Digoxin LanoxinLanoxicaps

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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
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General Structure
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Mechanism of Action

• Digoxin inhibits membrane bound sodium-potassium
  ATPase resulting in an increased intracellular
  Na and thus an increase in the intracellular
  Ca2 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 renin-angiotensin
  system.

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Digoxin
(-)
2

Ca

3Na

2K
NaCaX
ATPase

3Na
Ca2
RyR
ATP
Ca2
2

ATPase
Ca
SR
ADP
Contraction
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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 renin-angiotensin
  system.
• Slowing of the heart rate and decreased
  conduction velocity through the AV node.

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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

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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)

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Side Effects Toxicities

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

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Drug Interactions

• Amiodarone
• ?Digoxin by 70
• Verapamil
• ?Digoxin by 50-75
• Propafenone
• ?Digoxin by 30
• Quinidine
• ?Digoxin by 50-75
• Erythromycin
• ?Digoxin

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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

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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

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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)

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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

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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 (Xo(0.7)) / (3.37 L/hr x 24
  hr) ? 0.7Xo 80.88 mcg ? Xo 115.54 mcg ? Use
  125 mcg tabs qday

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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

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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/plant-biology
  /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?drugdigoxin
• Digoxin Structure. Retrieved March 8, 2006 from
  world wide web http//medpharm.chunma.ac.kr/Aldja
  /CVS/cardiac_glycoside/img/digoxin_structure.GIF