Shan Chen, PharmD Candidate; Troy Khusial, PharmD Candidate; Dipen Patel, PharmD Candidate; Satinder Singh, PharmD Candidate; Tatyana Yakubova, PharmD Candidate; Amy Wang, PharmD, BCPS, MBA; Timothy Nguyen, PharmD, BCPS, CCP, FASCP
DisclosuresUS Pharmacist. 2015;40(2):44-48.
The use of digoxin has been limited because the agent has a narrow therapeutic index and requires close monitoring. Digoxin can lead to many AEs and has multiple drug interactions. Despite its limitations, digoxin still has a place in therapy for HF, AF, and numerous off-label uses. It is considered adjunctive therapy, rather than first-line therapy.
US Pharmacist. 2015;40(2):44-48. © 2015 Jobson Publishing
| Dosing | Dosage Adjustment | Target Serum Concentration | Bioavailability | Pharmacokinetics |
|---|---|---|---|---|
| Heart Failure | ||||
| LD: not recommended; MD: 0.125–0.2 mg daily | MD: CrCl >120 mL/min—0.25 mg once daily; CrCl 80–120 mL/min—0.25 mg alternating with 0.125 mg once daily; CrCl 30–80 mL/min—0.125 mg once daily; CrCl <30 mL/min—0.125 mg q48h. Patients >70 y should receive 0.125 mg daily or every other day. Reduce by 50% in ESRD | 0.5–0.9 ng/mL | Oral: 70%; capsule: 90%; elixir: 80%; IV: 100% | Onset of action: IV—15–30 min; po—30–120 min Peak effect: IV— 1–3 h; po—2–6 h |
| Atrial Fibrillation | ||||
| LD: 0.25 mg po/IV q2h (max 1.5 mg/24 h); MD: 0.125–0.375 mg po/IV daily | MD: CrCl >50 mL/min—no adjustment necessary; CrCl 10–50 mL/min—25%-75% of normal daily dosage q36h; CrCl <10 mL/min—10%-25% of normal daily dosage q48h. Continuous RRT: 25%-75% of normal daily dosage q36h | 0.8–1.2 ng/mL | NA | NA |
CrCl: creatinine clearance; ESRD: end-stage renal disease; LD: loading dose; max: maximum; MD: maintenance dose; min: minute; NA: not applicable; RRT: renal replacement therapy.
Source: References 2, 3, 5, 6.
| Precipitant | Effect on Digoxin Concentration | Comments |
|---|---|---|
| Alprazolam | Increase | Elderly patients are especially likely to have elevated serum digoxin concentrations. Possible mechanism: reduced renal clearance of digoxin. Monitor concentrations and observe patient for digoxin toxicity |
| Aluminum salts (aluminum hydroxide, magaldrate) | Decrease | Digoxin absorption is decreased. Give digoxin 2 h before administering aluminum salts |
| Amphotericin B | Increase | Amphotericin B–induced hypokalemia may increase risk of digoxin toxicity |
| Antiarrhythmics (amiodarone, dronedarone, propafenone, quinidine) | Increase | These agents inhibit Pgp, thereby reducing digoxin clearance. Consider reducing digoxin by 30%-50% upon initiating antiarrhythmic |
| Anticholinergics | Increase | Decrease in GI motility may cause increased digoxin absorption |
| Antineoplastics (bleomycin, carmustine, cyclophosphamide, cytarabine, doxorubicin, methotrexate, vincristine) | Decrease | Decreased GI absorption of digoxin may lead to decreased digoxin concentrations. Substitute liquid form or liquid-containing digoxin capsules for tablet form |
| Azole antifungals (itraconazole, ketoconazole) | Increase | Inhibition of digoxin metabolism and clearance responsible for increased digoxin concentrations. Monitoring and possible dosage reductions of digoxin are warranted |
| Beta-blockers | Increase | Digoxin and beta-blockers slow AV conduction and decrease HR, increasing risk of bradycardia. Carvedilol may elevate digoxin concentrations, increasing risk of toxicity. Monitor digoxin concentrations and HR. Consider 25% dosage reduction in children |
| Bile-acid sequestrants | Decrease | These agents bind to digoxin, decreasing GI absorption and enterohepatic recycling. Separate administration of sequestrant and digoxin by as much as possible and adjust digoxin dosage as needed |
| CCBs (diltiazem, nifedipine, verapamil) | Increase | Non-DHP CCBs (e.g., verapamil, diltiazem) in combination may be helpful in controlling AF, but additive effects on AV-node conduction may result in heart block. Diltiazem, nisoldipine, and verapamil may increase digoxin concentrations by inhibiting renal and/or extrarenal digoxin clearance. Monitor serum digoxin concentrations closely and adjust dosage accordingly |
| Corticosteroids | Increase | Electrolyte disturbances caused by corticosteroids may predispose patient to digitalis-induced arrhythmia. Monitor potassium and magnesium, supplementing if necessary |
| Loop diuretics (furosemide) | Increase | Diuretics may cause electrolyte disturbances and predispose patient to digitalis-induced arrhythmia. Monitor potassium and magnesium, supplementing if necessary |
| Macrolide antibiotics (azithromycin, clarithromycin, erythromycin) | Increase | Antibiotics decrease inactivation of digoxin by bacterial metabolism in lower intestine, increasing digoxin's bioavailability. Effect may persist several wk after antibiotic stopped |
| Metoclopramide | Decrease | Increase in GI motility may cause decreased digoxin absorption |
| Potassium-sparing diuretics (amiloride, spironolactone) | Increase/decrease | May decrease positive inotropic effects of digoxin, and digoxin serum concentrations may be elevated. Spironolactone interferes with digoxin assay, resulting in falsely elevated concentrations. Monitor patient closely and watch for potentially false digoxin concentrations |
| Quinine | Increase | Concomitant use causes decreased biliary clearance of digoxin, which increases digoxin serum concentration and risk of toxicity |
| Rifamycins (rifampin) | Decrease | May increase digoxin clearance, leading to decreased serum digoxin concentrations |
| SSRIs (fluoxetine, paroxetine) | Increase | May displace digoxin from protein binding, resulting in increased serum digoxin concentrations |
| St. John's wort | Decrease | This Pgp inducer speeds up digoxin metabolism, leading to decreased digoxin concentrations |
| Sucralfate | Decrease | Concomitant use may result in decreased digoxin concentrations and efficacy. Separate administration by ≥2 h |
| Sympathomimetics (dopamine, epinephrine) | Increase | Coadministration may cause increased risk of cardiac arrhythmias. Mechanism unknown |
| Telmisartan | Increase | Coadministration leads to ~50% increase in peak digoxin levels and 20% increase in trough digoxin levels, which may cause toxicity |
| Tetracyclines | Increase | Tetracycline may alter GI flora, allowing for increased digoxin absorption |
| Thiazide diuretics (hydrochlorothiazide) | Increase | Diuretic-induced electrolyte disturbances may predispose patients to digoxin toxicity. Monitor potassium and magnesium, supplementing if needed |
| Thioamines (methimazole, propylthiouracil) | Increase | Hyperthyroid patients who become euthyroid have decreased digoxin clearance, leading to increased serum digoxin concentrations |
| Thyroid hormone (levothyroxine) | Decrease | Hypothyroid patients who become euthyroid develop increased digoxin clearance, resulting in decreased serum digoxin concentrations |
| Vasopressin receptor antagonists (conivaptan) | Increase | Conivaptan decreases digoxin clearance; this may increase serum digoxin concentrations, causing toxicity |
AF: atrial fibrillation; AV: atrioventricular; CCB: calcium channel blocker; DHP: dihydropyridine; GI: gastrointestinal; HR: heart rate; Pgp: P-glycoprotein; SSRI: selective serotonin reuptake inhibitor.
Source: References 2, 3.
| Noncardiac Adverse Effects Anorexia Nausea/vomiting Abdominal pain Visual disturbances: halos, photophobia, red-green or yellow-green vision Fatigue, weakness Confusion, delirium, psychosis |
Cardiac Adverse Effects Ventricular arrhythmias Atrioventricular block Atrial arrhythmias Sinus bradycardia |
Source: References 2, 3.
Shan Chen, PharmD Candidate, Troy Khusial, PharmD Candidate, Dipen Patel, PharmD Candidate and Satinder Singh, PharmD Candidate
Tatyana Yakubova, PharmD Candidate
LIU Pharmacy, Brooklyn, New York
Amy Wang, PharmD, BCPS, MBA
Assistant Professor of Pharmacy Practice LIU Pharmacy, Brooklyn, New York Clinical Pharmacotherapy Specialist, Cardiology Lenox Hill Hospital, New York, New York
Timothy Nguyen, PharmD, BCPS, CCP, FASCP
Associate Professor of Pharmacy Practice LIU Pharmacy, Brooklyn, New York Adjunct Clinical Pharmacology Professor Division of Physician Assistant Studies, LIU, Brooklyn, New York Adjunct Clinical Pharmacology Professor School of Nursing, Saint Peter's University, Englewood Cliffs, New Jersey
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