Summary

The combination of cisplatin and furosemide significantly increases the risk of nephrotoxicity and ototoxicity. This interaction occurs through additive toxic effects on the kidneys and inner ear, requiring careful monitoring and potential dose adjustments.

Introduction

Cisplatin is a platinum-based chemotherapy agent used to treat various cancers including testicular, ovarian, bladder, and lung cancers. It belongs to the alkylating agent class and works by forming DNA cross-links. Furosemide is a potent loop diuretic commonly prescribed for heart failure, edema, and hypertension. It works by inhibiting sodium and chloride reabsorption in the ascending limb of the loop of Henle in the kidneys.

Mechanism of Interaction

The interaction between cisplatin and furosemide involves additive nephrotoxic and ototoxic effects. Cisplatin causes direct tubular damage and reduces glomerular filtration rate, while furosemide can exacerbate kidney injury through volume depletion and electrolyte imbalances. Both drugs independently cause ototoxicity - cisplatin through direct damage to cochlear hair cells and furosemide through effects on the stria vascularis. When used together, these toxic effects are amplified, leading to increased risk of permanent kidney damage and hearing loss.

Risks and Symptoms

The primary risks of this drug combination include severe nephrotoxicity with potential for acute kidney injury or chronic kidney disease, and irreversible ototoxicity manifesting as high-frequency hearing loss or tinnitus. Additional risks include electrolyte imbalances (hypomagnesemia, hypokalemia), dehydration, and increased susceptibility to other nephrotoxic agents. The nephrotoxicity may be dose-dependent and cumulative, with elderly patients and those with pre-existing kidney disease at higher risk.

Management and Precautions

Close monitoring of kidney function through serum creatinine, blood urea nitrogen, and creatinine clearance is essential before, during, and after treatment. Baseline and periodic audiometry testing should be performed to detect early hearing changes. Adequate hydration and electrolyte monitoring are crucial. Consider dose reduction or alternative diuretics when possible. If concurrent use is necessary, minimize furosemide doses and duration. Avoid other nephrotoxic or ototoxic medications when possible. Patients should be counseled about signs of kidney problems and hearing changes.

Furosemide interactions with food and lifestyle

Furosemide should be taken with food or milk to reduce stomach upset. Alcohol consumption should be limited as it can increase the risk of dehydration and low blood pressure when combined with furosemide. Patients should maintain adequate fluid intake unless specifically restricted by their healthcare provider, as furosemide can cause dehydration. Salt substitutes containing potassium should be used cautiously, as furosemide can affect potassium levels. Excessive sun exposure should be avoided as furosemide may increase sensitivity to sunlight.