Tekturna HCT

Tekturna HCT may cause serious side effects:

• Injury or death to an unborn baby. See "Drug Precautions" and FDA Warning.
• 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. Drinking alcohol and taking certain medicines (barbiturates or narcotics) can cause low blood pressure to get worse. Lie down if you feel faint or dizzy, and call your doctor right away.
• Angioedema. Aliskiren can cause swelling of the face, lips, tongue, throat, arms and legs, or the whole body. 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 Tekturna HCT.
• Active or worsened Systemic Lupus Erythematosus (SLE). If you have SLE, tell your doctor right away if you get any new or worse symptoms.
• Eye problems. One of the medicines in Tekturna HCT can cause eye problems that may lead to vision loss. Symptoms of eye problems can happen within hours to weeks of starting Tekturna HCT. Tell your doctor right away if you have:
              ▪ Decrease in vision
              ▪ Eye pain

Common side effects of Tekturna HCT include:

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

Other less common side effects include skin rash.

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 Tekturna HCT. For a complete list of side effects, 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.

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

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.

Hydrochlorothiazide and aliskiren is a combination medicine used to treat high blood pressure (hypertension).

Hydrochlorothiazide and aliskiren may also be used for purposes not listed in this medication guide.

If you also take cholestyramine or colestipol, avoid taking these medicines within 4 hours before or 4 hours after you take hydrochlorothiazide and aliskiren.

Do not use potassium supplements or salt substitutes while you are taking this medicine, unless your doctor has told you to.

Avoid taking this medicine with a high-fat meal, which can make it harder for your body to absorb aliskiren.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid drinking alcohol. It can further lower your blood pressure and may increase some of the side effects of hydrochlorothiazide and aliskiren.

• If you have an allergy to aliskiren, hydrochlorothiazide, or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have a sulfa (sulfonamide) allergy, talk with your doctor.
• If you are taking any of these drugs: Cyclosporine, dofetilide, or itraconazole.
• If you are not able to pass urine.
• If you have kidney disease.
• If you have high blood sugar (diabetes) or kidney disease and are taking certain drugs for high blood pressure or your heart. Talk with your doctor.
• If you are breast-feeding. Do not breast-feed while you take Tekturna HCT.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Tekturna HCT with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Tekturna HCT affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• If you have high blood sugar (diabetes), this medicine may sometimes raise blood sugar. Talk with your doctor about how to keep your blood sugar under control.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Tekturna HCT.
• It may take 1 month to see the full effect.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• If you are taking a salt substitute that has potassium, potassium-sparing diuretics, or potassium, talk with your doctor.
• Talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• If you take cholestyramine or colestipol, talk with your pharmacist about how to take them with this medicine.
• Watch for gout attacks.
• If you have lupus, Tekturna HCT can make your lupus active or get worse. Tell your doctor right away if you get any new or worse signs.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
• If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• If you are 65 or older, use Tekturna HCT with care. You could have more side effects.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Trouble swallowing.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• This medicine can cause certain eye problems. If left untreated, this can lead to lasting eyesight loss. If eye problems happen, signs like change in eyesight or eye pain most often happen within hours to weeks of starting Tekturna HCT. Call your doctor right away if you have these signs.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

• 150 mg/12.5 mg tablets: white, biconvex ovaloid, film-coated tablets imprinted with NVR/LCI
• 150 mg/25 mg tablets: pale yellow, biconvex ovaloid, film-coated tablets imprinted with NVR/CLL
• 300 mg/12.5 mg tablets: violet white, biconvex ovaloid, film-coated tablets imprinted with NVR/CVI
• 300 mg/25 mg tablets: light yellow, biconvex ovaloid, film-coated tablets imprinted with NVR/CVV

Fetal Toxicity

Aliskiren

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Tekturna HCT as soon as possible [see Use in Specific Populations (8.1)].

Hydrochlorothiazide

Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults [see Use in Specific Populations (8.1)]. .

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. In general, avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with creatinine clearance (CrCl) less than 60 mL/min [see Contraindications (4), Drug Interactions (7) and Clinical Studies (14.3)].

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 ACEIs or angiotensin receptor antagonists. Anaphylactic reactions have been reported from postmarketing experience with unknown frequency. If angioedema involves the throat, tongue, glottis or larynx, or if the patient has a history of upper respiratory surgery, airway obstruction may occur and be fatal. Patients who experience these effects, even without respiratory distress, require prolonged observation and appropriate monitoring measures since treatment with antihistamines and corticosteroids may not be sufficient to prevent respiratory involvement. Prompt administration of subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and measures to ensure a patent airway may be necessary.

Discontinue Tekturna HCT immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister [see Contraindications (4)].

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 (RAAS). The volume or salt depletion should be corrected prior to administration of Tekturna HCT, or the treatment should start under close medical supervision.

A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

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 RAAS and by diuretics. Patients whose renal function may depend in part on the activity of the RAAS (e.g., patients with renal artery stenosis, severe heart failure, post-myocardial infarction or volume depletion) or patients receiving ARB, ACEI or nonsteroidal anti-inflammatory drug (NSAID), including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors), therapy may be at particular risk of developing acute renal failure on Tekturna HCT [see Warnings and Precautions (5.2), Drug Interactions (7), and Clinical Studies (14.4)]. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on Tekturna HCT.

Hypersensitivity Reactions

Hydrochlorothiazide (HCTZ)

Hypersensitivity reactions to HCTZ 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 (HCTZ)

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

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 less than 3.5 mEq/L) was 2.2%; the incidence of hyperkalemia (serum potassium greater than 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 RAAS can cause hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes, combination use with ARBs or ACEIs [see Contraindications (4), Warnings and Precautions (5.2), and Clinical Studies (14.4)], NSAIDs, including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors), or potassium supplements or potassium-sparing diuretics.

Hydrochlorothiazide (HCTZ)

HCTZ 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 (7)].

Acute Myopia and Secondary Angle-Closure Glaucoma

HCTZ, 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 HCTZ 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 (HCTZ)

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

HCTZ 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.

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

Clinical Studies Experience

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

• Fetal Toxicity [see Warnings and Precautions (5.1)].
• Anaphylactic Reactions and Head and Neck Angioedema [see Warnings and Precautions (5.3)].
• Hypotension [see Warnings and Precautions (5.4)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

Tekturna HCT

Tekturna HCT has been evaluated for safety in more than 2,700 patients, including over 700 treated for 6 months and 190 for over 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event (including uncontrolled hypertension) occurred in 2.7% of patients treated with Tekturna HCT versus 3.6% of patients given placebo.

Adverse events in placebo-controlled trials that occurred in at least 1% of patients treated with Tekturna HCT and at a higher incidence than placebo included dizziness (2.3% versus 1%), influenza (2.3% versus 1.6%), diarrhea (1.6% versus 0.5%), cough (1.3% versus 0.5%), vertigo (1.2% versus 0.5%), asthenia (1.2% versus 0%), and arthralgia (1% versus 0.5%).

Aliskiren

Aliskiren has been evaluated for safety in 6,460 patients, including 1,740 treated for longer than 6 months, and 1,250 for longer than 1 year. In placebo-controlled clinical trials, discontinuation of therapy due to a clinical adverse event, including uncontrolled hypertension occurred in 2.2% of patients treated with aliskiren, versus 3.5% of patients given placebo. These data do not include information from the ALTITUDE study which evaluated the use of aliskiren in combination with ARBs or ACEIs [see Contraindications (4), Warnings and Precautions (5.2), and Clinical Studies (14.4)].

Two cases of angioedema with respiratory symptoms were reported with aliskiren use in the clinical studies. Two other cases of periorbital edema without respiratory symptoms were reported as possible angioedema and resulted in discontinuation. The rate of these angioedema cases in the completed studies was 0.06%.

In addition, 26 other cases of edema involving the face, hands, or whole body were reported with aliskiren use, including 4 leading to discontinuation.

In the placebo-controlled studies, however, the incidence of edema involving the face, hands, or whole body was 0.4% with aliskiren compared with 0.5% with placebo. In a long-term active-controlled study with aliskiren and HCTZ arms, the incidence of edema involving the face, hands, or whole body was 0.4% in both treatment arms.

Aliskiren produces dose-related gastrointestinal (GI) adverse reactions. Diarrhea was reported by 2.3% of patients at 300 mg, compared to 1.2% in placebo patients. In women and the elderly (age 65 years and older) increases in diarrhea rates were evident starting at a dose of 150 mg daily, with rates for these subgroups at 150 mg comparable to those seen at 300 mg for men or younger patients (all rates about 2% to 2.3%). Other GI symptoms included abdominal pain, dyspepsia, and gastroesophageal reflux, although increased rates for abdominal pain and dyspepsia were distinguished from placebo only at 600 mg daily. Diarrhea and other GI symptoms were typically mild and rarely led to discontinuation.

Aliskiren was associated with a slight increase in cough in the placebo-controlled studies (1.1% for any aliskiren use versus 0.6% for placebo). In active-controlled trials with ACE inhibitor (ramipril, lisinopril) arms, the rates of cough for the aliskiren arms were 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%) and renal stones (0.2% versus 0%).

Single episodes of tonic-clonic seizures with loss of consciousness were reported in 2 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.

Hydrochlorothiazide (HCTZ)

Other adverse reactions that have been reported with HCTZ, without regard to causality, are listed below:

Body As A Whole: weakness

Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation

Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;

Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions

Metabolic: hyperglycemia, glycosuria, hyperuricemia

Musculoskeletal: muscle spasm

Nervous System/Psychiatric: restlessness

Renal: renal failure, renal dysfunction, interstitial nephritis

Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis

Special Senses: transient blurred vision, xanthopsia

Clinical Laboratory Test Abnormalities

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Tekturna HCT in patients with hypertension not concomitantly treated with an ARB or ACEI.

Blood Urea Nitrogen (BUN)/Creatinine: In patients with hypertension not concomitantly treated with an ARB or ACEI, elevations (greater than 50% increase) in BUN and creatinine occurred in 11.8% and 0.9%, respectively, of patients taking Tekturna HCT, and 7% and 1.1%, respectively, of patients given placebo in short-term controlled clinical trials. No patients were discontinued due to an increase in either BUN or creatinine.

Hemoglobin and Hematocrit: A greater than 20% decrease in hemoglobin and hematocrit were observed in <0.1% and 0.1%, respectively, of patients treated with Tekturna HCT, compared with 0% in placebo-treated patients. No patients were discontinued due to anemia.

Liver Function Tests: Occasional elevations (greater than 150%) in ALT (SGPT) were observed in 1.2% of patients treated with Tekturna HCT, compared with 0% in placebo-treated patients. No patients were discontinued due to abnormal liver function tests.

Post-Marketing Experience

The following adverse reactions have been reported in aliskiren or hydrochlorothiazide post-marketing experience. 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.

Aliskiren

Hypersensitivity: anaphylactic reactions and angioedema requiring airway management and hospitalization, urticaria, peripheral edema, hepatic enzyme increase with clinical symptoms of hepatic dysfunction, severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, pruritus, erythema, hyponatremia, nausea, vomiting.

Hydrochlorothiazide

Acute renal failure, renal disorder, aplastic anemia, erythema mutliforme, pyrexia, muscle spasm, asthenia, acute angle-closure glaucoma, bone marrow failure, worsening of diabetes control, hypokalemia, blood lipids increased, hyponatremia, hypomagnesemia, hypercalcemia, hyperchloremic alkalosis, impotence, visual impairment

Pathological changes in the parathyroid gland of patients with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. If hypercalcemia occurs, further diagnostic evaluation is necessary.

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

Applies to aliskiren / hydrochlorothiazide: oral tablet

Along with its needed effects, aliskiren / hydrochlorothiazide may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking aliskiren / hydrochlorothiazide:

• Chills
• cough
• diarrhea
• fever
• general feeling of discomfort or illness
• headache
• joint pain
• loss of appetite
• muscle aches and pains
• nausea
• runny nose
• shivering
• sore throat
• sweating
• trouble sleeping
• unusual tiredness or weakness
• vomiting

• Difficulty with swallowing
• dizziness
• fast heartbeat
• hives
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shortness of breath
• skin rash
• tightness in the chest

Get emergency help immediately if any of the following symptoms of overdose occur while taking aliskiren / hydrochlorothiazide:

• Coma
• confusion
• decreased urine output
• drowsiness
• dry mouth
• fainting
• increase in heart rate
• increased thirst
• irregular heartbeat
• irritability
• lightheadedness
• muscle cramps
• numbness, tingling, pain, or weakness in the hands or feet
• rapid breathing
• seizures
• sunken eyes
• swelling of the face, ankles, or hands
• trembling
• weak pulse
• weakness and heaviness of the legs
• wrinkled skin

Some side effects of aliskiren / hydrochlorothiazide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Difficulty with moving
• feeling of constant movement of self or surroundings
• lack or loss of strength
• muscle stiffness
• sensation of spinning