Vymada Special Precautions

Dual blockade of the renin-angiotensin-aldosterone system (RAAS): Combination with an ACE inhibitor is contraindicated due to the increased risk of angioedema (see CONTRAINDICATIONS). It must not be initiated until 36 hours after taking the last dose of ACE inhibitor therapy. If treatment is stopped, ACE inhibitor therapy must not be initiated until 36 hours after the last dose of the drug (see DOSAGE & ADMINISTRATION, CONTRAINDICATIONS and PRECAUTIONS).
Combination with direct renin inhibitors such as aliskiren is not recommended (see INTERACTIONS). The combination with aliskiren-containing products is contraindicated in patients with diabetes mellitus or in patients with renal impairment (eGFR <60 ml/min/1.73 m²) (see CONTRAINDICATIONS and INTERACTIONS).
Sacubitril-valsartan (Vymada) contains valsartan, and therefore should not be co-administered with another ARB-containing product (see DOSAGE & ADMINISTRATION and INTERACTIONS).
Hypotension: Treatment should not be initiated unless SBP is ≥100 mmHg. Patients with SBP <100 mmHg were not studied (see PHARMACOLOGY: PHARMACODYNAMICS under ACTIONS). Cases of symptomatic hypotension have been reported in patients in clinical studies (see ADVERSE REACTIONS), especially in patients ≥65 years old, patients with renal disease and patients with low SBP (<112 mmHg). When initiating therapy or during dose titration, blood pressure should be monitored routinely. If hypotension occurs, temporary down-titration or discontinuation of the drug is recommended (see DOSAGE & ADMINISTRATION). Dose adjustment of diuretics, concomitant antihypertensives and treatment of other causes of hypotension (e.g. hypovolemia) should be considered. Symptomatic hypotension is more likely to occur if the patient has been volume-depleted, e.g. by diuretic therapy, dietary salt restriction, diarrhea or vomiting. Sodium and/or volume depletion should be corrected before starting treatment, however, such corrective action must be carefully weighed against the risk of volume overload.
Impaired renal function: Evaluation of patients with heart failure should always include assessment of renal function. Patients with mild and moderate renal impairment are more at risk of developing hypotension. There is very limited clinical experience in patients with severe renal impairment (estimated GFR <30 ml/min/1.73m²) and these patients may be at greatest risk of hypotension (see DOSAGE & ADMINISTRATION). There is no experience in patients with end-stage renal disease and use of sacubitril-valsartan (Vymada) is not recommended.
Worsening renal function: Use may be associated with decreased renal function. The risk may be further increased by dehydration or concomitant use of non-steroidal anti-inflammatory agents (NSAIDs) (see INTERACTIONS). Down-titration should be considered in patients who develop a clinically significant decrease in renal function.
Hyperkalemia: Treatment should not be initiated if the serum potassium level is >5.4 mmol/l. Use may be associated with an increased risk of hyperkalemia, although hypokalemia may also occur (see ADVERSE REACTIONS). Monitoring of serum potassium is recommended, especially in patients who have risk factors such as renal impairment, diabetes mellitus or hypoaldosteronism or who are on a high potassium diet or on mineralocorticoid antagonists (see DOSAGE & ADMINISTRATION). If patients experience clinically significant hyperkalemia, adjustment of concomitant medicinal products, or temporary down-titration or discontinuation of treatment is recommended. If serum potassium level is >5.4 mmol/l discontinuation should be considered.
Angioedema: Angioedema has been reported in patients treated with sacubitril-valsartan. If angioedema occurs, treatment should be immediately discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. It must not be re-administered. In cases of confirmed angioedema where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms.
Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx likely to cause airway obstruction, appropriate therapy, e.g. adrenaline solution 1 mg/1 ml (0.3-0.5 ml), and/or measures necessary to ensure a patent airway, should be promptly administered.
Patients with prior history of angioedema were not studied. As they may be at higher risk for angioedema, caution is recommended if used in these patients. Sacubitril-valsartan (Vymada) is contraindicated in patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy or with hereditary or idiopathic angioedema (see CONTRAINDICATIONS).
Black patients have an increased susceptibility to develop angioedema (see ADVERSE REACTIONS).
Patients with renal artery stenosis: Sacubitril-valsartan may increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. Caution is required in patients with renal artery stenosis and monitoring of renal function is recommended.
Patients with NYHA functional classification IV: Caution should be exercised when initiating treatment in patients with NYHA functional classification IV due to limited clinical experience in this population.
B-type natriuretic peptide (BNP): BNP is not a suitable biomarker of heart failure in patients treated with sacubitril-valsartan because it is a neprilysin substrate (see PHARMACOLOGY: PHARMACODYNAMICS under ACTIONS).
Patients with hepatic impairment: There is limited clinical experience in patients with moderate hepatic impairment (Child-Pugh B classification) or with AST/ALT values more than twice the upper limit of the normal range. In these patients, exposure may be increased and safety is not established. Caution is therefore recommended when using it in these patients (see DOSAGE & ADMINISTRATION and PHARMACOLOGY: PHARMACOKINETICS under ACTIONS). Sacubitril-valsartan (Vymada) is contraindicated in patients with severe hepatic impairment, biliary cirrhosis or cholestasis (Child-Pugh C classification) (see CONTRAINDICATIONS).
Psychiatric disorders: Psychiatric events such as hallucinations, paranoia and sleep disorders, in context of psychotic events, have been associated with sacubitril-valsartan use. If patient experiences such events, discontinuation of sacubitril-valsartan treatment should be considered.
Effects on Ability to Drive and Use Machines: Sacubitril-valsartan (Vymada) has a minor influence on the ability to drive and use machines. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or fatigue may occur.