 300/25 ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Do not use aliskiren with ARBs or ACEIs in patients with diabetes [see Warnings and Precautions ( 5.2 ) and Clinical Studies ( 14.4 )]. Tekturna HCT is contraindicated in patients with known anuria or hypersensitivity to sulfonamide-derived drugs like HCTZ or to any of the components [see Warnings and Precautions ( 5.6 ) and Adverse Reactions ( 6.1 )] . Hypersensitivity reactions may range from urticaria to anaphylaxis.
Do not use with angiotensin receptor blockers (ARBs) or angiotensin- converting enzyme inhibitors (ACEIs) in patients with diabetes. ( 4 ) Anuria ( 4 ) Hypersensitivity to sulfonamide-derived drugs or to any of the components. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Avoid concomitant use with ARBs or ACEIs particularly in patients with renal impairment [creatinine clearance (CrCl) <60 mL/min]. ( 5.2 , 5.4 ) Anaphylactic Reactions and Head and Neck Angioedema. ( 5.3 ) Hypotension: Correct imbalances in volume and/or salt-depleted patients.
( 5.4 ) Impaired Renal Function: Monitor serum creatinine periodically. ( 5.5 ) Hyperkalemia: Monitor potassium levels periodically. ( 5.8 ) Acute Myopia and Secondary Angle Closure Glaucoma.
( 5.10 )
5.1Fetal Toxicity Aliskiren 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 HCT as soon as possible [see Use in Specific Populations ( 8.1 )]. Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults [see Use in Specific Populations ( 8.1 )].
5.2Renal Impairment/Hyperkalemia/Hypotension when Tekturna HCT is Given in Combination with ARBs or ACEIs Tekturna HCT 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 aliskiren with ACE inhibitors or ARBs, particularly in patients with creatinine clearance (CrCl) less than 60 mL/min [see Contraindications ( 4 ), Drug Interactions ( 7 ) and Clinical Studies ( 14.3 )] .
5.3Anaphylactic Reactions and Head and Neck Angioedema Aliskiren 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 HCT immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister [see Contraindications ( 4 )] .
5.4Hypotension Symptomatic hypotension may occur after initiation of treatment with Tekturna HCT 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). The volume or salt depletion should be corrected prior to administration of Tekturna HCT, 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.
5.5Impaired Renal Function Monitor renal function periodically in patients treated with Tekturna HCT. Changes in renal function, including acute renal failure, can be caused by drugs that affect the RAAS and by diuretics. Patients whose renal function may depend in part on the… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reactions (incidence ≥1.5% and more common than with placebo) are: dizziness and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Noden Pharma USA Inc. at 1-844-399-5701 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Studies Experience The following serious adverse reactions are discussed in greater detail in other sections of the label: Fetal Toxicity [see Warnings and Precautions ( 5.1 )]. Anaphylactic Reactions and Head and Neck Angioedema [see Warnings and Precautions ( 5.3 )]. Hypotension [see Warnings and Precautions ( 5.4 )].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Tekturna HCT Tekturna HCT has been evaluated for safety in more than 2,700 patients, including over 700 treated for 6 months and 190 for over 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event (including uncontrolled hypertension) occurred in 2.7% of patients treated with Tekturna HCT versus 3.6% of patients given placebo.
Adverse events in placebo-controlled trials that occurred in at least 1% of patients treated with Tekturna HCT and at a higher incidence than placebo included dizziness (2.3% versus 1%), influenza (2.3% versus 1.6%), diarrhea (1.6% versus 0.5%), cough (1.3% versus 0.5%), vertigo (1.2% versus 0.5%), asthenia (1.2% versus 0%), and arthralgia (1% versus 0.5%). Aliskiren Aliskiren has been evaluated for safety in 6,460 patients, including 1,740 treated for longer than 6 months, and 1,250 for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event, including uncontrolled hypertension occurred in 2.2% of patients treated with aliskiren, versus 3.5% of patients given placebo.
These data do not include information from the ALTITUDE study which evaluated the use of aliskiren in combination with ARBs or ACEIs [see Contraindications ( 4 ), Warnings and Precautions ( 5.2 ), and Clinical Studies ( 14.4 )]. Two cases of angioedema with respiratory symptoms were reported with aliskiren use in the clinical studies. Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation.
The rate of these angioedema cases in the completed studies was 0.06%. In addition, 26 other cases of edema involving the face, hands, or whole body were reported with aliskiren use, including 4 leading to discontinuation. In the placebo-controlled studies, however, the incidence of edema involving the face, hands, or whole body was 0.4% with aliskiren compared with 0.5% with placebo.
In a long-term active-controlled study with aliskiren and HCTZ arms, the incidence of edema involving the face, hands, or whole body was 0.4% in both treatment arms. Aliskiren produces dose-related gastrointestinal (GI) adverse reactions. Diarrhea was reported by 2.3% of patients at 300 mg, compared to 1.2% in placebo patients.
In women and the elderly (age 65 years and older) increases in diarrhea rates were evident starting at a dose of 150 mg daily, with rates for these subgroups at 150 mg comparable to those seen at 300 mg for men or younger patients (all rates about 2% to 2.3%). Other GI symptoms included abdominal pain, dyspepsia, and gastroesophageal reflux, although increased rates for abdominal pain and dyspepsia were distinguished from placebo only at 600 mg daily. Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation.
Aliskiren was associated with a slight increase in cough in the placebo-controlled studies (1.1% for any aliskiren use versus 0.6% for placebo). In active-controlled trials with ACE inhibitor (ramipril, lisinopril) arms, the rates of cough for the aliskiren arms were abou… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug interaction studies have been conducted with Tekturna HCT and other drugs, although studies with the individual aliskiren and HCTZ components are described below. Cyclosporine or Itraconazole: Avoid concomitant use. ( 5.9 , 7 , 12.3 ) Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Increased risk of renal impairment and loss of antihypertensive effect.
( 7 ) Antidiabetic Drugs: Dosage adjustment of antidiabetic may be required. ( 7 ) Cholestyramine and Colestipol: Reduced absorption of thiazides. ( 7 ) Lithium: Increased risk of lithium toxicity when used with diuretics.
( 7 ) Aliskiren Cyclosporine: Avoid coadministration of cyclosporine with aliskiren [see Warnings and Precautions ( 5.9 ) 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 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 on aliskiren and other agents that affect the RAAS [see Warnings and Precautions ( 5.4 , 5.5 , 5.8 )]. The concomitant use of aliskiren with an ARB or an ACEI in diabetic patients is contraindicated [see Contraindications ( 4 )]. Furosemide: Oral coadministration of aliskiren and furosemide reduced exposure to furosemide.
Monitor diuretic effects when furosemide is coadministered with aliskiren. Hydrochlorothiazide (HCTZ) When administered concurrently, the following drugs may interact with thiazide diuretics. Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.
Lithium: Diuretic agents increase the risk of lithium toxicity. Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists. Monitoring of serum lithium levels is recommended during concomitant use.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and COX-2 selective agents: When Tekturna HCT and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Ion-exchange Resins: Staggering the dosage of HCTZ and ion exchange resins (e.g., cholestyramine, colestipol) such that HCTZ is administered at least 4 hours before or 4 to 6 hours after the administration of resins would potentially minimize the interaction [see Clinical Pharmacology ( 12.3 )].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding not recommended. ( 8.2 )
8.1Pregnancy Risk Summary Tekturna HCT can cause fetal harm when administered to a pregnant woman. 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. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin- angiotensin system from other antihypertensive agents.
When pregnancy is detected, discontinue Tekturna HCT as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Aliskiren Use of drugs that act on the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
In patients taking Tekturna HCT during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Closely observe infants with histories of in utero exposure to Tekturna HCT for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Tekturna HCT, support blood pressure and renal perfusion Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function. Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults.
Data Animal Data No reproductive toxicity studies have been conducted with the combination of aliskiren and HCTZ. However, these studies have been conducted for aliskiren and HCTZ alone. Aliskiren In developmental toxicity studies, pregnant rats and rabbits received oral aliskiren hemifumarate during organogenesis at doses up to 20 and 7 times the maximum recommended human dose (MRHD) based on body surface area (mg/m 2 ), respectively, in rats and rabbits.
(Actual animal doses were up to 600 mg/kg/day in rats and up to 100 mg/kg/day in rabbits.) No teratogenicity was observed; however, fetal birth weight was decreased in rabbits at doses 3.2 times the MRHD based on body surface area (mg/m 2 ). Aliskiren was present in placentas, amniotic fluid and fetuses of pregnant rabbits. HCTZ When pregnant mice and rats were given HCTZ at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the MRHD), during their respective periods of major… [Excerpted — this section continues on DailyMed.]
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Tekturna HCT can cause fetal harm when administered to a pregnant woman. 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. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin- angiotensin system from other antihypertensive agents.
When pregnancy is detected, discontinue Tekturna HCT as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Aliskiren Use of drugs that act on the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.
In patients taking Tekturna HCT during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Closely observe infants with histories of in utero exposure to Tekturna HCT for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Tekturna HCT, support blood pressure and renal perfusion Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function. Hydrochlorothiazide Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults.
Data Animal Data No reproductive toxicity studies have been conducted with the combination of aliskiren and HCTZ. However, these studies have been conducted for aliskiren and HCTZ alone. Aliskiren In developmental toxicity studies, pregnant rats and rabbits received oral aliskiren hemifumarate during organogenesis at doses up to 20 and 7 times the maximum recommended human dose (MRHD) based on body surface area (mg/m 2 ), respectively, in rats and rabbits.
(Actual animal doses were up to 600 mg/kg/day in rats and up to 100 mg/kg/day in rabbits.) No teratogenicity was observed; however, fetal birth weight was decreased in rabbits at doses 3.2 times the MRHD based on body surface area (mg/m 2 ). Aliskiren was present in placentas, amniotic fluid and fetuses of pregnant rabbits. HCTZ When pregnant mice and rats were given HCTZ at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the MRHD), during their respective periods of major organogenesis, there was no evidence of fetal harm.
Thiazides can cross the pla… [Excerpted — this section continues on DailyMed.]
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of Tekturna HCT in pediatric patients have not been established. Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients [see Nonclinical Toxicology ( 13.2 )] . Neonates with a history of in utero exposure to Tekturna HCT : If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion.
Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
🧓 Geriatric Use ▾
8.5Geriatric Use In the short-term controlled clinical trials of Tekturna HCT, 325 (19.6%) patients treated with Tekturna HCT were 65 years and older and 53 (3.2%) were 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE Aliskiren Limited data are available related to overdosage in humans. The most likely manifestation of overdosage would be hypotension. If symptomatic hypotension should occur, supportive treatment should be initiated.
Aliskiren is poorly dialyzed. Therefore, hemodialysis is not adequate to treat aliskiren overexposure [see Clinical Pharmacology ( 12.3 )] . Hydrochlorothiazide (HCTZ) The most common signs and symptoms of overdose observed in humans are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis.
If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which HCTZ is removed by hemodialysis has not been established. The oral LD 50 of HCTZ is greater than 10 g/kg in both mice and rats.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Aliskiren 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 angiotensin-converting enzyme (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. All agents that inhibit the RAAS, including renin inhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma renin concentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA.
During treatment with aliskiren, however, the effect of increased renin levels is blocked, so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents. Hydrochlorothiazide (HCTZ) HCTZ is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Indirectly, the diuretic action of HCTZ reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of agents that block the production or function of angiotensin II tends to reverse the potassium loss associated with these diuretics. The mechanism of action of the antihypertensive effect of thiazides is unknown.
12.2Pharmacodynamics Tekturna HCT In placebo-controlled clinical trials, PRA was decreased with aliskiren monotherapy (ranging from 54% to 65%) and increased with hydrochlorothiazide monotherapy (ranging from 4% to 72%). Treatment with Tekturna HCT resulted in PRA reductions ranging from approximately 46% to 63% in various doses despite the increase in PRA with hydrochlorothiazide treatment. The clinical implications of the differences in effect on PRA are not known.
Aliskiren PRA reductions in clinical trials ranged from approximately 50% to 80%, were not dose-related and did not correlate with blood pressure reductions. The clinical implications of the differences in effect on PRA are not known. Hydrochlorothiazide (HCTZ) After oral administration of HCTZ, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.
Drug Interactions Hydrochlorothiazide (HCTZ) Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur. Skeletal muscle relaxants: Possible increased responsiveness to muscle relaxants such as curare derivatives. Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia may predispose the patient to digoxin toxicity.
12.3Pharmacokinetics Absorption and Distribution Tekturna HCT Following oral administration of Tekturna HCT combination tablets, the median peak plasma concentration time is within 1 hour for aliskiren and 2.5 hours for HCTZ. When taken with food, mean AUC and C max of aliskiren are decreased by 60% and 82%, respectively; mean AUC and C max of HCTZ increased by 13% and 10%, respectively. As a result, patients should establish a routine patte… [Excerpted — this section continues on DailyMed.]
🧬 Mechanism of Action ▾
12.1Mechanism of Action Aliskiren 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 angiotensin-converting enzyme (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. All agents that inhibit the RAAS, including renin inhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma renin concentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA.
During treatment with aliskiren, however, the effect of increased renin levels is blocked, so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents. Hydrochlorothiazide (HCTZ) HCTZ is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts.
Indirectly, the diuretic action of HCTZ reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of agents that block the production or function of angiotensin II tends to reverse the potassium loss associated with these diuretics. The mechanism of action of the antihypertensive effect of thiazides is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Tekturna HCT is supplied as biconvex, ovaloid film-coated tablets. All strengths are packaged in bottles and unit-dose blister packages (10 strips of 10 tablets) as described below. Table 6: Tekturna HCT Tablets Supply Tablet Color Imprint Imprint NDC 70839-XXX-XX Aliskiren/HCTZ Side 1 Side 2 Bottle of 30 Bottle of 90 Blister Packages of 100 150 mg/12.5 mg White NVR LCI 112-30 112-90 112-01 150 mg/25 mg Pale Yellow NVR CLL 125-30 125-90 125-01 300 mg/12.5 mg Violet White NVR CVI 312-30 312-90 312-01 300 mg/25 mg Light Yellow NVR CVV 325-30 325-90 325-01 Storage Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF) [See USP Controlled Room Temperature].
Protect from moisture. Dispense in original container.
📋 Description ▾
11 DESCRIPTION Tekturna HCT is a fixed combination of aliskiren hemifumarate, an orally active, nonpeptide, direct renin inhibitor, and HCTZ, a thiazide diuretic that is provided as tablets for oral administration. Aliskiren 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 •
0.5C 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. Aliskiren Hemifumarate Structural Formula Hydrochlorothiazide (HCTZ) Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder.
It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n -butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide is chemically described as 6-chloro-3,4-dihydro-2 H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Hydrochlorothiazide is a thiazide diuretic.
Its empirical formula is C 7 H 8 ClN 3 O 4 S 2 , its molecular weight is 297.73, and its structural formula is: Tekturna HCT tablets are formulated for oral administration to contain aliskiren and hydrochlorothiazide, USP 150/12.5 mg, 150/25 mg, 300/12.5 mg, and 300/25 mg. The inactive ingredients for all strengths of the tablets are colloidal silicon dioxide, crospovidone, hydroxypropyl methylcellulose, iron oxide colorants, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, talc, titanium dioxide, and wheat starch.
Hydrochlorothiazide Structural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy Inform female patients of childbearing age about the consequences of exposure to Tekturna HCT during pregnancy. Discuss treatment options with women planning to become pregnant.
Advise patients to report pregnancies to their physicians as soon as possible. Lactation Advise nursing women that breastfeeding is not recommended during treatment with Tekturna HCT [see Use in Specific Populations ( 8.2 )]. Symptomatic Hypotension Inform patients that lightheadedness can occur, especially during the first days of Tekturna HCT therapy, and that it should be reported to the prescribing physician.
Advise patients that if syncope occurs, Tekturna HCT 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. 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 physician.
Angioedema, including laryngeal edema, may occur at any time during treatment with Tekturna HCT. Potassium Supplements Advise patients receiving Tekturna HCT not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician. Relationship to Meals Instruct patients to establish a routine pattern for taking Tekturna HCT with regard to meals.
High-fat meals decrease absorption substantially. Non-melanoma Skin Cancer: Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics Absorption and Distribution Tekturna HCT Following oral administration of Tekturna HCT combination tablets, the median peak plasma concentration time is within 1 hour for aliskiren and 2.5 hours for HCTZ. When taken with food, mean AUC and C max of aliskiren are decreased by 60% and 82%, respectively; mean AUC and C max of HCTZ increased by 13% and 10%, respectively. As a result, patients should establish a routine pattern for taking Tekturna HCT with regard to meals.
Aliskiren Aliskiren is poorly absorbed (bioavailability about 2.5%). Following oral administration, peak plasma concentrations of aliskiren are reached within 1 to 3 hours. When taken with a high fat meal, mean AUC and C max of aliskiren are decreased by 71% and 85% respectively.
In the clinical trials of aliskiren, it was administered without requiring a fixed relation of administration to meals. Hydrochlorothiazide (HCTZ) The estimated absolute bioavailability of HCTZ after oral administration is about 70%. Peak plasma HCTZ concentrations (C max ) are reached within 2 to 5 hours after oral administration.
There is no clinically significant effect of food on the bioavailability of HCTZ. HCTZ binds to albumin (40% to 70%) and distributes into erythrocytes. Following oral administration, plasma HCTZ concentrations decline bi-exponentially, with a mean distribution half-life of about 2 hours and an elimination half-life of about 10 hours.
Metabolism and Elimination Aliskiren The effective half-life for aliskiren is 24 hours. Steady state blood levels are reached in about 7 to 8 days. About one-fourth of the absorbed dose appears in the urine as parent drug.
How much of the absorbed dose is metabolized is unknown. Based on the in vitro studies, the major enzyme responsible for aliskiren metabolism appears to be CYP3A4. Aliskiren does not inhibit the CYP450 isoenzymes (CYP 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) or induce CYP3A4.
Transporters: Pgp (MDR1/Mdr1a/1b) was found to be the major efflux system involved in intestinal absorption and elimination via biliary excretion of aliskiren in preclinical studies. The potential for drug interactions at the Pgp site will likely depend on the degree of inhibition of this transporter. Hydrochlorothiazide (HCTZ) About 70% of an orally administered dose of HCTZ is eliminated in the urine as unchanged drug.
Drug Interactions: Aliskiren The effect of coadministered drugs on the pharmacokinetics of aliskiren and vice versa, were studied in several single and multiple dose studies. Pharmacokinetic measures indicating the magnitude of these interactions are presented in Figure 5 (impact of coadministered drugs on aliskiren) and Figure 6 (impact on coadministered drugs). Figure 5: The Impact of Coadministered Drugs on the Pharmacokinetics of Aliskiren *Ketoconazole: A 400 mg once daily dose was not studied, but would be expected to increase aliskiren blood levels further. **Ramipril, valsartan, irbesartan: In general, avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with CrCl less than 60 mL/min [see Drug Interactions ( 7 )].
Warfarin: There was no clinically significant effect of a single dose of warfarin 25 mg on the pharmacokinetics of aliskiren. Figure 6: The Impact of Aliskiren on the Pharmacokinetics of Coadministered Drugs * Furosemide: Patients receiving furosemide may find its effects diminished after starting aliskiren. In patients with heart failure, co-administration of aliskiren (300 mg/day) reduced plasma AUC and C max of oral furosemide (60 mg/day) by 17% and 27%, respectively, and reduced 24 hour urinary furosemide excretion by 29%.
This change in exposure did not result in statistically significant difference in total urine volume and urinary sodium excretion over 24 hours. However, a transient decrease in urinary sodium excretion and urine volume effects up to 12 hours were observed when furosemide was co-administered with aliskiren 300 mg/day. **Ramipril, v… [Excerpted — this section continues on DailyMed.]
🧬 Pharmacodynamics ▾
12.2Pharmacodynamics Tekturna HCT In placebo-controlled clinical trials, PRA was decreased with aliskiren monotherapy (ranging from 54% to 65%) and increased with hydrochlorothiazide monotherapy (ranging from 4% to 72%). Treatment with Tekturna HCT resulted in PRA reductions ranging from approximately 46% to 63% in various doses despite the increase in PRA with hydrochlorothiazide treatment. The clinical implications of the differences in effect on PRA are not known.
Aliskiren PRA reductions in clinical trials ranged from approximately 50% to 80%, were not dose-related and did not correlate with blood pressure reductions. The clinical implications of the differences in effect on PRA are not known. Hydrochlorothiazide (HCTZ) After oral administration of HCTZ, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.
Drug Interactions Hydrochlorothiazide (HCTZ) Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur. Skeletal muscle relaxants: Possible increased responsiveness to muscle relaxants such as curare derivatives. Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia may predispose the patient to digoxin toxicity.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES
14.1Tekturna HCT In all clinical trials including over 6,200 patients, more than 2,700 patients were exposed to combinations of aliskiren and HCTZ. The safety and efficacy of Tekturna HCT were evaluated in patients with mild-to-moderate hypertension in an 8-week, randomized, double-blind, placebo-controlled, parallel-group, 15-arm factorial trial (n=2762). Patients were randomized to receive various combinations of aliskiren (75 mg to 300 mg) plus HCTZ (6.25 mg to 25 mg) once daily (without titrating up from monotherapy) and followed for blood pressure response.
The combination of aliskiren and HCTZ resulted in additive placebo-adjusted decreases in systolic and diastolic blood pressure at trough of 10–14/5–7 mmHg at doses of 150–300 mg/12.5–25 mg, compared to 5–8/2–3 mmHg for aliskiren 150 mg to 300 mg and 6–7/2–3 mmHg for HCTZ 12.5 mg to 25 mg, alone. Blood pressure reductions with the combinations were greater than the reductions with the monotherapies as shown in Table 1 . Table 1: Placebo-Subtracted Reductions in Seated Trough Cuff Blood Pressure in Combination with Hydrochlorothiazide (HCTZ) Hydrochlorothiazide, mg 0 6.25 12.5 25 Aliskiren, mg Placebo Mean Change Placebo- subtracted Placebo- subtracted Placebo- subtracted Placebo- subtracted 0 7.5/6.9 -- 3.5/2.1 6.4/3.2 6.8/2.4 75 -- 1.9/1.8 6.8/3.8 8.2/4.2 9.8/4.5 150 -- 4.8/2 7.8/3.4 10.1/5 12/5.7 300 -- 8.3/3.3 -- 12.3/7 13.7/7.3 The safety and efficacy of Tekturna HCT as initial therapy was evaluated in this trial.
All patients randomized to the combination groups received the combination treatment of Tekturna HCT at assigned doses as initial therapy without titration from monotherapy. The figures [see Indications and Usage ( 1 )] display the probability that a patient will achieve systolic or diastolic blood pressure goal with Tekturna HCT 300/25 mg, based upon their baseline systolic or diastolic blood pressure. At all levels of baseline blood pressure, the probability of achieving any given diastolic or systolic goal is greater with the combination than for either monotherapy.
The antihypertensive effect of Tekturna HCT was largely manifested within 1 week. The maximum antihypertensive effect was generally attained after about 4 weeks of therapy. One active-controlled trial investigated the addition of 300 mg aliskiren in obese hypertensive patients who did not respond adequately to HCTZ 25 mg, and showed incremental decreases of systolic and diastolic blood pressure of approximately 7/4 mmHg.
In long-term follow-up studies (without placebo control) the effect of the combination of aliskiren and HCTZ was maintained for over 1 year. The antihypertensive effect was independent of age and gender. There were too few non-Caucasians to assess differences in blood pressure effects by race.
14.2Aliskiren Monotherapy The antihypertensive effects of aliskiren have been demonstrated in 6 randomized, double-blind, placebo- controlled, 8-week clinical trials in patients with mild-to-moderate hypertension. The placebo response and placebo-subtracted changes from baseline in seated trough cuff blood pressure are shown in Table 2 . Table 2: Reductions in Seated Trough Cuff Blood Pressure in the Placebo-Controlled Studies of Aliskiren Monotherapy *p value less than 0.05 versus placebo by ANCOVA with Dunnett's procedure for multiple comparisons. † p value less than 0.05 versus placebo by ANCOVA for the pairwise comparison.
Aliskiren Daily Dose, mg 75 150 300 600 Study Placebo Mean Change Placebo-subtracted Placebo-subtracted Placebo-subtracted Placebo-subtracted 1 2.9/3.3 5.7/4* 5.9/4.5* 11.2/7.5* -- 2 5.3/6.3 -- 6.1/2.9* 10.5/5.4* 10.4/5.2* 3 10/8.6 2.2/1.7 2.1/1.7 5.1/3.7* -- 4 7.5/6.9 1.9/1.8 4.8/2* 8.3/3.3* -- 5 3.8/4.9 -- 9.3/5.4* 10.9/6.2* 12.1/7.6* 6 4.6/4.1 -- -- 8.4/4.9 † -- The studies included approximately 2,730 patients given doses of 75 mg to 600 mg of aliskiren and 1,231 patients given placebo. As shown in Table 2 , there is some increase in res… [Excerpted — this section continues on DailyMed.]
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Tekturna HCT No carcinogenicity, mutagenicity or fertility studies have been conducted with Tekturna HCT. However, these studies have been conducted for aliskiren as well as HCTZ alone. Aliskiren Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic (rasH2) mouse study with aliskiren hemifumarate at oral doses of up to 1500 mg aliskiren/kg/day.
Although there were no statistically significant increases in tumor incidence associated with exposure to aliskiren, mucosal epithelial hyperplasia with or without erosion/ulceration) was observed in the lower gastrointestinal tract at doses of 750 or more mg/kg/day in both species, with a colonic adenoma identified in 1 rat and a cecal adenocarcinoma identified in another, rare tumors in the strain of rat studied. On a systemic exposure (AUC 0-24hr ) basis, 1500 mg/kg/day in the rat was about 4 times and in the mouse about 1.5 times the MRHD (300 mg aliskiren/day).
Mucosal hyperplasia in the cecum or colon of rats was also observed at doses of 250 mg/kg/day (the lowest tested dose) as well as at higher doses in 4- and 13-week studies. Aliskiren hemifumarate was devoid of genotoxic potential in the Ames reverse mutation assay with S. typhimurium and E. coli, the in vitro Chinese hamster ovary cell chromosomal aberration assay, the in vitro Chinese hamster V79 cell gene mutation test and the in vivo mouse bone marrow micronucleus assay. Fertility of male and female rats was unaffected at doses of up to 250 mg aliskiren/kg/day (8 times the MRHD of 300 mg Tekturna/60 kg on a mg/m 2 basis).
Hydrochlorothiazide (HCTZ) Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of HCTZ in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice. HCTZ was not genotoxic in vitro in the Ames mutagenicity assay of S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene.
Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of HCTZ from 43 to 1300 mcg/mL, and in the Aspergillums Nidulans nondisjunction assay at an unspecified concentration. HCTZ was not teratogenic and had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.
These doses of HCTZ in mice and rats represent 19 and 1.5 times, respectively, the MRHD on a mg/m 2 basis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)
13.2Animal Toxicology and/or Pharmacology Reproductive Toxicology Studies [See Use in Specific Populations ( 8.1 ).] Juvenile Animal Studies Juvenile toxicity studies indicated increased systemic exposure to aliskiren 85- to 385-fold in 14 day and 8 day old rats respectively, compared with adult rats. The mdr1 gene expression in juvenile rats was also significantly lower when compared to adult rats. The increased aliskiren exposure in juvenile rats appears to be mainly attributed to lack of maturation of P-gp.
The overexposure in juvenile rats was associated with high mortality [see Use in Specific Populations ( 8.4 )] .
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Tekturna HCT No carcinogenicity, mutagenicity or fertility studies have been conducted with Tekturna HCT. However, these studies have been conducted for aliskiren as well as HCTZ alone. Aliskiren Carcinogenic potential was assessed in a 2-year rat study and a 6-month transgenic (rasH2) mouse study with aliskiren hemifumarate at oral doses of up to 1500 mg aliskiren/kg/day.
Although there were no statistically significant increases in tumor incidence associated with exposure to aliskiren, mucosal epithelial hyperplasia with or without erosion/ulceration) was observed in the lower gastrointestinal tract at doses of 750 or more mg/kg/day in both species, with a colonic adenoma identified in 1 rat and a cecal adenocarcinoma identified in another, rare tumors in the strain of rat studied. On a systemic exposure (AUC 0-24hr ) basis, 1500 mg/kg/day in the rat was about 4 times and in the mouse about 1.5 times the MRHD (300 mg aliskiren/day).
Mucosal hyperplasia in the cecum or colon of rats was also observed at doses of 250 mg/kg/day (the lowest tested dose) as well as at higher doses in 4- and 13-week studies. Aliskiren hemifumarate was devoid of genotoxic potential in the Ames reverse mutation assay with S. typhimurium and E. coli, the in vitro Chinese hamster ovary cell chromosomal aberration assay, the in vitro Chinese hamster V79 cell gene mutation test and the in vivo mouse bone marrow micronucleus assay. Fertility of male and female rats was unaffected at doses of up to 250 mg aliskiren/kg/day (8 times the MRHD of 300 mg Tekturna/60 kg on a mg/m 2 basis).
Hydrochlorothiazide (HCTZ) Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of HCTZ in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice. HCTZ was not genotoxic in vitro in the Ames mutagenicity assay of S. typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene.
Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of HCTZ from 43 to 1300 mcg/mL, and in the Aspergillums Nidulans nondisjunction assay at an unspecified concentration. HCTZ was not teratogenic and had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.
These doses of HCTZ in mice and rats represent 19 and 1.5 times, respectively, the MRHD on a mg/m 2 basis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)
📄 Patient Package Insert ▾
Patient Information Tekturna ® HCT (tek-turn-a HCT) (aliskiren and hydrochlorothiazide) Tablets Read the Patient Information that comes with Tekturna HCT before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition and treatment.
What is the most important information I should know about Tekturna HCT? Tekturna HCT can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant.
If you get pregnant while taking Tekturna HCT, tell your doctor right away. What is Tekturna HCT? Tekturna HCT contains 2 prescription medicines in 1 tablet that work together to lower blood pressure.
It contains: aliskiren (Tekturna), a direct renin inhibitor (DRI) hydrochlorothiazide (HCTZ), a diuretic (water pill) Aliskiren (Tekturna) reduces the effect of renin, and the harmful process that narrows blood vessels. Aliskiren also helps blood vessels relax and widen so blood pressure is lower. Hydrochlorothiazide reduces the amount of salt and water in your body so your blood pressure is lower.
Tekturna HCT may be used to lower high blood pressure in adults when 1 medicine to lower high blood pressure is not enough as the first medicine to lower high blood pressure if your doctor decides that you are likely to need more than 1 medicine Tekturna HCT has not been studied in children under 18 years of age. Your doctor may prescribe other medicines for you to take along with Tekturna HCT to treat your high blood pressure. What is high blood pressure (hypertension)?
Blood pressure is the force of blood in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to blood vessels.
Tekturna HCT can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure may lower your chance of having a stroke or heart attack. Who should not take Tekturna HCT?
Do not take Tekturna HCT if: you get pregnant. Stop taking Tekturna HCT and call your doctor right away. If you plan to become pregnant, talk to your doctor about other treatment options for your high blood pressure. you have diabetes and are taking a kind of medicine called an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI). you make very little or no urine due to kidney problems. you are allergic to aliskiren, hydrochlorothiazide, any of the other ingredients of Tekturna HCT listed at the end of this leaflet.
Tekturna HCT has not been studied in children under 18 years of age What should I tell my doctor before taking Tekturna HCT? Before taking Tekturna HCT, tell your doctor if you: have kidney problems are pregnant or planning to become pregnant. See “ What is the most important information I should know about Tekturna HCT? ” have any allergies or asthma have liver problems have systemic lupus erythematosus (SLE).
Tekturna HCT can make your SLE active or worse. have ever had an allergic reaction called angioedema, to another blood pressure medicine. Symptoms may include swelling of the face, lips, tongue, throat,arms, and legs, and may cause difficulty breathing (angioedema). are breastfeeding. It is not known if Tekturna HCT passes into your breast milk and if it can harm your baby. have any other medical problems Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.
Tekturna HCT and certain other medicines may affect each other and cause side effects. Especially tell your doctor if you are taking: a kind of medicine to control blood pressure called angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) cholesterol-lowering medicines simvastatin (Zocor ® ) or atorvastat… [Excerpted — this section continues on DailyMed.]
📄 Recent Major Changes ▾
Contraindications ( 4 ) 3/2015 Warnings and Precautions ( 5.1 , 5.2 , 5.5 , 5.8 ) 3/2015
📄 Package Label / Principal Display Panel ▾
Principal Display Panel - Tekturna HCT 150/12.5 mg Label NDC 70839-112-30 30 tablets Tekturna HCT ® (aliskiren and hydrochlorothiazide) Tablets 150 mg/12.5 mg Rx only NODEN PHARMA ™ Principal Display Panel - Tekturna HCT 150/12.5 mg Label
Principal Display Panel - Tekturna HCT 150/25 mg Label NDC 70839-125-30 30 tablets Tekturna HCT ® (aliskiren and hydrochlorothiazide) Tablets 150 mg/25 mg Rx only NODEN PHARMA ™ Principal Display Panel - Tekturna HCT 150/25 mg Label
Principal Display Panel - Tekturna HCT 300/12.5 mg Label NDC 70839-312-30 30 tablets Tekturna HCT ® (aliskiren and hydrochlorothiazide) Tablets 300 mg/12.5 mg Rx only NODEN PHARMA ™ Principal Display Panel - Tekturna HCT 300/12.5 mg Label
Principal Display Panel - Tekturna HCT 300/25 mg Label NDC 70839-325-30 30 tablets Tekturna HCT ® (aliskiren and hydrochlorothiazide) Tablets 300 mg/25 mg Rx only NODEN PHARMA ™ Principal Display Panel - Tekturna HCT 300/25 mg Label
About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |