What medications can cause kidney stones?

Medications That Can Cause Kidney Stones

Clinicians should routinely query patients about stone-provoking medications and supplements during evaluation for kidney stones, as certain drugs directly increase stone formation risk through crystallization in urine or metabolic effects. 1

Direct Stone-Forming Medications (Crystallization in Urine)

These poorly soluble drugs with high urinary excretion favor crystallization and represent 1-2% of all kidney stones 2:

High-Risk Medications

• Protease inhibitors (especially atazanavir) are among the most frequent causes of drug-induced stones in HIV patients 2
• Sulfodiazine used for cerebral toxoplasmosis treatment 2
• Ceftriaxone particularly with high doses or prolonged treatment 2
• Topiramate causes kidney stones in 1.5% of adults (2-4 times higher than expected), with even higher rates in men; this carbonic anhydrase inhibitor reduces urinary citrate excretion and increases urinary pH 3, 2

Moderate-Risk Medications

• Ephedrine-containing preparations with high doses or long-term use 2
• Approximately 20 other molecules can induce nephrolithiasis with prolonged exposure 2

Metabolically-Induced Stone Formation

These medications alter urinary chemistry to promote stone formation 2:

Carbonic Anhydrase Inhibitors

• Acetazolamide and topiramate promote stone formation by reducing urinary citrate excretion and increasing urinary pH 3, 2
• Concomitant use of topiramate with other carbonic anhydrase inhibitors or ketogenic diets creates a physiological environment that increases kidney stone risk and should be avoided 3

Calcium and Vitamin D Supplements

• Uncontrolled calcium/vitamin D supplements can cause metabolically-induced calculi 2
• Calcium supplements (as opposed to dietary calcium) may increase stone risk 4

Other Metabolic Disruptors

• Diuretics (certain types) can alter renal blood flow and intrarenal hemodynamics 1
• Various drugs that affect urinary pH, calcium, phosphate, oxalate, citrate, or uric acid excretion 2

Recently Identified Risk Signals

A 2025 pharmacovigilance study identified new drug associations not previously labeled 5:

• Lansoprazole (ROR 7.2) - proton pump inhibitor with significant risk signal 5
• Sodium oxybate/Xywav (ROR 7.1) - 877 reported cases 5
• Teduglutide (ROR 5.54) 5
• Adalimumab - highest number of reported cases (2,636) 5
• Infliximab - 1,266 reported cases 5
• Interferon beta-1a - 920 reported cases 5
• Teriparatide - 836 reported cases 5

Clinical Implications

Prevention Strategies

• Increased hydration is critical - patients on stone-forming medications should maintain urine output of at least 2 liters daily to lower concentration of crystallizing substances 3, 6
• Avoid combining carbonic anhydrase inhibitors with each other or with ketogenic diets 3
• Monitor high-risk patients more closely with periodic urinalysis and imaging 1

Important Caveats

• Antibiotics are NOT significant risk factors for kidney stones despite earlier concerns; apparent associations are due to reverse causality (urinary symptoms from undiagnosed stones leading to antibiotic prescription) 7
• Physical stone analysis using infrared spectroscopy or X-ray diffraction is needed to confirm drug-induced stones 2
• The incidence of metabolically-induced calculi is probably underestimated because diagnosis requires careful clinical inquiry 2
• Patient-specific factors (urine pH, diuresis volume) modulate individual risk 2