Hydrochlorothiazide

Hydrochlorothiazide (HCTZ) Alone or in Combination with Triamterene: (see CONTRAINDICATIONS ) Concomitant use of HCTZ alone or in combination with triamterene is contraindicated.

Hydrochlorothiazide generally should not be given with lithium as it reduces renal clearance and greatly increases risk of lithium toxicity.

Absorption of hydrochlorothiazide is impaired; single doses reduce absorption by up to 85%.

Absorption of hydrochlorothiazide is impaired; single doses reduce absorption by up to 43%.

Absorption of hydrochlorothiazide is significantly decreased when given simultaneously with colestipol hydrochloride.

Intensified electrolyte depletion, particularly hypokalemia may occur.

Closely monitor blood pressure, renal function and electrolytes in patients on enalapril maleate and hydrochlorothiazide and other agents that affect the RAS. Do not coadminister aliskiren with enalapril maleate and hydrochlorothiazide in patients with diabetes. Avoid use of aliskiren with enalapril maleate and hydrochlorothiazide in patients with renal impairment (GFR <60 mL/min).

Closely monitor blood pressure, renal function, and electrolytes in patients on irbesartan and hydrochlorothiazide tablets and other agents that affect the RAS. Do not coadminister aliskiren with irbesartan and hydrochlorothiazide tablets in patients with diabetes. Avoid use of aliskiren with irbesartan and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/min).

In general, avoid combined use of RAS inhibitors, closely monitor blood pressure, renal function, and electrolytes in patients on Lisinopril and Hydrochlorothiazide Tablets and other agents that affect the RAS. Do not co-administer aliskiren with Lisinopril and Hydrochlorothiazide Tablets in patients with diabetes. Avoid use of aliskiren with Lisinopril and Hydrochlorothiazide Tablets in patients with renal impairment (GFR < 60 mL/min).

Intensified electrolyte depletion, particularly hypokalemia may occur.

Drug Interactions Telmisartan Aliskiren: Do not co-administer aliskiren with telmisartan and hydrochlorothiazide tablets in patients with diabetes. Avoid use of aliskiren with telmisartan and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/min). Because lithium should not be used with diuretics, the use of lithium with telmisartan and hydrochlorothiazide is not recommended.

Dosage adjustment of oral antidiabetic drugs may be required when used concurrently with hydrochlorothiazide.

Potentiation of orthostatic hypotension may occur.

Coadministration resulted in higher plasma amantadine concentration; monitor amantadine levels.

Coadministration resulted in higher plasma amantadine concentration; monitor amantadine levels.

Potentiation of orthostatic hypotension may occur.

Interactions Common for Both Benazepril and Hydrochlorothiazide Potassium Supplements and Potassium Sparing Diuretics: Concomitant use with Benazepril HCl and Hydrochlorothiazide may effect potassium levels. Monitor lithium levels when used concomitantly with Benazepril HCl and Hydrochlorothiazide. Closely monitor blood pressure, renal function and electrolytes in patients on Benazepril HCl and Hydrochlorothiazide and other agents that affect the RAS.

Interactions common to both Candesartan Cilexetil and Hydrochlorothiazide Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including candesartan, may result in deterioration of renal function, including possible acute renal failure. Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Closely monitor blood pressure, renal function and electrolytes in patients on candesartan cilexetil and hydrochlorothiazide tablets and other agents that affect the RAS.

Concomitant administration resulted in significantly increased plasma levels of hydrochlorothiazide. Diflunisal decreased the hyperuricemic effect of hydrochlorothiazide.

Etodolac can reduce the natriuretic effect of thiazides in some patients with possible loss of blood pressure control. Close monitoring for renal insufficiency is advised.

Drug Interactions Potassium supplements and potassium-sparing diuretics As noted above (“Derangements of Serum Electrolytes”), the net effect of fosinopril sodium and hydrochlorothiazide may be to elevate a patient’s serum potassium, to reduce it, or to leave it unchanged. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with fosinopril sodium and hydrochlorothiazide tablets, a thiazide diuretic is coadministered with the ACE inhibitor. Fosinopril sodium and hydrochlorothiazide and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Dosage adjustment of the antidiabetic drug may be required when used with hydrochlorothiazide.

Dosage adjustment of the antidiabetic drug may be required.

Concomitant administration produces reduction in urinary potassium and chloride excretion. Patients at greater risk of renal failure from decreased renal blood flow.

Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations.

Monitor lithium levels in patients receiving losartan potassium and hydrochlorothiazide tablets and lithium. Hydrochlorothiazide The administration of a non-steroidal anti-inflammatory agent including a selective COX-2 inhibitor can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when losartan potassium and hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents including selective COX-2 inhibitors are used concomitantly, observe closely to determine if the desired effect of the diuretic is obtained.

NSAIAs can reduce the diuretic, natriuretic, and antihypertensive effects of hydrochlorothiazide; close patient monitoring is recommended.

Possible decreased response to pressor amines but not sufficient to preclude their use.

Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. Closely monitor blood pressure, renal function and electrolytes in patients on olmesartan medoxomil, amlodipine and hydrochlorothiazide and other agents that affect the RAS. Do not co-administer aliskiren with olmesartan medoxomil, amlodipine and hydrochlorothiazide in patients with diabetes [See Contraindications (4) ].

• Increased exposure to cyclosporin and tacrolimus • Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): • Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. Closely monitor blood pressure, renal function and electrolytes in patients on olmesartan medoxomil, amlodipine, and hydrochlorothiazide tablets and other agents that affect the RAS. Do not co-administer aliskiren with olmesartan medoxomil, amlodipine, and hydrochlorothiazide tablets in patients with diabetes [See Contraindications ( 4 )] .

7 DRUG INTERACTIONS • Lithium: Risk of lithium toxicity ( 7.2 ) • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic and antihypotensive effects; increased risk of renal toxicity ( 7.3 ) • Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.4 ) • Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose ( 7.5 ) • Antidiabetic drugs: Dosage adjustment may be required ( 7.6 ) • Cholestyramine and colestipol: Reduced absorption of thiazides ( 7.6 ) 7.1 Agents Increasing Serum Potassium Coadministration of olmesartan medoxomil and hydrochlorothiazide tablets with other drugs that raise serum potassium levels may result in hyperkalemia. 7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Hydrochlorothiazide In some patients the administration of a NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

7 DRUG INTERACTIONS Lithium: Risk of lithium toxicity ( 7.2 ) Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Reduced diuretic, natriuretic and antihypotensive effects; increased risk of renal toxicity ( 7.3 ) Dual inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.4 ) Colesevelam hydrochloride: Consider administering olmesartan at least 4 hours before colesevelam hydrochloride dose ( 7.5 ) Antidiabetic drugs: Dosage adjustment may be required ( 7.6 ) Cholestyramine and colestipol: Reduced absorption of thiazides ( 7.6 ) 7.1 Agents Increasing Serum Potassium Coadministration of olmesartan medoxomil and hydrochlorothiazide with other drugs that raise serum potassium levels may result in hyperkalemia. 7.2 Lithium Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Hydrochlorothiazide In some patients the administration of a NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

Additive effect or potentiation may occur when given concurrently.

Concomitant administration increases topiramate Cmax by 27% and AUC by 29%. Requires potassium monitoring.

Concomitant administration increases topiramate Cmax by 27% and AUC by 29%, requiring potassium monitoring.

Drug Interactions Agents Increasing Serum Potassium Coadministration of quinapril and hydrochlorothiazide with other drugs that raise serum potassium levels may result in hyperkalemia. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with quinapril and hydrochlorothiazide, a thiazide diuretic is coadministered with the ACE inhibitor. Quinapril and hydrochlorothiazide and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Pressor amines (e.g., norepinephrine) Both spironolactone and hydrochlorothiazide reduce the vascular responsiveness to norepinephrine. Therefore, caution should be exercised in the management of patients subjected to regional or general anesthesia while they are being treated with spironolactone and hydrochlorothiazide. Therefore, when spironolactone and hydrochlorothiazide tablets and NSAIDs are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

Topiramate Cmax and AUC increased; may require decrease in topiramate dose.

Acute renal failure has been reported in a few patients receiving indomethacin and formulations containing triamterene and hydrochlorothiazide. Caution is therefore advised when administering non-steroidal anti-inflammatory agents with triamterene and hydrochlorothiazide.

Possible increased responsiveness to the muscle relaxant may occur.

7 DRUG INTERACTIONS Valsartan-Hydrochlorothiazide: Lithium: Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or thiazides. Monitor lithium levels in patients taking valsartan and hydrochlorothiazide tablets. Hydrochlorothiazide: When administered concurrently, the following drugs may interact with thiazide diuretics: Antidiabetic Drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Irbesartan administration for 7 days had no effect on the pharmacokinetics of hydrochlorothiazide. Pharmacokinetics of irbesartan were not affected by coadministration.

Concomitant administration does not alter pharmacokinetics of either drug; isradipine provides additional antihypertensive effect with no unexpected adverse effects.

No pharmacokinetic interaction between losartan and hydrochlorothiazide.

Used together without unexpected adverse interactions in clinical practice.

Terazosin has been added to hydrochlorothiazide in controlled trials with no unexpected interactions observed.

Used concomitantly with terazosin in at least 50 patients with no interactions observed.

No significant interactions with digoxin, hydrochlorothiazide, hydralazine, sulfinpyrazone, oral contraceptives, tolbutamide, or warfarin have been observed.

Therefore, when amiloride and hydrochlorothiazide plus non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained. Hydrochlorothiazide When given concurrently the following drugs may interact with thiazide diuretics. Cholestyramine and Colestipol Resins Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.

Valsartan No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin.

The pharmacokinetics of benazepril are not affected by the following drugs: hydrochlorothiazide, furosemide, chlorthalidone, digoxin, propranolol, atenolol, nifedipine, amlodipine, naproxen, acetylsalicylic acid, or cimetidine.

Drug Interactions The following drugs have been coadministered with betaxolol and have not altered its pharmacokinetics: cimetidine, nifedipine, chlorthalidone, and hydrochlorothiazide.

Drug Interactions Bisoprolol fumarate and hydrochlorothiazide tablets may potentiate the action of other antihypertensive agents used concomitantly. Bisoprolol fumarate and hydrochlorothiazide tablets should not be combined with other beta-blocking agents. In patients receiving concurrent therapy with clonidine, if therapy is to be discontinued, it is suggested that bisoprolol fumarate and hydrochlorothiazide tablets be discontinued for several days before the withdrawal of clonidine.

Gold : Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including captopril and hydrochlorothiazide tablets. If a diuretic is also used, it may increase the risk of lithium toxicity (see PRECAUTIONS: Drug Interactions: Hydrochlorothiazide: Lithium ). Hydrochlorothiazide : When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, Barbiturates, or Narcotics : potentiation of orthostatic hypotension may occur.

No dosing adjustments required for the following: Oral Antidiabetic Agents Metformin (1000 mg) 20 mg ↔ ↔ Pioglitazone (45 mg) 50 mg ↔ ↔ Sitagliptin (100 mg) 20 mg ↔ ↔ Glimepiride (4 mg) 20 mg ↔ ↔ Voglibose (0.2 mg three times daily) 10 mg ↔ ↔ Other Medications Hydrochlorothiazide (25 mg) 50 mg ↔ ↔ Bumetanide (1 mg) 10 mg once daily for 7 days ↔ ↔ Valsartan (320 mg) 20 mg ↓12% [↓3%, ↓20%] ↔ Simvastatin (40 mg) 20 mg ↔ ↔ Anti-infective Agent Rifampin (600 mg once daily for 6 days) 10 mg ↓7% [↓22%, ↑11%] ↓22% [↓27%, ↓17%] Nonsteroidal Anti-inflammatory Agent Mefenamic Acid (loading dose of 500 mg followed by 14 doses of 250 mg every 6 hours) 10 mg ↑13% [↑3%, ↑24%] ↑51% [↑44%, ↑58%] ↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to dapagliflozin administered alone (geometric mean ratio of test: reference was lower than 0.80 or higher than 1.25) Effects of Dapagliflozin on Other Drugs Table 7 shows the effect of dapagliflozin on other coadministered drugs. No dosing adjustments required for the following: Oral Antidiabetic Agents Metformin (1000 mg) 20 mg ↔ ↔ Pioglitazone (45 mg) 50 mg ↓7% [↓25%, ↑15%] ↔ Sitagliptin (100 mg) 20 mg ↔ ↔ Glimepiride (4 mg) 20 mg ↔ ↑13% [0%, ↑29%] Other Medications Hydrochlorothiazide (25 mg) 50 mg ↔ ↔ Bumetanide (1 mg) 10 mg once daily for 7 days ↑13% [↓2%, ↑31%] ↑13% [↓1%, ↑30%] Valsartan (320 mg) 20 mg ↓6% [↓24%, ↑16%] ↑5% [↓15%, ↑29%] Simvastatin (40 mg) 20 mg ↔ ↑19% Digoxin (0.25 mg) 20 mg loading dose then 10 mg once daily for 7 days ↔ ↔ Warfarin (25 mg) 20 mg loading dose then 10 mg once daily for 7 days ↔ ↔ ↔ = no change (geometric mean ratio of test: reference within 0.80 to 1.25); ↓ or ↑ = parameter was lower or higher, respectively, with coadministration compared to the other medicine administered alone (geometric mean ratio of test: reference was lower than 0.80 or higher than 1.25).

Doxazosin tablets have been used with the following drugs or drug classes: 1) analgesic/anti-inflammatory (e.g., acetaminophen, aspirin, codeine and codeine combinations, ibuprofen, indomethacin); 2) antibiotics (e.g., erythromycin, trimethoprim and sulfamethoxazole, amoxicillin); 3) antihistamines (e.g., chlorpheniramine); 4) cardiovascular agents (e.g., atenolol, hydrochlorothiazide, propranolol); 5) corticosteroids; 6) gastrointestinal agents (e.g., antacids); 7) hypoglycemics and endocrine drugs; 8) sedatives and tranquilizers (e.g., diazepam); 9) cold and flu remedies.

7.3 In Vivo Drug Interaction Studies Based on drug interaction studies in healthy patients, febuxostat does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine [see Clinical Pharmacology (12.3) ].

7.3 In Vivo Drug Interaction Studies Based on drug interaction studies in healthy patients, febuxostat does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine [see Clinical Pharmacology ( 12.3 )].

Hydrochlorothiazide: Concomitant oral administration of 100 mg fluconazole and 50 mg hydrochlorothiazide for 10 days in 13 normal volunteers resulted in a significant increase in fluconazole AUC and C max compared to fluconazole given alone. Hydrochlorothiazide : In a pharmacokinetic interaction study, coadministration of multiple-dose hydrochlorothiazide to healthy volunteers receiving fluconazole increased plasma concentrations of fluconazole by 40%.

In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs.

In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs.

No clinically important pharmacokinetic interactions occurred when lisinopril was used concomitantly with propranolol or hydrochlorothiazide.

7.2 Drug Interactions with Hydrochlorothiazide Antidiabetic Drugs (oral agents and insulin) Dosage adjustment of the antidiabetic drug may be required. Ion Exchange Resins Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

Drug Interactions No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements.

Other Agents No clinically important pharmacokinetic interactions occurred when moexipril hydrochloride was administered concomitantly with hydrochlorothiazide, digoxin, or cimetidine.

• No pharmacokinetic interaction was observed when single doses of quinapril and hydrochlorothiazide were administered concomitantly.

• No pharmacokinetic interaction was observed when single doses of quinapril hydrochloride and hydrochlorothiazide were administered concomitantly.

Other No pharmacokinetic interactions were observed with hydrochlorothiazide or warfarin.

7 DRUG INTERACTIONS Table 1 Oral drugs that can be administered concomitantly with Velphoro Calcitriol Ciprofloxacin Digoxin Enalapril Furosemide HMG-CoA reductase inhibitors Hydrochlorothiazide Losartan Metoprolol Nifedipine Omeprazole Quinidine Warfarin Oral drugs that are to be separated from Velphoro Dosing Recommendations Doxycycline Acetylsalicylic acid Cephalexin Take at least 1 hour before Velphoro. Velphoro can be administered concomitantly with oral calcitriol, ciprofloxacin, digoxin, enalapril, furosemide, HMG‑CoA reductase inhibitors, hydrochlorothiazide, losartan, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

Other Drugs: Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen.

Other Drugs: Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen.

Diuretics Coadministration of tolterodine immediate release up to 8 mg (4 mg bid) for up to 12 weeks with diuretic agents, such as indapamide, hydrochlorothiazide, triamterene, bendroflumethiazide, chlorothiazide, methylchlorothiazide, or furosemide, did not cause any adverse electrocardiographic (ECG) effects.

7 DRUG INTERACTIONS No clinically significant pharmacokinetic interactions were observed when valsartan was coadministered with amlodipine, atenolol, cimetidine, digoxin, furosemide, glyburide, hydrochlorothiazide, or indomethacin.