Loop diurectics

Drug interaction

Furosemide, Bumetanide, Piretanide, Torasemide

Interacting drugPharmacodynamic interactionPharmacokinetic interactionClinical implications
ACE inhibitorsPotentiate the antihypertensive effect. ACE inhibitors may cause acute renal failure in patients with sodium depletion. Furosemide may interact with ACE inhibitors causing impaired renal functionRisk of hyponatremia, hypokalemia and arterial hypotension. Higher risk in patients with hypovolemia and sodium depletion. Loop diuretics should be stopped or the dose reduced before starting an ACE-inhibitor
AliskirenReduces the plasma levels of furosemideMonitor the clinical response
AlcoholIncreases the hypotensive responseMonitor BP
AminoglycosidesLoop diuretics can increase the risk of ototoxicity and nephrotoxicity (particularly if impaired renal function)Diuretics decrease the renal excretion of gentamicin and tobramycin, increasing their plasma levelsMonitoring of blood pressure, diuresis, electrolytes, and auditive and renal function
Amphotericin BIncreased risk of hyponatremia, hypopotassemia and nephrotoxicityReduce the dose of furosemide. Monitor serum levels of electrolytes and renal function
Antiarrhythmics:
- Class IA and III
Loop diuretics produce hypopotassemia and increase the risk of torsades de pointesMonitor the ECG.
Antibiotics:
- Aminoglycosides
- Polymyxins
- Vancomycin
Increased risk of ototoxicityFurosemide can decrease vancomycin serum levelsMonitor the auditory function
Angiotensin receptor blockers (ARBs)Potentiate their antihypertensive effect. ARBs may cause acute renal failure in patients with sodium depletionRisk of hyponatremia, hypokalemia and hypotension. Higher risk in patients with hypovolemia and sodium depletion
AntidiabeticsThe hypoglycaemic effects of antidiabetics antagonised. they may increase the requirements of insulinPlasma serum glucose levels
Anti-hypertensive agentsHypotensive effects may be enhanced Increased risk of postural hypotension. Titrate the dose of loop diuretics

- Alcohol
- Alprostadil
- General anesthetics
- Baclofen
- Levodopa
- Nitrates
- MAOIs
- Opioids
- Phenothiazines
- TADs
- Tizanidine
They may enhance the hypotensive effects of loop diureticsIncreased risk of postural hypotension. Monitor BP. Titrate the dose of loop diuretics
Anti-psychotic drugsHypokalaemia increases the risk of cardiac toxicity Avoid concurrent use with pimozide. Increased risk of ventricular arrhythmias with amisulpride or sertindoleMonitor the ECG Combination with caution.
β-blockers.Increase the risk of new-onset diabetes Monitor plasma glucose levels. Not recommended as monotherapy in patients with diabetes or metabolic syndrome
Bile-acid binding resins:
- Cholestyramine
- Colestipol
Decrease the diuretic and antihypertensive effectsReduce the absorption of the diureticReadjust the dose of the diuretic. Administer 2 to 3 hours apart
Carbamazepine Increased risk of hyponatraemia Monitor serum potassium levels
Cephalosporins:
- Cephacetrile
- Cephaloridine
- Cephalothin
These cephalosporins have nephrotoxic effectsFurosemide increases the half-life of the cephaloridinesGreater risk of nephrotoxicity. Reduce the dose of the diuretic
CiclosporinGreater risk ototoxic and nephrotoxic effectsIncrease the plasma levels of uric acidMonitor renal function and uricemia
Platinum compoundsIncreased risk of nephrotoxicity and ototoxicityMonitor renal and auditive function. The e of furosemide should be reduced and a positive fluid balance should be used
CNS drugs:
- Anxiolytics
- Hypnotics
- Phenothiazines
- TADs
Hypotensive effects may be exacerbated Hypokalaemia increases the risk of cardiac toxicityIncreased risk of postural hypotension. Titrate the dose of loop diuretics
GlucocorticoidsThey inhibit the diuretic and antihypertensive effects of loop diuretics and produce hypopotassemia and hyperglycemia and increase potassium lossMonitor the diuretic and antihypertensive effects. Monitor the glucemia and kalemia. Administer potassium salts if necessary
CyclosporineThis combination increases the risk of kidney and/or nerve damageThis combination should be administered under medical supervision
DigoxinHypercalcemia and hypopotassemia increase the risk of digitalis intoxicationMonitor ECG, renal function and kalemia. Use K+ supplements or K+-sparing diuretics
Drugs producing hypokalemia:
- ACTH
- Amphotericin B
- β2-agonists
- Carbenoxolone
- Corticosteroids
- Laxatives
- Reboxetine
- Tacrolimus
- Theophylline
These drugs increase the risk of hypokalemiaThe combination with K+-sparing diuretics reduce the risk of hypokalemia. Loop diuretics should be used with caution. Monitor signs of hypokalemia (ECG, fatigue, muscular pain) Administer potassium salts if necessary
FoodDecreases the diuretic effect of furosemideReduces the bioavailability and the Cp of furosemideFurosemide should be taken with an empty stomach
LithiumFurosemide decreases the renal clearance of lithiumIncreases the tubular reabsorption and the Cp of lithiumIncreases the toxicity of lithium. Close monitoring of serum lithium levels and electrolytes. Lithium dose reductions may be required Avoid the combination unless plasma levels can be monitored
Neuromuscular blockersLoop diuretics increase the potency and duration of succinylcholineReadjust the dose of neuromuscular blocker. Monitor the extubation of the patient
NitratesHypotensive effects can be exacerbated Increased risk of postural hypotension. Titrate the dose of loop diuretics
Nephrotoxic drugs:
- Aminoglycosides
- Amphotericin B
- Some cephalosporins
- NSAIDs
Loop diuretics also increase the risk of nephrotoxicity when coadministered with other nephrotoxic drugsMonitor the renal function. Loop diuretics should be used with caution in patients with impaired renal function
NSAIDsAntagonize the diuretic and antihypertensive effect of the diuretics by inhibiting the renal synthesis of prostaglandins. NSAIDs increase the risk of acute renal failure. Risk of ototoxicity with high doses of salicylatesIn rheumatic patients treated with high doses of salicylates furosemide may competitively inhibit the excretion of salicylates in the proximal tubuleAvoid dehydration, monitor patient's renal function and blood pressure. If renal insufficiency or hyperkalemia develops, both drugs should be discontinued until the condition is corrected
PhenytoinInhibits the diuretic effect of furosemideDecreases the intestinal absorption of furosemideReadjust the dose of furosemide
Potassium-sparing diuretics:
- Amiloride
- Eplerenone
- Spironolactone
- Triamterene
Exert additive diuretic effects and reduce the risk of hypokalemia and of cardiac arrhythmias Monitor BP and electrolyte balance. Potassium-sparing diuretics are preferred to K+ supplements as they correct both hypokalemia and hypomagnesemia
ProstaglandinsEnhance the hypotensive effectMonitor BP
QTc prolonging drugsLoop diuretics produce hypopotassemia and hypomagnesemia and increase the risk of torsades de pointesMonitor the QT on the ECG. Avoid QT prolonging drugs
Sexual hormonesOestrogens and progestogens reduce the diuretic and antihypertensive effect Monitor the diuretic response. Increase the dose if needed
Skeletal muscle relaxing drugsLoop diuretics can antagonize the effect of tubocurarine and may enhance the action of succinylcholineMonitor the response of skeletal muscle relaxants
SucralfateSucralfate decrease the gastro-intestinal absorption of furosemideThese drugs should be taken at least 2 hours apart
TheophyllineIncreased risk of hypokalemia and hypotensionIncreases the excretion and decreases the Cp of theophyllineMonitor the Cp of theophylline
Thiazide diureticsSequential nephron blockade. Synergistic diuretic effect. Increased risk of hypopotassemia. It may be needed in patients with resistant peripheral edemaCareful monitoring of fluid status and serum electrolytes to avoid dehydration, hypokalemia, hyponatremia, hypovolemia, hypotension or renal dysfunction
VasodilatorsLoop diuretics enhance the effect of hydralazineMonitor BP. Titrate the dose of loop diuretics

Abbreviations

BP: blood pressure
NSAIDs: non-steroidal anti-inflammatory drugs
TADs: Tricyclic antidepressants