wire [30:<30 mL/minute and is contraindicated in patients who are anuric. ESRD (requiring hemodialysis): There are no dosage adjustments provided in the manufacturer s labeling (has not been studied); however, no dosage adjustment necessary for aliskiren or amlodipine (Khadzhynov, 2012; Kungys 2003). Risk of hyperkalemia is increased with chronic aliskiren therapy; use with extreme caution. Hydrochlorothiazide is usually ineffective when CrCl> <30 mL/minute and is contraindicated in patients who are anuric. Dosing: Hepatic Impairment There are no dosage adjustments provided in the manufacturer s labeling; consider using lower doses. Use with caution; amlodipine elimination prolonged and exposure to hydrochlorothiazide increases. Administration Administer at the same time daily with or without a meal, but consistent administration with regard 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. Avoid salt substitutes containing potassium. Storage Store at 25 C (77 F); excursions permitted between 15 C to 30 C (59 F to 86 F) in original container; protect from heat and moisture. Drug Interactions Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. 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 Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination 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 Angiotensin-Converting Enzyme Inhibitors: Aliskiren may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme 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 Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy Antifungal Agents (Azole Derivatives, Systemic): May enhance the adverse/toxic effect of Calcium Channel Blockers. Specifically, itraconazole may enhance the negative inotropic effects of verapamil or diltiazem. Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Calcium Channel Blockers. Fluconazole and isavuconazonium likely exert weaker effects than other azoles and are addressed in separate monographs. Management: Concurrent use of felodipine or nisoldipine with itraconazole is specifically contraindicated. Frequent monitoring is warranted with any such combination; calcium channel blocker dose reductions may be required. Exceptions: Fluconazole; Isavuconazonium Sulfate. Consider therapy modification Antihepaciviral Combination Products: May increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated. 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 Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy AtorvaSTATin: May increase the serum concentration of Aliskiren. Monitor therapy Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy Barbiturates: May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Consider therapy modification Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy Calcium Salts: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy Canagliflozin: May enhance the hyperkalemic effect of Aliskiren. Canagliflozin may enhance the hypotensive effect of Aliskiren. Monitor therapy CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Monitor therapy Ceritinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of ceritinib with a narrow therapeutic index CYP3A substrate (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus) should be avoided when possible. Monitor therapy Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Cyclophosphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced. Monitor therapy CycloSPORINE (Systemic): May increase the serum concentration of Aliskiren. Avoid combination CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification CYP3A4 Inhibitors (Moderate): May increase the serum concentration of AmLODIPine. Monitor therapy CYP3A4 Inhibitors (Strong): May increase the serum concentration of AmLODIPine. Monitor therapy Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy Dasatinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Monitor therapy Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Monitor therapy Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Avoid combination Drospirenone: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy Efavirenz: May decrease the serum concentration of Calcium Channel Blockers. Monitor therapy Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification Furosemide: Aliskiren may decrease the serum concentration of Furosemide. Monitor therapy Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination 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 Heparins (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 HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination Ipragliflozin: May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Monitor therapy Itraconazole: May increase the serum concentration of Aliskiren. Avoid combination Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Monitor therapy Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Avoid combination Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Consider therapy modification Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Monitor therapy Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Monitor therapy Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nicorandil: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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 Opioid Analgesics: May enhance the adverse/toxic effect of Diuretics. Opioid Analgesics may diminish the therapeutic effect of Diuretics. Monitor therapy OXcarbazepine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of OXcarbazepine. Specifically, there may be an increased risk for hyponatremia. Monitor therapy Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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 Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy Potassium Salts: May enhance the hyperkalemic effect of Aliskiren. Monitor therapy Promazine: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. Avoid combination 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 QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Consider therapy modification Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). Consider therapy modification Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Management: Monitor for increased topiramate levels/adverse effects (e.g., hypokalemia) with initiation/dose increase of a thiazide diuretic. Closely monitor serum potassium concentrations with concomitant therapy. Topiramate dose reductions may be necessary. Consider therapy modification Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Monitor therapy Verapamil: May increase the serum concentration of Aliskiren. Monitor therapy Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Test Interactions See individual agents. Adverse Reactions Frequencies reported with combination product. See individual monographs for additional adverse effects reported with each agent. 1% to 10%: Cardiovascular: Peripheral edema (7%) Central nervous system: Dizziness (4%), headache (4%) Respiratory: Nasopharyngitis (3%) ALERT: U.S. Boxed Warning Fetal toxicity: When pregnancy is detected, discontinue therapy as soon as possible. Drugs that act directly on the renin-angiotensin-aldosterone system can cause injury and even death to the developing fetus. Warnings/Precautions Concerns related to adverse effects: Angina/MI: Increased angina and/or MI have occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade. Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia can occur with hydrochlorothiazide use. Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses 25 mg (Gurwitz 1997). Hyperkalemia: May occur; risk increased in patients with renal impairment, diabetes, or concomitant use with ACE inhibitors, ARBs, NSAIDs, 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 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. Hypersensitivity reactions may also occur with hydrochlorothiazide; risk is increased in patients with a history of allergy or bronchial asthma. 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. Ocular effects: Hydrochlorothiazide may cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation; discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain. Additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy Peripheral edema: The most common side effect of amlodipine is peripheral edema; occurs within 2-3 weeks of starting therapy. Photosensitivity: Photosensitization may occur with hydrochlorothiazide use. Renal effects: Changes in renal function, including acute renal failure, may occur with aliskiren; risk is increased in patients with renal artery stenosis, severe heart failure, post-myocardial infarction, volume depletion, or patients receiving ARB, ACEI, or NSAIDs. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function. Sulfonamide ( sulfa ) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO 2 NH 2 ). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes. Disease-related concerns: Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia. Diabetes: Use hydrochlorothiazide with caution in patients with prediabetes or diabetes; may see a change in glucose control. Use of aliskiren in patients with diabetes has demonstrated an increased incidence of renal impairment, hypotension, and hyperkalemia; use is contraindicated in patients with diabetes who are taking an ACE inhibitor or ARB. Hepatic impairment: Use with caution in patients with hepatic impairment; consider using lower doses. In progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma. Hypercholesterolemia: Use hydrochlorothiazide with caution in patients with moderate or high cholesterol concentrations. Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use amlodipine with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition. Hypokalemia: Use hydrochlorothiazide with caution in patients with hypokalemia; correct before initiating therapy. is essential
reformatory Aliskiren, Amlodipine, and Hydrochlorothiazide of fake
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