Digoxin (Lanoxin/Lanoxicaps)

Seth Adams
Duy Cao
Scott Davis
Cheryl Hanslovan
Bryan Ing
Kristin McKay
Vic Patel
Dan Rackham
Darren Smith
Phong Vuong

foxglove digitalis

General Structure

Mechanism of Action
Digoxin inhibits membrane bound sodium-potassium
ATPase resulting in an increased intracellular [Na +] and
thus an increase in the intracellular [Ca 2+] by stimulation of
Na+ and Ca2+ exchange.
Digoxin has an indirect effect on the sinoatrial and
atrioventricular nodes (vagomimetic actions).
Baroreceptor sensitization also results from digoxin. This
leads to increased afferent inhibitory activity and reduced
activity of the sympathetic nervous system and reninangiotensin system.

Digoxin

Ca

(-)

2+

2K

3Na

NaCaX
ATPase

3Na +

Ca2+

RyR
ATP

SR
Contraction

Ca

2+

ATPase

Ca2+
ADP

Net Effect
Positive inotropic action
(an increase in the force
and velocity of myocardial
systolic contraction).
A decrease in the degree of
activation of the
sympathetic nervous
system and reninangiotensin system.
Slowing of the heart rate
and decreased conduction
velocity through the AV
node.

Main Clinical Indications

Heart Failure
Increases cardiac output by positive inotropic actions
Therapeutic level of 0.5-1 mcg/L

Atrial Fibrillation
Rate control by vagomimetic actions
Therapeutic level of 0.5-2 mcg/L

Available Dosage Forms

Tablets ( F = 0.6 - 0.7)

125 mcg ( yellow, # Y3B ) or 250 mcg ( white, # X3A )

Capsules (Lanoxicaps) ( F = 0.9 0.95)

50 mcg ( red, # A2C ) , 100 mcg ( yellow, # B2C ), and 200 mcg ( green, #
C2C)

Pediatric Elixer ( F = 0.75 0.85)

50 mcg per 1 ml (10% alcohol)

Injection ( F = 1.0 )
250 mcg per 1 ml (1 ml ampule)

Pediatric Injection ( F = 1.0 )

100 mcg per 1 ml (1 ml ampule)

Side Effects & Toxicities

Yellow/green visual changes, halos around light
N&V and diarrhea (50-75% of patients)
Bradycardia (75-90% of patients)
Fatigue, malaise, confusion, headache, etc.
Anorexia

Drug Interactions
Amiodarone
[Digoxin] by 70%

Verapamil
[Digoxin] by 50-75%

Propafenone
[Digoxin] by 30%

Quinidine
[Digoxin] by 50-75%

Erythromycin
[Digoxin]

Pharmacokinetic Parameters

Absorption
After oral dosing:
Onset of action in 0.5 2 hours
Peak effect reached in 2 6 hours

Distribution
Skeletal and heart muscle, but not into adipose tissue
Up to 25-30% is bound to plasma proteins

Metabolism
Follows first-order kinetics
Limited metabolism via sugar hydrolysis and lactone ring reduction
Half-life = 1-2 days

Excretion
60-80% excreted unchanged in urine
Undergoes ACTIVE tubular secretion in the kidneys

Clinical Considerations
Doses must be individualized and depends on the type &
severity of the disease, age & weight of the patient, renal
function, and concomitant disease states
Normal dosage range is 125 500 mcg (50 200 mcg
capsules) a day in a single dose
Contraindications: Patients w/ ventricular fibrillation, renal
impairment, hypokalemia, hypomagnesemia,
hypercalcemia, and pulmonary disease
Patient must be advised not to take nonprescription cough
or cold medications, antacids, laxatives, or antidiarrheals
without consulting the pharmacist or physician
Pregnancy category C

Digoxin Equations

IBW = 50 (or 45.5) + 2.3 x (inches over 60)

CrCl = ((140 - Age) x IBW) / (72 x SCr) ( x 0.85 for females)

Clearance Digoxin: Cldig = (0.8 ml/min/kg x IBW) + CrCl

w/ CHF: Cl = (0.33 ml/min/kg x IBW) + (0.9 x CrCl) (these values were multiplied
by 0.06 to convert them from mL/min to L/hr)
w/ co-administration of amiodarone: Cl = 0.5 x Cl (without amiodarone)

Vd = 7.3 L/kg x IBW

w/ renal dysfunction: Vd = (3.8 L/kg x IBW) + (3.1 x CrCl)

LD = (Cp (desired level) x Vd) / (F)

MD = (Cp (desired level) x Cldig x Xo) / (F)

Sample Problems
WB is a 75-year-old female with PMH including
atrial fibrillation, type II diabetes, hypertension,
and renal insufficiency. She is 54 and weighs 75
kg. Her SCr is 3.4 mg/dL. Calculate a loading and
maintenance dose for Lanoxin tablets for Mrs. B.
Target Cpss = 1.0 mcg/L for atrial fibrillation

AS is a 78-year-old male with CHF. He is 510 and

weighs 73kg. His SCr is 1.1 mg/dL. Calculate a
dosing regimen using Lanoxicaps.
Target Cpss = 0.7 mcg/L for CHF

Problem Solutions - 1
WB w/ Renal Dysfunction:
IBW = 45.5 kg + 2.3 (4 in) = 54.7 kg
CrCl = ((140-75) x 54.7 kg (.85)) / (3.4 x 72) = 12.35 mL/min
Vd = (3.8 L/kg x 54.7 kg) + 3.1 (12.35 mL/min) = 246.15 L
Cldig= (0.8 mL/min/kg x 54.7 kg) + 12.35 mL/min = 56.11 mL/min = 3.37 L/hr
LD = (246.15 L x 1 mcg) / (0.7) = 351.64 mcg Use 375 mcg tabs once
MD = Cpss = 1 mcg/L = (X o(0.7)) / (3.37 L/hr x 24 hr) 0.7Xo = 80.88 mcg
Xo = 115.54 mcg Use 125 mcg tabs qday

Problem Solutions - 2
AS w/ Congestive Heart Failure:
IBW = 50.0 kg + 2.3 (10 in) = 73 kg
CrCl = ((140-78) x 73 kg) / (1.1 x 72) = 57.15 mL/min
Vd = (7.3 L/kg x 73 kg) = 532.9 L
Cldig= (0.33 mL/min/kg x 73 kg) + 0.9 (57.15 mL/min) = 75.52 mL/min = 4.53 L/hr
LD = (532.9 L x 0.7 mcg) / (0.95) = 392.66 mcg Use 400 mcg caps once
MD = Cpss = 0.7 mcg/L = (Xo(0.95)) / (4.53 L/hr x 24 hr) 0.95Xo = 76.1 mcg
Xo = 80.11 mcg Use 100 mcg caps qday

References

20th edition top 200 pharmacy drug cards. SFI Medical Publishing. 2004.

Class lecture. Pharmacy 750. 11/3/2005. Connie Covington

Tharp, R. (2006) Digoxin Dosing. Retrieved March 9, 2006 from the world wide web:
http://www.rxkinetics.com/dig.html

Medicinal Plants. (2006) Digoxin Image. Updated Aug 12, 2005. Retrieved March 8, 2006
from world wide web: http://www.science.siu.edu/plantbiology/PLB117/Nickrent.Lecs/Medicine.html

Rx-List. (2006) Digoxin. Updated March 12, 2006. Retrieved March 8, 2006 from world
wide web: http://www.rxlist.com/cgi/rxlist.cgi?drug=digoxin

Digoxin Structure. Retrieved March 8, 2006 from world wide web:

http://medpharm.chunma.ac.kr/Aldja/CVS/cardiac_glycoside/img/digoxin_structure.GIF