Diclofenac, ACE inhibitor and metformin in an older patient with CKD
Mrs. S., 68, attends a community pharmacy in Phnom Penh with a 3-day history of nausea, dizziness on standing, and reduced urine output. She has hypertension and type 2 diabetes and takes lisinopril 20 mg daily, metformin 1 g twice daily, amlodipine 10 mg daily, and furosemide 40 mg daily. Her most recent eGFR was 38 mL/min/1.73 m². For knee pain, she has taken diclofenac 50 mg three times daily for 10 days, obtained from a nearby drug shop, and drinks a bitter herbal tea daily 'to lower sugar.' Today her BP is 98/60 mmHg, pulse 96/min, and she reports no fever. A laboratory slip from 2 days ago shows potassium 5.8 mmol/L and creatinine 2.1 mg/dL (baseline 1.3). She asks for something stronger for pain and wants to know whether her diabetes medicine caused the dizziness. The pharmacy has no laboratory service on site.
1. Identify the drug-related problems that could explain her presentation. Explain the likely mechanisms and rank them by urgency.
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The most urgent problem is acute kidney injury with hyperkalaemia, probably multifactorial. Diclofenac inhibits prostaglandin-mediated afferent arteriolar dilation; lisinopril blocks efferent arteriolar constriction; furosemide can cause volume depletion. This combination can sharply reduce glomerular filtration and potassium excretion. A creatinine rise from 1.3 to 2.1 mg/dL and potassium 5.8 mmol/L fit this picture.
Metformin is also a problem. At an eGFR of 38, the dose should generally not exceed about 1,000 mg/day, and it should be stopped during acute illness because of lactic acidosis risk. She is taking 2,000 mg/day. The herbal tea is unverified and could contain hypoglycaemic or nephrotoxic substances; it should be stopped until the composition is known. Amlodipine may contribute to dizziness but is not the priority.
Ranking: hyperkalaemia and AKI require same-day referral; metformin accumulation is next; the unknown herbal product is third. This is not a case for a stronger NSAID.
2. What immediate advice and actions should the pharmacist take, including which medicines to stop or hold and what to monitor?
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Advise same-day hospital assessment because potassium 5.8 mmol/L with AKI can cause arrhythmia. Do not supply another NSAID or an OTC combination containing ibuprofen or diclofenac. Stop diclofenac immediately.
Hold metformin, lisinopril, and furosemide until the patient is assessed and volume status is known. Do not restart them without prescriber review. If she is dehydrated, intravenous fluids may be needed, but this must be supervised. Check an ECG if available, repeat potassium and creatinine urgently, and monitor urine output and blood pressure.
For pain, paracetamol may be considered if there is no contraindication, but it must not delay referral. Counsel her to bring all medicines and the herbal product to hospital, to avoid drug-shop self-medication, and to seek urgent care for palpitations, weakness, confusion, or no urine. Communicate with the prescriber and document the referral and advice.
3. After recovery, how should her renal function and medicines be reviewed to prevent recurrence?
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After recovery, recheck creatinine and potassium and establish a new baseline eGFR. Review metformin: if eGFR remains 30-44, the dose should be reduced and not exceed about 1,000 mg/day; if eGFR falls below 30, it should be stopped. Review lisinopril and furosemide with the prescriber, especially during dehydration, vomiting, or diarrhoea. Avoid NSAIDs and advise her to ask the pharmacist before buying pain medicines.
Ask specifically about herbal products and drug-shop purchases at each visit. Provide a written medicine list and sick-day rules: during vomiting, diarrhoea, or poor intake, contact the prescriber about holding metformin, ACE inhibitor, and diuretic. Arrange follow-up and document the counselling. This prevents the same combination from causing another AKI.