hydrochlorothiazide/aliskiren (Rx)

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

Contraindicated (20)

• 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.

• sparsentan

  sparsentan, aliskiren. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of aliskiren with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

• 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 (20)

• 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.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Aliskiren product labeling recommends avoiding concomitant use with CYP3A4 and P-gp inhibitors.

• 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 (203)

• 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.

• levoketoconazole

  levoketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• 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.

• methylphenidate transdermal

  methylphenidate transdermal decreases effects of hydrochlorothiazide by anti-hypertensive channel blocking. Use Caution/Monitor.

• 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 chloride/magnesium sulfate/polyethylene glycol

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

• 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.

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

• ibuprofen

  hydrochlorothiazide will increase the level or effect of ibuprofen 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.

• indapamide

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

• acarbose

  Minor (1)hydrochlorothiazide decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• acebutolol

  Monitor Closely (1)acebutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aceclofenac

  Monitor Closely (1)aceclofenac increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (1)acemetacin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acyclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  Minor (1)agrimony increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (1)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

  Monitor Closely (1)albuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)albuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aldesleukin

  Monitor Closely (1)aldesleukin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• amifostine

  Monitor Closely (2)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

  Monitor Closely (1)amiloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• aminohippurate sodium

  Minor (1)hydrochlorothiazide will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Minor (1)amiodarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• amoxicillin

  Monitor Closely (1)amoxicillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ampicillin

  Minor (1)hydrochlorothiazide increases levels of ampicillin by decreasing renal clearance. Minor/Significance Unknown.

• arformoterol

  Monitor Closely (1)arformoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)arformoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• artemether/lumefantrine

  Minor (1)artemether/lumefantrine will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aspirin

  Monitor Closely (2)aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  Monitor Closely (2)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.Minor (1)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

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)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

  Minor (1)atazanavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atenolol

  Monitor Closely (1)atenolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (2)atorvastatin increases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.
  
  atorvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• avanafil

  Monitor Closely (2)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.

• azilsartan

  Contraindicated (1)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.Serious - Use Alternative (1)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.

• balsalazide

  Minor (1)hydrochlorothiazide will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• beclomethasone, inhaled

  Monitor Closely (1)beclomethasone, inhaled increases toxicity of hydrochlorothiazide by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

• benazepril

  Contraindicated (1)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.Monitor Closely (1)benazepril increases toxicity of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects; increased risk of nephrotoxicity.

• bendroflumethiazide

  Monitor Closely (1)bendroflumethiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)bendroflumethiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• berotralstat

  Monitor Closely (1)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.

• betaxolol

  Monitor Closely (1)betaxolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• birch

  Minor (1)birch increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

  Monitor Closely (1)bisoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bitter melon

  Minor (1)bitter melon, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• bosutinib

  Monitor Closely (1)bosutinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• bretylium

  Monitor Closely (1)hydrochlorothiazide, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

• brimonidine

  Minor (1)brimonidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  Minor (1)budesonide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• bumetanide

  Monitor Closely (1)bumetanide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• buprenorphine, long-acting injection

  Monitor Closely (1)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

  Monitor Closely (1)hydrochlorothiazide increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

• calcitriol topical

  Minor (1)calcitriol topical, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

• calcium acetate

  Minor (1)hydrochlorothiazide increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium carbonate

  Minor (1)hydrochlorothiazide increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium chloride

  Minor (1)hydrochlorothiazide increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium citrate

  Minor (1)hydrochlorothiazide increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium gluconate

  Minor (1)hydrochlorothiazide increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• canagliflozin

  Monitor Closely (1)aliskiren and canagliflozin both increase serum potassium. Use Caution/Monitor.

• candesartan

  Contraindicated (1)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.Monitor Closely (1)candesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• captopril

  Contraindicated (1)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.Monitor Closely (1)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.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)carbamazepine, hydrochlorothiazide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of systemic hyponatremia.

• carbenoxolone

  Monitor Closely (1)hydrochlorothiazide and carbenoxolone both decrease serum potassium. Use Caution/Monitor.Minor (1)hydrochlorothiazide, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• carbidopa

  Monitor Closely (1)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

  Monitor Closely (1)carvedilol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefprozil

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of cefprozil by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.Minor (1)cefprozil will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ceftibuten

  Minor (1)ceftibuten will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (2)hydrochlorothiazide decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  celiprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cephalexin

  Minor (1)cephalexin will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorothiazide

  Monitor Closely (1)chlorothiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorothiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpropamide

  Minor (2)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

  Monitor Closely (1)chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cholestyramine

  Monitor Closely (1)cholestyramine decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• choline magnesium trisalicylate

  Monitor Closely (1)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.

• citalopram

  Monitor Closely (1)hydrochlorothiazide, citalopram. pharmacodynamic synergism. Use Caution/Monitor. Possible additive hyponatremia.

• clarithromycin

  Minor (2)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

  Minor (1)colestipol decreases levels of hydrochlorothiazide by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• conivaptan

  Minor (1)conivaptan will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cornsilk

  Monitor Closely (1)cornsilk increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

• corticotropin

  Monitor Closely (1)corticotropin increases toxicity of hydrochlorothiazide by increasing renal clearance. Use Caution/Monitor. May enhance hypokalemic effect of thiazide diuretics.

• cortisone

  Minor (1)cortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• cosyntropin

  Minor (1)cosyntropin, hydrochlorothiazide. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• crizotinib

  Monitor Closely (1)crizotinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cyclopenthiazide

  Monitor Closely (1)cyclopenthiazide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)cyclopenthiazide will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclophosphamide

  Serious - Use Alternative (1)hydrochlorothiazide increases toxicity of cyclophosphamide by decreasing renal clearance. Avoid or Use Alternate Drug. Increased myelosuppressive effects.

• cyclosporine

  Monitor Closely (1)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.Serious - Use Alternative (3)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.

• darunavir

  Minor (1)darunavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• deflazacort

  Monitor Closely (1)hydrochlorothiazide and deflazacort both decrease serum potassium. Use Caution/Monitor.Minor (1)deflazacort, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• dexamethasone

  Minor (1)dexamethasone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• diazoxide

  Monitor Closely (1)hydrochlorothiazide increases toxicity of diazoxide by unspecified interaction mechanism. Use Caution/Monitor. May enhance hyperglycemic effects of diazoxide.Minor (1)diazoxide, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dicloxacillin

  Monitor Closely (1)dicloxacillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• diflunisal

  Monitor Closely (2)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 increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (3)digoxin will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  hydrochlorothiazide increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.
  
  digoxin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dobutamine

  Monitor Closely (1)dobutamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)dobutamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• dofetilide

  Monitor Closely (1)dofetilide will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (1)hydrochlorothiazide increases levels of dofetilide by decreasing renal clearance. Contraindicated. Risk of prolonged QTc interval.

• dopexamine

  Monitor Closely (1)dopexamine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)dopexamine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• dronedarone

  Minor (1)dronedarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• drospirenone

  Monitor Closely (1)drospirenone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• elagolix

  Monitor Closely (1)elagolix will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eliglustat

  Monitor Closely (1)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

  Monitor Closely (1)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.

• enalapril

  Contraindicated (2)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.

• ephedrine

  Monitor Closely (1)ephedrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)ephedrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine

  Monitor Closely (1)epinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)epinephrine, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine racemic

  Monitor Closely (1)epinephrine racemic and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)epinephrine racemic, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epoprostenol

  Minor (1)epoprostenol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• eprosartan

  Contraindicated (1)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.Monitor Closely (1)eprosartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• erdafitinib

  Serious - Use Alternative (1)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.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)erythromycin base will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)erythromycin ethylsuccinate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)erythromycin lactobionate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)erythromycin stearate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• eslicarbazepine acetate

  Minor (1)eslicarbazepine acetate will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esmolol

  Monitor Closely (1)esmolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ethacrynic acid

  Monitor Closely (1)ethacrynic acid and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• etodolac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)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.

• exenatide injectable suspension

  Monitor Closely (1)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.

• fenbufen

  Minor (1)hydrochlorothiazide will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenoprofen

  Monitor Closely (2)fenoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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).

• fludrocortisone

  Minor (1)fludrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• flurbiprofen

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fo-ti

  Minor (1)fo-ti increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

• folic acid

  Minor (1)hydrochlorothiazide decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

• formoterol

  Monitor Closely (1)formoterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)formoterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• forskolin

  Minor (1)forskolin increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• fosamprenavir

  Minor (1)fosamprenavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fosinopril

  Contraindicated (1)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.

• fostamatinib

  Monitor Closely (1)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

  Monitor Closely (2)aliskiren decreases levels of furosemide by unspecified interaction mechanism. Use Caution/Monitor.
  
  furosemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• ganciclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• gentamicin

  Monitor Closely (1)hydrochlorothiazide and gentamicin both decrease serum potassium. Use Caution/Monitor.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glimepiride

  Minor (1)hydrochlorothiazide decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glipizide

  Minor (1)hydrochlorothiazide decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glyburide

  Minor (1)hydrochlorothiazide decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• goldenrod

  Minor (1)goldenrod increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrocortisone

  Minor (2)hydrocortisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.
  
  hydrocortisone will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ibuprofen

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (3)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (1)hydrochlorothiazide and indapamide both decrease serum potassium. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indinavir

  Minor (1)indinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• indomethacin

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• insulin aspart

  Minor (1)hydrochlorothiazide decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin degludec

  Monitor Closely (1)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.

• insulin degludec/insulin aspart

  Monitor Closely (1)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 detemir

  Minor (1)hydrochlorothiazide decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin glargine

  Minor (1)hydrochlorothiazide decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin glulisine

  Minor (1)hydrochlorothiazide decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin inhaled

  Monitor Closely (1)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.

• insulin lispro

  Minor (1)hydrochlorothiazide decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin NPH

  Minor (1)hydrochlorothiazide decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin regular human

  Minor (1)hydrochlorothiazide decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• irbesartan

  Contraindicated (1)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.Monitor Closely (2)irbesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  irbesartan decreases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid, hydrochlorothiazide. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

• isoproterenol

  Monitor Closely (1)isoproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)isoproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• istradefylline

  Monitor Closely (1)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.

• itraconazole

  Serious - Use Alternative (1)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.

• ivacaftor

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)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

  Monitor Closely (2)ketoprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (2)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. .Minor (1)hydrochlorothiazide will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• L-methylfolate

  Minor (1)hydrochlorothiazide decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

• labetalol

  Monitor Closely (1)labetalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lapatinib

  Minor (1)lapatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• lasmiditan

  Serious - Use Alternative (1)lasmiditan increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• letermovir

  Monitor Closely (1)letermovir increases levels of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (1)levalbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)levalbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• levodopa

  Monitor Closely (1)levodopa increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levoketoconazole

  Monitor Closely (2)levoketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lily of the valley

  Monitor Closely (1)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

  Monitor Closely (1)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.

• lisinopril

  Contraindicated (1)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.

• lithium

  Monitor Closely (1)hydrochlorothiazide increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

• lofexidine

  Serious - Use Alternative (1)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.

• lomitapide

  Monitor Closely (1)lomitapide increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

• lornoxicam

  Monitor Closely (1)lornoxicam increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Contraindicated (1)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.Monitor Closely (1)losartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lurasidone

  Monitor Closely (2)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.

• magnesium chloride

  Minor (1)hydrochlorothiazide decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

• magnesium citrate

  Minor (1)hydrochlorothiazide decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

• magnesium hydroxide

  Minor (1)hydrochlorothiazide decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium oxide

  Minor (1)hydrochlorothiazide decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium sulfate

  Minor (1)hydrochlorothiazide decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

• maitake

  Monitor Closely (1)maitake increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

• maraviroc

  Monitor Closely (1)maraviroc, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• meclofenamate

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• memantine

  Minor (1)hydrochlorothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  Minor (1)hydrochlorothiazide will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (1)metaproterenol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)metaproterenol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• metformin

  Minor (2)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

  Minor (1)hydrochlorothiazide increases toxicity of methotrexate by decreasing elimination. Minor/Significance Unknown. Increased myelosuppression.

• methoxsalen

  Monitor Closely (1)methoxsalen, hydrochlorothiazide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methyl aminolevulinate

  Serious - Use Alternative (1)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.

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal decreases effects of hydrochlorothiazide by anti-hypertensive channel blocking. Use Caution/Monitor.

• methylprednisolone

  Minor (1)methylprednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• metolazone

  Monitor Closely (1)hydrochlorothiazide and metolazone both decrease serum potassium. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (2)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.
  
  metoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• midodrine

  Minor (1)hydrochlorothiazide will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miglitol

  Minor (1)hydrochlorothiazide decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• minoxidil

  Minor (1)hydrochlorothiazide increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

• moexipril

  Contraindicated (1)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.

• mometasone inhaled

  Monitor Closely (1)mometasone inhaled increases toxicity of hydrochlorothiazide by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

• mycophenolate

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabumetone

  Monitor Closely (2)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.
  
  nabumetone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (1)nadolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nafcillin

  Monitor Closely (1)nafcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• naproxen

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  Minor (1)hydrochlorothiazide decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• nebivolol

  Monitor Closely (1)nebivolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nefazodone

  Monitor Closely (1)nefazodone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nefazodone will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nelfinavir

  Minor (1)nelfinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Minor (1)nicardipine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• nilotinib

  Minor (1)nilotinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• nirmatrelvir/ritonavir

  Serious - Use Alternative (1)nirmatrelvir/ritonavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Aliskiren product labeling recommends avoiding concomitant use with CYP3A4 and P-gp inhibitors.

• nitroglycerin rectal

  Monitor Closely (2)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. .

• noni juice

  Minor (1)noni juice increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (1)norepinephrine and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (2)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

  Minor (1)octacosanol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• ofloxacin

  Minor (1)hydrochlorothiazide will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oliceridine

  Monitor Closely (1)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

  Contraindicated (1)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.Monitor Closely (1)olmesartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olodaterol inhaled

  Monitor Closely (1)hydrochlorothiazide and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

• oxaprozin

  Monitor Closely (2)oxaprozin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• parecoxib

  Monitor Closely (1)parecoxib increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• penbutolol

  Monitor Closely (1)penbutolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• penicillin G aqueous

  Monitor Closely (1)penicillin G aqueous, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.Minor (1)hydrochlorothiazide increases levels of penicillin G aqueous by decreasing renal clearance. Minor/Significance Unknown.

• penicillin VK

  Minor (1)hydrochlorothiazide increases levels of penicillin VK by decreasing renal clearance. Minor/Significance Unknown.

• perindopril

  Contraindicated (1)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.

• pindolol

  Monitor Closely (1)pindolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pioglitazone

  Minor (1)hydrochlorothiazide decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• piperacillin

  Minor (1)hydrochlorothiazide increases levels of piperacillin by decreasing renal clearance. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (1)pirbuterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)pirbuterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• piroxicam

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pivmecillinam

  Monitor Closely (1)pivmecillinam, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ponatinib

  Monitor Closely (1)ponatinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• porfimer

  Monitor Closely (1)hydrochlorothiazide, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  Minor (1)posaconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• potassium acid phosphate

  Monitor Closely (1)potassium acid phosphate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)potassium chloride increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)potassium citrate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium citrate/citric acid

  Monitor Closely (1)aliskiren and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

• potassium phosphates, IV

  Serious - Use Alternative (1)aliskiren and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

• prednisolone

  Minor (1)prednisolone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• prednisone

  Minor (1)prednisone, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• probenecid

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• procainamide

  Monitor Closely (1)hydrochlorothiazide will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• propranolol

  Monitor Closely (1)propranolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quinapril

  Contraindicated (1)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.

• quinidine

  Monitor Closely (2)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.

• quinine

  Minor (1)hydrochlorothiazide will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ramipril

  Contraindicated (1)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.

• ranolazine

  Minor (1)ranolazine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• reishi

  Minor (1)reishi increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• repaglinide

  Minor (1)hydrochlorothiazide decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• rifampin

  Minor (1)rifampin will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• ritonavir

  Minor (2)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

  Minor (1)rose hips will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• rosiglitazone

  Minor (1)hydrochlorothiazide decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• sacubitril/valsartan

  Contraindicated (1)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.Monitor Closely (1)sacubitril/valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salicylates (non-asa)

  Monitor Closely (1)salicylates (non-asa) increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)salmeterol and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)salmeterol, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• salsalate

  Monitor Closely (2)salsalate increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sarecycline

  Monitor Closely (1)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.

• saxagliptin

  Minor (1)hydrochlorothiazide decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• shark cartilage

  Monitor Closely (1)hydrochlorothiazide, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

• shepherd's purse

  Minor (1)shepherd's purse, hydrochlorothiazide. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• simvastatin

  Minor (1)simvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• sitagliptin

  Minor (1)hydrochlorothiazide decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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 chloride/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)hydrochlorothiazide and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)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.

• sotalol

  Monitor Closely (1)sotalol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sotorasib

  Serious - Use Alternative (1)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.

• sparsentan

  Contraindicated (1)sparsentan, aliskiren. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Coadministration of aliskiren with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure).

• spironolactone

  Monitor Closely (1)spironolactone increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• squill

  Serious - Use Alternative (1)hydrochlorothiazide increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

• St John's Wort

  Minor (1)St John's Wort will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• stiripentol

  Monitor Closely (1)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

  Monitor Closely (1)succinylcholine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sulfadiazine

  Minor (1)hydrochlorothiazide increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Minor (3)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

  Monitor Closely (1)sulfasalazine increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  Minor (1)hydrochlorothiazide increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (2)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.Minor (1)hydrochlorothiazide will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tacrolimus

  Minor (1)tacrolimus will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• tadalafil

  Monitor Closely (2)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

  Contraindicated (1)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.Monitor Closely (1)telmisartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• temocillin

  Monitor Closely (1)temocillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• tepotinib

  Serious - Use Alternative (1)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.

• terbutaline

  Monitor Closely (1)terbutaline and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (2)terbutaline, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.
  
  hydrochlorothiazide, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• ticarcillin

  Monitor Closely (1)ticarcillin, hydrochlorothiazide. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• timolol

  Monitor Closely (1)timolol increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tizanidine

  Minor (1)tizanidine increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tolazamide

  Minor (1)hydrochlorothiazide decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolbutamide

  Minor (1)hydrochlorothiazide decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolfenamic acid

  Monitor Closely (1)tolfenamic acid increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (2)tolmetin increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Minor (1)hydrochlorothiazide will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolvaptan

  Monitor Closely (1)tolvaptan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)tolvaptan will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

• toremifene

  Monitor Closely (1)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

  Monitor Closely (1)torsemide and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• trandolapril

  Contraindicated (2)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.

• trazodone

  Monitor Closely (1)trazodone will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• treprostinil

  Minor (1)treprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

• tretinoin

  Serious - Use Alternative (1)hydrochlorothiazide, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)hydrochlorothiazide, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triamcinolone acetonide injectable suspension

  Minor (1)triamcinolone acetonide injectable suspension, hydrochlorothiazide. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• triamterene

  Monitor Closely (1)triamterene increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Minor (1)hydrochlorothiazide will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trientine

  Monitor Closely (1)hydrochlorothiazide decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

• trilostane

  Minor (1)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

  Monitor Closely (1)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.Minor (2)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.

• tucatinib

  Monitor Closely (1)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

  Monitor Closely (1)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

• valganciclovir

  Minor (1)hydrochlorothiazide will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valsartan

  Contraindicated (1)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.Monitor Closely (1)valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• vemurafenib

  Monitor Closely (1)vemurafenib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• verapamil

  Monitor Closely (2)verapamil will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  verapamil will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)hydrochlorothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• verteporfin

  Minor (1)hydrochlorothiazide, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• vilanterol/fluticasone furoate inhaled

  Monitor Closely (1)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

• vildagliptin

  Minor (1)hydrochlorothiazide decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• vitamin D

  Monitor Closely (1)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

  Monitor Closely (2)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.

• voriconazole

  Minor (1)voriconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• willow bark

  Minor (1)hydrochlorothiazide will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• xipamide

  Monitor Closely (1)xipamide increases effects of hydrochlorothiazide by pharmacodynamic synergism. Use Caution/Monitor.