Tekturna

Tekturna is a prescription medicine used to treat high blood pressure (known medically as hypertension). 

Tekturna 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. Lie down if you feel faint or dizzy. Call your doctor right away.
• Angioedema: Tekturna 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.

Common side effects of Tekturna include:

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

Less common side effects include 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. For a complete list of side effects, ask your doctor or pharmacist.

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Especially tell your doctor if you are taking:

• a kind of medicine called angiotensin receptor blocker or angiotensin converting enzyme inhibitor.
• atorvastatin (medicine to lower cholesterol in your blood).
• water pills (also called “diuretics”).
• medicines for treating fungus or fungal infections.
• cyclosporine (a medicine used to suppress the immune system).
• potassium-containing medicines, potassium supplements, or salt substitutes containing potassium.
• nonsteroidal anti-inflammatory drugs (like ibuprofen or naproxen).

Your doctor or pharmacist will know what medicines are safe to take together.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Tekturna, salt substitutes containing potassium should be avoided.

If you take too much Tekturna, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Tekturna is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Absorption

Bioavailability

Poorly absorbed; oral bioavailability is about 2.5%.1 2 9 10 16

Peak plasma concentrations usually attained within 1–3 hours following oral administration.1 2 9 13

Onset

Substantial proportion (85–90%) of antihypertensive effect attained within 2 weeks of initiation of therapy.1 6 9

Food

High-fat meal decreases mean AUC and peak plasma concentration by 71 and 85%, respectively; however, in clinical studies the drug was administered without requiring a fixed relation of administration to meals.1 2

Special Populations

In geriatric patients AUC may be increased.1 17 (See Geriatric Patients under Dosage and Administration and see Geriatric Use under Cautions.)

In patients with varying degrees of renal impairment, peak plasma concentration and AUC were increased; however, changes in exposure did not consistently correlate with severity of renal impairment.1 16 (See Renal Impairment under Dosage and Administration.)

In patients with mild to severe hepatic impairment, pharmacokinetics of drug not substantially altered.1 18

Distribution

Extent

Crosses the placenta and is distributed into the amniotic fluid and fetus in animals.1

Distributed into milk in rats; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 47–51%.2 16 20

Elimination

Metabolism

In vitro studies suggest CYP3A4 is the main enzyme responsible for metabolism.1 9 11 However, amount of absorbed dose that undergoes metabolism not established;1 drug appears to undergo minimal hepatic metabolism.2 9 11 13 16 Also a substrate for P-glycoprotein11 13 16 17 and OATP 2B1.24 25 26 27 30 32

Elimination Route

Unabsorbed drug excreted principally in feces as unchanged drug, and absorbed drug eliminated principally in feces via hepatobiliary clearance as unchanged drug and minimally in urine;1 2 9 10 11 13 16 17 20 approximately 25% of an absorbed oral dose is eliminated in urine as unchanged drug.1 9

Half-life

Accumulation half-life is approximately 24 hours.1 11

Terminal half-life is approximately 24–40 hours; 2 9 10 11 13 14 16 17 wide interpatient variability observed.11

Special Populations

Poorly removed by hemodialysis.1

• It is used to treat high blood pressure.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to aliskiren 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 are taking any of these drugs: Cyclosporine or itraconazole.
• 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.

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 with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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 kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of a high potassium level like a heartbeat that does not feel normal; change in thinking clearly and with logic; feeling weak, lightheaded, or dizzy; feel like passing out; numbness or tingling; or shortness of breath.
• Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
• Very bad dizziness or passing out.
• Seizures.
• Belly pain.
• Throwing up.
• Trouble swallowing.
• 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.

Fetal Toxicity

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 as soon as possible [see Use in Specific Populations (8.1)].

5.2 Renal Impairment/Hyperkalemia/Hypotension when Tekturna is Given in Combination with ARBs or ACEIs

Tekturna 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

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 immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister [see Dosage and Administration (2.1) and Contraindications (4)].

Hypotension

Symptomatic hypotension may occur after initiation of treatment with Tekturna 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, 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. Changes in renal function, including acute renal failure, can be caused by drugs that affect the RAAS. 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 for developing acute renal failure on Tekturna [see Warnings and Precautions (5.2), Drug Interactions (7), Use in Specific Populations (8.6), and Clinical Studies (14.3)]. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function.

Hyperkalemia

Monitor serum potassium periodically in patients receiving Tekturna. 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 (14.3)], NSAIDs, or potassium supplements or potassium sparing diuretics.

Cyclosporine or Itraconazole

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)].

Pregnancy

Risk Summary

Tekturna can cause fetal harm when administerd to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see Clinical Considerations]. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Tekturna as soon as possible.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal adverse reactions

Use of drugs that act on the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

In patients taking Tekturna during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Tekturna for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Tekturna, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.

Data

Animal Data

In developmental toxicity studies, pregnant rats and rabbits received oral aliskiren hemifumarate during organogenesis at doses up to 20 and 7 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2), respectively, in rats and rabbits. (Actual animal doses were up to 600 mg/kg/day in rats and up to 100 mg/kg/day in rabbits.) No teratogenicity was observed; however, fetal birth weight was decreased in rabbits at doses 3.2 times the MRHD based on body surface area (mg/m2). Aliskiren was present in placentas, amniotic fluid and fetuses of pregnant rabbits.

Lactation

There is no information regarding the presence of aliskiren in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including hypotension, hyperkalemia and renal impairment in nursing infants, advise a nursing woman that breastfeeding is not recommended during treatment with Tekturna.

Pediatric Use

Safety and effectiveness of aliskiren in pediatric patients younger than 18 years have not been established.

Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients [see Nonclinical Toxicology (13.2)].

Neonates with a history of in utero exposure to Tekturna

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

Of the total number of patients receiving aliskiren in clinical studies, 1,275 (19%) were 65 years or older and 231 (3.4%) were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. 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 in patients with severe renal impairment [creatinine clearance (CrCl) less than 30 mL/min] have not been established as these patients were excluded in clinical trials [see Clinical Studies (14)].

You should not take Tekturna if you are allergic to aliskiren.

If you have diabetes, do not use Tekturna together with certain heart or blood pressure medicines, such as:

• azilsartan (Edarbi, Edarbyclor), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro, Avalide), losartan (Cozaar, Hyzaar), olmesartan (Azar, Benicar), valsartan (Diovan, Exforge, Tribenzor), telmisartan (Micardis); or

• benazepril (Lotensin), captopril (Capoten, Capozide), enalapril (Vasotec, Vasoretic), fosinopril (Monopril), lisinopril (Prinivil, Zestoretic, Zestril), moexipril (Uniretic, Univasc), perindopril (Aceon), quinapril (Accupril, Accuretic), ramipril (Altace), or trandolapril (Mavik, Tarka).

You may also need to avoid taking these medicines with Tekturna if you have kidney disease.

To make sure this medicine is safe for you, tell your doctor if you have:

• kidney disease;

• heart disease;

• if you are on a low-salt diet; or

• if you have ever had an allergic reaction to an ACE inhibitor heart or blood pressure medicine (benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, trandolapril).

Do not use Tekturna if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Aliskiren can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

It is not known whether aliskiren passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Tekturna is not approved for use by anyone younger than 18 years old.