Table of Contents

DIGOXIN PHARMACOKINETIC MONITORING

A. KINETIC PARAMETERS

Bioavailability (F): 0.70 tablet; 0.80 liquid
Protein Binding: 25%
Volume of Distribution (Vd): 7.5L/kg; (CrCl<10mL/min = 5.0L/kg)
Cardiac tissue conc. 15-30 x Plasma conc.
Distribution time: 8 hours; increased in CHF
Half-Life (t˝): 36 hours; 4-6 days in renal failure
Therapeutic range: 1-2.5 nmol/L (0.5-2.0 ng/mL)
No maximum in atrial fib if tolerated

B. DOSING

 1. Loading Dose:

 

PATIENT

 

IV LOADING DOSE

 

PO LOADING DOSE

 

Inotropic Effect (CHF)

 

*0.01mg/kg LBW; give 50% initially, then 25% in divided doses q6h x 2

 

IV Loading Dose divided by0.70

Give same as per IV Load

 

Chronotropic Effect (Atrial Fibrillation)

 

*0.013-0.015mg/kg LBW; administer same as per above

 

IV Loading Dose divided by   0.70

Give same as per IV Load

*severe renal failure < 30mL/minute, assume Vd = 5L/kg or give 2/3 loading dose 

 2. Maintenance Dose: 

IV Maintenance Dose    = % daily loss x total body stores  = 0.01(14 + CrCl/5) x loading dose

PO Maintenance Dose= IV maintenance dose divided by 0.70

 C. DRUG LEVEL MONITORING 

1) Digoxin Serum Levels - when to measure:

   a)          concern about compliance, or inadequate digoxin history;

   b)          suspected toxicity of such severity that DigibindŽ may be required for therapy

c)          inadequate therapy despite high doses (little efficacy with levels <0.9nmol/L)

   d)          drug interactions (e.g. amiodarone, verapamil)

 Note: There is a large overlap between toxic and therapeutic levels.  When interpreting serum digoxin levels, monitor patient for efficacy and toxicity as level alone may be misleading.


2) Digoxin Serum Levels - draw times: 

Trough levels preferred or minimum 6 hours post dose (due to long distribution t1/2)

Steady state: 3-5 half-lives (= 5-7 days normal t1/2; 1-3 weeks renal dysfunction)

Drug interactions: 2 days after interacting drug added to therapy

D. DRUG INTERACTIONS 

 

Drugs which cause INCREASED serum digoxin levels

 

Drugs which cause DECREASED serum digoxin levels

 

amiodarone, anticholinergic drugs, diltiazem, propafenone, quinidine, spironolactone, verapamil

 

antacids, cholestyramine, domperidone, kaolin-pectin, metoclopramide, sulfasalazine

 E. TOXICITY 

 

System

 

Adverse Effect

 

Cardiovascular

 

apical slowing (<60bpm), AV conduction block, supraventricular tachycardia, ventricular extrasystoles

 

Central Nervous System

 

confusion, forgetfulness, hallucinations, dizziness, psychosis, nightmares

 

Visual

 

colour changes, halos

 

Gastrointestinal

 

anorexia, nausea, vomiting, diarrhea, abdominal pain (mesenteric ischemia)