What are the absolute contraindications for Entresto (sacubitril/valsartan)?

From the Guidelines

The absolute contraindications for Entresto (sacubitril/valsartan) are use within 36 hours of ACEI use, history of angioedema with or without an ACEI or ARB, pregnancy, lactation (no data), severe hepatic impairment (Child-Pugh C), concomitant aliskiren use in patients with diabetes, and known hypersensitivity to either ARBs or ARNIs.

Key Contraindications

• Use within 36 hours of ACEI use: This is due to the increased risk of angioedema associated with the concomitant use of ACE inhibitors and ARNIs, as noted in 1.
• History of angioedema with or without an ACEI or ARB: Patients with a history of angioedema should not be administered ARNI therapy due to the concern of recurrence, as stated in 1.
• Pregnancy and lactation: Entresto is contraindicated in pregnancy and lactation due to the lack of data on its safety, as mentioned in 1.
• Severe hepatic impairment (Child-Pugh C): The use of Entresto is contraindicated in patients with severe hepatic impairment, as indicated in 1.
• Concomitant aliskiren use in patients with diabetes: This combination is contraindicated due to the increased risk of adverse effects, as noted in 1.
• Known hypersensitivity to either ARBs or ARNIs: Patients with known hypersensitivity to these classes of medications should not be administered Entresto, as stated in 1. These contraindications highlight the importance of careful patient selection and monitoring when prescribing Entresto, as emphasized in 1 and 1.

From the FDA Drug Label

Sacubitril and valsartan is contraindicated: • in patients with hypersensitivity to any component • in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy • with concomitant use of ACE inhibitors. Do not administer within 36 hours of switching from or to an ACE inhibitor • with concomitant use of aliskiren in patients with diabetes

The absolute contraindications for Entresto (sacubitril/valsartan) are:

• Hypersensitivity to any component
• History of angioedema related to previous ACE inhibitor or ARB therapy
• Concomitant use of ACE inhibitors (do not administer within 36 hours of switching from or to an ACE inhibitor)
• Concomitant use of aliskiren in patients with diabetes 2 2

From the Research

Absolute Contraindications for Entresto (Sacubitril/Valsartan)

There are no explicit mentions of absolute contraindications for Entresto (sacubitril/valsartan) in the provided studies. However, some studies mention potential safety concerns and adverse events associated with the use of sacubitril/valsartan, including:

• Symptomatic hypotension 3
• Angio-oedema 3
• First-dose hypotension 4

Potential Contraindications

While not explicitly stated as absolute contraindications, the following conditions may require caution or careful consideration when prescribing sacubitril/valsartan:

• History of angio-oedema 3
• Severe hypotension 4
• Renal impairment or hyperkalemia (not mentioned in the provided studies, but potentially relevant based on the mechanism of action of sacubitril/valsartan)

Important Considerations

When prescribing sacubitril/valsartan, clinicians should be aware of the potential for adverse events and take steps to monitor patients and manage any concerns that arise, including:

• Gradual introduction of sacubitril/valsartan using a treatment sequence scheme 5
• Management of adverse events, such as hypotension and angio-oedema 5