D. McAuley, GlobalRPh Inc. There are many problems encountered in writing a program to effectively dose a drug such as digoxin. It is inherently difficult because of such components as narrow therapeutic index, difficult to define therapeutic endpoints, inter and intrapatient variability, and varying effects of pathological states and drugs on digoxin's disposition. In sum, there exists significant variability as far as a given dose and concentration produced in a given patient. It is important to be able to determine various patient attributes that may help predict drug concentrations for any given patient. There are several known attributes that have a direct correlation with the eventual therapeutic dose. Variables such as ideal body weight, serum creatinine, age, concomitant drug therapy all have great influence on the eventual therapeutic dosing regimen. The mathematical "backbone" of this program is based on the references below. You will notice two sets of responses when using this program. The first result is based on the "Jelliffe" method which attempts to predict the percentage of digoxin eliminated in a 24 hour period and the dose of digoxin required to maintain the concentration in the therapeutic range. The other result is based primarily on the "Jusko equations (below) and "KodaKimble" which attempts to calculate the effective digoxin clearance. After estimating the digoxin clearance, it is possible to make predictions regarding the steady state concentration: Css = (Maint dose x F) /( dig cl x T)
F= bioavailability factor  The "Jusko" Dosing section is based on the following equations. Initial dosing 1. Estimate Volume of Distribution (Jusko Equation) Vd = 226 + [(298 x CrCl) / (29.1 + CrCl)] x (BSA /
1.73) 2. Calculate Loading Dose LD = Vd x Cp/F where Vd = Volume of distribution (liters) Cp = target serum level (mcg/l) · IV push = 1 3. Estimate Clearance (KodaKimble) Cl = [(A x CrCl) + B] x C where A = 0.88, for patient with Acute CHF, otherwise=1 B = 23, for patient with Acute CHF, otherwise=40 · Quinidine = 0.65 4. Calculate Maintenance Dose MD = (Cl x Cp x tau) / F where Cl = Clearance (liters/hour) Cp = target serum level (mcg/l) 5. Estimate steadystate trough level Cpss = (MD x F) / (Cl x tau) where MD = Maintenance dose (mcg) F = bioavailability factor Adjust maintenance dose 1. Estimate Volume of Distribution (Jusko Equation  see above) 2. Calculate digoxin clearance Cl = [(MD x F) / Cp] / tau where MD = Maintenance dose (mcg) F = Bioavailability factor 3. Calculate Maintenance Dose MD = (Cl x Cp x tau) / F where Cl = Digoxin clearance (l/hr) Cp = target serum level (mcg/l) 4. Estimate steadystate trough level Cpss = (MD x F) / (Kel x Vd x tau) where MD = Maintenance dose (mcg) F = bioavailability factor 
General info: Loading dose: CHF: 812 mcg/kg in divided doses (q48h) over 12 to 24 hours. [Normally, give 50% of the total digitalizing dose in the initial dose, then give 25% of the total dose in each of the two subsequent doses at 8 to 12 hr intervalsObtain EKG 6 hours after each dose to assess potential toxicity (AV block, sinus bradycardia, atrial or nodal ectopic beats, ventricular arrhythmias); Other: vision changes, confusion.] If pt has renal insufficiency give 6 to 10 mcg/kg IBW. Afib: 10 to 15 mcg/kg IBW given as above. (If given IVPushadmin over at least 5 min). Maintenance dose: Digoxin clearance= [CRCL + 40] x 1.44 (add 20 instead of 40 if pt has CHF). Predicted Css= (Dose) (0.65 to 0.8)/ Digoxin clearance. Alternatively, maint dose= Loading dose x [0.14 + crcl/500 ] Avoid IM injectionscan lead to severe pain (If it must be given by this route, give deep IM followed by massage). Monitoring: Obtain blood samples at least 4 hrs after IV dose and 68hrs after oral dose. Serum levels: 0.5 to 2.0 ng/ml. Obtain first level within 24 hours of digitalization. Monitor BUN and serum creatinine q2days (qd if unstable). Monitor apical pulse daily.. Onset/peak: IV: 530min/ 14hrs Oral: 12hrs/ 28 hrs. Time to steady state: 57 days (average) ESRD: 1520 days. Halflife: 3848 hrs. (anephric: 46 days). Conversion from oral to IV: Decrease IV dose by 20 to 25%. When the maintenance dose is given IV, the onset and peak will occur earlier, however the duration of action is the same. Patients' on the "floors" may receive once daily IV maintenance doses, however, IV loading regimens (multiple doses) are restricted to pts on a monitor ICU's. [Oral bioavailability (tablets): 70 to 80%]. Factors that increase likelihood of digoxin toxicity: Hypokalemia, hypomagnesaemia, hypothyroidism, renal dysfunction, interacting drugs (eg quinidine, verapamil). Distribution: only a small fraction of digoxin in present in blood (little is removed by hemodialysis). Digoxin distributes very little into body fatdoses must be based on lean body weight. Distribution is not altered by obesity. There appears to be a gradual contraction in the volume of distribution as renal function deteriorates. Therefore, extreme caution is necessary when dosing patients with renal failure. Maximal response from any maintenance dose of digoxin will be obtained when serum concentrations are at steady state and maximal body stores for that dose have been obtained. It should be noted that any adjustment of dose or change in the elimination of digoxin requires a waiting period of 45 times the halflife (1 week with normal renal function) before the new steady state concentration is achieved.


Disclaimer 

Listed dosages are for  Adult patients ONLY. PLEASE READ THE
DISCLAIMER CAREFULLY BEFORE
ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE
TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
GlobalRPH does not directly or indirectly practice medicine or provide
medical services and therefore assumes no liability whatsoever of any
kind for the information and data accessed through the Service or for
any diagnosis or treatment made in reliance thereon. David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc. 