Entresto Dosage

Generic name: SACUBITRIL 24mg, VALSARTAN 26mg
Dosage form: tablet, film coated
Drug class: Angiotensin receptor blockers and neprilysin inhibitors

Medically reviewed by Drugs.com. Last updated on Apr 12, 2024.

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

For the recommended dosage for pediatric patients aged 1 year and older, refer to Table 1 if using the tablets, or Table 2 if using the oral pellets.

Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient.

Table 1: Recommended Dose and Titration for Pediatric Patients Using Tablets
†Use of the oral suspension or oral pellets (see Table 2) is recommended in these patients. Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan [see Dosage and Administration (2.4, 2.5)]. ‡Doses of 72 mg/78 mg can be achieved using three 24 mg/26 mg tablets [see Dosage Forms and Strengths (3)].
	Titration Step Dose (twice daily)
Weight (kg)	Starting	Second	Final
Less than 40 kg†	1.6 mg/kg	2.3 mg/kg	3.1 mg/kg
At least 40 kg, less than 50 kg	24 mg/26 mg	49 mg/51 mg	72 mg/78 mg‡
At least 50 kg	49 mg/51 mg	72 mg/78 mg‡	97 mg/103 mg

Table 2: Recommended Dose and Titration for Pediatric Patients using ENTRESTO SPRINKLE†
†When using capsules, more than one capsule may be needed to achieve recommended doses. Oral pellets are contained within each capsule. Use the entire contents of the capsules to achieve the dose. ‡Recommended mg/kg doses are of the combined amount of sacubitril and valsartan [see Dosage and administration (2.4)]. *For patients 50 kg or more, see Table 1.
	Titration Step Dose (twice daily)
Weight (kg)*	Starting	Second	Final
Less than 13 (use oral suspension‡)	1.6 mg/kg	2.3 mg/kg	3.1 mg/kg
13 to less than 19	12 mg/12 mg (Two 6 mg/6 mg capsules)	18 mg/18 mg (Three 6 mg/6 mg capsules)	24 mg/24 mg (Four 6 mg/6 mg capsules)
19 to less than 26	18 mg/18 mg (Three 6 mg/6 mg capsules)	24 mg/24 mg (Four 6 mg/6 mg capsules)	30 mg/32 mg (Two 15 mg/16 mg capsules)
26 to less than 34	24 mg/24 mg (Four 6 mg/6 mg capsules)	30 mg/32 mg (Two 15 mg/16 mg capsules)	45 mg/48 mg (Three 15 mg/16 mg capsules)
34 to less than 50*	30 mg/32 mg (Two 15 mg/16 mg capsules)	45 mg/48 mg (Three 15 mg/16 mg capsules)	60 mg/64 mg (Four 15 mg/16 mg capsules)

2.4 Preparation of Oral Suspension Using Tablets

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 Preparation and Administration of Oral Pellets

ENTRESTO SPRINKLE are oral pellets contained within capsules. Do not swallow the capsules. Do not chew or crush the oral pellets.

ENTRESTO SPRINKLE can also be substituted in patients unable to swallow tablets.

Use the entire contents of the capsules to achieve the dose.

To administer ENTRESTO oral pellets, open the capsule and sprinkle the full content onto 1 to 2 teaspoons of soft food. Consume the food containing the oral pellets immediately after adding them. Empty capsule shells must be discarded after use and not swallowed. Do not administer ENTRESTO oral pellets via nasogastric, gastrostomy, or other enteral tubes because it may cause obstruction of enteral tubes.

2.6 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 every 2 to 4 weeks in adults and every 2 weeks in pediatric patients 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 or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)].

2.7 Dose Adjustment for Severe Renal Impairment

In adults and pediatric patients with severe renal impairment estimated glomerular filtration rate (eGFR less than 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 or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)].

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

2.8 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 or oral pellets [see Dosage and Administration (2.3, 2.4, 2.5)].

No starting dose adjustment is needed for mild hepatic impairment.

Use in patients with severe hepatic impairment is not recommended.