ivabradine

Therapeutic Classification: heart failure agents

Pharmacologic Classification: hyperpolarization-activated cyclic nucleotide-gated channel blockers

REMS

To decrease the need for hospitalization due to worsening HF in patients with stable but symptomatic chronic HF (ejection fraction <35%, sinus rhythm ≥70 bpm, receiving highest tolerated doses of beta blockers or are unable to tolerate beta blockers).
Stable symptomatic HF due to dilated cardiomyopathy in pediatric patients ≥6 mo old who are in sinus rhythm with an elevated heart rate.

Inhibits the cardiac pacemaker I_f-current by acting as a hyperpolarization-activated cyclic nucleoside-gated channel blocker, resulting in ↓ spontaneous pacemaker activity of sinus node. Decreases heart rate without affecting contractility or ventricular repolarization.

Therapeutic effects:

Lowering of heart rate with reduced need for hospitalization in patients with HF.

Absorption: 40% absorbed following oral administration (undergoes first-pass metabolism); food delays absorption and ↑ levels.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized, primarily by the CYP3A4 enzyme system. The major metabolite is pharmacologically active and has the same potency as ivabradine. Metabolites excreted equally in urine and feces; 4% excreted unchanged in urine.

Half-Life: 6 hr.

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	12 hr

Contraindicated in:

Acute decompensated HF;
Clinically significant hypotension;
Sick sinus syndrome, sinoatrial block, or 2nd- or 3rd-degree heart block (unless a functioning demand pacemaker is in place, ↑ risk of bradycardia);
Clinically significant bradycardia;
Severe hepatic impairment;
Pacemaker dependence;
Concurrent use of strong CYP3A4 inhibitors;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Rep: Women of reproductive potential;
Pedi: Children <6 mo (safety and effectiveness not established).

CV: atrial fibrillation, bradycardia, heart block, hypertension, QT interval prolongation, sinus arrest, TORSADE DE POINTES

EENT: phosphenes (luminous phenomena)

Drug-drug:

Strong CYP3A4 inhibitors, including azole antifungals, macolides, protease inhibitors, and nefazodone, may ↑ levels; concurrent use contraindicated.
Moderate CYP3A4 inhibitors, including diltiazem and verapamil, may ↑ levels and risk of bradycardia; avoid concurrent use.
CYP3A4 inducers, including barbiturates, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
↑risk of bradycardia with negative chronotropes, including amiodarone, beta blockers, digoxin, and clonidine; monitor heart rate.
QT-interval prolonging drugs may ↑ risk of QT interval prolongation and torsade de pointes.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

PO (Adults ): 5 mg twice daily for 2 wk; dose may then be adjusted based on HR; not to exceed 7.5 mg twice daily; Patients with conduction defects or bradycardia: 2.5 mg twice daily initially.
PO (Children ≥6 mo and ≥40 kg): Tablets: 2.5 mg twice daily; adjust dose at 2-wk intervals by 2.5 mg twice daily to achieve HR ↓ of ≥20%; not to exceed 7.5 mg twice daily.
PO (Children ≥6 mo and <40 kg): Oral solution: 0.05 mg/kg twice daily; adjust dose at 2-wk intervals by 0.05 mg/kg twice daily to achieve a HR ↓ of ≥20%; not to exceed 0.2 mg/kg twice daily (6 mo–<1 yr) or 0.3 mg/kg twice daily (≥1 yr) up to max of 7.5 mg twice daily.

(Generic available)

Tablets: 5 mg; 7.5 mg
Oral solution: 1 mg/mL

Assess HR before, after 2 wk, and periodically during therapy. Adjust dose for a resting HR of 50–60 bpm. If HR >60 bpm,↑ dose by 2.5 mg twice daily, up to 7.5 mg twice daily. If HR 50–60 bpm, maintain dose. If HR <50 bpm or signs and symptoms of bradycardia (dizziness, fatigue, hypotension) occur,↓ dose by 2.5 mg twice daily; if current dose is 2.5 mg given twice daily, discontinue ivabradine.
Monitor ECG periodically during therapy. May cause atrial fibrillation and torsade de pointes. If atrial fibrillation occurs, discontinue ivabradine.

PO: Administer twice daily with meals.
- For oral solution, empty entire contents of ampule(s) into a medication cup. With a calibrated oral syringe, measure prescribed dose and administer orally. Discard unused oral solution; do not store or reuse. Solution is colorless.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. If dose is missed or patient spits out drug, omit dose; do not double doses.
Advise 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 medications, especially St. John’s wort.
Advise patient to avoid taking grapefruit juice during therapy; may ↑ risk of side effects.
Advise patient to notify health care provider if signs and symptoms of irregular or rapid heartbeat (heart pounding or racing, chest pressure, worsened shortness of breath, near fainting or fainting) or slower than normal HR (dizziness, fatigue, lack of energy) occur. In young children, signs and symptoms of slow HR include poor feeding, difficulty breathing, and turning blue.
Inform patient that ivabradine may cause phosphenes or luminous phenomena, a transiently enhanced brightness in a limited area of the visual field, halos, image decomposition, colored bright lights, or multiple images. Phosphenes are usually triggered by sudden variations in light intensity. Usually begin within 1st 2 mo of therapy; may occur repeatedly of mild to moderate intensity and resolve after therapy is discontinued.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and to avoid breastfeeding during therapy. Advise patient to notify health care provider immediately if pregnancy is suspected.

Lowering of heart rate with reduced need for hospitalization in patients with HF.

NDC Code

31722- Camber Pharmaceuticals, Inc.
- 31722-053- Ivabradine
  - 31722-053-60- 60 TABLET, FILM COATED in 1 BOTTLE (31722-053-60)

31722- Camber Pharmaceuticals, Inc.
- 31722-054- Ivabradine
  - 31722-054-60- 60 TABLET, FILM COATED in 1 BOTTLE (31722-054-60)

46708- Alembic Pharmaceuticals Limited
- 46708-679- Ivabradine
  - 46708-679-45- 180 TABLET, FILM COATED in 1 BOTTLE (46708-679-45)

46708- Alembic Pharmaceuticals Limited
- 46708-679- Ivabradine
  - 46708-679-60- 60 TABLET, FILM COATED in 1 BOTTLE (46708-679-60)

46708- Alembic Pharmaceuticals Limited
- 46708-680- Ivabradine
  - 46708-680-45- 180 TABLET, FILM COATED in 1 BOTTLE (46708-680-45)

46708- Alembic Pharmaceuticals Limited
- 46708-680- Ivabradine
  - 46708-680-60- 60 TABLET, FILM COATED in 1 BOTTLE (46708-680-60)

50742- Ingenus Pharmaceuticals, LLC
- 50742-362- IVABRADINE
  - 50742-362-60- 60 TABLET, FILM COATED in 1 BOTTLE (50742-362-60)

50742- Ingenus Pharmaceuticals, LLC
- 50742-363- IVABRADINE
  - 50742-363-60- 60 TABLET, FILM COATED in 1 BOTTLE (50742-363-60)

51407- Golden State Medical Supply, Inc.
- 51407-592- IVABRADINE
  - 51407-592-60- 60 TABLET, FILM COATED in 1 BOTTLE (51407-592-60)

51407- Golden State Medical Supply, Inc.
- 51407-593- IVABRADINE
  - 51407-593-60- 60 TABLET, FILM COATED in 1 BOTTLE (51407-593-60)

54752- Urquima, S.A.
- 54752-0020-
  - 54752-0020-1- 15 kg in 1 DRUM (54752-0020-1)

55513- Amgen Inc
- 55513-800- Corlanor
  - 55513-800-60- 60 TABLET, FILM COATED in 1 BOTTLE (55513-800-60)

55513- Amgen Inc
- 55513-800- Corlanor
  - 55513-800-99- 14 TABLET, FILM COATED in 1 BOTTLE (55513-800-99)

55513- Amgen Inc
- 55513-810- Corlanor
  - 55513-810-60- 60 TABLET, FILM COATED in 1 BOTTLE (55513-810-60)

55513- Amgen Inc
- 55513-813- Corlanor
  - 55513-813-28- 28 AMPULE in 1 CARTON (55513-813-28) / 5 mL in 1 AMPULE (55513-813-01)

59285- Optimus Drugs Private Limited
- 59285-020-
  - 59285-020-01- 50 kg in 1 DRUM (59285-020-01)

60687- American Health Packaging
- 60687-862- Ivabradine
  - 60687-862-21- 30 BLISTER PACK in 1 CARTON (60687-862-21) / 1 TABLET, FILM COATED in 1 BLISTER PACK (60687-862-11)

62332- Alembic Pharmaceuticals Inc.
- 62332-679- Ivabradine
  - 62332-679-45- 180 TABLET, FILM COATED in 1 BOTTLE (62332-679-45)

62332- Alembic Pharmaceuticals Inc.
- 62332-679- Ivabradine
  - 62332-679-60- 60 TABLET, FILM COATED in 1 BOTTLE (62332-679-60)

62332- Alembic Pharmaceuticals Inc.
- 62332-680- Ivabradine
  - 62332-680-45- 180 TABLET, FILM COATED in 1 BOTTLE (62332-680-45)

62332- Alembic Pharmaceuticals Inc.
- 62332-680- Ivabradine
  - 62332-680-60- 60 TABLET, FILM COATED in 1 BOTTLE (62332-680-60)

63552- Patheon Manufacturing Services LLC
- 63552-044-
  - 63552-044-01- 216 BOTTLE, PLASTIC in 1 CASE (63552-044-01) / 14 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

63552- Patheon Manufacturing Services LLC
- 63552-044-
  63552-044-02- 216 BOTTLE, PLASTIC in 1 CASE (63552-044-02) / 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

63552- Patheon Manufacturing Services LLC
- 63552-044-
  63552-044-03- 216 BOTTLE, PLASTIC in 1 CASE (63552-044-03) / 180 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

63552- Patheon Manufacturing Services LLC
- 63552-045-
  63552-045-01- 216 BOTTLE, PLASTIC in 1 CASE (63552-045-01) / 60 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

63552- Patheon Manufacturing Services LLC
- 63552-045-
  63552-045-02- 216 BOTTLE, PLASTIC in 1 CASE (63552-045-02) / 180 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

65977- Hetero Drugs Limited
- 65977-0098-
  65977-0098-1- 5 kg in 1 DRUM (65977-0098-1)

69452- Bionpharma Inc.
- 69452-190- ivabradine
  69452-190-17- 60 TABLET, FILM COATED in 1 BOTTLE (69452-190-17)

69452- Bionpharma Inc.
- 69452-190- ivabradine
  - 69452-190-30- 500 TABLET, FILM COATED in 1 BOTTLE (69452-190-30)

69452- Bionpharma Inc.
- 69452-191- ivabradine
  - 69452-191-17- 60 TABLET, FILM COATED in 1 BOTTLE (69452-191-17)

69452- Bionpharma Inc.
- 69452-191- ivabradine
  - 69452-191-30- 500 TABLET, FILM COATED in 1 BOTTLE (69452-191-30)

70710- Zydus Pharmaceuticals USA Inc.
- 70710-1471- ivabradine
  - 70710-1471-6- 60 TABLET in 1 BOTTLE (70710-1471-6)

70710- Zydus Pharmaceuticals USA Inc.
- 70710-1471- ivabradine
  - 70710-1471-8- 180 TABLET in 1 BOTTLE (70710-1471-8)

70710- Zydus Pharmaceuticals USA Inc.
- 70710-1472- ivabradine
  - 70710-1472-6- 60 TABLET in 1 BOTTLE (70710-1472-6)

70710- Zydus Pharmaceuticals USA Inc.
- 70710-1472- ivabradine
  - 70710-1472-8- 180 TABLET in 1 BOTTLE (70710-1472-8)

70771- Zydus Lifesciences Limited
- 70771-1863- ivabradine
  - 70771-1863-6- 60 TABLET in 1 BOTTLE (70771-1863-6)

70771- Zydus Lifesciences Limited
- 70771-1863- ivabradine
  - 70771-1863-8- 180 TABLET in 1 BOTTLE (70771-1863-8)

70771- Zydus Lifesciences Limited
- 70771-1864- ivabradine
  - 70771-1864-6- 60 TABLET in 1 BOTTLE (70771-1864-6)

70771- Zydus Lifesciences Limited
- 70771-1864- ivabradine
  - 70771-1864-8- 180 TABLET in 1 BOTTLE (70771-1864-8)

71666- Maithri Laboratories Private Limited
- 71666-003-
  - 71666-003-01- 50 kg in 1 DRUM (71666-003-01)

71666- Maithri Laboratories Private Limited
- 71666-003-
  71666-003-04- 10 kg in 1 DRUM (71666-003-04)

72205- Novadoz Pharmaceuticals LLC
- 72205-336- Ivabradine
  72205-336-18- 180 TABLET, FILM COATED in 1 BOTTLE (72205-336-18)

72205- Novadoz Pharmaceuticals LLC
- 72205-336- Ivabradine
  - 72205-336-60- 60 TABLET, FILM COATED in 1 BOTTLE (72205-336-60)

72205- Novadoz Pharmaceuticals LLC
- 72205-337- Ivabradine
  - 72205-337-18- 180 TABLET, FILM COATED in 1 BOTTLE (72205-337-18)

72205- Novadoz Pharmaceuticals LLC
- 72205-337- Ivabradine
  - 72205-337-60- 60 TABLET, FILM COATED in 1 BOTTLE (72205-337-60)

75852- ORIL Industrie
- 75852-816-
  - 75852-816-44- 1 BAG in 1 DRUM (75852-816-44) / 10.78 kg in 1 BAG

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