Sacubitril with valsartan oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of sacubitril with valsartan.
Drugs List
Therapeutic Indications
Uses
Symptomatic chronic cardiac failure with reduced ejection fraction
Dosage
Adults
Starting dose is one 49mg/51mg tablet twice a day.
The dose should be doubled at 2 to 4 weeks to the target dose of one 97mg/103mg tablet twice a day, as tolerated by the patient.
If patients experience tolerability issues (systolic blood pressure (SBP) less than or equal to 95mmHg, symptomatic hypotension, hyperkalaemia and renal dysfunction), adjustment of concomitant medicinal products, temporary down titration or discontinuation of sacubitril with valsartan is recommended.
Patients not currently taking an angiotensin converting enzyme inhibitor (ACE inhibitor) or an angiotensin II receptor blocker (ARB) or taking low doses of these medicinal products should have a starting dose of 24mg/26mg twice a day, doubling every 3 to 4 weeks.
Treatment should not be initiated in patients with serum potassium level greater than 5.4mmol/l or with SBP less than 100mmHg. A starting dose of 24mg/26mg twice a day should be considered for patients with SBP greater or equal to 100mmHg to 110mmHg.
Patients with Renal Impairment
Moderate renal impairment (eGFR 30 to 60 ml/minute/1.73 metre squared)
Starting dose of 24mg/26mg twice a day.
Severe renal impairment (eGFR less than 30 ml/minute/1.73 metre squared)
Starting dose of 24mg/26mg twice a day.
Patients with Hepatic Impairment
Moderate hepatic impairment or AST/ALT values more than twice the upper limit of the normal range
Starting dose is 24mg/26mg twice a day.
Additional Dosage Information
If a dose is missed, the patient should take the next dose at the scheduled time.
The valsartan contained within sacubitril with valsartan is more bioavailable than the valsartan in other marketed tablet formulations.
Contraindications
Children under 18 years
Hyperkalaemia where serum potassium over 5.4 mmol/l
Systolic blood pressure below 100mmHg
Within 36 hours of discontinuing an ACE inhibitor containing product
Biliary cirrhosis
Breastfeeding
Cholestasis
End stage renal disease
Hereditary angioneurotic oedema
History of angioedema
Idiopathic angioneurotic oedema
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Elderly
Aortic stenosis
Bilateral renal artery stenosis
Diabetes mellitus
Elevated serum transaminases - greater than twice the upper limit of normal
Hypertrophic obstructive cardiomyopathy
Hyponatraemia
Hypovolaemia
Mitral stenosis
Moderate hepatic impairment
New York Heart Association class IV failure
Renal impairment
Unilateral stenosis of solitary functioning kidney
Patients with primary aldosteronism may not benefit from this treatment
Switch to more suitable alternative before planned pregnancy
Advise ability to drive/operate machinery may be affected by side effects
Correct volume and/or salt depletion before initiating therapy
Evaluate renal function before and during treatment
Monitor blood pressure
Monitor serum potassium regularly
Reduce dose or discontinue if excessive hypotension occurs
Discontinue if psychiatric disturbances develop
Higher incidence of angioedema in black patients
Hypotension may occur during or after therapy
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
May affect results of some laboratory tests
Discontinue if angioedema occurs
Discontinue if hyperkalaemia occurs
Pregnancy confirmed: Advise patient to discontinue and consult doctor
Advise patient not to take NSAIDs unless advised by clinician
Advise on problems of salt substitutes/high intake of potassium-rich food
The combination of sacubitril with valsartan with direct renin inhibitors such as aliskiren is not recommended. The combination of sacubitril with valsartan with aliskiren containing products is contraindicated in patients with diabetes mellitus or in patients with renal impairment (eGFR less than 60 ml/minute/1.73 metre squared).
Monitoring of angioedema should be provided until all signs and symptoms are resolved. Angioedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or larynx likely to cause airway obstruction, appropriate therapy, e.g. adrenaline solution 1mg/1ml (0.3ml to 0.5ml), and/or measures necessary to ensure a patent airway, should be promptly administered.
Down-titration should be considered in patients who develop a clinically significant decrease in renal function.
Pregnancy and Lactation
Pregnancy
Sacubitril with valsartan is contraindicated during pregnancy.
The manufacturer does not recommend using sacubitril with valsartan during pregnancy during the first trimester and is contraindicated during the second and third trimesters of pregnancy. At the time of writing there is limited published information regarding the use of sacubitril with valsartan during the first trimester of pregnancy, however a small risk cannot be excluded. Exposure during the second and third trimesters of pregnancy have shown teratogenic effects including human foetotoxicity and neonatal toxicity.
Should exposure to sacubitril with valsartan occur from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Lactation
Sacubitril with valsartan is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues sacubitril with valsartan or discontinues breastfeeding. Animal data reports sacubitril with valsartan is excreted into the breast milk, however presence in human breast milk is unknown.
Side Effects
Anaemia
Angioedema
Asthenia
Cough
Diarrhoea
Dizziness
Fatigue
Gastritis
Hallucinations
Headache
Hyperkalaemia
Hypersensitivity reactions
Hypoglycaemia
Hypokalaemia
Hypotension
Nausea
Orthostatic hypotension
Paranoia
Pruritus
Rash
Renal failure
Renal impairment
Sleep disorders
Syncope
Vertigo
Effects on Laboratory Tests
B-type natriuretic peptide (BNP)
BNP is not a suitable biomarker of heart failure in patients treated with sacubitril and valsartan because it is a neprilysin substrate.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2019
Reference Sources
Summary of Product Characteristics: Entresto Film-coated tablets. Novartis Pharmaceuticals UK Ltd. Revised January 2021.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 10 October 2019
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.