Digoxin Dosing Calculator

Compare the Jelliffe, Koda-Kimble and Jusko digoxin dosing methods side by side: loading and maintenance doses with renal adjustment, bioavailability by formulation, interacting drugs, and correction from a measured level.

Key definitions

Jelliffe method

Estimates total body stores of digoxin (10 mcg/kg for heart failure, 14 mcg/kg for atrial fibrillation, reduced in severe renal impairment) and derives the daily maintenance dose from the percentage of stores lost per day: 14 + 0.2 x CrCl.

Koda-Kimble method

Estimates digoxin clearance directly in L/day: ((A x CrCl) + B) x interaction factor x 1.44, with A and B adjusted for heart failure severity. Maintenance dose = clearance x target concentration / bioavailability.

Jusko method

Estimates volume of distribution from creatinine clearance and body surface area, then sizes the loading dose as Vd x target concentration / bioavailability. Useful when a loading dose is needed without full digitalisation.

Bioavailability (F)

The fraction of an oral dose reaching the circulation: 1.00 IV, 0.95 capsule, 0.80 elixir, 0.75 tablet. The same body needs a larger oral than IV dose, and switching formulations changes the effective dose.

Digitalisation

The traditional practice of giving divided loading doses over 24 hours to reach therapeutic stores quickly. Modern practice usually avoids it, starting maintenance directly except where rapid effect is needed.

Why three methods, and why they disagree

Digoxin has been dosed by competing pharmacokinetic methods for fifty years because no single equation captures every patient, and each method makes different trade-offs. Jelliffe's method thinks in body stores: it estimates how much digoxin the body should contain, then replaces each day's losses. It is intuitive and needs only weight and creatinine clearance, but its fixed 10 or 14 mcg/kg stores and its linear loss percentage are approximations that wobble at the extremes of renal function and body size.

Koda-Kimble thinks in clearance: it estimates how fast the body eliminates digoxin in litres per day, incorporating heart failure severity (which reduces clearance beyond what creatinine shows) and interacting drugs as explicit factors, then sizes the maintenance dose as clearance times target concentration. It is the most complete of the three for maintenance dosing and the only one that handles interactions quantitatively. Jusko thinks in distribution volume: it estimates Vd from creatinine clearance and body surface area, which makes it the natural choice for the loading dose, the one question the other two answer less well.

The calculator shows all three because their disagreement is informative. When Jelliffe and Koda-Kimble agree, the dose is robust to method choice. When they diverge, usually in severe renal impairment or with interacting drugs, the divergence tells you the patient sits where the approximations are weakest, and that is exactly when a measured level should adjudicate. Treat the spread as a confidence interval, not a menu to pick the most convenient number from.

Targets, formulations and interacting drugs

The therapeutic targets have drifted downward over the decades as evidence accumulated that higher levels harm. For heart failure the target is 0.5 to 1.0 ng/mL, with post hoc analyses of the DIG trial showing mortality rising above 1.0 and the best outcomes at the low end. For atrial fibrillation rate control the range is 0.8 to 1.5 ng/mL. Levels must be drawn at least 6 to 8 hours after the dose, ideally just before the next one, because early post-dose levels reflect the distribution phase and overstate the clinically relevant concentration. Steady state takes about five half-lives: with a normal half-life of 36 to 48 hours, that is 7 to 10 days, longer in renal impairment.

Formulation matters more than prescribers expect. A patient stable on 250 mcg of tablets (F = 0.75, effective 187 mcg) who is switched to capsules (F = 0.95) receives a 27% dose increase without any change on the prescription. The calculator applies bioavailability explicitly so formulation switches are visible. Interacting drugs matter more still: amiodarone roughly halves digoxin clearance, so adding amiodarone to a stable digoxin patient without halving the dose reliably produces toxicity. Quinidine, verapamil and spironolactone reduce clearance by 25 to 35%. The calculator applies these as clearance factors in the Koda-Kimble estimate and flags the need for a repeat level.

Worked example: a 70-year-old man, 70 kg, 70 inches, creatinine 1.2 mg/dL, heart failure, tablets, no interactions. Creatinine clearance is 56.7 mL/min, clearance 139.3 L/day, Vd 457 L, half-life 54.6 hours. Jelliffe gives a loading dose of 933 mcg and maintenance of 237 mcg/day; Jusko gives a loading dose of 488 mcg; Koda-Kimble gives maintenance of 149 mcg/day. The spread is real and typical: the practical prescription is usually 125 to 187 mcg daily (tablet strengths constrain the choice), with a level at steady state to adjudicate.

Adjusting from a measured level

When a steady-state level is available on a known dose, the patient's own clearance replaces every estimate: patient clearance (L/h) = (dose x F / level) / 24, and the new maintenance dose = clearance x target x 24 / F. This is the most reliable dosing step in the whole process because it uses measured rather than estimated pharmacokinetics. The requirements are strict: steady state (at least five half-lives on the current dose), correct sampling time (6+ hours post-dose, trough preferred), stable renal function and no recent interacting-drug changes. A level drawn too early or during the distribution phase will mislead the adjustment more than no level at all.

Toxicity: recognition and risk factors

Digoxin toxicity is common, under-recognised and potentially fatal, and its presentation is famously nonspecific: anorexia, nausea, visual disturbance (notably xanthopsia, yellow-green vision), confusion and arrhythmia. The electrocardiogram may show the classic scooped ST depression, but the dangerous manifestations are arrhythmic: virtually any arrhythmia except rapidly conducted atrial fibrillation can be digoxin toxicity, with ventricular ectopy and heart block the most characteristic. Risk factors stack: renal impairment, hypokalaemia, hypomagnesaemia, hypercalcaemia, hypothyroidism, advanced age and interacting drugs. Low potassium is the great amplifier: it increases digoxin binding to the sodium-potassium pump, so toxicity can occur at therapeutic levels when potassium falls. Check potassium and magnesium with every digoxin level, and treat toxicity with dose interruption, potassium repletion and, in severe cases, digoxin-specific antibody fragments.

Limitations and pitfalls

All three methods assume stable renal function and average pharmacokinetics. In acute kidney injury the creatinine lags behind true filtration and every estimate overshoots; in the frail elderly with sarcopenia the creatinine flatters filtration and estimates undershoot clearance, risking toxicity at apparently reasonable doses. Obesity is handled here with ideal body weight for the creatinine clearance estimate when actual weight exceeds 120% of ideal, but digoxin distribution in obesity is imperfectly understood and levels are essential.

The interaction factors are population averages: an individual patient's response to adding amiodarone varies, which is why the calculator flags a repeat level rather than promising the adjusted dose is correct. Thyroid disease, critical illness and electrolyte disturbances change digoxin sensitivity without changing its pharmacokinetics, so the level target itself may need lowering. And none of the methods apply to children, whose digoxin pharmacokinetics differ substantially.

Key takeaways

• Target 0.5 to 1.0 ng/mL in heart failure (low end preferred) and 0.8 to 1.5 ng/mL in atrial fibrillation.
• Compare Jelliffe, Koda-Kimble and Jusko; use their agreement or disagreement as information about confidence.
• Account for formulation bioavailability: tablet 0.75, elixir 0.80, capsule 0.95, IV 1.00.
• Halve the dose (approximately) when adding amiodarone; reduce for quinidine, verapamil and spironolactone; recheck levels.
• Adjust from a steady-state level using the patient's own clearance; it beats every estimate.
• Draw levels 6+ hours post-dose at steady state; check potassium and magnesium alongside.

Frequently asked questions

What is the Jelliffe method?

It estimates total digoxin body stores from weight and indication, then derives the maintenance dose from the daily percentage lost (14 + 0.2 x CrCl), divided by bioavailability. Simple and long-established, weakest at renal extremes.

What is the Koda-Kimble method?

It estimates digoxin clearance in L/day incorporating heart failure severity and interacting drugs, then sizes maintenance as clearance x target / bioavailability. The most complete method for maintenance dosing.

What is the Jusko method?

It estimates volume of distribution from creatinine clearance and body surface area and sizes the loading dose as Vd x target / bioavailability. Best suited to the loading-dose question.

What digoxin level should be targeted?

0.5 to 1.0 ng/mL in heart failure (lower preferred), 0.8 to 1.5 ng/mL in atrial fibrillation. Draw at least 6 to 8 hours post-dose at steady state.

Which drugs interact with digoxin?

Amiodarone (halves clearance), quinidine (x0.65), verapamil (x0.70), spironolactone (x0.75). Recheck the level after starting or stopping any of them.

How is the dose adjusted from a measured level?

Patient clearance = (dose x F / level) / 24 L/h; new dose = clearance x target x 24 / F. Requires steady state, correct sampling time and stable renal function.

What are the signs of digoxin toxicity?

Nausea, visual disturbance (yellow-green vision), confusion, and arrhythmias, especially ventricular ectopy and heart block. Hypokalaemia amplifies toxicity even at therapeutic levels.

Does the tablet strength limit the dose?

Yes, practically. Digoxin tablets come in 62.5, 125 and 250 mcg strengths, so calculated doses are rounded to achievable regimens (e.g. 125 mcg daily or 125/250 on alternate days), then confirmed with a level.

Related calculators

• Lithium Dosing Calculator - another narrow-index drug dosed by kidney function and levels.
• Aminoglycoside Pharmacokinetic Dosing Calculator - level-based individualisation.
• Cardiology calculators - heart failure and rhythm tools.
• Nephrology calculators - creatinine clearance and kidney function tools.

References

1. Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871-878.
2. Bauman JL, Didomenico RJ, Viana M, Fitch M. A method of determining the dose of digoxin for heart failure in the modern era. Arch Intern Med. 2006;166(22):2539-2545. - American College of Cardiology