Furosemide

Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity.

Furosemide is incompatible with hyaluronidase.

Incompatible with hyaluronidase; physical or chemical incompatibility reported.

Furosemide reduces lithium's renal clearance and adds a high-risk of lithium toxicity. Avoid concomitant use with lithium.

Furosemide may increase ototoxic potential of aminoglycosides, especially with impaired renal function. Avoid this combination except in life-threatening situations.

Immediate chemical interaction with formation of precipitate when furosemide is injected into IV line containing milrinone. Furosemide should not be administered in IV lines containing milrinone.

Concomitant administration not recommended due to possible enhancement of aminoglycoside toxicity by altering serum and tissue concentrations.

Should not be administered concomitantly; diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

7.2 Ethacrynic Acid, Furosemide, Urea, or Mannitol Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.

May lead to severe hypotension and deterioration in renal function, including renal failure.

Nephrotoxicity reported following concomitant administration of cephalosporins with potent diuretics like furosemide. Monitor renal function.

Nephrotoxicity has been reported following concomitant administration of cephalosporins with potent diuretics. Monitor renal function.

Concomitant administration may result in nephrotoxicity. Renal function should be carefully monitored.

Furosemide can increase the risk of cephalosporin-induced nephrotoxicity even with minor or transient renal impairment.

Intravenous furosemide within 24 hours of chloral hydrate may cause flushing, sweating, restlessness, nausea, increased blood pressure, and tachycardia. Concurrent use is not recommended.

Risk of ototoxic and nephrotoxic effects when cisplatin and furosemide are given concomitantly.

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

Concomitant use is associated with increased risk of gouty arthritis secondary to furosemide-induced hyperuricemia and cyclosporine impairment of renal urate excretion.

Potassium-depleting diuretic causes enhanced hypokalemia. Monitor serum potassium levels and use potassium supplements if necessary.

Concurrent use should be avoided. Diuretic may cause ototoxicity and enhance aminoglycoside toxicity by altering serum and tissue antibiotic concentration.

Drugs undergoing significant renal tubular secretion like methotrexate may reduce furosemide effect. High-dose treatment may elevate serum levels and potentiate toxicity.

Concomitant use can cause unusually large or prolonged losses of fluid and electrolytes.

High-dose salicylates with furosemide may cause salicylate toxicity at lower doses due to competitive renal excretion.

Coadministration potentiates ototoxic effects of streptomycin.

Concomitant administration can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue.

NSAIDs reduce natriuretic effect of loop diuretics like furosemide in some patients.

NSAIDs reduced the natriuretic effect of loop diuretics. Monitor renal function and fluid status during concomitant use.

Combination of furosemide and acetylsalicylic acid may temporarily reduce creatinine clearance.

Potentiation of adrenergic blocking effects occurs with concurrent use.

Furosemide: Oral coadministration of aliskiren and furosemide reduced exposure to furosemide. Monitor diuretic effects when furosemide is coadministered with aliskiren.

Furosemide: Oral coadministration of aliskiren and furosemide reduced exposure to furosemide. Monitor diuretic effects when furosemide is coadministered with aliskiren.

Meloxicam (NSAID) can reduce the natriuretic effect of furosemide. Monitor diuretic efficacy including antihypertensive effect.

Monitor patients for increased toxicity when MRP2 inhibitors (e.g., abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, and tenofovir) are co-administered with COMETRIQ [see Clinical Pharmacology ( 12.3 )] .

Cefotaxime may potentiate the nephrotoxic effects of furosemide. Monitor renal function when used concurrently.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

In such high-risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact : Clinical studies, as well as post-marketing observations, showed that NSAIDS reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDS can reduce natriuretic effect of furosemide and thiazide diuretics.

In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDS reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function (7) · Diuretics: NSAIDS can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function (7) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Diflunisal can reduce the natriuretic effect of furosemide in some patients.

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

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Drugs Substrates of OCT2, OAT1, OAT3, MATE1, and MATE2-K Transporters Examples (not fully inclusive): Metformin, dofetilide, adefovir, cefaclor, furosemide Clinical Impact Increased risk for adverse reactions associated with increased concentrations of the drug due to inhibition of these transporters by fexinidazole [see Clinical Pharmacology (12.3) ] .

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Furosemide increases metformin plasma and blood C max by 22% and blood AUC by 15%. Pharmacokinetic parameters of both drugs are affected.

Ibuprofen can reduce the natriuretic effect of furosemide. Patient should be observed for signs of renal failure and to assure diuretic efficacy.

Ibuprofen can reduce the natriuretic effect of furosemide. Monitor for signs of renal failure and diuretic efficacy during concomitant therapy.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. Effects on Laboratory Tests INDOCIN reduces basal plasma renin activity (PRA), as well as those elevations of PRA induced by furosemide administration, or salt or volume depletion. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

NSAIDs can reduce the natriuretic effect of furosemide in some patients. Patients are at greater risk of renal failure secondary to decreased renal blood flow.

Ketorolac can reduce the natriuretic effect of furosemide. Close observation for signs of renal failure and diuretic efficacy is needed during concomitant therapy.

White precipitate has been noted when alkaline drugs like furosemide are administered with labetalol; these drugs should not be administered in the same infusion line.

Exposure to furosemide may be increased when coadministered with leflunomide. Monitor and adjust dose as required.

NSAIDs reduce the natriuretic effect of loop diuretics. Monitor for reduced diuretic efficacy.

May alter T4 and T3 serum transport or metabolism, affecting levothyroxine efficacy.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

At doses >80 mg IV, furosemide may cause protein binding site displacement. High doses can acutely lower total T4 levels and increase free-T4 fraction by competing for T4-binding sites on TBG, prealbumin, and albumin.

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

Meclofenamate sodium can reduce the natriuretic effect of furosemide. Close monitoring for renal failure and diuretic efficacy is recommended.

Mefenamic acid can reduce the natriuretic effect of furosemide. Patient should be observed for signs of renal failure and diuretic efficacy.

In such high risk patients, monitor for signs of worsening renal function (7) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Meloxicam can reduce natriuretic effect of furosemide. Monitor diuretic efficacy and antihypertensive effects.

Furosemide increased metformin plasma and blood Cmax by 22% and blood AUC by 15%. Metformin decreased furosemide Cmax by 31%, AUC by 12%, and half-life by 32%. Chronic interaction effects unknown.

Nabumetone can reduce the natriuretic effect of furosemide. Patient should be observed for signs of renal failure and diuretic efficacy during concomitant therapy.

Naproxen can reduce the natriuretic effect of furosemide. Monitor closely for signs of renal failure and diuretic efficacy.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Furosemide may decrease arterial responsiveness to norepinephrine's vasoconstricting effect.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function (7) Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Competes with penicillin G for renal tubular secretion, prolonging serum half-life.

Competes with penicillin G for renal tubular secretion, prolonging serum half-life of penicillin.

Competes with penicillin G for renal tubular secretion, prolonging serum half-life of penicillin.

Phenytoin interferes with renal action of furosemide and decreases intestinal absorption, leading to lower peak furosemide concentrations.

Diuretics Clinical Impact: Clinical studies, as well as postmarketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. In such high risk patients, monitor for signs of worsening renal function ( 7 ) Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

Salsalate can reduce the natriuretic effect of furosemide in some patients. Patient should be observed for signs of renal failure and to assure diuretic efficacy.

LOKELMA increases systemic exposure to furosemide by elevating gastric pH. Separate administration by at least 2 hours.

Furosemide may potentiate the action of succinylcholine.

Simultaneous administration of sucralfate and furosemide may reduce natriuretic and antihypertensive effects. Separate intake by at least two hours.

Sulindac can reduce natriuretic effect of furosemide; patient should be observed for signs of renal failure and to assure diuretic efficacy.

Teriflunomide may increase exposure of furosemide. Monitor patients and adjust dose as required.

NSAIDs can reduce the natriuretic effect of furosemide in some patients. Patient should be observed closely for signs of renal failure and to assure diuretic efficacy.

Furosemide may antagonize the skeletal muscle relaxing effect of tubocurarine.

Increases the effect of vasopressin on osmolar clearance and urine flow.

Epoprostenol decreases furosemide clearance by 13%, but this change is not likely to be clinically significant.

Coadministration increased renal clearance of trandolaprilat by 25% but no effect on furosemide or trandolaprilat pharmacokinetics or ACE inhibition.

No clinically significant pharmacokinetic interactions were observed when coadministered with valsartan.

Indomethacin may also affect plasma renin levels, aldosterone excretion, and renin profile evaluation.

Standard therapy includes antibiotics, such as penicillin and gentamicin; vasopressors, such as dopamine and isoproterenol; cardiac glycosides; and diuretics, such as furosemide.

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.

Loop Diuretics Furosemide administered concurrently with captopril does not alter the pharmacokinetics of captopril in renally impaired hypertensive patients.

Drug Interactions Probenecid Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine).

Drug Interactions Probenecid Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine).

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

There was no evidence of drug interactions in clinical studies in which dobutamine was administered concurrently with other drugs, including digitalis preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and acetaminophen.

Drug Interactions There was no evidence of drug interactions in clinical studies in which dobutamine was administered concurrently with other drugs, including digitalis preparations, furosemide, spironolactone, lidocaine, glyceryl trinitrate, isosorbide dinitrate, morphine, atropine, heparin, protamine, potassium chloride, folic acid, and acetaminophen.

7.5 Furosemide Tamsulosin Tamsulosin had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the dose of tamsulosin [see Clinical Pharmacology ( 12.3 ) ] .

Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.

7.1 Effects of Furosemide on Other Drugs Drug/Substance Class or Name Drug Interaction Effect Recommendations Aminoglycoside antibiotics Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function [see Warnings and Precautions ( 5.3 )]. Cisplatin There is a risk of ototoxic effects if cisplatin and furosemide are given concomitantly [see Warnings and Precautions ( 5.3 )]. Cisplatin and nephrotoxic drugs Nephrotoxicity Administer furosemide at lower doses and with positive fluid balance when used to achieve forced diuresis during cisplatin treatment.

Drug Interactions Furosemide may increase the ototoxic potential of aminoglycoside antibiotics, especially in the presence of impaired renal function. Furosemide should not be used concomitantly with ethacrynic acid because of the possibility of ototoxicity. Patients receiving high doses of salicylates concomitantly with furosemide, as in rheumatic disease, may experience salicylate toxicity at lower doses because of competitive renal excretory sites.

Metformin Hydrochloride Furosemide A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood C max by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the C max and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance.

Diuretics Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Warn patients against excessive alcohol intake ( 7 ) Drug Interactions In Vivo Assessment of Drug Interactions Table 5: Effect of Coadministered Drug on Plasma Metformin Systemic Exposure Coadministered Drug Dose of Coadministered Drug All metformin hydrochloride and coadministered drugs were given as single doses Dose of Metformin Hydrochloride Geometric Mean Ratio (ratio with/without coadministered drug) No Effect = 1.00 AUC AUC = AUC inf C max No dosing adjustments required for the following: Glyburide 5 mg 850 mg metformin 0.91 Ratio of arithmetic means 0.93 Furosemide 40 mg 850 mg metformin 1.09 1.22 Nifedipine 10 mg 850 mg metformin 1.16 1.21 Propranolol 40 mg 850 mg metformin 0.90 0.94 Ibuprofen 400 mg 850 mg metformin 1.05 1.07 Cationic drugs eliminated by renal tubular secretion may reduce metformin elimination [ See Warnings and Precautions (5.1) and Drug Interactions (7) . ] Cimetidine 400 mg 850 mg metformin 1.40 1.61 Carbonic anhydrase inhibitors may cause metabolic acidosis [ See Warnings and Precautions (5.1) and Drug Interactions (7) .] Topiramate 5 mg At steady state with topiramate 100 mg every 12 hours and metformin 500 mg every 12 hours; AUC = AUC 0-12h 5 mg metformin 1.25 1.17 Table 6: Effect of Metformin on Coadministered Drug Systemic Exposure Coadministered Drug Dose of Coadministered Drug All metformin hydrochloride and coadministered drugs were given as single doses Dose of Metformin Hydrochloride Geometric Mean Ratio (ratio with/without metformin) No Effect = 1.00 AUC AUC = AUC inf unless otherwise noted C max No dosing adjustments required for the following: Glyburide 5 mg 850 mg glyburide 0.78 Ratio of arithmetic means, p-value of difference < 0.05 0.63 Furosemide 40 mg 850 mg furosemide 0.87 0.69 Nifedipine 10 mg 850 mg nifedipine 1.10 AUC 0-24hr reported 1.08 Propranolol 40 mg 850 mg propranolol 1.01 1.02 Ibuprofen 400 mg 850 mg ibuprofen 0.97 Ratio of arithmetic means 1.01 Cimetidine 400 mg 850 mg cimetidine 0.95 1.01

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. Diuretics : NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics.

When therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine or naproxen were added to human plasma ( in vitro ), the plasma protein binding of nicardipine hydrochloride was not altered.

When therapeutic concentrations of furosemide, propranolol, dipyridamole, warfarin, quinidine or naproxen were added to human plasma (in vitro), the plasma protein binding of nicardipine hydrochloride capsules were not altered.

Table 3: No observed clinically important drug interactions of Veltassa Angiotensin-converting enzyme (ACE) inhibitors Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril Angiotensin II receptor blockers (ARB) Azilsartan, candesartan, irbesartan, losartan, olmesartan, valsartan β-adrenoceptor blockers (β-blocker) Metoprolol Loop diuretics Furosemide, bumetanide, torasemide Mineralocorticoid receptor antagonists (MRA) Eplerenone, finerenone, spironolactone Neprilysin inhibitors Sacubitril Sodium-glucose cotransporter-2 (SGLT-2) inhibitors Canagliflozin, dapagliflozin, empagliflozin Antibiotics Trimethoprim, amoxicillin, cephalexin Anticoagulants Warfarin, apixaban, rivaroxaban Anti-parathyroid agents and Thyroid preparations Cinacalcet Antithrombotic agents Clopidogrel, acetylsalicylic acid Blood glucose lowering drugs Glipizide Calcium channel blockers Amlodipine, verapamil Immunosuppressants Tacrolimus Others Lithium, allopurinol, atorvastatin, digoxin, phenytoin, riboflavin, sevelamer

Warfarin Increased and decreased PT/INR responses have been reported when phenytoin is coadministered with warfarin Other Corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Antiepileptic drugs a Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir, the active metabolite.

7.6 Other Neither ramipril nor its metabolites have been found to interact with food, digoxin, antacid, furosemide, cimetidine, indomethacin, and simvastatin.

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.

Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients.

7.7 Furosemide Tamsulosin hydrochloride capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the tamsulosin hydrochloride capsules dosage [see Clinical Pharmacology (12.3)].

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.

No clinically significant pharmacokinetic interaction has been found between trandolapril (or its metabolites) and furosemide.

Examples * cefaclor, ceftizoxime, famotidine, furosemide, oseltamivir carboxylate, penicillin G, sitagliptin * These examples are not a comprehensive list of all possible drugs that may fit this category.

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