dosage adjustment of Carvedilol in renal failure




Carvedilol.JPG

Carvedilol

CLINICAL USE

Beta-adrenoceptor blocker with alpha1-blocking action:
  • Hypertension, angina and heart failure

    DOSE IN NORMAL RENAL FUNCTION

  • Hypertension: 12.5–50 mg daily in single or divided doses
  • Angina: 12.5–25 mg twice daily
  • Heart failure: 3.125–25 mg twice daily (50 mg twice daily if wt>85 kg)

    PHARMACOKINETICS

  • Molecular weight                           :406.5
  • %Protein binding                           :>98
  • %Excreted unchanged in urine     : <2
  • Volume of distribution (L/kg)       :2
  • half-life – normal/ESRD (hrs)      :6–10/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unlikely dialysability. Dose as in normal renal function. Start with low doses and titrate according to response
  • HD                     :Not dialysed. Dose as in normal renal function. Start with low doses and titrate according to response
  • HDF/high flux   :Unknown dialysability. Dose as in normal renal function. Start with low doses and titrate according to response
  • CAV/VVHD      :Unlikely dialysability. Dose as in normal renal function. Start with low doses and titrate according to response

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Anaesthetics: enhanced hypotensive effect Analgesics: NSAIDs antagonise hypotensive effectAnti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone
  • Antibacterials: concentration reduced by rifampicin
  • Antidepressants: enhanced hypotensive effect with MAOIs
  • Antihypertensives: enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin
  • Antimalarials: increased risk of bradycardia with mefloquine
  • Antipsychotics enhanced hypotensive effect with phenothiazines
  • Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil
  • Ciclosporin: increased trough concentration, reduce dose by 20% in affected patients
  • Diuretics: enhanced hypotensive effect Moxisylyte: possible severe postural hypotension
  • Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine
  • Tropisetron: increased risk of ventricular arrhythmias – use with caution

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    OTHER INFORMATION

    First pass elimination of 60–75% following oral administration