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CKD Nephroprotection Pregnancy: Contraindicated in 2nd and 3rd trimester; avoid throughout

Canagliflozin (CKD)

Brand names: Invokana

Adult dose

Dose: 100 mg once daily
Route: Oral
Frequency: Once daily
Max: 100 mg/day for CKD/cardiac indication
SGLT2 inhibitor. CREDENCE trial: first RCT demonstrating nephroprotection with SGLT2i specifically in diabetic kidney disease. Same sick-day rules and DKA risk as empagliflozin. Examine feet regularly (amputation risk — CANVAS trial).

Paediatric dose

Route: Oral
Seek specialist opinion — not licensed in children

Dose adjustments

Renal

Glycaemic efficacy reduced below eGFR 60; nephroprotective effect maintained. Initiate down to eGFR 30 for CKD/cardiac indications. Avoid eGFR <30 for glycaemic indication.

Hepatic

Not recommended in severe hepatic impairment

Clinical pearls

  • CREDENCE trial (Perkovic et al. NEJM 2019): canagliflozin 100 mg vs placebo in T2DM + CKD — 30% relative risk reduction in renal failure, doubling creatinine, or renal/CV death. First SGLT2i trial powered for renal outcomes.
  • CANVAS trial: canagliflozin increased lower limb amputation risk (6.3 vs 3.4 per 1000 patient-years) — MHRA 2016 warning. Examine feet at every visit; high-risk amputees: consider alternative SGLT2i.
  • CANVAS also showed 26% increased fracture risk vs placebo — monitor bone density in high-risk patients. These signals are NOT seen with empagliflozin or dapagliflozin.
  • Rifampicin interaction: rifampicin is a UGT and CYP3A4 inducer — reduces canagliflozin AUC by ~51%; increase dose to 200 mg OD if combination unavoidable
  • Sick-day rules apply identically: hold during acute illness, surgery, contrast media — DKA can be euglycaemic

Contraindications

  • eGFR <30 for non-glycaemic indications in UK
  • Type 1 diabetes
  • Recurrent UTIs/genital infections
  • Hypersensitivity

Side effects

  • Genital mycotic infections
  • UTI
  • Euglycaemic DKA
  • Volume depletion
  • Lower limb amputations — MHRA 2016 warning (CANVAS trial)
  • Bone fractures (CANVAS trial)
  • Fournier gangrene

Interactions

  • Rifampicin — reduces canagliflozin levels; increase dose to 200 mg
  • Diuretics — additive volume depletion
  • UGT inducers (phenytoin, phenobarbital) — reduce levels

Monitoring

  • eGFR
  • Urinary albumin:creatinine ratio
  • Foot examination (amputation risk)
  • Blood pressure
  • Haematocrit

Reference: BNFc; BNF 90; CREDENCE Trial (Perkovic et al. NEJM 2019); CANVAS Trial (Neal et al. NEJM 2017); MHRA DSU 2016 (Amputation); NICE TA775. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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