ENTRESTO

ENTRESTO- sacubitril and valsartan tablet, film coated
Novartis Pharmaceuticals Corporation

WARNING: FETAL TOXICITY

  • When pregnancy is detected, discontinue ENTRESTO as soon as possible (5.1)
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus (5.1)

1 INDICATIONS AND USAGE

1.1 Adult Heart Failure

ENTRESTO is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

1.2 Pediatric Heart Failure

ENTRESTO is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. ENTRESTO reduces NT-proBNP and is expected to improve cardiovascular outcomes.

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations

ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO allow a washout period of 36 hours between administration of the two drugs [see Contraindications (4) and Drug Interactions (7.1)].

2.2 Adult Heart Failure

The recommended starting dose of ENTRESTO is 49/51 mg orally twice-daily.

Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

2.3 Pediatric Heart Failure

Refer to Table 1 for the recommended dose for pediatric patients aged one year and older. Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient.

Table 1: Recommended Dose Titration
Use of the Oral Suspension recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage and Administration (2.4)]. Doses of 72/78 mg can be achieved using three 24/26 mg tablets [see Dosage Forms and Strengths (3)].
Titration Step Dose (twice daily)
Starting Second Final
Pediatric PatientsLess than 40 kg 1.6 mg/kg 2.3 mg/kg 3.1 mg/kg
Pediatric PatientsAt least 40 kg, less than 50 kg 24/26 mg 49/51 mg 72/78 mg
Pediatric PatientsAt least 50 kg 49/51 mg 72/78 mg 97/103 mg

2.4 Preparation of Oral Suspension

ENTRESTO oral suspension can be substituted at the recommended tablet dosage in patients unable to swallow tablets.

ENTRESTO 800 mg/200 mL oral suspension can be prepared in a concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL). Use ENTRESTO 49/51 mg tablets in the preparation of the suspension.

To make an 800 mg/200 mL (4 mg/mL) oral suspension, transfer eight tablets of ENTRESTO 49/51 mg film-coated tablets into a mortar. Crush the tablets into a fine powder using a pestle. Add 60 mL of Ora-Plus® into the mortar and triturate gently with pestle for 10 minutes, to form a uniform suspension. Add 140 mL of Ora-Sweet® SF into mortar and triturate with pestle for another 10 minutes, to form a uniform suspension. Transfer the entire contents from the mortar into a clean 200 mL amber colored PET or glass bottle. Place a press-in bottle adapter and close the bottle with a child resistant cap.

The oral suspension can be stored for up to 15 days. Do not store above 25°C (77°F) and do not refrigerate. Shake before each use.

* Ora-Sweet SF® and Ora-Plus® are registered trademarks of Paddock Laboratories, Inc.

2.5 Dose Adjustment for Patients Not Taking an ACE inhibitor or ARB or Previously Taking Low Doses of These Agents

In patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents, start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)].

Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension [see Dosage and Administration (2.3, 2.4)].

2.6 Dose Adjustment for Severe Renal Impairment

In adults and pediatric patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2), start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)].

Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension [see Dosage and Administration (2.3, 2.4)].

No starting dose adjustment is needed for mild hepatic impairment.

Use in patients with severe hepatic impairment is not recommended.

2.7 Dose Adjustment for Hepatic Impairment

In adults and pediatric patients with moderate hepatic impairment (Child-Pugh B classification), start ENTRESTO at half the usually recommended starting dose. After initiation, increase the dose to follow the recommended dose escalation thereafter [see Dosage and Administration (2.2, 2.3)].

Note: Initiate pediatric patients weighing 40 to 50 kg who meet this criterion at 0.8 mg/kg twice daily using the oral suspension [see Dosage and Administration (2.3, 2.4)].

No starting dose adjustment is needed for mild or moderate renal impairment.

3 DOSAGE FORMS AND STRENGTHS

ENTRESTO is supplied as unscored, ovaloid, film-coated tablets in the following strengths:

ENTRESTO 24/26 mg, (sacubitril 24 mg and valsartan 26 mg) are violet white and debossed with “NVR” on one side and “LZ” on the other side.

ENTRESTO 49/51 mg, (sacubitril 49 mg and valsartan 51 mg) are pale yellow and debossed with “NVR” on one side and “L1” on the other side.

ENTRESTO 97/103 mg, (sacubitril 97 mg and valsartan 103 mg) are light pink and debossed with “NVR” on one side and “L11” on the other side.

4 CONTRAINDICATIONS

ENTRESTO is contraindicated:

  • in patients with hypersensitivity to any component
  • in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy [see Warnings and Precautions (5.2)]
  • with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions (7.1)]
  • with concomitant use of aliskiren in patients with diabetes [see Drug Interactions (7.1)]
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