Entresto Tablet

Introduction

Sacubitril/valsartan is a combination medication used to treat heart failure with reduced ejection fraction (HFrEF). This fixed-dose combination includes sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker (ARB). The combination aims to enhance the therapeutic effects on heart failure by addressing multiple pathways involved in the condition.

Uses

Sacubitril/valsartan is primarily used for:

Managing heart failure with reduced ejection fraction (HFrEF) to improve symptoms, reduce hospitalization, and enhance survival.
Providing a treatment option for patients who have not achieved adequate control of heart failure symptoms with other therapies.

Brand Name	Entresto
Type	Tablet
Weight	49 mg+51 mg
Generic	Sacubitril + Valsartan
Manufacturer	Novartis (Bangladesh) Ltd.
Available in	English বাংলা

Mechanism of Action

The combination works through two mechanisms:

Sacubitril inhibits neprilysin, an enzyme responsible for breaking down natriuretic peptides, bradykinin, and angiotensin II. This leads to increased levels of these peptides, which help reduce blood pressure and improve heart function.
Valsartan blocks the angiotensin II type 1 receptor, which helps decrease blood pressure, reduce fluid overload, and mitigate the adverse effects of angiotensin II on the heart and blood vessels.

How Long Does It Take to Work?

The onset of therapeutic effects is typically seen within 1 to 2 weeks of starting treatment, with the maximum benefit usually observed within 4 to 6 weeks. The full benefits in terms of symptom relief and functional improvement may take several months.

Absorption

Sacubitril/valsartan is well absorbed after oral administration. The absorption of sacubitril is rapid, while valsartan reaches peak plasma concentrations in about 2 to 4 hours. Food does not significantly affect the absorption of valsartan.

Route of Elimination

Both sacubitril and valsartan are eliminated primarily through the liver. Sacubitril is metabolized to its active metabolite, LBQ657, which has a similar therapeutic effect. Both sacubitril and valsartan are excreted in the urine and feces.

Dosage

Adult Heart Failure: The recommended starting dose is 49/51 mg orally twice daily. Double the dose after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Reduce the starting dose to 24/26 mg twice daily for:

Patients not currently taking an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents.
Patients with severe renal impairment.
Patients with moderate hepatic impairment.

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.

Recommended Dose Titration-

Pediatric Patients Less than 40 kg:

Starting: 1.6 mg/kg
Second: 2.3 mg/kg
Final: 3.1 mg/kg

Pediatric Patients At least 40 kg, less than 50 kg:

Starting: 24/26 mg
Second: 49/51 mg
Final: 49/51 mg

Pediatric Patients At least 50 kg:

Starting: 49/51 mg
Second: 72/78 mg
Final: 97/103 mg

The dosage of sacubitril/valsartan is individualized based on the patient's condition, kidney function, and other medications. Typical starting doses are:

Initial dose: 49/51 mg twice daily.
Maintenance dose: 97/103 mg twice daily, adjusted based on clinical response and tolerability.

The dosage may be adjusted based on renal function and concurrent medications.

Administration

Sacubitril/valsartan is administered orally in the form of tablets. It should be taken at the same time each day, with or without food, and the prescribed dosage should be followed closely.

Side Effects

Common side effects include:

Dizziness
Hyperkalemia (elevated potassium levels)
Low blood pressure (hypotension)
Cough
Fatigue

Serious side effects may include:

Angioedema (swelling of the deeper layers of the skin)
Severe hypotension
Renal impairment

Toxicity

Symptoms of toxicity may include severe hypotension, hyperkalemia, and significant renal impairment. In cases of overdose, symptomatic treatment and supportive care are recommended.

Precautions

Precautions include:

Monitoring renal function and potassium levels regularly.
Assessing blood pressure before initiating treatment and during therapy.
Using with caution in patients with a history of angioedema or those at risk of hypotension.

Interaction

Sacubitril/valsartan may interact with:

Potassium-sparing diuretics and potassium supplements, increasing the risk of hyperkalemia.
Other antihypertensive agents, which may enhance the blood pressure-lowering effects.
Nonsteroidal anti-inflammatory drugs (NSAIDs), which may reduce the antihypertensive effect and increase the risk of renal impairment.

Consult a healthcare provider for a detailed list of potential interactions.

Disease Interaction

Use with caution in:

Patients with severe renal impairment.
Patients with a history of angioedema.
Patients with liver dysfunction, as dose adjustments may be required.

Drug Interaction

Drug interactions may occur with:

Diuretics and other antihypertensives.
ACE inhibitors and ARBs.
Drugs affecting renal function.

Food Interactions

Food does not significantly impact the absorption of sacubitril/valsartan, but it is recommended to take the medication consistently with or without food to ensure stable drug levels.

Pregnancy Use

Sacubitril/valsartan is contraindicated during pregnancy. It is categorized as Category D, indicating that it may cause harm to the fetus based on human studies. Alternative treatments should be considered for pregnant patients.

Lactation Use

It is not known if sacubitril/valsartan is excreted in breast milk. Due to the potential risk to a nursing infant, it is recommended to either discontinue breastfeeding or avoid the use of this medication while breastfeeding.

Acute Overdose

In the event of an acute overdose, symptoms may include severe hypotension, hyperkalemia, and renal impairment. Treatment should be symptomatic and supportive, including the use of intravenous fluids and monitoring of electrolytes and renal function.

Contraindication

Sacubitril/valsartan is contraindicated in:

Patients with a history of angioedema related to previous ACE inhibitor or ARB therapy.
Pregnant women.
Patients with severe renal impairment not on dialysis.

Use Direction

Follow the prescribed dosage instructions carefully. Take the tablets orally, preferably at the same time each day, with or without food.

Storage Conditions

Store sacubitril/valsartan at room temperature, away from moisture and direct sunlight. Keep out of reach of children and follow any additional storage instructions provided with the medication.

Volume of Distribution

The volume of distribution for sacubitril and valsartan varies, with values indicating wide distribution throughout the body tissues.

Half Life

The elimination half-life of sacubitril is approximately 1.4 hours, while its active metabolite, LBQ657, has a half-life of about 11 hours. Valsartan has a half-life of about 9 hours.

Clearance

Sacubitril and valsartan are primarily cleared through hepatic metabolism and renal excretion. The clearance rates can vary based on liver function and other individual factors.

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