Which medications and vitamins are known to cause foul‑smelling urine in adults?

Medications and Vitamins Causing Foul-Smelling Urine

The most common medications causing foul-smelling urine are B-vitamins (particularly riboflavin/B2), antibiotics (especially sulfonamides like trimethoprim-sulfamethoxazole and ampicillin), and asparagus-containing supplements, though true medication-induced malodorous urine is relatively uncommon and often confused with ammonia production from bacterial urease activity in patients with bacteriuria.

Primary Medication Culprits

B-Vitamins and Riboflavin

• Riboflavin (vitamin B2) supplementation causes bright yellow, strongly odorous urine due to enhanced urinary excretion of the vitamin once tissue saturation is reached 1.
• Certain drugs including chlorpromazine and boric acid derivatives promote riboflavinuria by forming molecular complexes with riboflavin, doubling urinary riboflavin levels and intensifying urine odor 1.
• The phenothiazine ring of chlorpromazine shares structural features with riboflavin's isoalloxazine ring, leading to increased urinary excretion 1.

Sulfonamide Antibiotics

• Trimethoprim-sulfamethoxazole (TMP-SMX) commonly produces characteristic sulfur-like malodorous urine due to sulfamethoxazole metabolites 2, 3.
• This effect is particularly notable in elderly patients receiving TMP-SMX for urinary tract infections, where the medication itself—not the infection—may be responsible for the odor 3, 4.

Other Antibiotics

• Ampicillin and other penicillins can produce musty or ammonia-like urine odor through metabolite excretion 2.
• Ciprofloxacin and other fluoroquinolones occasionally cause altered urine odor, though less commonly than sulfonamides 2, 3.

Important Clinical Distinctions

Distinguishing Medication Effects from Infection

• Foul-smelling urine alone is NOT a reliable indicator of urinary tract infection in elderly patients, with studies showing urine odor incorrectly predicted UTI in one-third of cases 5.
• The ammonia smell commonly attributed to UTIs actually results from bacterial urease converting urea to ammonia in voided urine, not from the infection itself 6.
• In patients with asymptomatic bacteriuria (present in 15-50% of elderly), malodorous urine reflects bacterial colonization rather than active infection requiring treatment 3, 4.

Uremic Toxins in Renal Disease

• Patients with chronic kidney disease accumulate uremic retention solutes including urea, which undergoes bacterial conversion to ammonia, producing characteristic odor 7, 8.
• P-cresylsulfate and other protein-bound uremic toxins contribute to altered urine characteristics in advanced renal disease 7.

Practical Clinical Algorithm

When evaluating malodorous urine:

1. Review current medications for B-vitamin supplements, sulfonamides, or phenothiazines as the most likely pharmaceutical causes 1.

2. Assess for true UTI symptoms beyond odor alone—require recent-onset dysuria PLUS frequency, urgency, systemic signs, or costovertebral tenderness before attributing smell to infection 3, 4.

3. Consider timing: If odor began immediately after starting a new medication (especially TMP-SMX or B-complex vitamins), the drug is the likely cause 2, 1.

4. Evaluate renal function: In patients with CKD stage 4-5, uremic toxin accumulation may contribute to altered urine characteristics 9, 7.

Common Pitfalls to Avoid

• Never diagnose UTI based on urine odor alone in elderly patients, as this leads to inappropriate antibiotic use and promotes resistance 3, 5.
• Do not overlook medication review when patients complain of new-onset malodorous urine—B-vitamins and sulfonamides are frequently the culprit 1.
• Recognize that ammonia smell in incontinent patients often reflects bacterial urease activity in soiled incontinence products rather than active infection 6, 5.