hydrochlorothiazide/aliskiren (Rx)

Brand and Other Names:Tekturna HCT
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

hydrochlorothiazide/aliskiren

tablet

  • 12.5mg/150mg
  • 12.5mg/300mg
  • 25mg/150mg
  • 25mg/300mg

Hypertension

Add-on or initial therapy: Initiate with 12.5 mg/150 mg PO qDay; after 2-4 weeks, may increase dose if needed; not to exceed 25 mg/300 mg

Add-on therapy: Initiate by adding lowest available dose of alternative component (hydrochlorothiazide 12.5 mg or aliskiren 150 mg)

Replacement therapy: May be substituted for individually titrated components

Renal Impairment

CrCl <30 mL/min: Use caution; hydrochlorothiazide usually ineffective when CrCl <30 mL/min and contraindicated in anuric patients; hyperkalemia and progressive renal dysfunction may occur with aliskiren

CrCl ≥30 mL/min: Dose adjustment not necessary

Hepatic Impairment

Dose adjustment not necessary

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and hydrochlorothiazide/aliskiren

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            Contraindicated (19)

            • azilsartan

              azilsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • benazepril

              benazepril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • candesartan

              candesartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • captopril

              captopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • enalapril

              enalapril, aliskiren. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Aliskiren use contraindicated with ACEIs in patients with diabetes; avoid coadministration with ACEIs if GFR <60 mL/min; dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

              enalapril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • eprosartan

              eprosartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • fosinopril

              fosinopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • irbesartan

              irbesartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • lisinopril

              lisinopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • losartan

              losartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • moexipril

              moexipril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • olmesartan

              olmesartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • perindopril

              perindopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • quinapril

              quinapril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • ramipril

              ramipril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • sacubitril/valsartan

              sacubitril/valsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • telmisartan

              telmisartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • trandolapril

              trandolapril, aliskiren. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Aliskiren use contraindicated with ACEIs in patients with diabetes; avoid coadministration with ACEIs if GFR <60 mL/min; dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

              trandolapril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • valsartan

              valsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            Serious - Use Alternative (19)

            • aminolevulinic acid oral

              aminolevulinic acid oral, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              hydrochlorothiazide increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

            • azilsartan

              aliskiren, azilsartan. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Coadministration associated with increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension.

            • captopril

              aliskiren, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Aliskiren use contraindicated with ACEIs in patients with diabetes. Avoid coadministration with ACEIs if CrCl<60mL/min.

            • carbamazepine

              carbamazepine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

            • cyclophosphamide

              hydrochlorothiazide increases toxicity of cyclophosphamide by decreasing renal clearance. Avoid or Use Alternate Drug. Increased myelosuppressive effects.

            • cyclosporine

              cyclosporine will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use. Coadministration of 200 mg and 600 mg cyclosporine, with 75 mg aliskiren resulted in an approximately 2.5-fold increase in Cmax and 5-fold increase in AUC of aliskiren

              cyclosporine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid concurrent use. Coadministration of 200 mg and 600 mg cyclosporine, with 75 mg aliskiren resulted in an approximately 2.5-fold increase in Cmax and 5-fold increase in AUC of aliskiren

              cyclosporine, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

            • dofetilide

              hydrochlorothiazide increases levels of dofetilide by decreasing renal clearance. Contraindicated. Risk of prolonged QTc interval.

            • erdafitinib

              erdafitinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

            • isocarboxazid

              isocarboxazid, hydrochlorothiazide. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

            • itraconazole

              itraconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Consider an alternative with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, closely monitor for respiratory depression and sedation, and consider decreasing alfentanil dose necessary.

            • lasmiditan

              lasmiditan increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • methyl aminolevulinate

              hydrochlorothiazide, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • potassium phosphates, IV

              aliskiren and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

            • sotorasib

              sotorasib will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • squill

              hydrochlorothiazide increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

            • tepotinib

              tepotinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • tretinoin

              hydrochlorothiazide, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

            Monitor Closely (201)

            • acebutolol

              acebutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aceclofenac

              aceclofenac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • acemetacin

              acemetacin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • albiglutide

              hydrochlorothiazide decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • albuterol

              albuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • aldesleukin

              aldesleukin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • amifostine

              amifostine, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

              amifostine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amiloride

              amiloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • aspirin

              aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • amiodarone

              amiodarone will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • amoxicillin

              amoxicillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • arformoterol

              arformoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • aspirin

              aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aspirin rectal

              aspirin rectal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              aspirin rectal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atorvastatin

              atorvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              atorvastatin increases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.

            • atenolol

              atenolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • avanafil

              avanafil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              avanafil increases effects of aliskiren by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • beclomethasone, inhaled

              beclomethasone, inhaled increases toxicity of hydrochlorothiazide by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

            • berotralstat

              berotralstat will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • benazepril

              benazepril increases toxicity of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects; increased risk of nephrotoxicity.

            • bendroflumethiazide

              bendroflumethiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • betaxolol

              betaxolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bisoprolol

              bisoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bosutinib

              bosutinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bretylium

              hydrochlorothiazide, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • bumetanide

              bumetanide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection decreases effects of hydrochlorothiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • calcifediol

              hydrochlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

            • canagliflozin

              aliskiren and canagliflozin both increase serum potassium. Use Caution/Monitor.

            • candesartan

              candesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • captopril

              captopril, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

            • carbenoxolone

              hydrochlorothiazide and carbenoxolone both decrease serum potassium. Use Caution/Monitor.

            • carbidopa

              carbidopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

            • carvedilol

              carvedilol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cefprozil

              hydrochlorothiazide will increase the level or effect of cefprozil by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • celecoxib

              celecoxib will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              celecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • celiprolol

              celiprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              hydrochlorothiazide decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • chlorothiazide

              chlorothiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • chlorthalidone

              chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • cholestyramine

              cholestyramine decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • citalopram

              hydrochlorothiazide, citalopram. pharmacodynamic synergism. Use Caution/Monitor. Possible additive hyponatremia.

            • cornsilk

              cornsilk increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • corticotropin

              corticotropin increases toxicity of hydrochlorothiazide by increasing renal clearance. Use Caution/Monitor. May enhance hypokalemic effect of thiazide diuretics.

            • crizotinib

              crizotinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cyclopenthiazide

              cyclopenthiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • cyclosporine

              cyclosporine increases toxicity of hydrochlorothiazide by unspecified interaction mechanism. Use Caution/Monitor. Coadministration of hydrochlorothiazide with cyclosporine may increase the risk of hypermagnesemia, hyperuricemia, and possible nephrotoxicity.

            • deflazacort

              hydrochlorothiazide and deflazacort both decrease serum potassium. Use Caution/Monitor.

            • diazoxide

              hydrochlorothiazide increases toxicity of diazoxide by unspecified interaction mechanism. Use Caution/Monitor. May enhance hyperglycemic effects of diazoxide.

            • dichlorphenamide

              dichlorphenamide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              diclofenac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              diclofenac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dicloxacillin

              dicloxacillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • diflunisal

              diflunisal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • diflunisal

              diflunisal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • digoxin

              digoxin will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

              digoxin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              hydrochlorothiazide increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.

            • dobutamine

              dobutamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • dofetilide

              dofetilide will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • dopexamine

              dopexamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • drospirenone

              drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • elagolix

              elagolix will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eliglustat

              eliglustat increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • empagliflozin

              empagliflozin, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

            • ephedrine

              ephedrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • epinephrine

              epinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • epinephrine racemic

              epinephrine racemic and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • eprosartan

              eprosartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • erythromycin base

              erythromycin base will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esmolol

              esmolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ethacrynic acid

              ethacrynic acid and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • etodolac

              etodolac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              etodolac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • exenatide injectable solution

              hydrochlorothiazide decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • fenoprofen

              fenoprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • exenatide injectable suspension

              hydrochlorothiazide decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • fenoprofen

              fenoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fentanyl

              fentanyl decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl intranasal

              fentanyl intranasal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transdermal

              fentanyl transdermal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • fentanyl transmucosal

              fentanyl transmucosal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

            • flurbiprofen

              flurbiprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              flurbiprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • formoterol

              formoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • fostamatinib

              fostamatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • furosemide

              aliskiren decreases levels of furosemide by unspecified interaction mechanism. Use Caution/Monitor.

              furosemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • gentamicin

              hydrochlorothiazide and gentamicin both decrease serum potassium. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • ibuprofen

              ibuprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ibuprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • ibuprofen IV

              ibuprofen IV will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              hydrochlorothiazide will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

              ibuprofen IV increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

            • ibuprofen/famotidine

              ibuprofen/famotidine will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • indacaterol, inhaled

              hydrochlorothiazide, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.

              indacaterol, inhaled, hydrochlorothiazide. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

            • indapamide

              hydrochlorothiazide and indapamide both decrease serum potassium. Use Caution/Monitor.

            • indomethacin

              indomethacin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              indomethacin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • insulin degludec

              hydrochlorothiazide decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • irbesartan

              irbesartan decreases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.

            • insulin degludec/insulin aspart

              hydrochlorothiazide decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • insulin inhaled

              hydrochlorothiazide decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.

            • irbesartan

              irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • isoproterenol

              isoproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • ivacaftor

              ivacaftor increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • juniper

              juniper, hydrochlorothiazide. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

            • ketoconazole

              ketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketoprofen

              ketoprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              ketoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketorolac

              ketorolac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              ketorolac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketorolac intranasal

              ketorolac intranasal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              ketorolac intranasal increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • labetalol

              labetalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • letermovir

              letermovir increases levels of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levalbuterol

              levalbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • levodopa

              levodopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • lily of the valley

              hydrochlorothiazide increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

            • liraglutide

              hydrochlorothiazide decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

            • lithium

              hydrochlorothiazide increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

            • lomitapide

              lomitapide increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

            • lornoxicam

              lornoxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • losartan

              losartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lurasidone

              lurasidone increases effects of aliskiren by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

              lurasidone increases effects of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

            • maitake

              maitake increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

            • maraviroc

              maraviroc, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • meclofenamate

              meclofenamate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              meclofenamate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mefenamic acid

              mefenamic acid increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              mefenamic acid will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • meloxicam

              meloxicam will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              meloxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaproterenol

              metaproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • nabumetone

              nabumetone will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • methoxsalen

              methoxsalen, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • metolazone

              hydrochlorothiazide and metolazone both decrease serum potassium. Use Caution/Monitor.

            • metoprolol

              metoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              hydrochlorothiazide, metoprolol. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: May cause idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma, which can lead to permanent vision loss.

            • mometasone inhaled

              mometasone inhaled increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

            • mycophenolate

              hydrochlorothiazide will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • nabumetone

              nabumetone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nadolol

              nadolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nafcillin

              nafcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • naproxen

              naproxen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

              naproxen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nebivolol

              nebivolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nefazodone

              nefazodone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nitroglycerin rectal

              nitroglycerin rectal, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              nitroglycerin rectal, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

            • norepinephrine

              norepinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • oxaprozin

              oxaprozin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • oliceridine

              oliceridine decreases effects of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

            • olmesartan

              olmesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • olodaterol inhaled

              hydrochlorothiazide and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

            • oxaprozin

              oxaprozin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • parecoxib

              parecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • penbutolol

              penbutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • penicillin G aqueous

              penicillin G aqueous, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • pindolol

              pindolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pirbuterol

              pirbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • piroxicam

              piroxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              piroxicam will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • pivmecillinam

              pivmecillinam, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • ponatinib

              ponatinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • porfimer

              hydrochlorothiazide, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • potassium acid phosphate

              potassium acid phosphate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium chloride

              potassium chloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium citrate

              potassium citrate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • potassium citrate/citric acid

              aliskiren and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

            • probenecid

              hydrochlorothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • procainamide

              hydrochlorothiazide will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • propranolol

              propranolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quinidine

              quinidine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              quinidine will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • sacubitril/valsartan

              sacubitril/valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salsalate

              salsalate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • salicylates (non-asa)

              salicylates (non-asa) increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salmeterol

              salmeterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • salsalate

              salsalate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • shark cartilage

              hydrochlorothiazide, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              hydrochlorothiazide and sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

            • sotalol

              sotalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • spironolactone

              spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • succinylcholine

              succinylcholine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulfasalazine

              sulfasalazine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sulindac

              sulindac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              sulindac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • tadalafil

              tadalafil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              tadalafil increases effects of aliskiren by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • telmisartan

              telmisartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolmetin

              tolmetin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • temocillin

              temocillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • terbutaline

              terbutaline and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • ticarcillin

              ticarcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • timolol

              timolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolfenamic acid

              tolfenamic acid increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolmetin

              tolmetin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolvaptan

              tolvaptan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • toremifene

              hydrochlorothiazide, toremifene. Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics decrease renal calcium excretion and may increase risk of hypercalcemia in patients taking toremifene.

            • torsemide

              torsemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

            • trazodone

              trazodone will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • triamterene

              triamterene increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • trientine

              hydrochlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

            • trimethoprim

              trimethoprim and aliskiren both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

            • tucatinib

              tucatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • umeclidinium bromide/vilanterol inhaled

              umeclidinium bromide/vilanterol inhaled and hydrochlorothiazide both decrease serum potassium. Modify Therapy/Monitor Closely. Electrocardiographic changes and/or hypokalemia associated with non?potassium-sparing diuretics may worsen with concomitant beta-agonists, particularly if recommended dose is exceeded

            • valsartan

              valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • vemurafenib

              vemurafenib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • verapamil

              verapamil will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vilanterol/fluticasone furoate inhaled

              vilanterol/fluticasone furoate inhaled and hydrochlorothiazide both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics

            • vitamin D

              hydrochlorothiazide increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

            • voclosporin

              voclosporin and aliskiren both increase serum potassium. Use Caution/Monitor.

              voclosporin, aliskiren. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • xipamide

              xipamide increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor.

            Minor (177)

            • acarbose

              hydrochlorothiazide decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • aceclofenac

              hydrochlorothiazide will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              hydrochlorothiazide will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acyclovir

              hydrochlorothiazide will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • agrimony

              agrimony increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • albuterol

              albuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • aminohippurate sodium

              hydrochlorothiazide will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • amiodarone

              amiodarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ampicillin

              hydrochlorothiazide increases levels of ampicillin by decreasing renal clearance. Minor/Significance Unknown.

            • arformoterol

              arformoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • aspirin

              hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin rectal

              hydrochlorothiazide will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              hydrochlorothiazide will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • atazanavir

              atazanavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • balsalazide

              hydrochlorothiazide will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • birch

              birch increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • bitter melon

              bitter melon, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • brimonidine

              brimonidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • budesonide

              budesonide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • calcitriol topical

              calcitriol topical, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

            • calcium acetate

              hydrochlorothiazide increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium carbonate

              hydrochlorothiazide increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium chloride

              hydrochlorothiazide increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium citrate

              hydrochlorothiazide increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • calcium gluconate

              hydrochlorothiazide increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

            • carbenoxolone

              hydrochlorothiazide, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

            • cefadroxil

              cefadroxil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefprozil

              cefprozil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftibuten

              ceftibuten will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpropamide

              hydrochlorothiazide will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • chlorthalidone

              chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • clarithromycin

              clarithromycin will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              clarithromycin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • colestipol

              colestipol decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • conivaptan

              conivaptan will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cortisone

              cortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • cosyntropin

              cosyntropin, hydrochlorothiazide. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

            • cyclopenthiazide

              cyclopenthiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • darunavir

              darunavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • deflazacort

              deflazacort, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • dexamethasone

              dexamethasone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • diazoxide

              diazoxide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

            • diclofenac

              hydrochlorothiazide will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diflunisal

              hydrochlorothiazide will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • dobutamine

              dobutamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • dopexamine

              dopexamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • dronedarone

              dronedarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ephedrine

              ephedrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epinephrine

              epinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epinephrine racemic

              epinephrine racemic, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • epoprostenol

              epoprostenol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

            • erythromycin base

              erythromycin base will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • etodolac

              hydrochlorothiazide will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fenbufen

              hydrochlorothiazide will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fenoprofen

              hydrochlorothiazide will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • flurbiprofen

              hydrochlorothiazide will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • fo-ti

              fo-ti increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

            • folic acid

              hydrochlorothiazide decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

            • formoterol

              formoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • forskolin

              forskolin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • fosamprenavir

              fosamprenavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ganciclovir

              hydrochlorothiazide will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • glimepiride

              hydrochlorothiazide decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • glipizide

              hydrochlorothiazide decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • glyburide

              hydrochlorothiazide decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • goldenrod

              goldenrod increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • ibuprofen

              hydrochlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indapamide

              hydrochlorothiazide will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indinavir

              indinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • indomethacin

              hydrochlorothiazide will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • insulin aspart

              hydrochlorothiazide decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin detemir

              hydrochlorothiazide decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin glargine

              hydrochlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin glulisine

              hydrochlorothiazide decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin lispro

              hydrochlorothiazide decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin NPH

              hydrochlorothiazide decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • insulin regular human

              hydrochlorothiazide decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • isoproterenol

              isoproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • ketoprofen

              hydrochlorothiazide will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac

              hydrochlorothiazide will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac intranasal

              hydrochlorothiazide will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • L-methylfolate

              hydrochlorothiazide decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

            • lapatinib

              lapatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • levalbuterol

              levalbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • lornoxicam

              hydrochlorothiazide will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • magnesium chloride

              hydrochlorothiazide decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

            • magnesium citrate

              hydrochlorothiazide decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

            • magnesium hydroxide

              hydrochlorothiazide decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

            • magnesium oxide

              hydrochlorothiazide decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

            • magnesium sulfate

              hydrochlorothiazide decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

            • meclofenamate

              hydrochlorothiazide will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mefenamic acid

              hydrochlorothiazide will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meloxicam

              hydrochlorothiazide will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • memantine

              hydrochlorothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mesalamine

              hydrochlorothiazide will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metaproterenol

              metaproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • metformin

              hydrochlorothiazide will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • methotrexate

              hydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.

            • methylprednisolone

              methylprednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • metolazone

              hydrochlorothiazide will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • midodrine

              hydrochlorothiazide will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • miglitol

              hydrochlorothiazide decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • minoxidil

              hydrochlorothiazide increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

            • nabumetone

              hydrochlorothiazide will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • naproxen

              hydrochlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • nateglinide

              hydrochlorothiazide decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • nefazodone

              nefazodone will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nelfinavir

              nelfinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nicardipine

              nicardipine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • noni juice

              noni juice increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • norepinephrine

              norepinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              hydrochlorothiazide decreases effects of norepinephrine by pharmacodynamic antagonism. Minor/Significance Unknown. May decrease responsiveness to norepinephrine but not enough to preclude effectiveness of the pressor agent therapeutic use.

            • octacosanol

              octacosanol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • ofloxacin

              hydrochlorothiazide will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • oxaprozin

              hydrochlorothiazide will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • parecoxib

              hydrochlorothiazide will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • penicillin G aqueous

              hydrochlorothiazide increases levels of penicillin G aqueous by decreasing renal clearance. Minor/Significance Unknown.

            • penicillin VK

              hydrochlorothiazide increases levels of penicillin VK by decreasing renal clearance. Minor/Significance Unknown.

            • pioglitazone

              hydrochlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • piperacillin

              hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.

            • pirbuterol

              pirbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • piroxicam

              hydrochlorothiazide will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • posaconazole

              posaconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • prednisolone

              prednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • prednisone

              prednisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • quinine

              hydrochlorothiazide will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • reishi

              reishi increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • repaglinide

              hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • rifampin

              rifampin will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ritonavir

              ritonavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              ritonavir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • rose hips

              rose hips will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • rosiglitazone

              hydrochlorothiazide decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • salicylates (non-asa)

              hydrochlorothiazide will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • salmeterol

              salmeterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

            • salsalate

              hydrochlorothiazide will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • saxagliptin

              hydrochlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • shepherd's purse

              shepherd's purse, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

            • simvastatin

              simvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • St John's Wort

              St John's Wort will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • sitagliptin

              hydrochlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • sulfadiazine

              hydrochlorothiazide increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

              hydrochlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

            • sulfasalazine

              hydrochlorothiazide will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulfisoxazole

              hydrochlorothiazide increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

            • sulindac

              hydrochlorothiazide will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tacrolimus

              tacrolimus will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • terbutaline

              terbutaline, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

              hydrochlorothiazide, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

            • tizanidine

              tizanidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

            • tolazamide

              hydrochlorothiazide decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • tolbutamide

              hydrochlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • tolfenamic acid

              hydrochlorothiazide will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tolmetin

              hydrochlorothiazide will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tolvaptan

              tolvaptan will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • treprostinil

              treprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

            • triamterene

              hydrochlorothiazide will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • trilostane

              trilostane, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Trilostane reduces K+ loss while maintaining the natriuretic effect. Mechanism: inhibition of mineralocorticoid steroid synthesis.

            • trimethoprim

              hydrochlorothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

              hydrochlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

            • valganciclovir

              hydrochlorothiazide will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • verapamil

              hydrochlorothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • verteporfin

              hydrochlorothiazide, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

            • vildagliptin

              hydrochlorothiazide decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

            • voriconazole

              voriconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • willow bark

              hydrochlorothiazide will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

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            Adverse Effects

            Adverse reactions reported with combination product and individual agents

            >10%

            Increased BUN

            1-10%

            Dizziness (2%)

            Vertigo (1%)

            Hypokalemia (2%)

            Increased uric acid level (2%)

            Hyperkalemia (1%)

            Diarrhea (2%)

            Increased ALT (1%)

            Flu-like syndrome (2%)

            Cough (1%)

            Weakness (1%)

            Arthralgia (1%)

            Aliskiren

            • Diarrhea (2.3%)
            • Cough (1.1%)
            • Rash (1%)
            • Increased creatinine kinase (1%)
            • Increased BUN (≤ 7%)
            • Hyperkalemia (≤1%)

            <1%

            Decreased hematocrit

            Decreased hemoglobin

            Aliskiren

            • Gastroesophageal reflux
            • Periorbital edema
            • Toxic epiderma necrolysis
            • Increased uric acid
            • Severe hypotension
            • Stevens Johnson syndrome

            Frequency Not Defined

            Hydrochlorothiazide

            • AnorexiaEpigastric distress
            • Hypotension
            • Orthostatic hypotension
            • Photosensitivity
            • Anaphylaxis
            • Anemia
            • Confusion
            • Erythema multiforme
            • Stevens-Johnson syndrome
            • Exfoliative dermatitis including toxic epidermal necrolysis
            • Dizziness
            • Hypokalemia and/or hypomagnesemia
            • Hyperuricemia
            • Headache

            Postmarketing Reports

            Aliskiren

            • Nausea/vomiting
            • Hyponatremia

            Hydrochlorothiazide

            • Non-melanoma skin cancer (hydrochlorothiazide)
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            Warnings

            Black Box Warnings

            Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

            Contraindications

            Hypersensitivity to aliskiren, hydrochlorothiazide, or sulfonamides

            Anuria

            Concomitant use with ACEIs or ARBs in patients with diabetes

            Cautions

            Caution in volume- or salt-depleted patients

            Not for initial treatment

            Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported with aliskiren, necessitating hospitalization and intubation; may occur at any time during treatment and has occurred with and without a history of angioedema with ACE inhibitors or angiotensin receptor antagonist; patients who experience these effects, even without respiratory distress, require prolonged observation and appropriate monitoring measures; 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 therapy immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister

            Acute transient myopia and acute angle-closure glaucoma has been reported, particularly with history of sulfonamide or penicillin allergy (hydrochlorothiazide is a sulfonamide)

            Patients whose renal function may depend in part on activity of renin-angiotensin– aldosterone system (RAAS; e.g., patients with renal artery stenosis, severe heart failure, postmyocardial infarction or volume depletion) or patients receiving ARB, ACE inhibitors or nonsteroidal anti-inflammatory drug (NSAID), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors), therapy may be at particular risk of developing acute renal failure; monitor renal function periodically; consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function

            Hydrochlorothiazide can cause hypokalemia and hyponatremia; hypomagnesemia can also result in hypokalemia

            Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients

            If patient becomes pregnant, discontinue therapy; patient should inform doctor right away; therapy is not for patients who plan to become pregnant

            Symptomatic hypotension may occur after initiation of treatment 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); volume or salt depletion should be corrected prior to administration of therapy, or 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 blood pressure has stabilized

            Coadministration with ACE inhibitors or ARBs

            • When aliskiren was prescribed with ACE inhibitors or angiotensin receptor blockers (ARBs) in the ALTITUDE study, an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension was observed after 18-24 months
            • The ALTITUDE trial included patients with hypertension plus type 2 diabetes and renal impairment who were at high risk of cardiovascular and renal events
            • Coadministration of aliskiren with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment; their use is contraindicated in patients with diabetes
            • Avoid use of aliskiren with ARBs or ACEIs in moderate to severe renal impairment (ie, GFR <60 mL/min)
            • Hyperkalemia: Increases in serum potassium >5.5 mEq/L were infrequent with aliskiren (0.9% compared to 0.6% with placebo); however, when used in combination with an ACE inhibitor in a diabetic population, increases in serum potassium were more frequent (5.5%)
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            Pregnancy & Lactation

            Pregnancy

            Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

            Aliskiren

            • Use of drugs that act on renin-angiotensin system in second and third trimesters of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death
            • In patients taking this combination drug during pregnancy, perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on the week of gestation; 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 the drug combination for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occur in neonates with a history of in utero exposure to the drug combination, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function

            Lactation

            Limited published studies report that hydrochlorothiazide is present in human milk; however, there is insufficient information to determine the effects hydrochlorothiazide on the breastfed infant or effects of hydrochlorothiazide on milk production; because of potential for serious adverse reactions, including hypotension, electrolyte imbalances and renal impairment in nursing infants, advise a nursing woman that breastfeeding is not recommended during therapy

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Hydrochlorothiazide: Thiazide diuretic; affects renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride

            Aliskiren: Direct renin inhibitor; decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin I

            Pharmacokinetics

            Hydrochlorothiazide

            • Half-Life: 6-15 hr
            • Bioavailability: 70%
            • Onset: 2 hr (diuresis); 4-6 hr (peak effect)
            • Duration: 6-12 hr (diuresis); 1 wk (HTN)
            • Vd: 3.6-7.8 L/kg
            • Peak Plasma:1.5-2.5 hr
            • Protein Bound: 68%
            • Metabolism: Minimally metabolized
            • Clearance: 335 mL/min
            • Excretion: Urine 50-70%
            • Dialyzable: No
            • Aliskiren: 1 hr

            Aliskiren

            • Onset: Within 2 weeks
            • Bioavailability: 3%
            • Peak Plasma Time: 1-3 hr
            • Metabolism: Metabolized by CYP3A4
            • Half-Life: 24 hr
            • Excretion: Urine (25% as parent compound in urine)
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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.