What are the potential drug interactions with Lasix (Furosemide) in an elderly patient with hypertension, diabetes, and impaired renal function?

Drug Interactions with Lasix (Furosemide) in Elderly Patients with Hypertension, Diabetes, and Impaired Renal Function

Furosemide has numerous clinically significant drug interactions that require careful monitoring and dose adjustments, particularly in elderly patients with multiple comorbidities and impaired renal function. 1

Critical Drug-Drug Interactions to Avoid

Ototoxic Medications

• Avoid combining furosemide with aminoglycoside antibiotics (gentamicin, tobramycin) as this significantly increases the risk of irreversible hearing loss, especially with impaired renal function 1
• Never use furosemide concomitantly with ethacrynic acid due to severe ototoxicity risk 1
• Cisplatin combined with furosemide poses dual risks of both ototoxicity and enhanced nephrotoxicity; if forced diuresis is needed during cisplatin treatment, use lower furosemide doses with positive fluid balance 1

Lithium

• Lithium should generally not be given with diuretics because furosemide reduces lithium's renal clearance, creating a high risk of lithium toxicity 1

ACE Inhibitors and ARBs

• Furosemide combined with ACE inhibitors or ARBs may lead to severe hypotension and deterioration in renal function, including acute renal failure 1
• An interruption or reduction in dosage of furosemide, ACE inhibitors, or ARBs may be necessary when used together 1
• The American Geriatrics Society specifically warns about using trimethoprim-sulfamethoxazole with ACE inhibitors or ARBs in patients with reduced kidney function due to increased hyperkalemia risk 2

NSAIDs and Salicylates

• NSAIDs (including indomethacin) may reduce the natriuretic and antihypertensive effects of furosemide by inhibiting prostaglandin synthesis 1
• High-dose salicylates (as in rheumatic disease) may cause salicylate toxicity at lower doses due to competitive renal excretory sites 1
• The European Society of Cardiology notes that aspirin can worsen renal function in patients with chronic kidney disease or those taking nephrotoxic drugs 2

Anticoagulants

• Avoid combining furosemide with anticoagulants and antiplatelets as this increases bleeding risk, particularly in elderly patients 2
• The European Society of Cardiology specifically cautions against combining anticoagulants with NSAIDs, which may be co-prescribed with diuretics 2

Interactions Requiring Dose Adjustment or Monitoring

Medications Affecting Furosemide Efficacy

• Phenytoin interferes directly with renal action of furosemide and decreases intestinal absorption, leading to lower peak serum concentrations 1
• Sucralfate may reduce the natriuretic and antihypertensive effects of furosemide; separate administration by at least 2 hours 1

Medications with Enhanced Toxicity Risk

• Methotrexate and other drugs undergoing significant renal tubular secretion may have reduced effects when combined with furosemide, while furosemide may decrease their renal elimination, potentially elevating serum levels and toxicity 1
• Cephalosporin antibiotics combined with furosemide increase nephrotoxicity risk even with minor or transient renal impairment 1
• Cyclosporine with furosemide increases risk of gouty arthritis due to furosemide-induced hyperuricemia and cyclosporine's impairment of renal urate excretion 1

Cardiovascular Drug Interactions

• Furosemide antagonizes the skeletal muscle relaxing effect of tubocurarine and may potentiate succinylcholine 1
• Potentiation occurs with ganglionic or peripheral adrenergic blocking drugs 1
• Furosemide may decrease arterial responsiveness to norepinephrine, though norepinephrine can still be used effectively 1

Thyroid Hormone Interactions

• High doses of furosemide (>80 mg) may inhibit binding of thyroid hormones to carrier proteins, resulting in transient increase in free thyroid hormones followed by overall decrease in total thyroid hormone levels 1

Special Considerations for Elderly Patients with Diabetes and Renal Impairment

Hyperglycemia Risk

• Furosemide may increase blood glucose levels and affect urine glucose tests in diabetic patients 1
• Blood glucose should be checked periodically in diabetics receiving furosemide, even in those with suspected latent diabetes 1

Potassium-Altering Medications

• The American Geriatrics Society expanded recommendations to avoid concurrent use of medications that increase serum potassium with furosemide, as the diuretic causes hypokalemia while other medications (ACE inhibitors, ARBs, potassium-sparing diuretics, trimethoprim-sulfamethoxazole) increase potassium 2
• The European Society of Cardiology notes that potassium-sparing diuretics (amiloride, triamterene) combined with ACE inhibitors or NSAIDs cause hyperkalaemia more frequently in elderly patients 2

Renal Function Monitoring

• In elderly patients with impaired renal function, altered pharmacokinetics require more cautious dosing 2
• The European Society of Cardiology recommends using the CKD-EPI equation for estimating glomerular filtration rate in older adults, as creatinine-based equations may misclassify kidney disease in over 30% of elderly patients due to reduced muscle mass 2
• Renal function should be monitored at least yearly, but more frequently in elderly patients, those with baseline renal impairment, or those on concomitant medications affecting renal function 2

Essential Monitoring Parameters

Electrolyte Monitoring

• Serum electrolytes (particularly potassium), CO2, creatinine, and BUN should be determined frequently during the first few months of furosemide therapy and periodically thereafter 1
• Furosemide may lower serum calcium (rarely causing tetany) and magnesium; these electrolytes should be monitored periodically 1

Clinical Monitoring

• Observe for signs of fluid or electrolyte imbalance: hyponatremia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, or hypocalcemia manifesting as dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances 1

Common Pitfalls to Avoid

• Do not assume thiazides are ineffective in renal impairment; research shows hydrochlorothiazide can be as effective as furosemide in stage 4-5 chronic kidney disease for blood pressure control 3, 4
• Avoid chloral hydrate within 24 hours of furosemide due to risk of flushing, sweating, restlessness, nausea, increased blood pressure, and tachycardia 1
• In patients with urinary retention (bladder emptying disorders, prostatic hyperplasia, urethral narrowing), furosemide can cause acute urinary retention; these patients require careful monitoring, especially initially 1
• Patients at high risk for radiocontrast nephropathy may experience higher incidence of renal function deterioration with furosemide compared to intravenous hydration alone 1