Drugs Details

Drugs Info of Tekamlo
Drugs Details
  • Drugs Type  : Multum
  • Date : 19th Jun 2015 02:43 am
  • Brand Name : Tekamlo
  • Generic Name : aliskiren and amlodipine (Pronunciation: AL is KYE ren and am LOE de peen)
Descriptions

Tekamlo is a single tablet for oral administration of aliskiren hemifumarate (an orally active, nonpeptide, potent direct renin inhibitor) and amlodipine besylate (a dihydropyridine calcium channel blocker).

Aliskiren hemifumarate

Aliskiren hemifumarate is chemically described as (2S,4S,5S,7S)-N-(2-carbamoyl-2-methylpropyl)-5-amino-4hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxypropoxy)phenyl]-octanamide hemifumarate and its structural formula is:

 

Aliskiren hemifumarate Structural Formula Illustration

Molecular formula: C30H53N3O6 • 0.5 C4H4O4

Aliskiren hemifumarate is a white to slightly yellowish powder with a molecular weight of 609.8 (free base- 551.8). It is highly soluble in water, and freely soluble in methanol, ethanol and isopropanol.

Amlodipine besylate

Amlodipine besylate, USP is chemically described as 3-Ethyl 5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(ochlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulfonate, and its structural formula is:

 

Amlodipine besylate Structural Formula Illustration

Molecular formula: C20H25CIN2O5•C6H6O3S

Amlodipine besylate is a white to pale yellow crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol.

Tekamlo tablets are formulated for oral administration to contain aliskiren hemifumarate and amlodipine besylate providing for the following available combinations: 150 mg/5 mg, 150 mg/10 mg, 300 mg/5 mg and 300 mg/10 mg aliskiren / amlodipine. The inactive ingredients for all strengths of the tablets may contain colloidal silicon dioxide, crospovidone, hypromellose, iron oxide red, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, talc, and titanium dioxide.

What are the possible side effects of this drug (Tekamlo)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • swelling in your hands, ankles, or feet;
  • feeling like you might pass out;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; or
  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple...

Read All Potential Side Effects and See Pictures of Tekamlo »

What are the precautions when taking aliskiren and amlodipine tablets (Tekamlo)?

Before taking this product, tell your doctor or pharmacist if you are allergic to either aliskiren or amlodipine; or to other calcium channel blockers (such as nifedipine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, kidney disease, loss of too much body water (dehydration), untreated mineral imbalance (such as low sodium, high potassium), certain structural heart problems (aortic/mitral stenosis), liver disease.

This product may increase your potassium levels. Before using potassium supplements or salt substitutes that contain...

This monograph has been modified to include the generic and brand name in many instances.

Indications

Tekamlo is indicated for the treatment of hypertension, alone or with other antihypertensive agents, 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 amlodipine. There are no controlled trials demonstrating risk reduction with Tekamlo.

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 one 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 also have 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 (for example, 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.

Data from the high-dose multifactorial study [see Clinical Studies] provide estimates of the probability of reaching a target blood pressure with Tekamlo compared to aliskiren or amlodipine monotherapy. The figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with Tekamlo 300 mg/10 mg, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable because of a small number of subjects with high baseline blood pressures.

Figure 1: Probability of Achieving Systolic Blood Pressure (SBP) < 140 mmHg

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Figure 2: Probability of Achieving Diastolic Blood Pressure (DBP) < 90 mmHg

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Figure 3: Probability of Achieving Systolic Blood Pressure (SBP) < 130 mmHg

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Figure 4: Probability of Achieving Diastolic Blood Pressure (DBP) < 80 mmHg

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The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal (e.g. SBP < 140 mmHg or < 130 mmHg) for the high dose groups evaluated in the study. 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. For example, the mean baseline SBP/DBP for patients participating in this multifactorial study was 157/100 mmHg. A patient with a baseline blood pressure of 157/100 mmHg has about a 49% likelihood of achieving a goal of < 140 mmHg (systolic) and 50% likelihood of achieving < 90 mmHg (diastolic) on aliskiren alone, and the likelihood of achieving these goals on amlodipine alone is about 62% (systolic) and 69% (diastolic). The likelihood of achieving these goals on Tekamlo rises to about 74% (systolic) and 83% (diastolic). The likelihood of achieving these goals on placebo is about 25% (systolic) and 27% (diastolic) [see DOSAGE AND ADMINISTRATION and Clinical Studies].

Dosage Administration

General Considerations

The recommended initial once-daily dose of Tekamlo is 150 mg/5 mg. Titrate as needed to a maximum of 300 mg/10 mg.

The blood pressure lowering effects are largely attained within 1-2 weeks. If blood pressure remains uncontrolled after 2 to 4 weeks of therapy, titrate the dose to a maximum of Tekamlo 300 mg/10 mg once daily.

Add-on Therapy

Use Tekamlo for patients not adequately controlled with aliskiren alone or amlodipine besylate (or another dihydropyridine calcium channel blocker) alone.

Switch a patient who experiences dose-limiting adverse reactions on either component alone to Tekamlo containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions.

Replacement Therapy

Switch patients receiving aliskiren and amlodipine besylate from separate tablets to a single tablet of Tekamlo containing the same component doses. When substituting for individual components, increase the dose of one or both of the components if blood pressure control has not been satisfactory.

Use with Other Antihypertensive Drugs

Tekamlo may be administered with some other antihypertensive agents. In diabetics, do not use in combination with angiotensin receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs) [see CONTRAINDICATIONS]. Concomitant use of aliskiren with an ARB or ACEI is not recommended in patients with GFR < 60 ml/min [see WARNINGS AND PRECAUTIONS]. It is not known whether Tekamlo decreases blood pressure further when added to maximum dosages of ACE inhibitors and beta blockers [see Clinical Studies].

Relationship to Meals

Advise patients to establish a routine pattern for taking Tekamlo with regard to meals. High-fat meals decrease absorption substantially [see CLINICAL PHARMACOLOGY].

How Supplied

Dosage Forms And Strengths

  • 150 mg aliskiren/5 mg amlodipine tablets: Non-scored light yellow, ovaloid convex shaped film-coated tablet with a beveled edge with debossing “T2” on one side and “NVR” on the reverse side of the tablet.
  • 150 mg aliskiren/10 mg amlodipine tablets: Non-scored yellow, ovaloid convex shaped film-coated tablet with a beveled edge with debossing “T7” on one side and “NVR” on the reverse side of the tablet.
  • 300 mg aliskiren/5 mg amlodipine tablets: Non-scored dark yellow, ovaloid convex shaped film-coated tablet with a beveled edge with debossing “T11” on one side and “NVR” on the reverse side of the tablet.
  • 300 mg aliskiren /10 mg amlodipine tablets: Non-scored brown yellow, ovaloid convex shaped film-coated tablet with a beveled edge with debossing “T12” on one side and “NVR” on the reverse side of the tablet.

Storage And Handling

Tekamlo (aliskiren and amlodipine) is supplied as follows:

150 mg aliskiren/5 mg amlodipine Tablets - Non-scored light yellow, ovaloid convex-shaped, film-coated tablet with a beveled edge with debossing “T2” on one side and “NVR” on the reverse side of the tablet. The tablet dimensions are approximately 16 x 6.3 mm.

150 mg aliskiren/10 mg amlodipine Tablets - Non-scored yellow, ovaloid convex shaped, film-coated tablet with a beveled edge with debossing “T7” on one side and “NVR” on the reverse side of the tablet. The tablet dimensions are approximately 16 x 6.3 mm.

300 mg aliskiren/5 mg amlodipine Tablets - Non-scored dark yellow, ovaloid convex-shaped, film-coated tablet with a beveled edge with debossing “T11” on one side and “NVR” on the reverse side of the tablet. The tablet dimensions are approximately 21 x 8.3 mm.

300 mg aliskiren/10 mg amlodipine Tablets - Non-scored brown yellow, ovaloid convex shaped, film-coated tablet with a beveled edge with debossing “T12” on one side and “NVR” on the reverse side of the tablet. The tablet dimensions are approximately 21 x 8.3 mm.

All strengths are packaged in bottles and unit-dose blister packages (10 strips of 10 tablets) as described below.

Table 2: Tekamlo Tablets Supply

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Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) in original container.

Protect from heat and moisture.

Dispense in original container.

Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: October 2013


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Studies Experience

The following serious adverse reactions are discussed in greater detail in other sections of the label:

  • Risk of fetal/neonatal morbidity and mortality [see WARNINGS AND PRECAUTIONS]
  • Head and neck angioedema [see WARNINGS AND PRECAUTIONS]
  • Hypotension [see WARNINGS AND PRECAUTIONS]

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.

Tekamlo

Tekamlo has been evaluated for safety in more than 2800 patients, including 372 patients for 1 year or longer.

In a placebo-controlled study, there were 51% males, 62% Caucasians, 20% Blacks, 18% Hispanics, and 17% who were over 65 years of age. In this study, the overall incidence of adverse events on therapy with Tekamlo was similar to the individual components. Discontinuation of therapy due to a clinical adverse event in this study occurred in 1.7% of patients treated with Tekamlo (2.2% in the highest dose group) versus 1.5% of patients given placebo.

Peripheral edema is a known, dose-dependent adverse effect of amlodipine. The incidence of peripheral edema for Tekamlo in short-term double-blind placebo-controlled studies was lower than or equal to that of the corresponding amlodipine doses.

The adverse event in a placebo-controlled trial that occurred in at least 2% of patients treated with Tekamlo and at a higher incidence than placebo was peripheral edema (6.2% versus 1.0%). The incidence rate of peripheral edema at high dose was 8.9%.

In a long-term safety trial, the safety profile of adverse events was similar to that seen in the short-term controlled trials.

Aliskiren

Aliskiren has been evaluated for safety in 6460 patients, including 1740 treated for longer than 6 months, and 1250 for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy because of 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 ACEI [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and Clinical Studies].

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) increases in diarrhea rates were evident starting at a dose of 150 mg daily, with rates for these subgroups at 150 mg similar to those seen at 300 mg for men or younger patients (all rates about 2%). 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 about one-third to one-half the rates in the ACE inhibitor arms.

Other adverse reactions with increased rates for aliskiren compared to placebo included rash (1% versus 0.3%), elevated uric acid (0.4% versus 0.1%), gout (0.2% versus 0.1%), and renal stones (0.2% versus 0%).

Single episodes of tonic-clonic seizures with loss of consciousness were reported in two patients treated with aliskiren in the clinical trials. One patient had predisposing causes for seizures and had a negative electroencephalogram (EEG) and cerebral imaging following the seizures; for the other patient, EEG and imaging results were not reported. Aliskiren was discontinued and there was no rechallenge in either case.

No clinically meaningful changes in vital signs or in ECG (including QTc interval) were observed in patients treated with aliskiren.

Amlodipine besylate

Amlodipine (Norvasc®) has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. Other adverse events that have been reported < 1% but > 0.1% of patients in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain were:

Cardiovascular: arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, postural hypotension, vasculitis

Central and Peripheral Nervous System: neuropathy peripheral, paresthesia, tremor, vertigo

Gastrointestinal: anorexia, constipation, dyspepsia,** dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia

General: allergic reaction, asthenia,** back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease

Musculoskeletal System: arthralgia, arthrosis, muscle cramps,** myalgia

Psychiatric: sexual dysfunction (male** and female), insomnia, nervousness, depression, abnormal dreams, anxiety, depersonalization

Respiratory System: dyspnea, epistaxis

Skin and Appendages: angioedema, erythema multiforme, pruritus,** rash,** rash erythematous, rash maculopapular

**These events occurred in less than 1% in placebo-controlled trials, but the incidence of these side effects was between 1% and 2% in all multiple dose studies.

Special Senses: abnormal vision, conjunctivitis, diplopia, eye pain, tinnitus

Urinary System: micturition frequency, micturition disorder, nocturia

Autonomic Nervous System: dry mouth, sweating increased

Metabolic and Nutritional: hyperglycemia, thirst

Hemopoietic: leukopenia, purpura, thrombocytopenia

Other events reported with amlodipine at a frequency of ≤ 0.1% of patients include: cardiac failure, pulse irregularity, extrasystoles, skin discoloration, urticaria, skin dryness, alopecia, dermatitis, muscle weakness, twitching, ataxia, hypertonia, migraine, cold and clammy skin, apathy, agitation, amnesia, gastritis, increased appetite, loose stools, rhinitis, dysuria, polyuria, parosmia, taste perversion, abnormal visual accommodation, and xerophthalmia. Other reactions occurred sporadically and cannot be distinguished from medications or concurrent disease states such as myocardial infarction and angina.

Clinical Laboratory Test Abnormalities

RBC count, hemoglobin and hematocrit: Small mean changes from baseline were seen in RBC count, hemoglobin and hematocrit in patients treated with both Tekamlo and aliskiren monotherapy. This effect is also seen with other agents acting on the renin angiotensin system. In aliskiren monotherapy trials these decreases led to slight increases in rates of anemia compared to placebo (0.1% for any aliskiren use, 0.3% for aliskiren 600 mg daily, vs. 0% for placebo). No patients discontinued due to anemia.

Blood Urea Nitrogen (BUN) / Creatinine: In patients with hypertension not concomitantly treated with an ARB or ACEI, elevations in BUN ( > 40 mg/dL) and creatinine ( > 2.0 mg/dL) in patients treated with Tekamlo were < 1.0%.

Serum Potassium: In patients with hypertension not concomitantly treated with an ARB or ACEI, increases in serum potassium > 5.5 mEq/L were infrequent (0.9% compared to 0.6% with placebo) [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Post-marketing Experience

The following adverse reactions have been identified during postapproval use of either aliskiren or amlodipine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure:

Hypersensitivity: angioedema requiring airway management and hospitalization

Aliskiren: Peripheral edema, severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, urticaria, hepatic enzyme increase with clinical symptoms of hepatic dysfunction, pruritus, erythema

Hypersensitivity: anaphylactic reactions and angioedema requiring airway management and hospitalization

Amlodipine: The following postmarketing event has been reported infrequently where a causal relationship is uncertain: gynecomastia. In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine.

Read the Tekamlo (aliskiren and amlodipine tablets) Side Effects Center for a complete guide to possible side effects

Interactions

No drug interaction studies have been conducted with Tekamlo and other drugs, although studies with the individual aliskiren and amlodipine besylate components are described below.

Aliskiren

Cyclosporine: Avoid co-administration of cyclosporine with aliskiren.

Itraconazole: Avoid co-administration of itraconazole with aliskiren [see CLINICAL PHARMACOLOGY].

Non-Steroidal Anti-Inflammatory Agents(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, co-administration of NSAIDs, including selective COX-2 inhibitors with agents that affect the renin-angiotensin-aldosterone system, 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: The concomitant use of aliskiren with other agents acting on the renin-angiotensin-aldosterone system 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. Monitor blood pressure, renal function, and electrolytes in patients on aliskiren and other agents that affect the renin-angiotensin-aldosterone system [see WARNINGS AND PRECAUTIONS].

The concomitant use of aliskiren with an ARB or an ACEI in diabetic patients is contraindicated and should be avoided in patients with moderate renal impairment [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Furosemide: Oral co-administration of aliskiren and furosemide reduced exposure to furosemide. Monitor diuretic effects when furosemide is co-administered with aliskiren.

Amlodipine besylate

Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

CYP3A4 Inhibitors: Co-administration with CYP3A inhibitors (moderate and strong) result in increased systemic exposure to amlodipine warranting dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A4 inhibitors to determine the need for dose adjustment.

CYP3A4 Inducers: No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be monitored when amlodipine is co-administered with CYP3A4 inducers.

Read the Tekamlo Drug Interactions Center for a complete guide to possible interactions


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Fetal Toxicity

Pregnancy Category D

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].

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 Tekturna HCT.

Renal 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 [see CONTRAINDICATIONS and Clinical Studies].

Avoid use of Tekturna HCT with ARBs or ACEIs in patients with moderate renal impairment (GFR < 60 ml/min).

Anaphylactic 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 ACE inhibitors or angiotensin receptor antagonists. Anaphylactic reactions have been reported from post-marketing 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 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.

Hypotension

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. 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.

Impaired 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 renin-angiotensin-aldosterone system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin-aldosterone system (e.g., patients with renal artery stenosis, severe heart failure, post-myocardial infarction or volume depletion) or patients receiving ARB, ACEI or non-steroidal anti-inflammatory (NSAID) therapy may be at particular risk of developing acute renal failure on Tekturna HCT [see CONTRAINDICATIONS, Clinical Studies]. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Tekturna HCT.

Hypersensitivity Reactions

Hydrochlorothiazide

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.

Systemic Lupus Erythematosus

Hydrochlorothiazide

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Lithium Interaction

Hydrochlorothiazide

Lithium generally should not be given with thiazides [see DRUG INTERACTIONS].

Serum Electrolyte Abnormalities

Tekturna HCT

In the short-term controlled trials of various doses of Tekturna HCT, in patients with hypertension not concomitantly treated with an ARB or ACEI, the incidence of hypertensive patients who developed hypokalemia (serum potassium < 3.5 mEq/L) was 2.2%; the incidence of hyperkalemia (serum potassium > 5.5 mEq/L) was 0.8%. No patients discontinued due to increase or decrease of serum potassium.

Aliskiren

Monitor serum potassium periodically in patients receiving aliskiren. Drugs that affect the renin-angiotensinaldosterone system can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes, combination use with ARBs or ACEI [see CONTRAINDICATIONS, and Clinical Studies], NSAIDs, or potassium supplements or potassium sparing diuretics.

Hydrochlorothiazide

Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion.

If hypokalemia is accompanied by clinical signs (e.g., muscular weakness, paresis, or ECG alterations), Tekturna HCT should be discontinued. Correction of hypokalemia and any coexisting hypomagnesemia is recommended prior to the initiation of thiazides.

Cyclosporine or Itraconazole

Aliskiren

When aliskiren was given with cyclosporine or itraconazole, the blood concentrations of aliskiren were significantly increased. Avoid concomitant use of aliskiren with cyclosporine or itraconazole [see DRUG INTERACTIONS].

Acute Myopia and Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Metabolic Disturbances

Hydrochlorothiazide

Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and triglycerides.

Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.

Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving Tekturna HCT.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION)

Healthcare professionals should instruct their patients to read the Patient Package Insert before starting Tekturna HCT and to reread each time the prescription is renewed. Patients should be instructed to inform their doctor or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to Tekturna HCT during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

Symptomatic Hypotension

A patient receiving Tekturna HCT should be cautioned that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to the prescribing physician. The patients should be told that if syncope occurs, Tekturna HCT should be discontinued until the physician has been consulted.

All patients should be cautioned 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

Patients should be advised and told to report immediately 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

A patient receiving Tekturna HCT should be told not to use potassium supplements or salt substitutes containing potassium without consulting the prescribing physician.

Relationship to Meals

Patients should establish a routine pattern for taking Tekturna HCT with regard to meals. High-fat meals decrease absorption substantially.

Nonclinical Toxicology

Carcinogenesis, 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 hydrochlorothiazide 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 one rat and a cecal adenocarcinoma identified in another, rare tumors in the strain of rat studied. On a systemic exposure (AUC0-24hr) basis, 1500 mg/kg/day in the rat is about 4 times and in the mouse about 1.5 times the maximum recommended human dose (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 maximum recommended human dose of 300 mg Tekturna/60 kg on a mg/m² basis).

Hydrochlorothiazide

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 hydrochlorothiazide 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.

Hydrochlorothiazide 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 hydrochlorothiazide from 43 to 1300 mcgm/mL, and in the Aspergillums Nidulans nondisjunction assay at an unspecified concentration.

Hydrochlorothiazide 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 hydrochlorothiazide in mice and rats represent 19 and 1.5 times, respectively, the maximum recommended human dose on a mg/m² basis. (Calculations assume an oral dose of 25 mg/day and a 60-kg patient.)

Use In Specific Populations

Pregnancy

Pregnancy Category D

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. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. 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. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

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. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Tekturna HCT, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. 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.

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.

Reproductive toxicity studies of aliskiren hemifumarate did not reveal any evidence of teratogenicity at oral doses up to 600 mg aliskiren/kg/day (20 times the maximum recommended human dose [MRHD] of 300 mg/day on a mg/m² basis) in pregnant rats or up to 100 mg aliskiren/kg/day (seven times the MRHD on a mg/m² basis) in pregnant rabbits. Fetal birth weight was adversely affected in rabbits at 50 mg/kg/day (3.2 times the MRHD on a mg/m² basis). Aliskiren was present in placenta, amniotic fluid and fetuses of pregnant rabbits.

When pregnant mice and rats were given hydrochlorothiazide 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.

Hydrochlorothiazide

Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (pre eclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of hydrochlorothiazide for other indications (e.g. heart disease) in pregnancy should be avoided.

Nursing Mothers

It is not known whether aliskiren is excreted in human milk, but aliskiren was secreted in the milk of lactating rats. Thiazides appear in human milk. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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

In the short-term controlled clinical trials of Tekturna HCT, 325 (19.6%) patients treated with Tekturna HCT were ≥ 65 years and 53 (3.2%) were ≥ 75 years.

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.

Renal Impairment

Safety and effectiveness of Tekturna HCT in patients with severe renal impairment (CrCl ≤ 30 mL/min) have not been established. No dose adjustment is required in patients with mild (CrCl 60-90 mL/min) or moderate (CrCl 30-60) renal impairment.

Hepatic Impairment

Aliskiren

No dose adjustment is necessary for patients with mild-to-severe liver disease.

Hydrochlorothiazide

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

Aliskiren

Limited data are available related to overdosage in humans. The most likely manifestation of overdosage would be hypotension. If symptomatic hypotension should occur, provide supportive treatment.

Aliskiren is poorly dialyzed. Therefore, hemodialysis is not adequate to treat aliskiren overexposure [see CLINICAL PHARMACOLOGY].

Amlodipine besylate

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. Marked and potentially prolonged systemic hypotension up to and including shock with fatal outcome have been reported. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.

If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit. Administration of activated charcoal to healthy volunteers immediately or up to two hours after ingestion of amlodipine has been shown to significantly decrease amlodipine absorption.

ContrainDications

Do not use aliskiren with ARBs or ACEIs in patients with diabetes [see WARNINGS AND PRECAUTIONS, Clinical Studies].

Tekamlo is contraindicated in patients with known hypersensitivity to any of the components.


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism 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

Hydrochlorothiazide 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 hydrochlorothiazide 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.

Pharmacodynamics

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

After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.

Drug Interactions

Hydrochlorothiazide

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.

Pharmacokinetics

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 hydrochlorothiazide. When taken with food, mean AUC and Cmax of aliskiren are decreased by 60% and 82%, respectively; mean AUC and Cmax of hydrochlorothiazide 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 Cmax 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

The estimated absolute bioavailability of hydrochlorothiazide after oral administration is about 70%. Peak plasma hydrochlorothiazide concentrations (Cmax) are reached within 2 to 5 hours after oral administration. There is no clinically significant effect of food on the bioavailability of hydrochlorothiazide.

Hydrochlorothiazide binds to albumin (40 to 70%) and distributes into erythrocytes. Following oral administration, plasma hydrochlorothiazide 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 – 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 CYP 3A4. Aliskiren does not inhibit the CYP450 isoenzymes (CYP 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) or induce CYP 3A4.

Transporters: Pgp (MDR1/Mdr1a/1b) was found to be the major efflux system involved in absorption and disposition 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

About 70% of an orally administered dose of hydrochlorothiazide is eliminated in the urine as unchanged drug.

Drug interactions

Aliskiren

The effect of co-administered 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 co-administered drugs on aliskiren) and Figure 6 (impact on co-administered drugs).

Figure 5: The impact of co-administered drugs on the pharmacokinetics of aliskiren

View Enlarged Table

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 co-administered drugs

View Enlarged Table

Furosemide: In patients with heart failure, co-administration of aliskiren (300 mg/day) reduced plasma AUC and Cmax 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.

Hydrochlorothiazide

Drugs that alter gastrointestinal motility: The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents (e.g. atropine, biperiden), apparently due to a decrease in gastrointestinal motility and the stomach emptying rate. Conversely, pro-kinetic drugs may decrease the bioavailability of thiazide diuretics.

Cholestyramine: In a dedicated drug interaction study, administration of cholestyramine 2 hours before hydrochlorothiazide resulted in a 70% reduction in exposure to hydrochlorothiazide. Further, administration of hydrochlorothiazide 2 hours before cholestyramine, resulted in 35% reduction in exposure to hydrochlorothiazide.

Antineoplastic agents (e.g. cyclophosphamide, methotrexate): Concomitant use of thiazide diuretics may reduce renal excretion of cytotoxic agents and enhance their myelosuppressive effects.

Special Populations

Pediatric Patients

The pharmacokinetics of aliskiren have not been investigated in patients < 18 years of age.

Geriatric Patients

Aliskiren

The pharmacokinetics of aliskiren were studied in the elderly ( ≥ 65 years). Exposure (measured by AUC) is increased in elderly patients. Hydrochlorothiazide A limited amount of data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly subjects compared to young healthy volunteers.

Race

Too few non-Caucasians have been studied with Tekturna HCT to assess pharmacokinetic differences among races. The pharmacokinetic differences among Blacks, Caucasians, and Japanese are minimal with aliskiren therapy.

Renal Impairment

Aliskiren

The pharmacokinetics of aliskiren were evaluated in patients with varying degrees of renal impairment. Rate and extent of exposure (AUC and Cmax) of aliskiren in subjects with renal impairment did not show a consistent correlation with the severity of renal impairment [see Use in Specific Populations].

The pharmacokinetics of aliskiren following administration of a single oral dose of 300 mg was evaluated in patients with End Stage Renal Disease (ESRD) undergoing hemodialysis. When compared to matched healthy subjects, changes in the rate and extent of aliskiren exposure (Cmax and AUC) in ESRD patients undergoing hemodialysis were not clinically significant.

Timing of hemodialysis did not significantly alter the pharmacokinetics of aliskiren in ESRD patients. Therefore, no dose adjustment is warranted in ESRD patients receiving hemodialysis.

Hydrochlorothiazide

In a study in individuals with impaired renal function, the mean elimination half-life of hydrochlorothiazide was doubled in individuals with mild/moderate renal impairment (30 < CLcr < 90 mL/min) and tripled in severe renal impairment ( ≤ 30 mL/min), compared to individuals with normal renal function (CLcr > 90 mL/min) [see Use in Specific Populations].

Hepatic Impairment

Aliskiren

The pharmacokinetics of aliskiren were not significantly affected in patients with mild-to-severe liver disease [see Use in Specific Populations].

Clinical Studies

Tekturna HCT

In all clinical trials including over 6,200 patients, more than 2,700 patients were exposed to combinations of aliskiren and hydrochlorothiazide. 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, 15arm factorial trial (n=2762). Patients were randomized to receive various combinations of aliskiren (75 mg to 300 mg) plus hydrochlorothiazide (6.25 mg to 25 mg) once daily (without titrating up from monotherapy) and followed for blood pressure response. The combination of aliskiren and hydrochlorothiazide 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 hydrochlorothiazide 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

View Enlarged Table

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] 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 hydrochlorothiazide 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 hydrochlorothiazide 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.

Aliskiren Monotherapy

The antihypertensive effects of aliskiren have been demonstrated in six 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

Study Placebo Mean Change Aliskiren Daily Dose, mg
75 150 300 600
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 -- -- 8.4/4.91† --
*p < 0.05 vs. placebo by ANCOVA with Dunnett's procedure for multiple comparisons.
†p < 0.05 vs. placebo by ANCOVA for the pairwise comparison

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 response with administered dose in all studies, with reasonable effects seen at 150 mg to 300 mg, and no clear further increase at 600 mg. A substantial proportion (85% to 90%) of the blood pressure lowering effect was observed within 2 weeks of treatment. Studies with ambulatory blood pressure monitoring showed reasonable control throughout the interdosing interval, e.g., the ratios of mean daytime to mean nighttime ambulatory BP ranged from 0.6 to 0.9.

Patients in the placebo-controlled trials continued open-label aliskiren for up to one year. A persistent blood pressure lowering effect was demonstrated by a randomized withdrawal study (patients randomized to continued drug or placebo), which showed a statistically significant difference between patients kept on aliskiren and those randomized to placebo. With cessation of treatment, blood pressure gradually returned toward baseline levels over a period of several weeks. There was no evidence of rebound hypertension after abrupt cessation of therapy.

The effectiveness of aliskiren was demonstrated across all demographic subgroups, although Black patients tended to have smaller reductions in blood pressure than Caucasians and Asians, as has been seen with ACE inhibitors and ARBs.

Aliskiren in Combination with Other Antihypertensives

Valsartan

Aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg were studied alone and in combination in an 8week, 1,797-patient, randomized, double-blind, placebo-controlled, parallel-group, 4-arm, dose-escalation study. The dosages of aliskiren and valsartan were started at 150 mg and 160 mg, respectively, and increased at four weeks to 300 mg and 320 mg, respectively. Seated trough cuff blood pressure was measured at baseline, 4, and 8 weeks. Blood pressure reductions with the combinations were greater than the reductions with the monotherapies as shown in Table 3.

Table 3: Placebo-Subtracted Reductions in Seated Trough Cuff Blood Pressure of Aliskiren in Combination with Valsartan

Aliskiren, mg Placebo Mean Change Valsartan, mg
0 160 320
0 4.6/4.1* -- 5.6/3.9 8.2/5.6
150 -- 5.4/2.7 10.0/5.7 --
300 -- 8.4/4.9 -- 12.6/8.1
* The placebo change is 5.2/4.8 for Week 4 endpoint which was used for the dose groups containing aliskiren 150 mg or valsartan 160 mg.
Amlodipine

Aliskiren 150 mg and 300 mg and amlodipine besylate 5 mg and 10 mg were studied alone and in combination in an 8week, 1,685-patient, randomized, double-blind, placebo-controlled, multifactorial study. Treatment with aliskiren and amlodipine resulted overall in significantly greater reductions in diastolic and systolic blood pressure compared to the respective monotherapy components as shown in Table 4.

Table 4: Placebo-Subtracted Reductions in Seated Trough Cuff Blood Pressure in Combination with Amlodipine

Aliskiren, mg Placebo mean change Amlodipine, mg
0 5 10
0 5.4/6.8 __ 5.6/9.0 8.5/14.3
150 -- 2.6/3.9 8.6/13.9 10.8/17.1
300 -- 4.9/8.6 9.6/15.0 11.1/16.4
ACE Inhibitors

Aliskiren has not been studied when added to maximal doses of ACE inhibitors to determine whether aliskiren produces additional blood pressure reduction.

There are no trials of the Tekturna HCT combination tablet demonstrating reductions in cardiovascular risk in patients with hypertension, but the hydrochlorothiazide component has demonstrated such benefits.

Aliskiren in Patients with Diabetes treated with ARB or ACEI (ALTITUDE study)

Patients with diabetes with renal disease (defined either by the presence of albuminuria or reduced GFR) were randomized to aliskiren 300 mg daily (n=4283) or placebo (n=4296). All patients were receiving background therapy with an ARB or ACEI. The primary efficacy outcome was the time to the first event of the primary composite endpoint consisting of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, onset of end stage renal disease, renal death, and doubling of serum creatinine concentration from baseline sustained for at least one month. After a median follow up of about 27 months, the trial was terminated early for lack of efficacy. Higher risk of renal impairment, hypotension and hyperkalemia was observed in aliskiren compared to placebo treated patients, as shown in the table below.

Table 5: Incidence of selected adverse events in ALTITUDE

  Aliskiren
N=4283
Placebo
N=4296
Serious Adverse Events* (%) Adverse Events (%) Serious Adverse Events* (%) Adverse Events (%)
Renal impairment† 4.7 12.4 3.3 10.4
Hypotension †† 2.0 18.6 1.7 14.8
Hyperkalemia††† 1.1 36.9 0.3 27.1
†renal failure, renal failure acute, renal failure chronic, renal impairment
††dizziness, dizziness postural, hypotension, orthostatic hypotension, presyncope, syncope
††† Given the variable baseline potassium levels of patients with renal insufficiency on dual RAAS therapy, the reporting of adverse event of hyperkalemia was at the discretion of the investigator.
* A Serious Adverse Event (SAE) is defined as: an event which is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, or is medically significant (i.e. defined as an event that jeopardizes the patient or may require medical or surgical intervention to prevent one of the outcomes previously listed).

The risk of stroke (2.7% aliskiren vs 2.0% placebo) and death (6.9% aliskiren vs. 6.4% placebo) were also numerically higher in aliskiren treated patients.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Tekamlo™
(tek'-am-lo)
(aliskiren and amlodipine) Tablets

Read the Patient Information that comes with Tekamlo before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your condition and treatment. If you have any questions about Tekamlo, ask your doctor or pharmacist.

What is the most important information I should know about Tekamlo?

Tekamlo 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 Tekamlo, tell your doctor right away.

What is Tekamlo?

Tekamlo is a prescription medicine that may be used:

  • as the first medicine to lower your high blood pressure if your doctor decides that you are likely to need more than one medicine.
  • to treat your high blood pressure when one medicine to lower your high blood pressure has not worked well enough.
  • if you are already taking the medicines aliskiren and amlodipine to treat your high blood pressure.

Tekamlo contains:

  • aliskiren, a direct renin inhibitor (DRI)
  • amlodipine, a calcium channel blocker (CCB)

Your doctor may prescribe other medicines for you to take along with Tekamlo to treat your high blood pressure.

It is not known if Tekamlo is safe and works in children under 18 years of age.

Who should not take Tekamlo?

  • If you get pregnant, stop taking Tekamlo 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.
  • If you have diabetes and are taking a kind of medicine called an angiotensin-receptor-blocker or angiotensin-converting-enzyme-inhibitor.
  • If you are allergic (hypersensitive) to aliskiren, amlodipine or other dihydropyridines (calcium­channel blockers, a group of medicines to lower blood pressure to which amlodipine belongs) or any of the other ingredients of Tekamlo listed at the end of this leaflet.

What should I tell my doctor before taking Tekamlo?

Before taking Tekamlo, tell your doctor if you:

  • have kidney problems
  • have liver problems
  • have ever had an allergic reaction to another blood pressure medicine. Symptoms may include: swelling of the face, lips, tongue, throat, arms and legs, and trouble breathing.
  • suffer from heart disorders or if you experienced a heart attack
  • have any other medical problems
  • are pregnant or planning to become pregnant. See “What is the most important information I should know about Tekamlo?”
  • are breastfeeding. It is not known if Tekamlo passes into your breast milk and if it can harm your baby. You and your doctor should decide if you will take Tekamlo or breastfeed. You should not do both.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Tekamlo and certain other medicines may affect each other and cause side effects.

Especially tell your doctor if you take:

  • a kind of medicine called angiotensin receptor blocker or angiotensin converting enzyme inhibitor
  • water pills (also called “diuretics”)
  • medicines for treating fungus or fungal infections
  • cyclosporine (Gengraf®, Neoral, Sandimmune), a medicine used to suppress the immune system
  • potassium-containing medicines, potassium supplements, or salt substitutes containing potassium
  • non-steroidal anti-inflammatory drugs (like ibuprofen or naproxen)
  • simvastatin (Zocor®) or atorvastatin (Lipitor®)
  • medicines used to treat AIDS or HIV infections (such as ritonavir, indinavir)

Know your medicines. Keep a list of all your medicines. Show this list to your doctor or pharmacist when you get a new medicine. Your doctor or pharmacist will know what medicines are safe to take together.

How should I take Tekamlo?

  • Take Tekamlo exactly as prescribed by your doctor. It is important to take Tekamlo every day to control your blood pressure.
  • Take Tekamlo one time a day, about the same time each day.
  • Take Tekamlo the same way every day, either with or without a meal.
  • Your doctor may change your dose of Tekamlo if needed. Do not change the amount of Tekamlo you take without talking to your doctor.
  • If you miss a dose of Tekamlo, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Just take the next dose at your regular time.
  • If you take too much Tekamlo, call your doctor or a Poison Control Center, or go to the nearest hospital emergency room.

What are the possible side effects of Tekamlo?

Tekamlo may cause serious side effects:

  • Harm to an unborn baby, causing injury or death. See “What is the most important information I should know about Tekamlo?”
  • Severe Allergic Reactions and Angioedema. Aliskiren, one of the medicines in Tekamlo, can cause difficulty breathing or swallowing, tightness of the chest, hives, general rash, swelling, itching, dizziness, vomiting, or abdominal pain (signs of a severe allergic reaction). Aliskiren can also cause swelling of your face, lips, tongue, throat, arms and legs, or the whole body (signs of angioedema). Get medical help right away and tell your doctor if you get any one or more of these symptoms. Angioedema can happen at any time while you are taking Tekamlo.
  • Low blood pressure (hypotension). Your blood pressure may get too low if you also take water pills, are on a low-salt diet, get dialysis treatments, have heart problems, or get sick with vomiting or diarrhea. Lie down if you feel faint or get dizzy. Call your doctor right away.
  • Possible increased chest pain or risk of heart attack. It is rare, but when you first start taking Tekamlo or increase your dose, you may have a heart attack or your angina may get worse. If that happens, call your doctor right away or go directly to a hospital emergency room.
  • Renal impairment or failure. Aliskiren, one of the medicines in Tekamlo, may cause renal disorder with symptoms such as severely decreased urine output or decreased urine output (signs of renal impairment or failure).

The most common side effects of Tekamlo include:

  • Swelling of your lower legs

Common side effects of Tekamlo include

  • diarrhea
  • cough
  • dizziness
  • flu-like symptoms
  • tiredness
  • high levels of potassium in the blood (hyperkalemia)

Less common side effects include rash, severe skin reactions (signs may include severe blistering of the lips, eyes or mouth, rash with fever and skin peeling) and liver disorder (signs may include nausea, loss of appetite, dark colored urine or yellowing of skin and eyes).

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of Tekamlo. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How do I store Tekamlo?

  • Store Tekamlo tablets at room temperature between 59°F to 86°F (15°C to 30°C).
  • Keep the original prescription bottle and store in a dry place.
  • Protect Tekamlo from heat and moisture.

Keep Tekamlo and all medicines out of the reach of children.

General information about Tekamlo

Medicines are sometimes prescribed for conditions not listed in the patient information leaflet. Do not take Tekamlo for a condition for which it was not prescribed. Do not give Tekamlo to other people, even if they have the same condition or symptoms you have. It may harm them.

This leaflet summarizes the most important information about Tekamlo. If you have questions about Tekamlo talk with your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals.

For more information about Tekamlo, visit www.Tekamlo.com, or call 1-888­NOW-NOVA (1-888-669-6682).

What are the ingredients in Tekamlo?

Active Ingredients: Aliskiren hemifumarate and amlodipine

Inactive ingredients: Colloidal silicon dioxide, crospovidone, hypromellose, iron oxide red, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, talc, and titanium dioxide.

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 through the body and causes damage to blood vessels. Tekamlo 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.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ALISKIREN/AMLODIPINE - ORAL

 

(AL-is-KYE-ren/am-LOE-di-peen)

 

COMMON BRAND NAME(S): Tekamlo

 

WARNING: This drug can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy. Therefore, it is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication. If you are planning pregnancy, become pregnant, or think you may be pregnant, contact your doctor immediately.

 

USES: This product is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This product contains 2 medications: aliskiren and amlodipine. Aliskiren is a direct renin inhibitor and amlodipine is a calcium channel blocker. They both work to relax the blood vessels so that blood can flow more easily.

These medications are used together when one drug is not controlling your blood pressure. Your doctor may direct you to start taking the individual medications first, and then switch you to this combination product if it is the best dose combination for you.

 

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking aliskiren/amlodipine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily. Some foods may decrease how well this drug is absorbed by the body. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose.

Do not take with fruit juices (such as apple, grapefruit, or orange) since they may decrease the absorption of this drug.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

It may take 1 to 2 weeks before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

Consumer Overview Side Effect

SIDE EFFECTS: Dizziness or lightheadedness may occur as your body adjusts to the medication. Swelling hands/ankles/feet, flushing, or diarrhea may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fainting, fast heartbeat, symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat), change in the amount of urine.

Some people who already have severe heart disease may rarely develop worsening chest pain or a heart attack after starting this medication or increasing the dose. Get medical help right away if you experience: worsening chest pain, symptoms of a heart attack (such as chest/jaw/left arm pain, shortness of breath, unusual sweating).

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Tekamlo (aliskiren and amlodipine tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking this product, tell your doctor or pharmacist if you are allergic to either aliskiren or amlodipine; or to other calcium channel blockers (such as nifedipine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, kidney disease, loss of too much body water (dehydration), untreated mineral imbalance (such as low sodium, high potassium), certain structural heart problems (aortic/mitral stenosis), liver disease.

This product may increase your potassium levels. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor or pharmacist.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Too much sweating, diarrhea, or vomiting may cause dehydration and increase your risk of lightheadedness. Report prolonged diarrhea or vomiting to your doctor. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the effects of this product, especially dizziness and diarrhea.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details. (See also Warning section.)

It is unknown if aliskiren or amlodipine passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: See also How to Use and Precautions sections.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this medication include: drugs that may increase the level of potassium in the blood (including amiloride, triamterene, ACE inhibitors such as lisinopril/fosinopril/quinapril, ARBs such as irbesartan/candesartan/telmisartan, birth control pills containing drospirenone).

Other medications can affect the removal of aliskiren from your body, which may affect how aliskiren works. Examples include azole antifungals (such as itraconazole), cyclosporine, quinidine, among others.

Check the labels on all your medicines (such as cough-and-cold products, diet aids, or NSAIDs such as ibuprofen, naproxen) because they may contain ingredients that could increase your blood pressure. Ask your pharmacist for more details.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting, fast heartbeat.

 

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise, and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (such as kidney function, blood potassium levels) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Check your blood pressure regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised November 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Tekamlo

Generic Name: aliskiren and amlodipine (Pronunciation: AL is KYE ren and am LOE de peen)

  • What is this drug (Tekamlo)?
  • What are the possible side effects of this drug (Tekamlo)?
  • What is the most important information I should know about this drug (Tekamlo)?
  • What should I discuss with my health care provider before taking this drug (Tekamlo)?
  • How should I take this drug (Tekamlo)?
  • What happens if I miss a dose (Tekamlo)?
  • What happens if I overdose (Tekamlo)?
  • What should I avoid while taking this drug (Tekamlo)?
  • What other drugs will affect this drug (Tekamlo)?
  • Where can I get more information?

What is this drug (Tekamlo)?

Aliskiren is an anti-hypertensive (blood pressure lowering) medication. It works by decreasing substances in the body that narrow blood vessels and raise blood pressure.

Amlodipine is in a group of drugs called calcium channel blockers. Amlodipine relaxes (widens) blood vessels and improves blood flow.

The combination of aliskiren and amlodipine is used to treat high blood pressure (hypertension).

Aliskiren and amlodipine may also be used for purposes not listed in this medication guide.

What are the possible side effects of this drug (Tekamlo)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • swelling in your hands, ankles, or feet;
  • feeling like you might pass out;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; or
  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects may include:

  • diarrhea;
  • stomach pain, upset stomach; or
  • cough.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Tekamlo (aliskiren and amlodipine tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about this drug (Tekamlo)?

Do not use aliskiren and amlodipine if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant.

You should not take this medication if you are allergic to aliskiren or amlodipine, or if you are also using cyclosporine (Gengraf, Neoral, Sandimmune) or itraconazole (Sporanox).

Before you take aliskiren and amlodipine, tell your doctor if you have kidney or liver disease, congestive heart failure, coronary artery disease, an electrolyte imbalance (such as low potassium or magnesium), if you are on a low-salt diet, or if you have ever had an allergic reaction to a blood pressure medication.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Side Effects Centers
  • Tekamlo

Patient Detailed How Take

What should I discuss with my health care provider before taking this drug (Tekamlo)?

You should not take this medication if you are allergic to aliskiren or amlodipine, or if you are also using cyclosporine (Gengraf, Neoral, Sandimmune) or itraconazole (Sporanox).

If you have diabetes or kidney disease, you may not be able to take aliskiren and amlodipine if you are also taking any of the following heart or blood pressure medications:

  • azilsartan (Edarbi, Edarbyclor), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro, Avalide), losartan (Cozaar, Hyzaar), olmesartan (Benicar), valsartan (Diovan), telmisartan (Micardis); or
  • benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik, Tarka).

To make sure you can safely take aliskiren and amlodipine, tell your doctor if you have any of these other conditions:

  • kidney disease (or if you are on dialysis);
  • liver disease;
  • congestive heart failure;
  • coronary artery disease (hardened arteries);
  • an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);
  • if you are on a low-salt diet; or
  • if you have ever had an allergic reaction to a blood pressure medication, such as benazepril (Lotensin), candesartan (Atacand), enalapril (Vasotec), lisinopril (Prinivil, Zestril), losartan (Cozaar, Hyzaar), olmesartan (Benicar, Azor), quinapril (Accupril), ramipril (Altace), telmisartan (Micardis, Twynsta), valsartan (Diovan, Exforge), and others.

FDA pregnancy category D. Do not use aliskiren and amlodipine if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Aliskiren and amlodipine can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking aliskiren and amlodipine.

It is not known whether this medication passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are taking aliskiren and amlodipine.

How should I take this drug (Tekamlo)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your chest pain may become worse when you first start taking amlodipine or when your dose is increased. Call your doctor if your chest pain is severe or ongoing.

Aliskiren and amlodipine may be taken with or without food, but take it the same way each time.

Your blood pressure will need to be checked often. Visit your doctor regularly.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low-salt diet, or taking diuretics (water pills). Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Tekamlo

Patient Detailed Avoid Taking

What happens if I miss a dose (Tekamlo)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Tekamlo)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include rapid heartbeats, severe dizziness, warmth or tingly feeling, and fainting.

What should I avoid while taking this drug (Tekamlo)?

Avoid taking this medication with foods that are high in fat, which can make it harder for your body to absorb aliskiren.

What other drugs will affect this drug (Tekamlo)?

Tell your doctor about all other heart or blood pressure medications you are taking.

Tell your doctor about all other medicines you use, especially:

  • atorvastatin (Lipitor, Caduet), simvastatin (Zocor, Simcor, Vytorin, Juvisync);
  • antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);
  • NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;
  • a potassium supplement such as K-Dur, Klor-Con;
  • salt substitutes that contain potassium; or
  • a diuretic (water pill).

This list is not complete and other drugs may interact with aliskiren and amlodipine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about aliskiren and amlodipine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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