C3.1 R4(e): Perform & document a pharmacokinetic interpretation (OTHER drug)

Clinical Pharmacy Note RE: Digoxin

ID: 84 yo female admitted for G- bacteremia and hypercapnic respiratory failure

  • PMHx: Afib, HTN, chronic back pain, PVD, scoliosis, recurrent falls and fractures, chronic cellulitis x 8 mos, venous insufficiency ulcers, childhood polio

S:

  • RASS -1, AO x 3
  • Met patient in room to assess for SEs of digoxin:
    • Denies drowsiness, dizziness. Has headaches but this is ongoing from PTA and have not worsened in hospital
    • Denies any visual disturbances and able to identify red and green colours
    • Denies N/V and nurse’s flow sheet shows no diarrhea
    • Denies any change in appetite – ate 1/4 sandwich and 1/3 soup today for lunch
    • At baseline – has muscle weakness to both her arms (L>R) due to childhood polio. Has weak strength of flexion and extension of thigh
  • Denies any chest pain, palpitations or SOB

O:

  • v/s: T 36.3, HR 75, BP 130/65, MAP 93, RR 21 (on 2L NP)
  • ECG (Mar 14): Afib with RVR (130 bpm)
  • ECG (Mar 15): Afib rate controlled (90 bpm), inverted T waves
  • On Mar 14, received digoxin 0.5mg IV at 1340h and 0.25mg IV at 2200h for afib with RVR. No maintenance doses have been ordered
  • Digoxin level on Mar 15 1135h: 4.2 nmol/L (target for afib: 1-2.5nmol/L)
  • Relevant labs (Mar 15): K+ 4.8 mmol/L, eGFR 13 mL/min (eGFR 75 mL/min in Nov 2016)

A:

  1. Digoxin load is effective in controlling her rate for afib
  2. Trough level was taken appropriately and is supratherapeutic, likely due to her AKI
  3. Currently exhibiting no SEs of digoxin. No indication or role for use of digifab at this time
  4. PTA, refused treatment for afib and hypertension.  On admission, afib may have been exacerbated by infection and hypercapnic respiratory failure which are currently being managed. The decision on whether or not to initiate long term management for afib should factor in her goals of therapy for comfort care.

P: Suggest

  1. Not to continue digoxin (no maintenance doses have been ordered)
  2. Daily monitoring for s/s of afib: dizziness, syncope, palpitations, dyspnea (currently no cardiac monitoring d/t goals of therapy for comfort care)
  3. Daily monitoring of safety of digoxin: HR, K+, eGFR, sCr, u/o, worsening of headaches, dizziness, drowsiness, vision changes (flicking lights/halos, blurry or yellow/green vision, red-green colour blindness), worsening of muscle weakness

Other calculations:

  • Dosing of digoxin load IV:
    • LD usually given:
      50% of calculated LD as an IV or PO bolus then 25% of calculated LD q6h x 2

      • Could calculate based on IBW (challenging as wt unknown and pt has scoliosis)
      • If estimate: ~50kg + 5 feet 5, IBW = 56.5kg, CrCl = 16 mL/min,
        LD = 0.56-1.13mg (0.01-0.02mg/kg *IBW/F)
      • If renal impairment (avoid in AKI if possible): reduce loading dose by 50%
        • LD = 0.28-0.56mg
          (Max ~ 0.25mg IV, then 6 hours later – 0.125mg IV Q6H x 2 doses)
      • Could also give PO (F: 07 for tablets)
    • UTD states may generally admin as loading dose: 0.25mg with repeat dosing to a max of 1.5mg over 24hrs
      • In acute renal failure: pt Vd may be increased and reduction in LD may not be necessary; however, maintenance dosing will require adjustment
    • VGH PDTM:
      • Digitalization: 0.01 to 0.015 mg/kg of lean body weight divided into 2 or 3 equal parts and given at 6 hourly intervals
  • Monitoring of digoxin loads:
    • at least 4 -6 hrs after an IV dose
    • at least 6-12 hrs after a PO dose
  • Other option for rate control in the setting of hypotension and shock:
    amiodarone infusion (no renal dosing adjustment necessary for renal impairment)

DIG

D: Randomized, double-blind, placebo-controlled trial (1997)

P N = 6800, HF and LVEF < 45%, NSR
302 clinical centers in US and CanadaExcluded: afib/flutter, cardiac surgery or PCI within previous 4 weeks or need for cardiac surgery or PCI in near future
I Digoxin
C Placebo
O Efficacy:

  • NSS for death
  • Hospitalizations for worsening HF – RR: 0.72 (0.66-0.79, p<0.001)
  • Subgroup analysis: high risk patients – those with lower EF or enlarged hearts and those in NYHA III or IV – benefit appeared greater

Safety:

  • Most common reasons for suspected digoxin toxicity: ventricular fibrillation or tachycardia, supraventricular arrhythmia, 2nd or 3rd degree AV block

**Retrospective Analysis: Relationship of serum digoxin concentration to mortality and morbidity in the DIG trial** (2005):

For women:

  • 0.5-0.9ng/mL: Beneficial effect of digoxin on morbidity and no excess mortality
  • > 1.2ng/mL (= 1.5 nmol/L): Risk for mortality was greater than placebo

**Association of serum digoxin concentration and outcomes in patients with heart failure (2003): Post-hoc analysis of the DIG trial

For men:

  • 0.5-0.8ng/mL: associated with reduction in mortality
  • 0.9-1.1ng/mL: not associated with reduction in mortality
  • > 1.2ng/mL (= 1.5 nmol/L): higher mortality in men

Take-home messages:

  • Efficacy of digoxin in heart failure:
    • Reducing risk for hospitalizations for worsening HF
  • Monitor digoxin trough levels (30min prior to dose)
    • Levels should at least be 8-12 hours after dose
    • CCS AF guidelines: maximum trough digoxin serum concentration: 1.5 nmol/L
      • DIG trial suggests that > 1.5 nmol/L associated with greater mortality in HF
    • CCS compendium for HF
      • Digoxin trough level in HF patients with severe renal dysfunction: <1nmol/L
      • If rapid deterioration in renal fx, hold digoxin and R/A when stable
      • Role of digoxin: in patients who are in SR + moderate to severe symptoms, despite optimized HF therapy → relieve symptoms + reduce hospitalizations
  • Concurrent atrial fibrillation:
    • Digoxin – target HR of <100bpm
    • Not as effective as controlling HR vs BB or CCBs during exercise
      – should not be used as monotherapy for active patients
    • CCS guidelines for atrial fibrillation:
      If used for treating patients with concomitant LV systolic dysfunction, its use should be dictated by the recommendations of the CCS HF Clinical Guidelines

1.0ng/mL = 1.3 mmol/L – associated with increased mortality in HF