valsartan/amlodipine/hydrochlorothiazide (Rx)

Brand and Other Names:Exforge HCT
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Dosing & Uses

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Dosage Forms & Strengths

valsartan/amlodipine/hydrochlorothiazide

tablet

  • 5mg/160mg/12.5mg
  • 5mg/160mg/25mg
  • 10mg/160mg/12.5mg
  • 10mg/160mg/25mg
  • 10mg/320mg/25mg

Hypertension

5-10 mg amlodipine/160-320 mg valsartan/12.5-25 mg hydrochlorothiazide qDay; may titrate dose after 2 weeks

Use in patients not adequately controlled with monotherapy; may use as initial therapy in patients likely to need multiple drugs to achieve blood pressure goals

Indicated for patients not adequately controlled on any 2 of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics, OR

Indicated for substitution for the individually titrated drug components

May increase dose after 2 weeks if needed

Not to exceed 10 mg/320 mg/25 mg PO once-daily

Renal & Hepatic Impairment

Renal impairment

  • Mild or moderate (CrCl ≥30 mL/min): No dose adjustment necessary
  • Severe (CrCl <30 mL/min): Safety and effectiveness not established

Hepatic impairment

  • Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination
  • Amlodipine: Extensively metabolized by liver and half-life increased (56 hr) with impaired hepatic function
  • Valsartan: No dose adjustment necessary with mild-to-severe hepatic impairment
  • Hydrochlorothiazide: Minor alterations of fluid and electrolyte balance may cause hepatic coma in patients with impaired hepatic function

Safety/efficacy not established

Hypertension

Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination

Initiate with 2.5 mg PO qDay; may titrate dose after 2 weeks

Indicated for patients not adequately controlled on any 2 of the following antihypertensive classes: calcium channel blockers, angiotensin receptor blockers, and diuretics, OR

Indicated for substitution for the individually titrated drug components

May increase dose after 2 weeks if needed

Not to exceed 10 mg/320 mg/25 mg PO once-daily

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Interactions

Interaction Checker

and valsartan/amlodipine/hydrochlorothiazide

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            Contraindicated (2)

            • aliskiren

              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.

            • dantrolene

              dantrolene, amlodipine. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Rare incidence of cardiovascular collapse and marked hyperkalemia observed when coadministered; may be higher risk with nondihydropyridine calcium channel blockers.

            Serious - Use Alternative (40)

            • abametapir

              abametapir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • 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.

            • apalutamide

              apalutamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • baricitinib

              valsartan will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.

            • benazepril

              valsartan, benazepril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • captopril

              valsartan, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • carbamazepine

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

            • chloramphenicol

              chloramphenicol will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • chloroquine

              chloroquine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • conivaptan

              conivaptan will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.

            • cyclophosphamide

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

            • cyclosporine

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

            • diltiazem

              diltiazem will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use with amlodipine and diltiazem reported an a 60% increase in amlodipine AUC. Monitor increased effects and toxicities (eg, bradycardia, sinus arrest, decreased cardiac output) if amiodarone is concomitantly used with nondihydropyridine calcium channel blocker (ie, diltiazem).

            • dofetilide

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

            • eluxadoline

              valsartan increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

            • enalapril

              valsartan, enalapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • enzalutamide

              enzalutamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fosinopril

              valsartan, fosinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • idelalisib

              idelalisib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • isocarboxazid

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

            • ivosidenib

              ivosidenib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lisinopril

              valsartan, lisinopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • lithium

              valsartan increases toxicity of lithium by decreasing renal clearance. 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.

              lofexidine, amlodipine. 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.

              lofexidine, valsartan. 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.

            • lonafarnib

              amlodipine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

              lonafarnib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • 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.

            • moexipril

              valsartan, moexipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • nifedipine

              nifedipine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • perindopril

              valsartan, perindopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • potassium phosphates, IV

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

            • quinapril

              valsartan, quinapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • ramipril

              valsartan, ramipril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • simvastatin

              amlodipine increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently.

            • squill

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

            • trandolapril

              valsartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • tretinoin

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

            • tretinoin topical

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

            • voxelotor

              voxelotor will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (359)

            • acebutolol

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

              acebutolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and acebutolol both increase serum potassium. Use Caution/Monitor.

              acebutolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • aceclofenac

              valsartan and aceclofenac both increase serum potassium. Use Caution/Monitor.

              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.

            • acemetacin

              valsartan and acemetacin both increase serum potassium. Use Caution/Monitor.

            • albiglutide

              valsartan increases effects of albiglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • aldesleukin

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

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

            • 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.

            • alfuzosin

              alfuzosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • 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, amlodipine. 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.

              amifostine, valsartan. 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.

              valsartan and amiloride both increase serum potassium. Modify Therapy/Monitor Closely.

            • amiodarone

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

            • apalutamide

              apalutamide will decrease the level or effect of valsartan by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

            • asenapine

              asenapine and amlodipine both increase anti-hypertensive channel blocking. 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.

              valsartan, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • aspirin rectal

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

              valsartan and aspirin rectal both increase serum potassium. Use Caution/Monitor.

            • aspirin/citric acid/sodium bicarbonate

              valsartan and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Use Caution/Monitor.

              aspirin/citric acid/sodium bicarbonate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

              valsartan, aspirin/citric acid/sodium bicarbonate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • atenolol

              atenolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              atenolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

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

              valsartan and atenolol both increase serum potassium. Use Caution/Monitor.

            • atogepant

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

            • avanafil

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

            • atorvastatin

              atorvastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              valsartan increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • avanafil

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

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

            • avapritinib

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

            • beclomethasone, inhaled

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

            • benazepril

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

            • bendroflumethiazide

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

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

            • axitinib

              amlodipine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • betaxolol

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

            • belzutifan

              belzutifan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • betaxolol

              betaxolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              betaxolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              valsartan and betaxolol both increase serum potassium. Use Caution/Monitor.

            • bisoprolol

              bisoprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              bisoprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              valsartan and bisoprolol both increase serum potassium. Use Caution/Monitor.

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

            • bosentan

              bosentan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for decreased effects of amlodipine (CYP3A4 substrate) if bosentan is initiated/dose increased. Also, monitor toxicities of amlodipine if bosentan is discontinued/dose decreased.

            • bretylium

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

            • bretylium

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

            • bretylium

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

            • brimonidine

              brimonidine increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • bumetanide

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

              valsartan increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. 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.

            • butabarbital

              butabarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • calcium acetate

              calcium acetate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium carbonate

              calcium carbonate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium chloride

              calcium chloride decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium citrate

              calcium citrate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium gluconate

              calcium gluconate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.

            • canagliflozin

              valsartan 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.

            • carbamazepine

              carbamazepine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              carbamazepine will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • carbenoxolone

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

              valsartan increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. 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.

              carbidopa increases effects of amlodipine 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, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              carvedilol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and carvedilol both increase serum potassium. Use Caution/Monitor.

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

            • caspofungin

              caspofungin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • cefprozil

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

            • celecoxib

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

            • celiprolol

              celiprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              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.

            • celecoxib

              valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.

              celecoxib decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • chlorothiazide

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

            • celiprolol

              valsartan and celiprolol both increase serum potassium. Use Caution/Monitor.

              celiprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • cenobamate

              cenobamate will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

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

            • chlorothiazide

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

            • chlorthalidone

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

              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.

            • choline magnesium trisalicylate

              valsartan and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

              choline magnesium trisalicylate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, choline magnesium trisalicylate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • citalopram

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

            • clarithromycin

              clarithromycin will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased effect of calcium channel blockers may lead to hypotension, edema, decreased HR, and acute kidney injury due to reduced renal blood flow

              clarithromycin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • clevidipine

              amlodipine and clevidipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • 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.

            • cyclopenthiazide

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

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

            • cobicistat

              cobicistat will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • crizotinib

              crizotinib increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • cyclosporine

              cyclosporine and valsartan both increase Other (see comment). Use Caution/Monitor. Cyclosporine and valsartan both increase the risk of hyperkalemia and nephrotoxicity.

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

              amlodipine increases levels of cyclosporine by unspecified interaction mechanism. Modify Therapy/Monitor Closely. A prospective study in renal transplant recipients averaged a 40% increase in cyclosporine trough levels.

            • dabrafenib

              dabrafenib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dalteparin

              dalteparin increases toxicity of valsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • darunavir

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

            • deferasirox

              deferasirox will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

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

            • diclofenac

              valsartan and diclofenac both increase serum potassium. Use Caution/Monitor.

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

              diclofenac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, diclofenac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • dicloxacillin

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

            • diflunisal

              valsartan and diflunisal both increase serum potassium. Use Caution/Monitor.

              diflunisal decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, diflunisal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • diflunisal

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

            • digoxin

              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.

              valsartan will increase the level or effect of digoxin by decreasing renal clearance. Use Caution/Monitor. Monitor digoxin levels closely when coadministered with drugs that may decrease glomerular filtration or tubular secretion.

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

            • diltiazem

              amlodipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • dobutamine

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

            • dobutamine

              valsartan increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. 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.

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

            • doxazosin

              doxazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • drospirenone

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

            • dronedarone

              dronedarone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.

            • drospirenone

              valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

            • efavirenz

              efavirenz will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eltrombopag

              eltrombopag will decrease the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • 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.

            • encorafenib

              encorafenib will increase the level or effect of valsartan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

              encorafenib, amlodipine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enoxaparin

              enoxaparin increases toxicity of valsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • 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 amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eplerenone

              valsartan, eplerenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • eprosartan

              eprosartan and valsartan both increase serum potassium. Use Caution/Monitor.

            • erythromycin base

              erythromycin base will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • erythromycin stearate

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

              erythromycin stearate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esmolol

              esmolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              valsartan and esmolol both increase serum potassium. Use Caution/Monitor.

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

            • esmolol

              esmolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • ethacrynic acid

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

            • ethacrynic acid

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

            • etodolac

              etodolac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and etodolac both increase serum potassium. Use Caution/Monitor.

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

              valsartan, etodolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • exenatide injectable solution

              valsartan increases effects of exenatide injectable solution by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              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

              valsartan increases effects of exenatide injectable suspension by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              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.

            • fedratinib

              fedratinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenoprofen

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

            • felodipine

              amlodipine and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • fenbufen

              valsartan and fenbufen both increase serum potassium. Use Caution/Monitor.

            • fenoprofen

              valsartan and fenoprofen both increase serum potassium. Use Caution/Monitor.

              fenoprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, fenoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • 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).

            • finerenone

              amlodipine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              amlodipine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluconazole

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

            • flurbiprofen

              flurbiprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and flurbiprofen both increase serum potassium. Use Caution/Monitor.

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

              valsartan, flurbiprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • fluvastatin

              valsartan increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • formoterol

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

            • fosamprenavir

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

            • fosphenytoin

              fosphenytoin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fostemsavir

              fostemsavir will increase the level or effect of valsartan by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

            • furosemide

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

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

            • gemfibrozil

              gemfibrozil will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • gentamicin

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

            • gentamicin

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

            • glyburide

              glyburide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • griseofulvin

              griseofulvin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • heparin

              heparin increases toxicity of valsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • hydrochlorothiazide

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

            • ibuprofen

              valsartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

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

              valsartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ibuprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • ibuprofen IV

              ibuprofen IV decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

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

              valsartan, ibuprofen IV. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              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.

            • iloperidone

              iloperidone and amlodipine both increase additive vasodilation. Use Caution/Monitor. Calcium channel blockers with iloperidone may potentiate the hypotensive effects.

            • 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

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

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

            • indinavir

              indinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • indomethacin

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

            • indomethacin

              valsartan and indomethacin both increase serum potassium. Use Caution/Monitor.

              indomethacin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, indomethacin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • insulin aspart

              valsartan increases effects of insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin aspart protamine/insulin aspart

              valsartan increases effects of insulin aspart protamine/insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec

              valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

              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.

              valsartan, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin degludec/insulin aspart

              valsartan, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              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

              valsartan increases effects of insulin detemir by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • 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.

            • insulin glargine

              valsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin glulisine

              valsartan increases effects of insulin glulisine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

              valsartan, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

              valsartan increases effects of insulin inhaled by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin isophane human/insulin regular human

              valsartan increases effects of insulin isophane human/insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro

              valsartan increases effects of insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro protamine/insulin lispro

              valsartan increases effects of insulin lispro protamine/insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin NPH

              valsartan increases effects of insulin NPH by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin regular human

              valsartan increases effects of insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • irbesartan

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

            • isavuconazonium sulfate

              amlodipine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoproterenol

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

            • isradipine

              amlodipine and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole will increase the level or effect of amlodipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • 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 valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • ketoprofen

              valsartan and ketoprofen both increase serum potassium. Use Caution/Monitor.

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

              valsartan, ketoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ketoprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • ketorolac

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

            • ketorolac

              valsartan and ketorolac both increase serum potassium. Use Caution/Monitor.

              ketorolac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, ketorolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ketorolac intranasal

              valsartan and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

              ketorolac intranasal decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, ketorolac intranasal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • labetalol

              labetalol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              labetalol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and labetalol both increase serum potassium. Use Caution/Monitor.

            • ketorolac intranasal

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

            • lemborexant

              amlodipine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • labetalol

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

            • lenacapavir

              lenacapavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lesinurad

              lesinurad decreases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • letermovir

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

              letermovir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              valsartan increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • levalbuterol

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

            • levodopa

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

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

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

            • levoketoconazole

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

              levoketoconazole will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • 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

              valsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

              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

              amlodipine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lopinavir

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

            • lorlatinib

              lorlatinib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lornoxicam

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

              valsartan and lornoxicam both increase serum potassium. Use Caution/Monitor.

            • losartan

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

            • lovastatin

              lovastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • lurasidone

              lurasidone increases effects of amlodipine 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 valsartan 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 supplement

              magnesium supplement, amlodipine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Calcium channel blockers may increase toxic effects of magnesium; magnesium may increase hypotensive effects of calcium channel blockers.

            • maitake

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

            • maitake

              maitake increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • maraviroc

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

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

            • meclofenamate

              meclofenamate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, meclofenamate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

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

              valsartan and meclofenamate both increase serum potassium. 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

              valsartan and mefenamic acid both increase serum potassium. Use Caution/Monitor.

              mefenamic acid decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, mefenamic acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • mefloquine

              mefloquine increases levels of amlodipine by decreasing metabolism. Use Caution/Monitor. Risk of arrhythmia.

            • meloxicam

              valsartan, meloxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              valsartan and meloxicam both increase serum potassium. Use Caution/Monitor.

              meloxicam decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              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.

            • metformin

              amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

            • methoxsalen

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

            • methyclothiazide

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

            • methylphenidate

              methylphenidate will decrease the level or effect of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

              methylphenidate will decrease the level or effect of valsartan by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methylphenidate transdermal

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

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

            • metolazone

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

            • metolazone

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

            • metoprolol

              valsartan and metoprolol both increase serum potassium. Use Caution/Monitor.

              metoprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • metyrapone

              metyrapone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • midazolam intranasal

              amlodipine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • 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.

            • mifepristone

              mifepristone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • mitotane

              mitotane decreases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • 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

              valsartan and nabumetone both increase serum potassium. Use Caution/Monitor.

              nabumetone decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

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

              valsartan, nabumetone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • moxisylyte

              moxisylyte and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nadolol

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

            • nadolol

              nadolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              nadolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and nadolol both increase serum potassium. Use Caution/Monitor.

            • nafcillin

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

            • naproxen

              naproxen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and naproxen both increase serum potassium. Use Caution/Monitor.

              valsartan, naproxen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

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

            • nebivolol

              nebivolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

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

            • nebivolol

              valsartan and nebivolol both increase serum potassium. Use Caution/Monitor.

              nebivolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • 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. .

            • nefazodone

              nefazodone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • nelfinavir

              nelfinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • nevirapine

              nevirapine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              amlodipine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nifedipine

              amlodipine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nilotinib

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

            • nirmatrelvir

              nirmatrelvir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

            • nisoldipine

              amlodipine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nitroglycerin rectal

              nitroglycerin rectal, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. Observe for possible additive hypotensive effects during concomitant use. .

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

            • nitroglycerin sublingual

              amlodipine, nitroglycerin sublingual. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Marked orthostatic hypotension reported with concomitant use.

            • norepinephrine

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

            • 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.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. May inhibit organic anion transporter polypeptides; decrease dose of angiotensin receptor blockers and monitor patients for signs and symptoms of hypotension and/or worsening renal function; if such events occur, consider further dose reduction of angiotensin receptor blocker or switching to alternative to angiotensin receptor blocker

            • nitroprusside sodium

              amlodipine increases effects of nitroprusside sodium by pharmacodynamic synergism. Use Caution/Monitor.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. if such events occur, consider further dose reduction of calcium channel blocker or switching to alternative to calcium channel blocker

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by altering metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. if such events occur, consider further dose reduction of calcium channel blocker or switching to alternative to calcium channel blocker

            • oxaprozin

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

              oxaprozin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and oxaprozin both increase serum potassium. Use Caution/Monitor.

              valsartan, oxaprozin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • paclitaxel

              paclitaxel will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • parecoxib

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

            • paclitaxel protein bound

              paclitaxel protein bound will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • parecoxib

              valsartan and parecoxib both increase serum potassium. Use Caution/Monitor.

            • pazopanib

              pazopanib will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • penbutolol

              penbutolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and penbutolol both increase serum potassium. Use Caution/Monitor.

              penbutolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              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.

            • pentobarbital

              pentobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pindolol

              valsartan and pindolol both increase serum potassium. Use Caution/Monitor.

              pindolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

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

            • phenobarbital

              phenobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pirbuterol

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

            • phenoxybenzamine

              phenoxybenzamine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phentolamine

              phentolamine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phenytoin

              amlodipine will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • pindolol

              pindolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • pioglitazone

              pioglitazone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • piroxicam

              piroxicam decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and piroxicam both increase serum potassium. Use Caution/Monitor.

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

              valsartan, piroxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • pitavastatin

              valsartan increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • pivmecillinam

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

            • porfimer

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

            • posaconazole

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

            • potassium acid phosphate

              valsartan and potassium acid phosphate both increase serum potassium. Use Caution/Monitor.

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

            • potassium chloride

              valsartan and potassium chloride both increase serum potassium. Use Caution/Monitor.

              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.

              valsartan and potassium citrate both increase serum potassium. Use Caution/Monitor.

            • potassium citrate/citric acid

              valsartan 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.

            • potassium iodide

              potassium iodide and valsartan both increase serum potassium. Use Caution/Monitor. Potassium salts may increase the hyperkalemic effects of ARBs; the effect may be the result of aldosterone suppression in patients receiving ARBs.

            • pravastatin

              pravastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              valsartan increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • prazosin

              prazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and propranolol both increase serum potassium. Use Caution/Monitor.

              propranolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              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 hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • repaglinide

              repaglinide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • ribociclib

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

            • rifabutin

              rifabutin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              rifampin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              ritonavir will increase the level or effect of valsartan by Mechanism: decreasing hepatic clearance. Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic efflux transporter MRP2; coadministration of inhibitors of the efflux transporter may increase the systemic exposure to valsartan

            • ritonavir

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

            • rosiglitazone

              rosiglitazone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • rucaparib

              rucaparib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • sacubitril/valsartan

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

            • salicylates (non-asa)

              valsartan and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

              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

              valsartan and salsalate both increase serum potassium. Use Caution/Monitor.

              salsalate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, salsalate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • salsalate

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

            • saquinavir

              saquinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              saquinavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • shark cartilage

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

            • silodosin

              silodosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • simvastatin

              simvastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • 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.

              amlodipine, sodium sulfate/?magnesium sulfate/potassium chloride. Either increases effects of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

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

            • sodium sulfate/potassium sulfate/magnesium sulfate

              amlodipine, sodium sulfate/potassium sulfate/magnesium sulfate. Either increases effects of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

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

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

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

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

            • St John's Wort

              St John's Wort will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

            • sotalol

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

              sotalol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • sotalol

              valsartan and sotalol both increase serum potassium. Use Caution/Monitor.

              sotalol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • spironolactone

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

            • spironolactone

              valsartan and spironolactone both increase serum potassium. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol, amlodipine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • succinylcholine

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

            • sulfasalazine

              sulfasalazine decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, sulfasalazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              valsartan and sulfasalazine both increase serum potassium. Use Caution/Monitor.

              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.

              valsartan, sulindac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              valsartan and sulindac both increase serum potassium. Use Caution/Monitor.

              sulindac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • synthetic human angiotensin II

              valsartan decreases effects of synthetic human angiotensin II by pharmacodynamic antagonism. Use Caution/Monitor.

            • tadalafil

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

            • tacrolimus

              amlodipine will increase the level or effect of tacrolimus by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Adjust dose when appropriate.

            • tadalafil

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

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

            • tazemetostat

              tazemetostat will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              amlodipine will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • telmisartan

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

            • temocillin

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

            • terbutaline

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

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

            • tecovirimat

              tecovirimat will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • ticarcillin

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

            • temsirolimus

              amlodipine increases toxicity of temsirolimus by Other (see comment). Use Caution/Monitor. Comment: Combination of mTOR inhibitors with calcium channel blockers increases risk of angioedema.

            • terazosin

              terazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • timolol

              timolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

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

              timolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

              valsartan and timolol both increase serum potassium. Use Caution/Monitor.

            • tinidazole

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

            • tolfenamic acid

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

            • tizanidine

              tizanidine increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tipranavir

              tipranavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Tipranavir is used with ritonavir (boosted therapy) which is a potent CYP3A4 inhibitor.

            • tolfenamic acid

              valsartan and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              valsartan and tolmetin both increase serum potassium. Use Caution/Monitor.

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

              valsartan, tolmetin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              tolmetin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • tolvaptan

              valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

              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

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

            • torsemide

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

            • treprostinil

              treprostinil increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • triamterene

              valsartan and triamterene both increase serum potassium. Modify Therapy/Monitor Closely.

              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.

            • trimagnesium citrate anhydrous

              trimagnesium citrate anhydrous, amlodipine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Possible additive effect of magnesium and calcium channel blockers on reduction of ionic calcium may increase risk of hypotension or muscle weakness.

            • trimethoprim

              valsartan and trimethoprim 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.

            • 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.

            • verapamil

              amlodipine and verapamil both increase anti-hypertensive channel blocking. 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 valsartan both increase serum potassium. Use Caution/Monitor.

              voclosporin, valsartan. 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

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

              voriconazole increases levels of amlodipine by decreasing metabolism. Use Caution/Monitor.

            • xipamide

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

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

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

            Minor (193)

            • 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.

            • acetazolamide

              acetazolamide will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

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

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

            • albuterol

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

            • amobarbital

              amobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • aminohippurate sodium

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

            • 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.

            • 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.

            • colestipol

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

            • cornsilk

              cornsilk increases effects of valsartan by pharmacodynamic synergism. Minor/Significance Unknown.

            • anastrozole

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

            • aprepitant

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

            • armodafinil

              armodafinil will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

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

            • atazanavir

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

            • atracurium

              amlodipine increases effects of atracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • brimonidine

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

            • cisatracurium

              amlodipine increases effects of cisatracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • cornsilk

              cornsilk increases effects of amlodipine by pharmacodynamic synergism. 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.

            • cyclophosphamide

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

            • dasatinib

              dasatinib will increase the level or effect of amlodipine 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.

              dexamethasone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • 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.

            • entecavir

              valsartan, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • 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.

            • etodolac

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

            • etravirine

              etravirine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.

              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.

            • food

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

            • formoterol

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

            • forskolin

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

              forskolin increases effects of hydrochlorothiazide by pharmacodynamic synergism. 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.

            • grapefruit

              grapefruit will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

            • ibuprofen

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

            • incobotulinumtoxinA

              amlodipine increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • 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.

            • larotrectinib

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

            • levalbuterol

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

            • lithium

              amlodipine increases toxicity of lithium by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of neurotoxicity.

            • 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.

            • maitake

              maitake increases effects of amlodipine by pharmacodynamic synergism. 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.

            • metipranolol ophthalmic

              metipranolol ophthalmic increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.

            • 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.

            • nelfinavir

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

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of valsartan by Other (see comment). Minor/Significance Unknown. Valsartan is a substrate of the hepatic uptake transporters OATP1B1 and MRP2. Ritonavir inhibits these transporters. No dosage modification needed since induction reaches maximal effect after several days and the short duration of nirmatrelvir/ritonavir treatment.

            • noni juice

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

              valsartan and noni juice both increase serum potassium. 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 valsartan by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • 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.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of valsartan by decreasing elimination. Minor/Significance Unknown. May inhibit hepatic efflux transporter MRP2; decrease dose of angiotensin receptor blockers and monitor patients for signs and symptoms of hypotension and/or worsening renal function; if such events occur, consider further dose reduction of angiotensin receptor blocker or switching to alternative to angiotensin receptor blocker

            • onabotulinumtoxinA

              amlodipine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • oxaprozin

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

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pancuronium

              amlodipine increases effects of pancuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • 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.

            • porfimer

              amlodipine decreases levels of porfimer by unspecified interaction mechanism. 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.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rapacuronium

              amlodipine increases effects of rapacuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • reishi

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

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

              reishi increases effects of valsartan 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.

            • rocuronium

              amlodipine increases effects of rocuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

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

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

            • rufinamide

              rufinamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sitagliptin

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

            • ruxolitinib

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

            • ruxolitinib topical

              amlodipine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • shepherd's purse

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

            • simvastatin

              valsartan increases toxicity of simvastatin by Other (see comment). Minor/Significance Unknown. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • succinylcholine

              amlodipine increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • 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.

            • 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 amlodipine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

              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.

            • treprostinil

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

            • 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.

            • 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.

            • vecuronium

              amlodipine increases effects of vecuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • 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.

              amlodipine increases levels of verteporfin by pharmacodynamic synergism. Minor/Significance Unknown.

            • vildagliptin

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

            • voclosporin

              voclosporin will increase the level or effect of valsartan by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            >10%

            Amlodipine

            • Edema (1.8-10.8%)

            1-10%

            Amlodipine

            • Headache (7.3%)
            • Fatigue (4.5%)
            • Palpitation (0.7-4.5%)
            • Dizziness (1.1-3.4%)
            • Flushing (0.7-2.6%)
            • Nausea (2.9%)
            • Abdominal pain (1.6%)
            • Somnolence (1.4%)

            Valsartan

            • Hyperkalemia (4-10%)
            • Dizziness (2-8%)
            • Hypotension (1-7%)
            • Fatigue (3%)

            Hydrochlorothiazide

            • Anorexia
            • Epigastric distress
            • Hypokalemia
            • Hypotension
            • Phototoxicity

            <1%

            Hydrochlorothiazide

            • Anaphylaxis
            • Stevens-Johnson syndrome
            • Toxic epidermal necrolysis
            • Disorder of hematopoietic structure
            • Hepatotoxicity
            • Pancreatitis

            Frequency Not Defined

            Valsartan

            • Headache
            • Cough (rare, esp compared to ACE inhibitors)

            Hydrochlorothiazide

            • Confusion
            • Hypomagnesemia
            • Metabolic acidosis
            • Dizziness
            • Fatigue
            • Headach
            • Hypercalcemia
            • Hyperuricemia, Hyperglycemia, Hyperlipidemia, Hypercholesterolemia, Muscle weakness or cramps, Nausea, Purpura, Rash, Vertigo, Vomiting

            Postmarketing Reports

            Valsartan

            • Hypersensitivity: Angioedema (rare)
            • Digestive: Elevated liver enzymes, hepatitis (rare)
            • Renal: Impaired renal function, renal failure
            • Clinical laboratory tests: Hyperkalemia
            • Dermatologic: Alopecia, bullous dermatitis
            • Blood and lymphatic: Thrombocytopenia (rare)
            • Vascular: Vasculitis

            Hydrochlorothiazide

            • Non-melanoma skin cancer
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            Warnings

            Black Box Warnings

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

            Contraindications

            Hypersensitivity to valsartan, amlodipine, sulfonamide drugs, or other ingredients

            Pregnancy (2nd and 3rd trimesters): Significant risk of fetal/neonatal morbidity and mortality

            Anuria

            Coadministration with aliskiren in patients with diabetes

            Cautions

            Avoid with severe hepatic impairment or renal impairment (ie, CrCl <30 mL/min)

            Excessive hypotension may occur (rare); caution if volume/salt depleted, initiate cautiously in patients with heart failure, recent MI, or those undergoing surgery or dialysis

            Worsening angina and acute MI may occur after starting or increasing amlodipine dose, particularly with severe obstructive CAD

            Patients whose renal function may depend in part on the activity of the renin angiotensin system (eg, patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion); correct volume depletion prior to initiation

            Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy; closely monitor blood pressure; monitor renal function and potassium in susceptible patients

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

            Hydrochlorothiazide may exacerbate systemic lupus erythematosus

            Instruct patients to protect skin from sun and undergo regular skin cancer screening

            Hydrochlorothiazide may alter glucose tolerance and raise cholesterol and triglycerides

            Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.

            Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium; monitor calcium levels in patients with hypercalcemia receiving therapy

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            Pregnancy & Lactation

            Pregnancy

            Angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death; most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents; published reports include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan

            When pregnancy is detected discontinue Diovan HCT as soon as possible

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

            Valsartan

            • Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death
            • Perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on week of gestation; however, oligohydramnios may not appear until after fetus has sustained irreversible injury; if oligohydramnios is observed, consider alternative drug treatment
            • Closely observe neonates with histories of in utero exposure to drug for hypotension, oliguria, and hyperkalemia; in neonates with a history of in utero exposure to this drug combination, if oliguria or hypotension occurs, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function

            Hydrochlorothiazide

            • Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma; hydrochlorothiazide can cause placental hypoperfusion; accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma
            • Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia; since they do not prevent or alter course of EPH (edema, proteinuria, hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women; use of hydrochlorothiazide for other indications (eg, heart disease) in pregnancy should be avoided

            Lactation

            There is limited information regarding presence of drug in human milk, effects on breastfed infant, or on milk production; valsartan is present in rat milk; hydrochlorothiazide is present in human breast milk

            Because of potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment with this drug combination

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Amlodipine: Calcium channer blocker; blocks contractile effects of calcium on cardiac and vascular smooth muscle cells; results in peripheral arterial vasidilation, decreased peripheral vascular resistance, and blood pressure reduction

            Valsartan: Angiotensin receptor blocker; blocks vasoconstriction and sodium retaining effects of angiotensin II on cardiac, vascular smooth muscle, adrenal, and renal cells

            Hydrochlorothiazide: Thiazide diuretic; directly promotes the excretion of sodium and chloride in the kidney leading to reductions in intravascular volume

            Pharmacokinetics

            Bioavailability

            • Amlodipine: 64-90%
            • Valsartan: 10-35%
            • Hydrochlorothiazide: 50-80%

            Peak Concentration Time

            • Amlodipine: 6 hr
            • Valsartan: 3 hr
            • Hydrochlorothiazide: 2 hr

            Half-Life

            • Amlodipine: 30-50 hr (terminal elimination half-life)
            • Valsartan: 6 hr
            • Hydrochlorothiazide: 5.8-18.9 hr

            Vd

            • Amlodipine: 21 L/kg
            • Valsartan: 17 L/kg
            • Hydrochlorothiazide: 3.6-7.8 L/kg

            Protein Bound

            • Amlodipine: 93%
            • Valsartan: 95%
            • Hydrochlorothiazide: 68%

            Metabolism

            • Amlodipine: 90% converted to inactive metabolites via hepatic metabolism
            • Valsartan: 20% metabolized via CYP2C9
            • Hydrochlorothiazide: Not metabolized

            Excretion

            • Amlodipine: 10% parent compound and 60% metabolites excreted in urine
            • Valsartan: 83% (feces); 13% (urine)
            • Hydrochlorothiazide: 61% excreted unchanged in urine
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            Images

            No images available for this drug.
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            Patient Handout

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

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.