Comprehensive Guide to Sacubitril/Valsartan: Uses, Dosage, Side Effects, and More

1. What is Sacubitril/Valsartan?

2. Overview of Sacubitril/Valsartan

Generic Name

Sacubitril/Valsartan

Brand Name

Entresto, generics

Drug Group

Angiotensin receptor-neprilysin inhibitor (ARNI, cardiovascular)

Commonly Used For

This medication is used to:

• Treat heart failure with reduced ejection fraction (HFrEF).
• Reduce hospitalizations in heart failure patients.
• Improve survival rates in HFrEF.

Key Characteristics

• Form: Oral tablets (24/26 mg, 49/51 mg, 97/103 mg of sacubitril/valsartan) (detailed in Dosage section).
• Mechanism: Inhibits neprilysin to increase natriuretic peptides and blocks AT1 receptors, reducing cardiac stress.
• Approval: FDA-approved (2015 for Entresto) and EMA-approved for HFrEF.

3. Indications and Uses of Sacubitril/Valsartan

Sacubitril/Valsartan is indicated for cardiovascular conditions, leveraging its dual mechanism to improve heart function and outcomes:

• Heart Failure with Reduced Ejection Fraction (HFrEF): Treats HFrEF (NYHA Class II-IV) in adults, reducing morbidity and mortality, supported by the PARADIGM-HF trial, per American Heart Association (AHA) guidelines.
• Heart Failure with Preserved Ejection Fraction (HFpEF): Investigated for HFpEF, showing benefits in reducing hospitalizations, with emerging data from the PARAGON-HF trial, under cardiology review.
• Post-Myocardial Infarction (MI) Heart Failure: Used off-label to manage HFrEF following MI, improving ventricular remodeling, supported by cardiology research.
• Hypertension with Heart Failure Risk: Employed off-label to control blood pressure in patients with hypertension and early heart failure signs, enhancing cardiovascular protection, per hypertension studies.
• Chronic Kidney Disease (CKD) in HFrEF: Explored off-label to slow CKD progression in HFrEF patients, reducing albuminuria, with nephrology evidence.
• Diastolic Dysfunction: Investigated off-label for diastolic heart failure, improving relaxation and filling pressures, with data from echocardiography research.
• Cardiomyopathy: Used off-label in non-ischemic cardiomyopathy to reduce symptoms and hospitalizations, supported by cardiac imaging studies.
• Pulmonary Hypertension Secondary to Left Heart Disease: Managed off-label to alleviate pulmonary pressures in HFrEF-related pulmonary hypertension, with pulmonology data.
• Post-Cardiac Surgery Recovery: Employed off-label to support heart function post-coronary artery bypass grafting (CABG) or valve surgery, improving recovery, noted in surgical cardiology reports.

Note: This drug requires monitoring for kidney function and blood pressure; consult a healthcare provider for initiation and adjustments.

4. Dosage of Sacubitril/Valsartan

Important Note: The dosage of this ARNI must be prescribed by a healthcare provider. Dosing varies by patient tolerance and prior therapy, with gradual titration based on clinical evaluation.

Dosage for Adults

• Heart Failure with Reduced Ejection Fraction (HFrEF):
  • Initial: 24/26 mg twice daily for 2–4 weeks, with or without food.
  • Titration: Increase to 49/51 mg twice daily for 2–4 weeks, then to 97/103 mg twice daily if tolerated, maximum 97/103 mg twice daily.
• Switch from ACE Inhibitors/ARBs:
  • Discontinue ACEi/ARB for 36 hours, then start at 24/26 mg twice daily, titrating as above.

Dosage for Children

• 1–17 years (weight-based, HFrEF):
  • 0.8 mg/kg of sacubitril component twice daily, up to a maximum of 97/103 mg based on weight and tolerance, under pediatric cardiologist supervision.
  • Not recommended under 1 year.

Dosage for Pregnant Women

• Pregnancy Category D: Contraindicated due to fetal toxicity (angiotensin II blockade); use alternatives. Consult an obstetrician if exposed.

Dosage Adjustments

• Renal Impairment: No adjustment needed if eGFR ≥30 mL/min/1.73 m²; avoid if <30 mL/min/1.73 m².
• Hepatic Impairment:
  • Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Maximum 49/51 mg twice daily; severe (Child-Pugh C): Avoid.
• Elderly: Start with 24/26 mg twice daily; titrate cautiously to 97/103 mg if tolerated.
• Concomitant Medications: Adjust if combined with potassium-sparing diuretics or NSAIDs, increasing hyperkalemia risk.

Additional Considerations

• Take this active ingredient twice daily with or without food, using water.
• Monitor blood pressure and kidney function during titration.

5. How to Use Sacubitril/Valsartan

• Administration:
  • Swallow tablets whole with a glass of water, with or without food; avoid crushing or chewing.
  • Take at consistent times daily (e.g., morning and evening) for adherence.
• Timing: Use twice daily, adjusting based on tolerance and blood pressure response.
• Monitoring: Watch for dizziness, swelling, or signs of kidney issues (e.g., reduced urine output).
• Additional Tips:
  • Store at 20–25°C (68–77°F), protecting from moisture and heat.
  • Keep out of reach of children due to toxicity risk.
  • Report severe hypotension, confusion, or signs of angioedema immediately.

6. Contraindications for Sacubitril/Valsartan

This drug is contraindicated in:

• Hypersensitivity: Patients with a known allergy to Sacubitril, Valsartan, or ARNI components.
• Severe Renal Impairment: Contraindicated if eGFR <30 mL/min/1.73 m².
• Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C.
• Concurrent Use with ACE Inhibitors: Avoid within 36 hours due to angioedema risk.
• Pregnancy: Contraindicated due to fetal harm.

7. Warnings & Precautions for Sacubitril/Valsartan

General Warnings

• Hypotension: Risk of symptomatic hypotension, especially in volume-depleted patients; monitor blood pressure.
• Angioedema: Risk with prior ACEi/ARB use or in Black patients; discontinue if swelling occurs.
• Hyperkalemia: Elevated potassium levels; check levels regularly.
• Kidney Impairment: Risk of acute kidney injury; monitor renal function.
• Fetal Toxicity: Contraindicated in pregnancy; use contraception.

Additional Warnings

• Cough: Persistent dry cough, less common than with ACEi; assess respiratory symptoms.
• Liver Injury: Rare elevation of liver enzymes; monitor in chronic use.
• Neutropenia: Rare with Valsartan component; monitor blood counts.
• Electrolyte Imbalance: Risk of hyponatremia or hypomagnesemia; correct as needed.
• Hypersensitivity Reactions: Rare anaphylaxis; discontinue if severe.

Use in Specific Populations

• Pregnancy: Category D; avoid unless life-saving; use alternatives.
• Breastfeeding: Avoid due to potential excretion; monitor infant.
• Elderly: Higher risk of hypotension; start with lower doses.
• Children: Limited to 1+ years; supervise closely.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about kidney disease, electrolyte issues, or medication history before starting this medication.
• Avoid abrupt cessation; taper if switching therapies.

8. Overdose and Management of Sacubitril/Valsartan

Overdose Symptoms

Overdose may cause:

• Dizziness, hypotension, or fainting.
• Severe cases: Acute kidney injury, hyperkalemia, or angioedema.
• Nausea, weakness, or fatigue as early signs.
• Cardiac arrest with extremely high doses.

Immediate Actions

• Contact the Medical Team: Seek immediate medical help.
• Supportive Care: Administer IV fluids, monitor vital signs, and correct electrolytes.
• Specific Treatment: Manage hypotension with vasopressors if needed; no specific antidote.
• Monitor: Check kidney function, potassium levels, and blood pressure for 24–48 hours.

Additional Notes

• Overdose risk is low; store securely.
• Report persistent symptoms (e.g., severe dizziness, swelling) promptly.

9. Side Effects of Sacubitril/Valsartan

Common Side Effects

• Hypotension (10–15%, manageable with hydration)
• Hyperkalemia (5–10%, monitored with diet)
• Cough (3–8%, less severe than ACEi)
• Dizziness (2–7%, reduces with tolerance)
• Fatigue (2–6%, improves with rest)
  These effects may subside with dose adjustment.

Serious Side Effects

Seek immediate medical attention for:

• Cardiovascular: Severe hypotension or syncope.
• Renal: Acute kidney injury or oliguria.
• Allergic: Angioedema or anaphylaxis.
• Metabolic: Hyperkalemia or hyponatremia.
• Hepatic: Jaundice or liver failure.

Additional Notes

• Regular monitoring for blood pressure, kidney function, and electrolytes is advised.
• Report any unusual symptoms (e.g., swelling, severe weakness) immediately to a healthcare provider.

10. Drug Interactions with Sacubitril/Valsartan

This active ingredient may interact with:

• ACE Inhibitors/ARBs: Increases angioedema risk; avoid concurrent use.
• Potassium-Sparing Diuretics: Enhances hyperkalemia; monitor levels.
• NSAIDs: Reduces renal function; adjust dose.
• Lithium: Increases toxicity; monitor levels.
• Antihypertensives: Potentiates hypotension; titrate carefully.

Action: Provide your healthcare provider with a complete list of medications.

11. Patient Education or Lifestyle

• Medication Adherence: Take this ARNI as prescribed to manage heart failure, following the exact schedule.
• Monitoring: Report dizziness, swelling, or fatigue immediately.
• Lifestyle: Avoid dehydration; limit salt intake.
• Diet: Take with or without food; monitor potassium-rich foods (e.g., bananas).
• Emergency Awareness: Know signs of hypotension or kidney issues; seek care if present.
• Follow-Up: Schedule regular check-ups every 1–3 months to monitor heart function, kidney health, and electrolytes.

12. Pharmacokinetics of Sacubitril/Valsartan

• Absorption: Well-absorbed orally (peak at 1.5–2 hours for valsartan, 0.5–1 hour for sacubitril); enhanced with food for valsartan.
• Distribution: Volume of distribution ~75–100 L for valsartan, ~103 L for sacubitril; 94–97% protein-bound.
• Metabolism: Sacubitril converted to active LBQ657 via esterases; valsartan unchanged; hepatic via CYP2C9 minor role.
• Excretion: Primarily biliary/fecal (52–68% for sacubitril, 83% for valsartan); renal (37–48% for sacubitril metabolites); half-life 9–13 hours (valsartan), 11–13 hours (LBQ657).
• Half-Life: 9–13 hours for valsartan, 11–13 hours for LBQ657, with sustained cardiovascular effects.

13. Pharmacodynamics of Sacubitril/Valsartan

This drug exerts its effects by:

• Inhibiting neprilysin to increase natriuretic peptides (e.g., ANP, BNP), promoting diuresis and vasodilation.
• Blocking AT1 receptors to reduce vasoconstriction and aldosterone release.
• Improving cardiac remodeling and reducing preload/afterload in HFrEF.
• Exhibiting dose-dependent risks of hypotension and hyperkalemia.

14. Storage of Sacubitril/Valsartan

• Temperature: Store at 20–25°C (68–77°F); protect from moisture.
• Protection: Keep in original container, away from light.
• Safety: Store in a locked container out of reach of children due to toxicity risk.
• Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.

15. Frequently Asked Questions (FAQs) About Sacubitril/Valsartan

Q: What does Sacubitril/Valsartan treat?
A: This medication treats heart failure with reduced ejection fraction.

Q: Can this active ingredient cause dizziness?
A: Yes, dizziness may occur; stay hydrated.

Q: Is Sacubitril/Valsartan safe for children?
A: Yes, for 1+ years with a doctor’s guidance.

Q: How is this drug taken?
A: Orally as tablets twice daily, as directed.

Q: How long is Sacubitril/Valsartan treatment?
A: Long-term for heart failure management.

Q: Can I use Sacubitril/Valsartan if pregnant?
A: No, avoid due to fetal risk; consult a doctor.

16. Regulatory Information for Sacubitril/Valsartan

This medication is approved by:

• U.S. Food and Drug Administration (FDA): Approved in 2015 (Entresto) for HFrEF.
• European Medicines Agency (EMA): Approved for HFrEF management.
• Other Agencies: Approved globally for heart failure; consult local guidelines.

17. References

1. U.S. Food and Drug Administration (FDA). (2023). Entresto (Sacubitril/Valsartan) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Sacubitril/Valsartan Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Sacubitril/Valsartan: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Guidelines on Cardiovascular Diseases: Sacubitril/Valsartan.
   • WHO’s recommendations for Sacubitril/Valsartan in heart failure.
5. New England Journal of Medicine. (2022). Sacubitril/Valsartan in Heart Failure.
   • Peer-reviewed article on Sacubitril/Valsartan efficacy (note: access may require a subscription).