CLINICAL USE

Angiotensin-converting enzyme inhibitor:Hypertension Heart failure

DOSE IN NORMAL RENAL FUNCTION

2–8 mg daily

PHARMACOKINETICS

  • Molecular weight                           :441.6
  • %Protein binding                           :60 (
  • 10 to 20

    • as perindoprilat)

  • %Excreted unchanged in urine     : 4–12
  • Volume of distribution (L/kg)       :0.2
  • half-life – normal/ESRD (hrs)      :1/27

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Initially 2 mg daily, adjust according to response
  • 10 to 20     : Initially 2 mg daily, adjust according to response
  • <10           : Initially 2 mg daily, adjust according to response

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unknown dialysability. Dose as in GFR <10 mL/min
  • HD                     :Dialysed. Dose as in GFR
  • <10           : mL/min
  • HDF/high flux   :Dialysed. Dose as in GFR
  • <10           : mL/min
  • CAV/VVHD      :Dialysed. Dose as in GFR=10–20 mL/min

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Anaesthetics: enhanced hypotensive effect
  • Analgesics: antagonism of hypotensive effect and increased risk of renal impairment with NSAIDs; hyperkalaemia with ketorolac and other NSAIDs
  • Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity
  • Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics
  • Epoetin: increased risk of hyperkalaemia; antagonism of hypotensive effect
  • Lithium: reduced excretion (possibility of enhanced lithium toxicity)
  • Potassium salts: increased risk of hyperkalaemia
  • Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity

    ADMINISTRATION

    Reconstition

    –

    Route

    Oral

    Rate of Administration

    –

    Comments

    –

    OTHER INFORMATION

    Active metabolite perindoprilat has a half- life of 25–30 hoursTitrate dose according to response; normal doses have been used in CKD 5Small volume of distribution due to low lipophilicity. Close monitoring of renal function during therapy is necessary in those with renal insufficiency
    Renal failure has been reported in association with ACE inhibitors in patients with renal artery stenosis, post renal transplant and those with severe congestive heart failureHigh incidence of anaphylactoid reactions has been reported in patients dialysed with high-flux polyacrylonitrile membranes and treated concomitantly with an ACE inhibitor – this combination should therefore be avoidedHyperkalaemia and other side-effects are more common in patients with renal impairment

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