digoxin

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**BEERS Drug**

Pronunciation:
di-jox-in

Trade Name(s)

• Lanoxin
• Toloxin 

Ther. Class.
antiarrhythmics
inotropics

Pharm. Class.
digitalis glycosides

Indications

• Heart failure.
• Atrial fibrillation and atrial flutter (slows ventricular rate).
• Paroxysmal atrial tachycardia.

Action

• Increases the force of myocardial contraction.
• Prolongs refractory period of the AV node.
• Decreases conduction through the SA and AV nodes.

Therapeutic Effect(s):

Increased cardiac output (positive inotropic effect) and slowing of the heart rate (negative chronotropic effect).

Pharmacokinetics

Absorption: 60–80% absorbed after oral administration of tablets; 70–85% absorbed after administration of elixir; 80% absorbed from IM sites (IM route not recommended due to pain/irritation).

Distribution: Widely distributed; crosses placenta and enters breast milk.

Metabolism and Excretion: Excreted almost entirely unchanged by the kidneys.

Half-life: 36–48 hr (↑ in renal impairment).

TIME/ACTION PROFILE (antiarrhythmic or inotropic effects, provided that a loading dose has been given)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Uncontrolled ventricular arrhythmias;
• AV block (in absence of pacemaker);
• Idiopathic hypertrophic subaortic stenosis;
• Constrictive pericarditis;
• Known alcohol intolerance (elixir only).

Use Cautiously in:

• Hypokalemia (↑ risk of digoxin toxicity);
• Hypercalcemia (↑ risk of toxicity, especially with mild hypokalemia);
• Hypomagnesemia (↑ risk of digoxin toxicity);
• Diuretic use (may cause electrolyte abnormalities including hypokalemia and hypomagnesemia);
• Hypothyroidism;
• Myocardial infarction;
• Renal impairment (dose ↓ required);
• Obesity (base dose on ideal body weight);
• OB:  Monitor neonates for signs/symptoms of digoxin toxicity; monitor levels in mother during pregnancy as levels may fluctuate during pregnancy and post-partum periods; may lead to ↑ risk of arrhythmias during labor and delivery;
• Lactation: Similar concentrations in serum and breast milk result in subtherapeutic levels in infant, use with caution;
• Geri:  Very sensitive to toxic effects; dose adjustments required for age-related ↓ in renal function and body weight.

Adverse Reactions/Side Effects

CV: ARRHYTHMIAS, bradycardia, ECG changes, AV block, SA block

EENT: blurred vision, yellow or green vision

GI: anorexia, nausea, vomiting, diarrhea

Hemat: thrombocytopenia

Metabolic: electrolyte imbalances with acute digoxin toxicity

Neuro: fatigue, headache, weakness.

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Thiazide  and  loop diuretics,  piperacillin/tazobactam,  amphotericin B,  corticosteroids, and excessive use of  laxatives  may cause hypokalemia which may ↑ risk of toxicity.
•  Quinidine  and  ritonavir  may ↑ levels and lead to toxicity; ↓ digoxin dose by 30–50%.
•  Amiodarone  may ↑ levels and lead to toxicity; ↓ digoxin dose by 50%.
•  Cyclosporine,  itraconazole,  mirabegron,  propafenone,  quinine,  spironolactone, and  verapamil  may ↑ levels and lead to toxicity; serum level monitoring/dose ↓ may be required.
• Levels may be ↓ by some  antineoplastics  ( bleomycin,  carmustine,  cyclophosphamide,  cytarabine,  doxorubicin,  methotrexate,  procarbazine,  vincristine ),  activated charcoal,  cholestyramine,  colestipol,  metoclopramide,  penicillamine,  rifampin, or  sulfasalazine.
• In a small percentage (10%) of patients gut bacteria metabolize digoxin to inactive compounds macrolide anti-infectives  ( erythromycin,  azithromycin,  clarithromycin ) and  tetracyclines , by killing these bacteria, will cause ↑ levels and toxicity; dose may need to be ↓ for up to 9 wk.
• Additive bradycardia may occur with  beta blockers,  diltiazem,  verapamil,  clonidine,  ivabradine, and other  antiarrhythmics  ( quinidine,  disopyramide ).
• Concurrent use of  sympathomimetics  may ↑ risk of arrhythmias.
•  Thyroid   hormones  may ↓ therapeutic effects.

Drug-Natural Products:

•  Licorice and stimulant natural products ( aloe ) may ↑ risk of potassium depletion.
•  St. John's wort  may ↓ levels and effect.

Drug-Food:

Concurrent ingestion of a high-fiber meal may ↓ absorption. Administer digoxin 1 hr before or 2 hrs after such a meal.

Route/Dosage

For rapid effect, a larger initial loading/digitalizing dose should be given in several divided doses over 12–24 hr. Maintenance doses are determined for digoxin by renal function. All dosing must be evaluated by individual response. In general, doses required for atrial arrhythmias are higher than those for inotropic effect.

IV IM (Adults): Digitalizing dose– 0.5–1 mg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Children  >10 yr): Digitalizing dose– 8–12 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Children  5–10 yr): Digitalizing dose– 15–30 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Children  2–5 yr): Digitalizing dose– 25–35 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Children  1–24 mo): Digitalizing dose– 30–50 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Infants –full term): 20–30 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

IV IM (Infants –premature): Digitalizing dose– 15–25 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.

PO (Adults): Digitalizing dose– 0.75–1.5 mg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 0.125–0.5 mg/day depending on patient's lean body weight, renal function, and serum level.

PO Geriatric Patients: Initial daily dose should not exceed 0.125 mg.

PO (Children  >10 yr): Digitalizing dose– 10–15 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 2.5–5 mcg/kg given daily as a single dose.

PO (Children  5–10 yr): Digitalizing dose– 20–35 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 5–10 mcg/kg given daily in 2 divided doses.

PO (Children  2–5 yr): Digitalizing dose– 30–40 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 7.5–10 mcg/kg given daily in 2 divided doses.

PO (Children  1–24 mo): Digitalizing dose– 35–60 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 10–15 mcg/kg given daily in 2 divided doses.

PO (Infants –full term): Digitalizing dose– 25–35 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 6–10 mcg/kg given daily in 2 divided doses.

PO (Infants –premature): Digitalizing dose– 20–30 mcg/kg given as 50% of the dose initially and one quarter of the initial dose in each of 2 subsequent doses at 6–12 hr intervals.  Maintenance dose– 5–7.5 mcg/kg given daily in 2 divided doses.

Availability (generic available)

Elixir (lime flavor): 0.05 mg/mL

Cost:

Generic: $42.10/60 mL

Solution for injection: 0.25 mg/mL

Solution for injection (pediatric): 0.1 mg/mL

Tablets: 0.0625 mg, 0.125 mg, 0.25 mg

Cost:

Generic: All strengths $27.75/10

Assessment

• Monitor apical pulse for 1 full min before administering. Withhold dose and notify health care professional if pulse rate is <60 bpm in an adult, <70 bpm in a child, or <90 bpm in an infant. Notify health care professional promptly of any significant changes in rate, rhythm, or quality of pulse.
• Pedi:  Heart rate varies in children depending on age, ask health care professional to specify at what heart rates digoxin should be withheld.
• Monitor BP periodically in patients receiving IV digoxin.
• Monitor ECG during IV administration and 6 hr after each dose. Notify health care professional if bradycardia or new arrhythmias occur.
• Observe IV site for redness or infiltration; extravasation can lead to tissue irritation and sloughing.
• Monitor intake and output ratios and daily weights. Assess for peripheral edema, and auscultate lungs for rales/crackles throughout therapy.
• Before administering initial loading dose, determine whether patient has taken any digoxin in the preceding 2–3 wk.

Lab Test Considerations:

Evaluate serum electrolyte levels (especially potassium, magnesium, and calcium) and renal and hepatic function periodically during therapy. Notify health care professional before giving dose if patient is hypokalemic. Hypokalemia, hypomagnesemia, or hypercalcemia may make the patient more susceptible to digitalis toxicity. Pedi:  Neonates may have falsely elevated serum digoxin concentrations due to a naturally occurring substance chemically similar to digoxin.

Toxicity Overdose:

Therapeutic serum digoxin levels range from 0.5–2 ng/mL. Serum levels may be drawn 6–8 hr after a dose is administered; usually drawn immediately before the next dose. Geri:  Older adults are at increased risk for toxic effects of digoxin (on Beers list) due to age-related decreased renal clearance; may exist even when serum creatinine levels are normal. Digoxin requirements in older adult may change and a formerly therapeutic dose can become toxic.

• Observe for signs and symptoms of toxicity.  In adults and older children,  first symptoms of toxicity usually include abdominal pain, anorexia, nausea, vomiting, visual disturbances, bradycardia, and other arrhythmias.  In infants and small children,  first signs of overdose are usually cardiac arrhythmias. If these appear, withhold drug and notify health care professional immediately.
• If signs of toxicity occur and are not severe, discontinuation of digoxin may be all that is required.
• Correct electrolyte abnormalities, thyroid dysfunction, and concomitant medications. Administer potassium to maintain serum potassium between 4.0 and 5.5 mmol/L. Monitor ECG for evidence of potassium toxicity (peaked T waves).
• Treatment of life-threatening arrhythmias may include administration of digoxin immune Fab  (Digibind) , which binds to the digitalis glycoside molecule in the blood and is excreted by the kidneys.

Potential Diagnoses

• Decreased cardiac output (Indications) 
• Deficient knowledge, related to medication regimen (Patient/Family/Teaching) 

Implementation

• Do not confuse Lanoxin (digoxin) with levothyroxine or naloxone.
• High Alert: Digoxin has a narrow therapeutic range. Medication errors associated with digoxin include miscalculation of pediatric doses and insufficient monitoring of digoxin levels. Have second practitioner independently check original order and dose calculations.

• For rapid digitalization, initial dose is higher than maintenance dose; 50% of total digitalizing dose is given initially. Administer remainder of dose in 25% increments at 4–8 hr intervals.

  • When changing from parenteral to oral dose forms, dose adjustments may be necessary because of pharmacokinetic variations in percentage of digoxin absorbed: 100 mcg (0.1 mg) digoxin injection = 125 mcg (0.125 mg) tablet or 125 mcg (0.125 mg) of elixir.
• PO Administer oral preparations consistently with regard to meals. Tablets can be crushed and administered with food or fluids if patient has difficulty swallowing. Use calibrated measuring device for elixir; calibrated dropper is not accurate for doses of less than 0.2 mL or 10 mcg.
• IM Administer deep into gluteal muscle and massage well to reduce painful local reactions. Do not administer more than 2 mL of digoxin in each IM site. IM administration is not generally recommended.

Patient/Family Teaching

• Instruct patient to take medication as directed, at same time each day. Teach parents or caregivers of infants and children how to accurately measure medication. Take missed doses within 12 hr of scheduled dose or omit. Do not double doses. Consult health care professional if doses for 2 or more days are missed. Do not discontinue medication without consulting health care professional.
• Teach patient to take pulse and to contact health care professional before taking medication if pulse rate is <60 or >100.
• Pedi:  Teach parents or caregivers that changes in heart rate, especially bradycardia, are among the first signs of digoxin toxicity in infants and children. Instruct parents or caregivers in apical heart rate assessment and ask them to notify health care professional if heart rate is outside of range set by health care professional before administering the next scheduled dose.
• Review signs and symptoms of digitalis toxicity with patient and family. Advise patient to notify health care professional immediately if these or symptoms of HF occur. Inform patient that these symptoms may be mistaken for those of colds or flu.
• Instruct patient to keep digoxin tablets in their original container and not to mix in pill boxes with other medications; may look similar to and may be mistaken for other medications.
• Advise patient that sharing of this medication can be dangerous.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products, especially St. John's wort. Advise patient to avoid taking antacids or antidiarrheals within 2 hr of digoxin.
• Advise patient to notify health care professional of this medication regimen before treatment.
• Patients taking digoxin should carry identification describing disease process and medication regimen at all times.
• Geri:  Review fall prevention strategies with older adults and their families.
• Advise female patient to notify health care professional if pregnancy is planned or suspected, may increase risk for low birth weight or preterm birth. Monitor neonates for signs and symptoms of digoxin toxicity (vomiting, cardiac arrhythmias).
• Emphasize the importance of routine follow-up exams to determine effectiveness and to monitor for toxicity.

Evaluation/Desired Outcomes

• Decrease in severity of HF.
• Increase in cardiac output.
• Decrease in ventricular response in atrial tachyarrhythmias.
• Termination of paroxysmal atrial tachycardia.