Tekturna (aliskiren hemifumarate)

Dosage of aliskiren hemifumarate is expressed in terms of aliskiren.

Aliskiren is administered orally. The manufacturer recommends that patients establish a routine pattern for taking aliskiren with regard to meals; administration with a high-fat meal substantially decreases absorption of the drug.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Ace Inhibitors; Arbs; Eras; Aliskiren/Sparsentan

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Sparsentan is an antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor which are thought to contribute to the pathogenesis of IgA nephropathy.(1) Coadministration with renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) may result in additive inhibition of angiotensin. RAAS inhibitors include ACE inhibitors, angiotensin II receptor blockers (ARBs), and aliskiren.

CLINICAL EFFECTS: Concurrent use of sparsentan with renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) may result in hypotension, syncope, hyperkalemia, and changes in renal function (including renal failure).(1)

PREDISPOSING FACTORS: Patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion may be at risk of developing acute kidney injury on sparsentan.(1) Patients with advanced kidney disease or taking concomitant potassium-increasing drugs (e.g., potassium supplements, potassium-sparing diuretics), or using potassium-containing salt substitutes are at increased risk for developing hyperkalemia.(1)

PATIENT MANAGEMENT: Do not coadminister sparsentan with renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs). Prior to initiating treatment with sparsentan, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs).(1) RAAS inhibitors include ACE inhibitors, angiotensin II receptor blockers (ARBs), and aliskiren.

DISCUSSION: The US manufacturer of sparsentan states that concomitant use of sparsentan with renin-angiotensin-aldosterone system (RAAS) inhibitors and endothelin receptor antagonists (ERAs) is contraindicated.(1) RAAS inhibitors include ACE inhibitors, angiotensin II receptor blockers (ARBs), and aliskiren.

Aliskiren/Cyclosporine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Aliskiren is a substrate for the P-glycoprotein (P-gp) system. Cyclosporine is a potent inhibitor of P-gp.(1)

CLINICAL EFFECTS: The concurrent use of aliskiren and cyclosporine may result in elevated levels of aliskiren. This may result in increased effect and toxicity of aliskiren such as hypotension.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of aliskiren states that concurrent use of cyclosporine should be avoided.(1) The UK manufacturer of aliskiren states that the concurrent use of potent P-gp inhibitors such as cyclosporine is contraindicated.(2)

DISCUSSION: In a study in healthy subjects, concurrent cyclosporine (200 mg and 600 mg) increased the maximum concentration (Cmax) and area-under-curve (AUC) of aliskiren (75 mg) by 2.5-fold and 5-fold, respectively.(1,2)

Aliskiren/Quinidine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Aliskiren is a substrate for the P-glycoprotein (P-gp) system. Quinidine is a potent inhibitor of P-gp.(1)

CLINICAL EFFECTS: The concurrent use of aliskiren and quinidine may result in elevated levels of aliskiren. This may result in increased effect and toxicity of aliskiren including hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The UK manufacturer states the use of aliskiren and potent P-glycoprotein inhibitors are contraindicated.(1)

DISCUSSION: In a study in healthy subjects, concurrent cyclosporine (200 mg and 600 mg), another potent inhibitor of P-glycoprotein, increased the maximum concentration (Cmax) and area-under-curve (AUC) of aliskiren (75 mg) by 2.5-fold and 5-fold, respectively.(1)

Aliskiren/Selected P-Glycoprotein (P-Gp) Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Aliskiren is a substrate for the P-glycoprotein (P-gp) system. Inhibitors of P-gp may increase the absorption of aliskiren.(1-3)

CLINICAL EFFECTS: The concurrent use of aliskiren and P-gp inhibitors may result in elevated levels of aliskiren. This may result in increased effect and toxicity of aliskiren including hypotension.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of aliskiren states that concurrent use of itraconazole should be avoided.(1) The UK manufacturer of aliskiren states that the concurrent use of P-gp inhibitors such as itraconazole is contraindicated.(2) The US manufacturer of itraconazole states that concurrent administration of aliskiren is not recommended during and two weeks after itraconazole treatment.(4) The manufacturer of daraxonrasib states P-gp substrates should be administered at least 4 hours apart from daraxonrasib.(7)

DISCUSSION: In a study in healthy subjects, concurrent itraconazole (100 mg) increased the maximum concentration (Cmax) and area-under-curve (AUC) of aliskiren (150 mg) by 5.8-fold and 6.5-fold, respectively.(2,3) Selected P-gp inhibitors linked to this monograph include: aumolertinib, clarithromycin, daraxonrasib, indinavir, itraconazole, lopinavir/ritonavir, propafenone, rifampin, vepdegestrant, and vimseltinib.(4,5)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Aliskiren/Ace Inhibitors; Arbs

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: In the ALTITUDE study, concurrent use of aliskiren for 18-24 months in patients maintained on either an ACE inhibitor or an ARB resulted in an increase in non-fatal stroke, renal complications, hyperkalemia, and hypotension.(1,2)

PREDISPOSING FACTORS: Patients with Type II diabetes and/or renal impairment may be at a higher risk from this combination.(1)

PATIENT MANAGEMENT: Novartis no longer recommends the concurrent use of aliskiren with either an ACE inhibitor or an ARB.(1,3) Hypertension regimens of patients receiving concurrent therapy should be re-evaluated.(1) Concurrent use of aliskiren in diabetic patients receiving either an ACE inhibitor or an ARB is contraindicated.(2,4) Avoid the combination in patients with CrCl less than 60 ml/min.(5)

DISCUSSION: ALTITUDE was a multinational study designed to evaluate the use of aliskiren for more than 1 year in patients with Type II diabetes and renal impairment, who are known to have a high risk for cardiovascular and renal events. Aliskiren was given with optimal cardiovascular treatment, including an ACE inhibitor or ARB. After 18-24 months of concurrent therapy with aliskiren and either an ACE inhibitor or an ARB, there was an increase in non-fatal stroke, renal complications, hyperkalemia, and hypotension.(1,2)

Selected P-Glycoprotein (P-Gp) Substrates/Venetoclax

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Venetoclax is an inhibitor of the P-glycoprotein (P-gp) system and may increase the absorption of P-gp substrates.(1)

CLINICAL EFFECTS: Concurrent use of venetoclax with P-gp substrates may result in elevated levels and toxicities of the substrate.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of venetoclax states that the concurrent use of P-gp substrates should be avoided. If concurrent therapy cannot be avoided, the P-gp substrate should be taken at least 6 hours before venetoclax.(1) If concurrent therapy with afatinib is unavoidable and not tolerated, the US manufacturer of afatinib states that the afatinib dose should be reduced by 10 mg. Resume the previous dose of afatinib if venetoclax is discontinued.(2) The manufacturer of ubrogepant recommends a dosage adjustment of ubrogepant when coadministered with P-gp inhibitors. The initial dose of ubrogepant should not exceed 50 mg. If a second dose of ubrogepant is needed, the dose should not exceed 50 mg.(8)

DISCUSSION: In vitro data suggests venetoclax is a P-gp inhibitor at therapeutic doses in the gut.(1) Administration of a single venetoclax 100 mg dose with digoxin increased the maximum concentration (Cmax) and area-under-the-curve of digoxin by 35% and 9%, respectively.(1) Selected P-gp substrates linked to this monograph include: afatinib, aliskiren, betrixaban, bilastine, cyclosporine, dabigatran, digoxin, edoxaban, everolimus, loperamide, sirolimus, talazoparib, topotecan, and ubrogepant.(1-9)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Aliskiren/Furosemide

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown.

CLINICAL EFFECTS: Concurrent use of aliskiren may decrease levels and effectiveness of furosemide.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor patients receiving concurrent aliskiren and furosemide for decreased furosemide effects. The dose of furosemide may need to be adjusted if aliskiren is initiated or discontinued, or furosemide may need to be replaced with an alternative diuretic agent.

DISCUSSION: Concurrent aliskiren decreased furosemide maximum concentration (Cmax) and area-under-curve (AUC) by 50% and 30%, respectively. There were no significant effects on aliskiren levels.(1) Concurrent aliskiren decreased furosemide Cmax and AUC by 27% and 17%, respectively and 24-hour urinary furosemide excretion was reduced by 29%. There were no significant effects on aliskiren levels.(2)

Aliskiren/Nsaids; Salicylates

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown. It is believed to be related to inhibition of prostaglandin synthesis by the NSAIDs. Use of an NSAID in combination with aliskiren, whose hypotensive effects may be related to the increase in hypotensive prostaglandins, may negate any decrease in blood pressure.

CLINICAL EFFECTS: Concurrent use of aliskiren with NSAIDs may result in decreased antihypertensive effects. In patients with existing renal impairment, the use of these agents together may also result in further deterioration of renal clearance caused by renal hypoperfusion.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients maintained on aliskiren should be monitored for a loss of blood pressure control and a change in renal function if an NSAID is added to their regimen. Patients receiving concurrent therapy may require higher doses of aliskiren. If blood pressure control cannot be achieved or if the patient's renal function deteriorates, the NSAID may need to be discontinued. Patients should be monitored for hypotension if NSAIDs are withdrawn from concurrent aliskiren therapy.

DISCUSSION: Indomethacin has been shown to inhibit the antihypertensive effect of captopril, cilazapril, enalapril, losartan, perindopril, and valsartan. Ibuprofen has been shown to decrease the antihypertensive effects of captopril. Two separate case reports describe individuals suspected of ACEI-associated angioedema precipitated by NSAIDs. Both cases reported symptom resolution after cessation of the NSAID. Studies have shown that sulindac does not affect the antihypertensive effects of captopril and enalapril.

Aliskiren/Potassium Sparing Diuretics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aliskiren may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium sparing diuretics with aliskiren may result in hyperkalemia.

PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus.

PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with a potassium sparing diuretic and aliskiren. In all patients taking eplerenone who start taking aliskiren, check serum potassium and creatinine levels after 3-7 days of concurrent therapy.

DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. There are case reports of hyperkalemia during concurrent therapy with ARBs and spironolactone and with aliskiren and spironolactone. Based on this data, serum potassium levels should be monitored in patients receiving concomitant aliskiren with potassium sparing diuretics.

Aliskiren/Potassium Supplements

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aliskiren may decrease the renal excretion of potassium.

CLINICAL EFFECTS: Concurrent use of potassium supplements with aliskiren may result in hyperkalemia.

PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus.

PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and aliskiren.

DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. Increased potassium levels have also been seen with aliskiren. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with aliskiren.

Selected Antihypertensives And Vasodilators/Apomorphine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Apomorphine causes dose-dependent decreases in blood pressure. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and apomorphine may result in orthostatic hypotension with or without dizziness, nausea, or syncope.(1)

PREDISPOSING FACTORS: The risk of orthostatic hypotension may be increased during dose escalation of apomorphine and in patients with renal or hepatic impairment.(1)

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Healthy volunteers who took sublingual nitroglycerin (0.4 mg) concomitantly with apomorphine experienced a mean largest decrease in supine systolic blood pressure (SBP) of 9.7 mm Hg and in supine diastolic blood pressure (DBP) of 9.3 mm Hg, and a mean largest decrease in standing SBP and DBP of 14.3 mm Hg and 13.5 mm Hg, respectively. The maximum decrease in SBP and DBP was 65 mm Hg and 43 mm Hg, respectively. When apomorphine was taken alone, the mean largest decrease in supine SBP and DBP was 6.1 mm Hg and 7.3 mm Hg, respectively, and in standing SBP and DBP was 6.7 mm Hg and 8.4 mm Hg, respectively.(1)

Selected Antihypertensives/Tizanidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)

Concomitant use of aliskiren and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonist in patients with diabetes mellitus. (See Use in Combination with Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Antagonists under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)

Known hypersensitivity to aliskiren or any ingredient in the formulation.

Use in pediatric patients younger than 2 years of age. (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

• Pregnancy

• Hyperkalemia
• Hyponatremia
• Hypotension
• Hypovolemia

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min

Common adverse effects reported in hypertensive patients receiving aliskiren include diarrhea, headache, dizziness, fatigue, cough, back pain, flu-like symptoms, rash, hyperkalemia, small increases in BUN or serum creatinine concentration, and increased serum creatine kinase (CK, creatine phosphokinase, CPK) concentrations.

Rare or Very Rare

• Abnormal hepatic function tests
• Anaphylaxis
• Anemia
• Angioedema
• Hyperkalemia
• Hyperuricemia
• Hyponatremia
• Hypotension
• Kidney stone
• Periorbital edema
• Peripheral edema
• Seizure disorder
• Stevens-johnson syndrome
• Toxic epidermal necrolysis

More Frequent

• Diarrhea

Less Frequent

• Cough
• Skin rash

Rare or Very Rare

• Acute abdominal pain
• Dizziness
• Dyspepsia
• Erythema
• Gastroesophageal reflux disease
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Nausea
• Pruritus of skin
• Urticaria
• Vomiting

No enhanced messaging available.

Safety of aliskiren therapy has been evaluated in pediatric patients 6-17 years of age receiving the drug for up to 52 weeks. (See Uses: Hypertension in Pediatric Patients.) In these studies, no unanticipated adverse effects were observed; adverse effects in pediatric patients 6 years of age or older are expected to be similar to those observed in adults. Preclinical studies in rats indicate a potential for a substantial increase in exposure to aliskiren in pediatric patients. The manufacturer states that aliskiren is contraindicated in children younger than 2 years of age and should not be used in children 2 to younger than 6 years of age or in children who weigh less than 20 kg.

If oliguria or hypotension occurs in neonates with a history of in utero exposure to aliskiren, blood pressure and renal function should be supported; exchange transfusions or dialysis may be required. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Aliskiren can cause fetal harm when administered to a pregnant woman. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Aliskiren is distributed into milk in rats; it is not known whether the drug is distributed into human milk. Breast-feeding is not recommended during treatment with aliskiren.

When the total number of patients studied in clinical trials of aliskiren is considered, 19% were 65 years of age or older, while 3.4% were 75 years of age or older. In clinical trials of aliskiren in fixed combination with hydrochlorothiazide, 19.6% of patients were 65 years of age or older and 3.2% were 75 years of age and older. Although no overall differences in efficacy or safety were observed between geriatric and younger patients and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.