dofetilide

Therapeutic Classification: antiarrhythmics (class III)

REMS

Maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFL]) in patients with AF/AFL lasting >1 wk and who have been converted to normal sinus rhythm.
Conversion of AF and AFL to normal sinus rhythm.

Blocks cardiac ion channels responsible for transport of potassium.
Increases monophasic action potential duration.
Increases effective refractory period.

Therapeutic effects:

Prevention of recurrent AF/AFL.
Conversion of AF/AFL to normal sinus rhythm.

Absorption: Well absorbed (>90%) following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme; 80% excreted by kidneys via cationic renal secretion, mostly as unchanged drug; 20% excreted as inactive metabolites.

Half-Life: 10 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	within hrs	2–3 hr‡	12–24 hr

‡Steady state levels are achieved after 2–3 days.

Contraindicated in:

Hypersensitivity;
Congenital or acquired prolonged QT syndromes;
Baseline QTc interval >440 msec (500 msec in patients with ventricular conduction abnormalities);
CCr <20 mL/min;
Concurrent use of verapamil, cimetidine, dolutegravir, ketoconazole, itraconazole, trimethoprim, megestrol, prochlorperazine, hydrochlorothiazide, or other QT-interval prolonging drugs;
Lactation: Lactation.

Use Cautiously in:

Underlying electrolyte abnormalities (↑ risk of serious arrhythmias; correct prior to administration);
CCr 20–60 mL/min (↓ dose);
Severe hepatic impairment;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

CV: chest pain, QT interval prolongation, TORSADES DE POINTES

Neuro: dizziness, headache

Drug-drug:

Hydrochlorothiazide, verapamil, cimetidine, ketoconazole, itraconazole, trimethoprim, megestrol, dolutegravir, and prochlorperazine↑ levels and risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
QT interval prolonging drugs may ↑ risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
Amiloride, metformin, and triamterene may ↑ levels; use with caution.
CYP3A4 inhibitors, including macrolides, azole antifungals, protease inhibitors, amiodarone, diltiazem, and nefazodone, may ↑ levels and risk of arrhythmias; concurrent use should be undertaken with caution.
Should not be used concurrently with other class I or III antiarrhythmics due to ↑ risk of arrhythmias.
Hypokalemia or hypomagnesemia from potassium-depleting diuretics↑ the risk of arrhythmias; correct abnormalities prior to administration.
Concurrent use of digoxin may ↑ risk of arrhythmias.

Drug-Food:

Grapefruit juice may ↑ levels; avoid concurrent use.

Dosing should be adjusted according to renal function and assessment of QT interval.
PO (Adults ): Starting dose: 500 mcg twice daily; Maintenance dose: 250 mcg twice daily (not to exceed 500 mcg twice daily).

Renal Impairment

PO (Adults ): CCr 40–60 mL/min: Starting dose: 250 mcg twice daily; Maintenance dose: 125 mcg twice daily. CCr 20–40 mL/min: Starting dose: 125 mcg twice daily; Maintenance dose: 125 mcg once daily.

(Generic available)

Capsules: 125 mcg; 250 mcg; 500 mcg

Monitor ECG continuously during initiation of therapy and for ≥3 days or ≥12 hr after electrical or pharmacological conversion to sinus rhythm, whichever is greater, and then periodically during therapy. Evaluate QTc interval (or QT interval if HR <60 bpm) before starting therapy and every 3 mo during therapy. If QTc interval >440 msec (500 msec in patients with ventricular conduction abnormalities), discontinue dofetilide and monitor patient until QTc interval returns to baseline.
Within 2–3 hr after first dose, evaluate QTc interval (or QT interval if HR <60 bpm). If QTc or QT interval ↑ by >15% compared to baseline or if QTc or QT interval >500 msec (550 msec in patients with ventricular conduction abnormalities), adjust doses as follows: If initial dose was 500 mcg twice daily, change to 250 mcg twice daily; if initial dose was 250 mcg twice daily, change to 125 mcg twice daily; if initial dose was 125 mcg twice daily, change to 125 mcg once daily. Determine QTc or QT interval within 2–3 hr after each subsequent dose for hospital doses 2–5. No further down titration of dose is recommended. Discontinue dofetilide if at any time after 2nd dose is given QTc or QT interval >500 msec (550 msec in patients with ventricular conduction abnormalities).
Assess the patient’s medication history including OTC, Rx, and natural/herbal products, with emphasis on those that interact with dofetilide (see Interactions).

Lab Test Considerations:

Calculate CCr prior to administration to determine dose and every 3 mo during therapy.
- Correct hypokalemia before starting therapy. Maintain serum potassium in normal range during dofetilide therapy.

Dofetilide must be initiated or reinitiated and monitored for ≥3 days in a setting that provides continuous ECG monitoring and has personnel trained in the management of serious ventricular arrhythmias. Due to the potential for life-threatening ventricular arrhythmias, dofetilide is usually used for patients with highly symptomatic AF/AFL.
- Patients with AF should be anticoagulated according to usual protocol prior to electrical or pharmacological cardioversion.
- Make sure patient has an adequate supply of dofetilide prior to discharge to prevent interruption of therapy.
- Patients should not be discharged from the hospital within 12 hr of electrical or pharmacological conversion to normal sinus rhythm.
PO: Administer at the same time each day without regard to food.

Instruct patient to take medication as directed, even if feeling well. If a dose is missed, skip dose; do not double next dose. Take next dose at usual time.
Advise patient to avoid grapefruit juice during therapy; may increase drug levels.
Advise patient to read Medication Guide prior to starting therapy and each Rx refill in case of changes. Emphasize need for adherence with therapy, potential for drug interactions, and need for periodic monitoring to minimize the risk of serious arrhythmias.
Instruct patient or family member on how to take pulse. Advise patient to report changes in HR or rhythm to health care provider.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to inform health care provider of medication regimen prior to treatment or surgery.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other Rx, OTC, or herbal products.
Advise patient to consult health care provider immediately if they faint, become dizzy, or have fast heartbeat. If health care provider is unavailable, instruct patient to go to nearest hospital emergency department, take remaining dofetilide capsules to hospital, and show them to health care provider. If symptoms associated with altered electrolyte balance such as excessive or prolonged diarrhea, sweating, or vomiting or loss of appetite or thirst occur, notify health care provider immediately.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.
Emphasize the importance of routine follow-up exams to monitor progress.

Prevention of recurrent AF/AFL.
Conversion of AF/AFL to normal sinus rhythm.
- If patients do not convert to normal sinus rhythm within 24 hr of initiation of therapy, electrical conversion should be considered.

NDC Code

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5800- Tikosyn
  - 0069-5800-60- 60 CAPSULE in 1 BOTTLE (0069-5800-60)

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5800- Tikosyn
  - 0069-5800-61- 14 CAPSULE in 1 BOTTLE (0069-5800-61)

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5810- Tikosyn
  - 0069-5810-60- 60 CAPSULE in 1 BOTTLE (0069-5810-60)

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5810- Tikosyn
  - 0069-5810-61- 14 CAPSULE in 1 BOTTLE (0069-5810-61)

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5820- Tikosyn
  - 0069-5820-60- 60 CAPSULE in 1 BOTTLE (0069-5820-60)

0069- Pfizer Laboratories Div Pfizer Inc
- 0069-5820- Tikosyn
  - 0069-5820-61- 14 CAPSULE in 1 BOTTLE (0069-5820-61)

0904- Major Pharmaceuticals
- 0904-6681- Dofetilide
  - 0904-6681-08- 40 BLISTER PACK in 1 CARTON (0904-6681-08) / 1 CAPSULE in 1 BLISTER PACK

0904- Major Pharmaceuticals
- 0904-6682- Dofetilide
  - 0904-6682-08- 40 BLISTER PACK in 1 CARTON (0904-6682-08) / 1 CAPSULE in 1 BLISTER PACK

0904- Major Pharmaceuticals
- 0904-6683- Dofetilide
  - 0904-6683-08- 40 BLISTER PACK in 1 CARTON (0904-6683-08) / 1 CAPSULE in 1 BLISTER PACK

0904- Major Pharmaceuticals
- 0904-7522- Dofetilide
  - 0904-7522-08- 40 BLISTER PACK in 1 CARTON (0904-7522-08) / 1 CAPSULE in 1 BLISTER PACK

0904- Major Pharmaceuticals
- 0904-7523- Dofetilide
  - 0904-7523-08- 40 BLISTER PACK in 1 CARTON (0904-7523-08) / 1 CAPSULE in 1 BLISTER PACK

0904- Major Pharmaceuticals
- 0904-7524- Dofetilide
  - 0904-7524-08- 40 BLISTER PACK in 1 CARTON (0904-7524-08) / 1 CAPSULE in 1 BLISTER PACK

14096- Apicore US LLC
- 14096-192-
  - 14096-192-01- 5 kg in 1 DRUM (14096-192-01)

16729- Accord Healthcare, Inc.
- 16729-490- Dofetilide
  - 16729-490-12- 60 CAPSULE in 1 BOTTLE (16729-490-12)

16729- Accord Healthcare, Inc.
- 16729-491- Dofetilide
  - 16729-491-12- 60 CAPSULE in 1 BOTTLE (16729-491-12)

16729- Accord Healthcare, Inc.
- 16729-492- Dofetilide
  - 16729-492-12- 60 CAPSULE in 1 BOTTLE (16729-492-12)

42413- Enaltec Labs Pvt Ltd
- 42413-0170-
  - 42413-0170-1- 1 BAG in 1 CONTAINER (42413-0170-1) / 1 kg in 1 BAG

42794- Sigmapharm Laboratories, LLC
- 42794-044- Dofetilide
  - 42794-044-10- 60 CAPSULE in 1 BOTTLE, PLASTIC (42794-044-10)

42794- Sigmapharm Laboratories, LLC
- 42794-045- Dofetilide
  - 42794-045-10- 60 CAPSULE in 1 BOTTLE, PLASTIC (42794-045-10)

42794- Sigmapharm Laboratories, LLC
- 42794-046- Dofetilide
  - 42794-046-10- 60 CAPSULE in 1 BOTTLE, PLASTIC (42794-046-10)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-061- DOFETILIDE
  - 47335-061-79- 4 BLISTER PACK in 1 CARTON (47335-061-79) / 10 CAPSULE in 1 BLISTER PACK (47335-061-66)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-061- DOFETILIDE
  - 47335-061-86- 60 CAPSULE in 1 BOTTLE (47335-061-86)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-062- DOFETILIDE
  - 47335-062-79- 4 BLISTER PACK in 1 CARTON (47335-062-79) / 10 CAPSULE in 1 BLISTER PACK (47335-062-66)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-062- DOFETILIDE
  - 47335-062-86- 60 CAPSULE in 1 BOTTLE (47335-062-86)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-063- DOFETILIDE
  - 47335-063-79- 4 BLISTER PACK in 1 CARTON (47335-063-79) / 10 CAPSULE in 1 BLISTER PACK (47335-063-66)

47335- Sun Pharmaceutical Industries, Inc.
- 47335-063- DOFETILIDE
  - 47335-063-86- 60 CAPSULE in 1 BOTTLE (47335-063-86)

49812- Veranova, L.P.
- 49812-0261-
  - 49812-0261-1- 1 CONTAINER in 1 CONTAINER (49812-0261-1) / 1 kg in 1 CONTAINER

50137- Veranova, L.P.
- 50137-4245-
  50137-4245-1- 1 kg in 1 CONTAINER (50137-4245-1)

51862- Mayne Pharma Inc.
- 51862-005- Dofetilide
  51862-005-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (51862-005-60)

51862- Mayne Pharma Inc.
- 51862-025- Dofetilide
  - 51862-025-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (51862-025-60)

51862- Mayne Pharma Inc.
- 51862-125- Dofetilide
  - 51862-125-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (51862-125-60)

59651- Aurobindo Pharma Limited
- 59651-038-
  - 59651-038-37- 50 kg in 1 DRUM (59651-038-37)

59651- Aurobindo Pharma Limited
- 59651-118- Dofetilide
  59651-118-05- 500 CAPSULE in 1 BOTTLE (59651-118-05)

59651- Aurobindo Pharma Limited
- 59651-118- Dofetilide
  - 59651-118-60- 60 CAPSULE in 1 BOTTLE (59651-118-60)

59651- Aurobindo Pharma Limited
- 59651-119- Dofetilide
  - 59651-119-05- 500 CAPSULE in 1 BOTTLE (59651-119-05)

59651- Aurobindo Pharma Limited
- 59651-119- Dofetilide
  - 59651-119-60- 60 CAPSULE in 1 BOTTLE (59651-119-60)

59651- Aurobindo Pharma Limited
- 59651-120- Dofetilide
  - 59651-120-05- 500 CAPSULE in 1 BOTTLE (59651-120-05)

59651- Aurobindo Pharma Limited
- 59651-120- Dofetilide
  - 59651-120-60- 60 CAPSULE in 1 BOTTLE (59651-120-60)

63190- Industriale Chimica s.r.l.
- 63190-0670-
  - 63190-0670-3- 30 kg in 1 DRUM (63190-0670-3)

63190- Industriale Chimica s.r.l.
- 63190-0670-
  63190-0670-5- 25 kg in 1 DRUM (63190-0670-5)

63190- Industriale Chimica s.r.l.
- 63190-0680-
  63190-0680-3- 30 kg in 1 DRUM (63190-0680-3)

63190- Industriale Chimica s.r.l.
- 63190-0680-
  63190-0680-5- 5 kg in 1 DRUM (63190-0680-5)

63278- FARMAK, A.S.
- 63278-1079-
  63278-1079-0- 1 kg in 1 DRUM (63278-1079-0)

69452- Bionpharma Inc.
- 69452-131- Dofetilide
  69452-131-17- 60 CAPSULE in 1 BOTTLE (69452-131-17)

69452- Bionpharma Inc.
- 69452-132- Dofetilide
  - 69452-132-17- 60 CAPSULE in 1 BOTTLE (69452-132-17)

69452- Bionpharma Inc.
- 69452-133- Dofetilide
  - 69452-133-17- 60 CAPSULE in 1 BOTTLE (69452-133-17)

69766- MSN Life Sciences Private Limited
- 69766-022-
  - 69766-022-02- 25 kg in 1 DRUM (69766-022-02)

69766- MSN Life Sciences Private Limited
- 69766-022-
  69766-022-04- 20 kg in 1 DRUM (69766-022-04)

72205- Novadoz Pharmaceuticals LLC
- 72205-039- Dofetilide
  72205-039-37- 4 BLISTER PACK in 1 CARTON (72205-039-37) / 10 CAPSULE in 1 BLISTER PACK (72205-039-11)

72205- Novadoz Pharmaceuticals LLC
- 72205-039- Dofetilide
  - 72205-039-60- 60 CAPSULE in 1 BOTTLE (72205-039-60)

72205- Novadoz Pharmaceuticals LLC
- 72205-040- Dofetilide
  - 72205-040-37- 4 BLISTER PACK in 1 CARTON (72205-040-37) / 10 CAPSULE in 1 BLISTER PACK (72205-040-11)

72205- Novadoz Pharmaceuticals LLC
- 72205-040- Dofetilide
  - 72205-040-60- 60 CAPSULE in 1 BOTTLE (72205-040-60)

72205- Novadoz Pharmaceuticals LLC
- 72205-041- Dofetilide
  - 72205-041-37- 4 BLISTER PACK in 1 CARTON (72205-041-37) / 10 CAPSULE in 1 BLISTER PACK (72205-041-11)

72205- Novadoz Pharmaceuticals LLC
- 72205-041- Dofetilide
  - 72205-041-60- 60 CAPSULE in 1 BOTTLE (72205-041-60)

72603- NorthStar RxLLC
- 72603-130- DOFETILIDE
  - 72603-130-01- 60 CAPSULE in 1 BOTTLE (72603-130-01)

72603- NorthStar RxLLC
- 72603-131- DOFETILIDE
  - 72603-131-01- 60 CAPSULE in 1 BOTTLE (72603-131-01)

72603- NorthStar RxLLC
- 72603-132- DOFETILIDE
  - 72603-132-01- 60 CAPSULE in 1 BOTTLE (72603-132-01)

72664- VGYAAN Pharmaceuticals LLC
- 72664-229- Dofetilide
  - 72664-229-60- 60 CAPSULE in 1 BOTTLE (72664-229-60)

72664- VGYAAN Pharmaceuticals LLC
- 72664-230- Dofetilide
  - 72664-230-60- 60 CAPSULE in 1 BOTTLE (72664-230-60)

72664- VGYAAN Pharmaceuticals LLC
- 72664-231- Dofetilide
  - 72664-231-60- 60 CAPSULE in 1 BOTTLE (72664-231-60)

75907- Dr. Reddy's Labratories Inc.
- 75907-054- Dofetilide
  - 75907-054-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (75907-054-60)

75907- Dr. Reddy's Labratories Inc.
- 75907-055- Dofetilide
  - 75907-055-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (75907-055-60)

75907- Dr. Reddy's Labratories Inc.
- 75907-056- Dofetilide
  - 75907-056-60- 60 CAPSULE in 1 BOTTLE, PLASTIC (75907-056-60)

76055- Sionc Pharmaceutical Private Limited
- 76055-0013-
  - 76055-0013-1- 25 kg in 1 DRUM (76055-0013-1)

76282- EXELAN PHARMACEUTICALS, INC.
- 76282-755- Dofetilide
  76282-755-60- 60 CAPSULE in 1 BOTTLE (76282-755-60)

76282- EXELAN PHARMACEUTICALS, INC.
- 76282-756- Dofetilide
  - 76282-756-60- 60 CAPSULE in 1 BOTTLE (76282-756-60)

76282- EXELAN PHARMACEUTICALS, INC.
- 76282-757- Dofetilide
  - 76282-757-60- 60 CAPSULE in 1 BOTTLE (76282-757-60)

84280- The Janz Corporation
- 84280-5125- Dofetilide
  - 84280-5125-6- 60 CAPSULE in 1 BOTTLE (84280-5125-6)

84280- The Janz Corporation
- 84280-5250- Dofetilide
  - 84280-5250-6- 60 CAPSULE in 1 BOTTLE (84280-5250-6)

84280- The Janz Corporation
- 84280-5500- Dofetilide
  - 84280-5500-6- 60 CAPSULE in 1 BOTTLE (84280-5500-6)

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆