Renal Impairment, an NSAID and a Sulfonylurea on One Prescription
A 72-year-old woman, 48 kg, with type 2 diabetes and osteoarthritis attends the medicine OPD with a three-day history of dysuria. Serum creatinine is 1.6 mg/dL; the laboratory reports an eGFR of 26 mL/min/1.73 m². Her regular medicines are metformin 1000 mg twice daily, glibenclamide 5 mg once daily and ramipril 5 mg once daily. The junior resident writes: ciprofloxacin 500 mg twice daily for 7 days, and diclofenac 50 mg three times daily for 10 days, to be dispensed immediately. She has no known drug allergies, and the urine sample was sent to culture this morning but no report is available yet. The pharmacy holds ciprofloxacin 250 mg and 500 mg tablets, paracetamol 500 mg and topical diclofenac gel; the prescriber is on ward rounds and cannot be reached for two hours.
1. Calculate her Cockcroft–Gault creatinine clearance and use it to judge the ciprofloxacin prescription. State what you would dispense today and why.
Read the worked answer
Cockcroft–Gault (female):
CrCl = [(140 − age) × weight] ÷ (72 × serum creatinine) × 0.85 = [(140 − 72) × 48] ÷ (72 × 1.6) × 0.85 = (68 × 48) ÷ 115.2 × 0.85 = 3264 ÷ 115.2 × 0.85 = 28.3 × 0.85 ≈ 24 mL/min
Both the reported eGFR (26) and the calculated CrCl (24) sit below 30 mL/min, so this is severe renal impairment.
Judgement on the ciprofloxacin order. 500 mg twice daily is a normal-renal-function regimen and delivers 1000 mg/day. In CrCl below 30 the total daily dose must be reduced - typically to 250–500 mg given roughly every 18–24 hours, the exact interval being taken from the current product label. The prescribed order is therefore approximately double the appropriate exposure and risks CNS toxicity (seizures, confusion) and QT prolongation.
What to dispense today. Do not dispense the order as written and do not simply substitute on my own authority. Escalate to the duty medical officer or clinical pharmacist (the resident is unreachable), obtain a documented corrected regimen - for example ciprofloxacin 250 mg once daily, adjusted once culture and sensitivity return - and dispense that. Do not withhold treatment for symptomatic UTI while waiting; document the intervention, the contact and the amended order in the prescription record.
2. Rank the three drug-related risks in this prescription and explain the mechanism of each.
Read the worked answer
1. Diclofenac plus ramipril in chronic kidney disease - highest risk. An NSAID blocks prostaglandin-mediated afferent arteriolar vasodilatation, while an ACE inhibitor dilates the efferent arteriole. Together they drop glomerular filtration pressure and can precipitate acute kidney injury, and the combination also promotes hyperkalaemia and fluid retention. In a patient already at CrCl 24, oral diclofenac is effectively contraindicated; the risk of a further, possibly irreversible fall in function outweighs short-term analgesic benefit.
2. Metformin at this level of function. Metformin is contraindicated once eGFR falls below 30. Reduced renal clearance allows accumulation, and any precipitating event - dehydration, contrast, AKI from the diclofenac - can tip the patient into lactic acidosis. It should be stopped today and the prescriber asked to review glucose control.
3. Glibenclamide, aggravated by ciprofloxacin. Glibenclamide is a long-acting sulfonylurea with renally cleared active metabolites, so it accumulates in CKD and causes prolonged hypoglycaemia in older, low-weight patients. Fluoroquinolones such as ciprofloxacin independently disturb glycaemic control and are associated with severe hypoglycaemia when combined with a sulfonylurea. This is a compounded interaction, not two separate issues.
The ciprofloxacin dose error, though not an interaction, carries the same weight as risk 2 and must be corrected in the same intervention.
3. Draft the note you would leave for the prescriber and outline the counselling you would give the patient.
Read the worked answer
Note to the prescriber (to be attached to the chart and repeated by phone):
"72 F, 48 kg, SCr 1.6 mg/dL. Cockcroft–Gault CrCl ≈ 24 mL/min (lab eGFR 26) - both below 30.
- Ciprofloxacin 500 mg BD is a full-dose regimen; please approve 250 mg once daily (or per label interval for CrCl <30), to be reviewed on culture.
- Diclofenac 50 mg TDS withheld - NSAID with ramipril in CKD risks AKI and hyperkalaemia. Please approve paracetamol (renal-appropriate maximum, e.g. 500 mg–1 g three times daily, not exceeding 3 g/day) plus topical diclofenac gel.
- Metformin should be stopped at eGFR <30; glibenclamide risks prolonged hypoglycaemia and is potentiated by ciprofloxacin - please review both.
- Ramipril: continue unless potassium/creatinine dictate otherwise; check U&E and glucose in 48–72 h. Pharmacist, date/time."
Counselling: explain that one antibiotic tablet has been changed because her kidneys clear drugs more slowly; that the pain tablet has been stopped because it can harm her kidneys when taken with her blood-pressure medicine; that she should use the gel and paracetamol instead and report reduced urine output, swelling or dizziness; that she must watch for shakiness or sweating (hypoglycaemia) and report it; and that she should keep hydrated and attend for the repeat blood test. Confirm understanding with teach-back.