Skip to Content

Aliskiren

Pronunciation

Pronunciation

(a lis KYE ren)

Index Terms

  • Aliskiren Hemifumarate
  • SPP100

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tekturna: 150 mg, 300 mg

Brand Names: U.S.

  • Tekturna

Pharmacologic Category

  • Renin Inhibitor

Pharmacology

Aliskiren is a direct renin inhibitor, resulting in blockade of the conversion of angiotensinogen to angiotensin I. Angiotensin I suppression decreases the formation of angiotensin II (Ang II), a potent blood pressure-elevating peptide (via direct vasoconstriction, aldosterone release, and sodium retention). Ang II also functions within the Renin-Angiotensin-Aldosterone System (RAAS) as a negative inhibitory feedback mediator within the renal parenchyma to suppress the further release of renin. Thus, reductions in Ang II levels suppress this feedback loop, leading to further increased plasma renin concentrations (PRC) and subsequent activity (PRA). This disinhibition effect can be potentially problematic for ACE inhibitor and ARB therapy, as increased PRA could partially overcome the pharmacologic inhibition of the RAAS. As aliskiren is a direct inhibitor of renin activity, blunting of PRA despite the increased PRC (from loss of the negative feedback) may be clinically advantageous. The effect of aliskiren on bradykinin levels is unknown.

Absorption

Poor; absorption decreased by high-fat meal. Aliskiren is a substrate of P-glycoprotein; concurrent use of P-glycoprotein inhibitors may increase absorption.

Metabolism

Extent of metabolism unknown; in vitro studies indicate metabolism via CYP3A4

Excretion

Urine (~25% of absorbed dose excreted unchanged in urine); feces (unchanged via biliary excretion)

Onset of Action

Maximum antihypertensive effect: Within 2 weeks

Time to Peak

1 to 3 hours

Half-Life Elimination

~24 hours (range: 16 to 32 hours)

Special Populations: Elderly

AUC is increased in elderly patients 65 years of age and older.

Use: Labeled Indications

Hypertension: Treatment of hypertension, alone or in combination with other antihypertensive agents

Note: According to the Eighth Joint National Committee (JNC 8) guidelines, aliskiren is not recommended for the initial treatment of hypertension (James, 2013).

Contraindications

US labeling: Hypersensitivity to aliskiren or any component of the formulation; concomitant use with an ACE inhibitor or ARB in patients with diabetes mellitus

Canadian labeling: Additional contraindications (not in US labeling): History of angioedema with aliskiren, ACE inhibitors, or ARBs; hereditary or idiopathic angioedema; pregnancy, breast-feeding; concomitant use with ACE inhibitors or ARBs in patients with GFR <60 mL/minute/1.73 m2; patients <2 years of age.

Dosing: Adult

Hypertension: Initial: 150 mg once daily; may increase to 300 mg once daily (maximum: 300 mg daily). Usual dosage range (ASH/ISH [Weber, 2014]): 150 to 300 mg once daily. Note: Prior to initiation, correct hypovolemia and/or closely monitor volume status in patients on concurrent diuretics during treatment initiation.

Dosing: Geriatric

Refer to adult dosing. No initial dosage adjustment required.

Dosing: Renal Impairment

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute:

US labeling: There are no dosage adjustments provided in the manufacturer’s labeling; however, no dosage adjustment necessary (Vaidyanathan, 2007). Risk of hyperkalemia and progressive renal dysfunction may occur; use with caution.

Canadian labeling: GFR <30 mL/minute/1.73 m2: Avoid use

ESRD (requiring hemodialysis): There are no dosage adjustments provided in the manufacturer’s labeling; however, no dosage adjustment necessary (Khadzhynov, 2012). Risk of hyperkalemia is increased with chronic therapy; use with extreme caution. Note: Hemodialysis eliminates a minimal fraction; does not significantly alter overall aliskiren exposure.

Dosing: Hepatic Impairment

Initial: No dosage adjustment necessary.

Administration

Administer at the same time daily; may take with or without a meal, but consistent administration with regards to meals is recommended.

Dietary Considerations

May be taken with or without food; however, a high-fat meal reduces absorption. Consistent administration with regards to meals is recommended.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Drug Interactions

ACE Inhibitors: Aliskiren may enhance the hyperkalemic effect of ACE Inhibitors. Aliskiren may enhance the hypotensive effect of ACE Inhibitors. Aliskiren may enhance the nephrotoxic effect of ACE Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Angiotensin II Receptor Blockers: Aliskiren may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

AtorvaSTATin: May increase the serum concentration of Aliskiren. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Canagliflozin: May enhance the hyperkalemic effect of Aliskiren. Canagliflozin may enhance the hypotensive effect of Aliskiren. Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of Aliskiren. Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Drospirenone: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Monitor therapy

Grapefruit Juice: May decrease the serum concentration of Aliskiren. Management: Avoid concomitant use of aliskiren and grapefruit juice. Separation of aliskiren and grapefruit juice administration by several hours may reduce the chance for interaction. Monitor for decreased aliskiren levels/effects. Consider therapy modification

Heparin: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Itraconazole: May increase the serum concentration of Aliskiren. Avoid combination

Ketoconazole (Systemic): May increase the serum concentration of Aliskiren. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Potassium Salts: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Verapamil: May increase the serum concentration of Aliskiren. Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Adverse Reactions

1% to 10%:

Dermatologic: Skin rash (1%)

Gastrointestinal: Diarrhea (2%)

Neuromuscular & skeletal: Increased creatine phosphokinase (>300% increase: 1%)

Renal: Increased blood urea nitrogen (≤7%), increased serum creatinine (≤7%)

Respiratory: Cough (1%)

<1% (Limited to important or life-threatening): Anaphylaxis, decreased hematocrit, decreased hemoglobin, gastroesophageal reflux disease, hepatic insufficiency, hyperkalemia, increased uric acid, nausea, rhabdomyolysis, seizure, severe hypotension, Stevens-Johnson syndrome, tonic-clonic seizures, vomiting

ALERT: U.S. Boxed Warning

Use in pregnancy:

When pregnancy is detected, discontinue aliskiren as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus.

Warnings/Precautions

Concerns related to adverse effects:

• Hyperkalemia: May occur (rarely) during monotherapy; risk may increase in patients with predisposing factors (eg, renal dysfunction, diabetes mellitus, or concomitant use with ACE inhibitors, ARBs, NSAIDs including COX-2 inhibitors, potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts).

• Hypersensitivity: Anaphylaxis and angioedema have been reported. Since the effect of aliskiren on bradykinin levels is unknown, the risk of kinin-mediated etiologies of angioedema occurring is also unknown. Use with caution in any patient with a history of angioedema (of any etiology) as angioedema, some cases necessitating hospitalization and intubation, has been observed (rarely) with aliskiren use. Discontinue immediately following the occurrence of anaphylaxis or angioedema; do not readminister. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Early, aggressive, and appropriate management is critical.

• Hypotension: During the initiation of therapy, symptomatic hypotension may occur (rarely), particularly in volume or salt-depleted patients or with concomitant use of other agents acting on the renin-angiotensin-aldosterone system. Prior to initiation, correct hypovolemia or salt depletion, or closely monitor during treatment initiation. If hypotension does occur, this is not a contraindication for further use; once blood pressure has been stabilized, aliskiren usually can be continued without difficulty.

• Skin reactions: Serious skins reactions including Stevens Johnson syndrome and toxic epidermal necrolysis (TEN) have been reported.

Disease-related concerns:

• Diabetes mellitus: Use (monotherapy or combined with ACE-inhibitors or ARBs) in patients with type 2 diabetes mellitus has demonstrated an increased incidence of renal impairment, hypotension, and hyperkalemia; use is contraindicated in patients with diabetes mellitus who are taking an ACE inhibitor or ARB.

• Renal impairment: Use with caution or avoid in patients with deteriorating renal function or low renal blood flow (eg, renal artery stenosis, severe heart failure, post-MI, volume depletion); may increase risk of developing acute renal failure and hyperkalemia. Concomitant use with an ACE inhibitor, ARB, or NSAID (including COX-2 inhibitors) may increase risk of developing acute renal failure; concomitant use with an ACE inhibitor or ARB should be avoided in patients with GFR <60 mL/minute.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.

Monitoring Parameters

Blood pressure; serum potassium, BUN, serum creatinine

Pregnancy Risk Factor

D

Pregnancy Considerations

[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. The use of drugs which act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Use is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience cough, diarrhea, back pain, flu-like symptoms, headache, or loss of strength and energy. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weak, shortness of breath, numbness or tingling feeling), severe dizziness, passing out, seizures, abdominal pain, vomiting, dysphagia, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in your mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide