Aliskiren

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Aliskiren
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

Disclaimer

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Black Box Warning

WARNING: FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
* When pregnancy is detected, discontinue Aliskiren as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Overview

Aliskiren is a renin inhibitor that is FDA approved for the {{{indicationType}}} of hypertension. There is a Black Box Warning for this drug as shown here. Common adverse reactions include diarrhea, dizziness, headache, and elevated serum creatinine.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension
  • 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.
  • Patients should establish a routine pattern for taking Tekturna with regard to meals. High fat meals decrease absorption substantially.
  • Dosing Information
  • The usual recommended starting dose is 150 mg once daily.
  • In patients whose blood pressure is not adequately controlled, the daily dose may be increased to 300 mg.
  • Doses above 300 mg did not give an increased blood pressure response but resulted in an increased rate of diarrhea. The antihypertensive effect of a given dose is substantially attained (85-90%) by 2 weeks.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aliskiren in adult patients.

Non–Guideline-Supported Use

Diabetic Nephropathy
  • Dosing Information
  • 300 mg PO qd[1]

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

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

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Aliskiren in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Aliskiren in pediatric patients.

Contraindications

Warnings

WARNING: FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
* When pregnancy is detected, discontinue Aliskiren as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Fetal Toxicity
Renal Impairment/Hyperkalemia/Hypotension when Tekturna is given in combination with ARBs or ACEIs
  • Avoid use of Tekturna with ARBs or ACEIs in patients with moderate renal impairment (GFR <60 ml/min).
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 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.
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. 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
Hyperkalemia
Cyclosporine or Itraconazole

Adverse Reactions

Clinical Trials Experience

  • 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.
  • Data described below reflect the evaluation of the safety of Tekturna in more than 6,460 patients, including over 1,740 treated for longer than 6 months, and more than 1,250 patients 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 Tekturna vs. 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.
Angioedema
  • Two cases of angioedema with respiratory symptoms were reported with Tekturna 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 Tekturna 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 Tekturna compared with 0.5% with placebo. In a long term active control study with Tekturna and HCTZ arms, the incidence of edema involving the face, hand or whole body was 0.4% in both treatment arms.
Gastrointestinal
  • Tekturna 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 comparable to those seen at 300 mg for men or younger patients (all rates about 2.0-2.3%). 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.
Cough
  • Tekturna was associated with a slight increase in cough in the placebo-controlled studies (1.1% for any Tekturna use vs. 0.6% for placebo). In active-controlled trials with ACE inhibitor (ramipril, lisinopril) arms, the rates of cough for the Tekturna arms were about one-third to one-half the rates in the ACE inhibitor arms.
Seizures
  • Single episodes of tonic-clonic seizures with loss of consciousness were reported in two patients treated with Tekturna in the clinical trials. One of these patients did have 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). Tekturna was discontinued and there was no re-challenge.
Miscellaneous
  • Other adverse effects with increased rates for Tekturna compared to placebo included rash (1% vs. 0.3%), elevated uric acid (0.4% vs. 0.1%), gout (0.2% vs. 0.1%) and renal stones (0.2% vs. 0%).
  • Aliskiren’s effect on ECG intervals was studied in a randomized, double-blind, placebo and active-controlled (moxifloxacin), 7-day repeat dosing study with Holter-monitoring and 12 lead ECGs throughout the interdosing interval. No effect of aliskiren on QT interval was seen.

Clinical Laboratory Findings

  • In controlled clinical trials, clinically relevant changes in standard laboratory parameters were rarely associated with the administration of Tekturna in patients with hypertension not concomitantly treated with an ARB or ACEI. In multiple-dose studies in hypertensive patients, Tekturna had no clinically important effects on total cholesterol, HDL, fasting triglycerides, or fasting glucose.
Blood Urea Nitrogen, Creatinine
Hemoglobin and Hematocrit
  • Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.08 g/dL and 0.16 volume percent, respectively, for all aliskiren monotherapy) were observed. The decreases were dose-related and were 0.24 g/dL and 0.79 volume percent for 600 mg daily. This effect is also seen with other agents acting on the renin angiotensin system, such as angiotensin inhibitors and angiotensin receptor blockers and may be mediated by reduction of angiotensin II which stimulates erythropoietin production via the AT1 receptor. These decreases led to slight increases in rates of anemia with aliskiren compared to placebo were observed (0.1% for any aliskiren use, 0.3% for aliskiren 600 mg daily, vs 0% for placebo). No patients discontinued therapy due to anemia.
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).
Uric Acid
  • Aliskiren monotherapy produced small median increases in serum uric acid levels (about 6 μmol/L) while HCTZ produced larger increases (about 30 μmol/L). The combination of aliskiren with HCTZ appears to be additive (about 40 μmol/L increase). The increases in uric acid appear to lead to slight increases in uric acid-related AEs: elevated uric acid (0.4% vs 0.1%), gout (0.2% vs. 0.1%), and renal stones (0.2% vs 0%).
Creatine Kinase
  • Increases in creatine kinase of >300% were recorded in about 1% of aliskiren monotherapy patients vs. 0.5% of placebo patients. Five cases of creatine kinase rises, three leading to discontinuation and one diagnosed as subclinical rhabdomyolysis, and another as myositis, were reported as adverse events with aliskiren use in the clinical trials. No cases were associated with renal dysfunction.

Postmarketing Experience

  • The following adverse reactions have been reported in aliskiren 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.

Drug Interactions

  • Itraconazole

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category D
  • 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, 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 for hypotension, oliguria, and hyperkalemia.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Aliskiren in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Aliskiren during labor and delivery.

Nursing Mothers

  • It is not known whether aliskiren is excreted in human breast milk. Aliskiren was secreted in the milk of lactating rats. 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 of aliskiren in pediatric patients <18 years have not been established.
  • Neonates with a history of in utero exposure to Tekturna

Geriatic Use

There is no FDA guidance on the use of Aliskiren with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Aliskiren with respect to specific gender populations.

Race

There is no FDA guidance on the use of Aliskiren with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Aliskiren in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Aliskiren in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Aliskiren in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Aliskiren in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Aliskiren in the drug label.

Condition1

Description

IV Compatibility

There is limited information regarding IV Compatibility of Aliskiren in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

Description

Management

Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Aliskiren in the drug label.

Pharmacology

There is limited information regarding Aliskiren Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Aliskiren Mechanism of Action in the drug label.

Structure

There is limited information regarding Structure of Aliskiren in the drug label.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Aliskiren in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Aliskiren in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Aliskiren in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Aliskiren in the drug label.

Condition1

Description

How Supplied

There is limited information regarding Aliskiren How Supplied in the drug label.

Storage

There is limited information regarding Aliskiren Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Aliskiren |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Aliskiren |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Aliskiren in the drug label.

Precautions with Alcohol

Alcohol-Aliskiren interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Tekturna®[2]

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Parving, Hans-Henrik; Brenner, Barry M.; McMurray, John J.V.; de Zeeuw, Dick; Haffner, Steven M.; Solomon, Scott D.; Chaturvedi, Nish; Persson, Frederik; Desai, Akshay S.; Nicolaides, Maria; Richard, Alexia; Xiang, Zhihua; Brunel, Patrick; Pfeffer, Marc A. (2012). "Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes". New England Journal of Medicine. 367 (23): 2204–2213. doi:10.1056/NEJMoa1208799. ISSN 0028-4793.
  2. ↑ "TEKTURNA (aliskiren hemifumarate) tablet, film coated [Novartis Pharmaceuticals Corporation]".
  3. ↑ "http://www.ismp.org". External link in |title= (help)


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