Metformin

Explanation

Hydroxychloroquine can cause severe and potentially fatal hypoglycaemia, "in the presence or absence of antidiabetic agents" (the label explicitly states that it "may enhance the effects of insulin and antidiabetic drugs and, consequently, increase the hypoglycaemic risk — a decrease in the dosage of insulin and other antidiabetic drugs may be necessary", and recommends monitoring blood glucose in diabetic patients). The combination with metformin adds up the hypoglycaemic effects. Note: the hydroxychloroquine label indicates it does not inhibit OCT2 in vitro, so the mechanism is essentially pharmacodynamic. Monitor glycaemia at the start of the combination and whenever the hydroxychloroquine dose changes, warn the patient about hypoglycaemia signs (sweating, tremor, palpitations, confusion) and consider reducing the metformin or other antidiabetic dose.

Explanation

Systemic corticosteroids increase insulin resistance and hepatic glucose production, antagonising the effect of antidiabetics — the Prontuário states explicitly that antidiabetics antagonise the hyperglycaemic effects of corticosteroids and that in diabetics these should only be used when strictly necessary. During prolonged or high-dose corticosteroid therapy, blood glucose must be monitored and antidiabetic therapy adjusted (often the metformin dose must be increased or insulin added).

Explanation

Metformin is eliminated renally through the organic cation transporter OCT2, and trimethoprim (a co-trimoxazole component) is an OCT2 inhibitor, which can raise metformin concentrations and the risk of lactic acidosis, especially in patients with reduced renal function, the elderly or with other causes of acidosis; the co-trimoxazole label recommends avoiding co-administration with OCT2 substrates (metformin is explicitly mentioned) and monitoring glycaemia. During the combination, monitor renal function, signs of lactic acidosis (malaise, myalgia, abdominal pain, dyspnoea, drowsiness) and consider temporarily stopping metformin in at-risk patients.

Explanation

Explanation

Tenofovir and metformine are both essentially eliminated renally — tenofovir by glomerular filtration and tubular secretion, metformine by tubular secretion via OCT2. Coadministration may compete for tubular secretion, potentially elevating levels of both. The main risk is additive nephrotoxicity: tenofovir may cause proximal tubular nephrotoxicity (Fanconi syndrome), while metformine requires adequate renal function to prevent accumulation and lactic acidosis. Recommendation: assess GFR before initiation and monitor periodically (creatinine, electrolytes, proteinuria). Adjust metformine dose if GFR <30 mL/min. Consider alternative to tenofovir (entecavir) if renal deterioration occurs.

Explanation

The FDA cephalexin label documents: "Metformin: increased metformin concentrations. Monitor for hypoglycemia" (section 7.1). Cephalexin competes with metformin for renal tubular secretion via the OCT2 transporter, reducing metformin elimination and increasing its systemic exposure. In the diabetic patient on metformin, cephalexin antibiotic therapy may translate into higher antidiabetic levels and increased risk of hypoglycaemia — especially in patients with borderline renal function or prolonged fasting. The practical guidance is to warn about hypoglycaemia symptoms (sweating, tremor, confusion) and consider more frequent glucose monitoring during antibiotic therapy.

Explanation

The FDA tafenoquine label documents that co-administration with OCT2/MATE transporter substrates (e.g., dofetilide, metformin) should be avoided; if unavoidable, monitor for related toxicities and consider dose reduction (section 7.1). Metformin depends on tubular secretion via OCT2 and MATE for its elimination; inhibition of these transporters by tafenoquine raises metformin plasma concentrations. The clinical risk is metformin toxicity — gastrointestinal symptoms, renal function and, in rare cases, lactic acidosis, especially if renal impairment already exists. As tafenoquine is used in a short regimen (single dose in malaria prophylaxis), the ideal is to avoid the combination on the day of administration; if unavoidable, monitor and consider adjustment.

Explanation

Metformin is renally excreted and requires eGFR >30 mL/min to prevent accumulation and lactic acidosis. Canagliflozin causes volume loss (glycosuria + osmotic diuresis) that may reduce eGFR and increase metformin levels. Particularly elevated risk in: (1) elderly, (2) patients with borderline eGFR (30-45), (3) concomitant diuretic use, (4) dehydration from acute illness. Strategy: check eGFR before and 3 months after starting SGLT2. Discontinue SGLT2 if dehydrated or eGFR <45.

Explanation

Explanation

Fluoxetine may slightly reduce renal blood flow via prostaglandin inhibition, but the effect is significantly less than with NSAIDs. The risk of metformin accumulation is low in patients with normal renal function. In patients with borderline GFR (45-60), consider monitoring GFR. There is no evidence of clinically significant interaction in most patients.

Explanation

Explanation

Topiramate inhibits carbonic anhydrase, causing hyperchloraemic metabolic acidosis (5-10%). Metformine may cause lactic acidosis (rare but serious). Although the mechanisms differ, topiramate-induced metabolic acidosis may mask early signs of metformine-induced lactic acidosis. Monitor serum bicarbonate and GFR regularly.