INTERACTIONS Cyclosporine: Avoid coadministration of cyclosporine with aliskiren [see Warnings and Precautions ( 5.7 ) and Clinical Pharmacology ( 12.3 )] . Itraconazole: Avoid coadministration of itraconazole with aliskiren [see Warnings and Precautions ( 5.7 ) and Clinical Pharmacology ( 12.3 )].
Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs) including selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors with agents that affect the RAAS, including aliskiren, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving aliskiren and NSAID therapy. The antihypertensive effect of aliskiren may be attenuated by NSAIDs.
Dual
Blockade of the Renin-Angiotensin-Aldosterone System (RAAS): The concomitant use of aliskiren with other agents acting on the RAAS such as ACEIs or ARBs is associated with an increased risk of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two drugs that inhibit the renin-angiotensin system do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of aliskiren with ACE inhibitors or ARBs, particularly in patients with CrCl less than 60 mL/min. Monitor blood pressure, renal function, and electrolytes in patients taking aliskiren and other agents that affect the RAAS [see Warnings and Precautions ( 5.4 , 5.5 , 5.6 )]. The concomitant use of aliskiren with an ARB or an ACEI in diabetic patients is contraindicated [see Contraindications ( 4 )]. Furosemide: Oral coadministration of aliskiren and furosemide reduced exposure to furosemide. Monitor diuretic effects when furosemide is coadministered with aliskiren. Cyclosporine or Itraconazole: Avoid concomitant use. ( 5.7 , 7 , 12.3 )
Nonsteroidal
Anti-Inflammatory Drugs (NSAIDs): Increased risk of renal impairment and loss of antihypertensive effect. ( 7 )
Do not use aliskiren with ARBs or ACEIs in patients with diabetes [see Warnings and Precautions (5.2) and Clinical Studies (14.3) ]. Aliskiren tablets are contraindicated in patients with known hypersensitivity to any of the components [see Warnings and Precautions (5.3) ]. Aliskiren tablets are contraindicated in pediatric patients less than 2 years of age because of the risk of high aliskiren exposures identified in juvenile animals due to immaturity of transporters and metabolic enzymes [see Use in Specific Populations (8.4) ]. Do not use with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) in patients with diabetes. (4) Hypersensitivity to any of the components. (4) Aliskiren tablets are contraindicated in pediatric patients less than 2 years of age. (4)
AND PRECAUTIONS Avoid concomitant use with ARBs or ACEIs particularly in patients with renal impairment [creatinine clearance (CrCl) <60 mL/min]. ( 5.2 , 5.4 )
Anaphylactic
Reactions and Head and Neck Angioedema. ( 5.3 ) Hypotension: Correct imbalances in volume and/or salt depleted patients. ( 5.4 )
Impaired Renal
Function: Monitor serum creatinine periodically. ( 5.5 ) Hyperkalemia: Monitor potassium levels periodically. ( 5.6 )
5.1 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 aliskiren tablets as soon as possible [ see Use in Specific Populations (8.1) ].
5.2 Renal Impairment/Hyperkalemia/Hypotension when Aliskiren Tablets are Given in Combination with ARBs or ACEIs Aliskiren tablets are 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 <span class="opacity-50 text-xs">[see Contraindications (4) , Drug Interactions (7) and Clinical Studies (14.3) ]</span> .
5.3 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 aliskiren tablets 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 aliskiren tablets immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) and Contraindications (4) ]</span>.
5.4 Hypotension Symptomatic hypotension may occur after initiation of treatment with aliskiren tablets 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 aliskiren tablets, 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.
5.5 Impaired Renal Function Monitor renal function periodically in patients treated with aliskiren tablets. 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 aliskiren tablets <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) , Drug Interactions (7) , Use in Specific Populations (8.6) , and Clinical Studies (14.3) ]</span> . Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function.
5.6 Hyperkalemia Monitor serum potassium periodically in patients receiving aliskiren tablets. 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 <span class="opacity-50 text-xs">[see Contraindications (4) , Warnings and Precautions (5.2) , and Clinical Studies (14.3) ]</span> , NSAIDs, or potassium supplements or potassium sparing diuretics.
5.7 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) ] .