AQUMELDI

AQUMELDI should be initiated by a physician experienced in the treatment of paediatric patients with heart failure. 04 mg/kg (max 2 mg) as a single initial dose. • Before giving a test dose, blood pressure (BP) and renal function should be checked.

If the BP is below the 5th percentile or creatinine is above normal limit for age, then enalapril should not be given. • Test dose should be at the lower end of the range for less stable patients and in infants <30 days of age. • Blood pressure should be monitored at intervals for 1–2 hours after the initial dose.

If systolic BP is below the 5th percentile enalapril should be stopped and appropriate clinical care given. 3 mg/kg (max 20 mg) per day in one or two divided doses 8 hours after test dose. The dose should be individualised according to blood pressure, serum creatinine and potassium response.

5 × baseline, consider enalapril dose up- titration. • If SBP is below the 5th percentile and serum creatinine is more than 2 × baseline, enalapril should be stopped. 5 and 2 × baseline, enalapril dose should be titrated down. • If SBP is above the 5th percentile and serum creatinine is more than 2 × baseline, enalapril dose should be titrated down.

5 to 2 × baseline the enalapril should be continued at the same dose. 5 mmol/l pause enalapril treatment. Once hyperkalaemia has resolved, restart enalapril on the same or a lower dose level. If hyperkalaemia recurs, repeat the above and restart at a lower level.

5 mmol/l, despite multiple dose decreases, discontinue enalapril. If a dose of AQUMELDI is missed the next dose should be given as usual. Do not give a double dose to make up for a forgotten dose. 3). 73 m2: Dose adjustment not required.

73 m2: Start with 50% of the single dose and dose at 12 hour intervals. • For dialysis: Start with 25% of the normal single dose and dose at 12 hour intervals. The dose should be increased to the highest possible tolerated dose depending on the effect.

Depending on the clinical condition of the patient, the creatinine and potassium concentrations should be checked within 2 weeks after the start of treatment and then at least once a year. Hepatic impairment No data is available for treatment of paediatric subjects with liver impairment.

Dose adjustment is not considered necessary however such children should only be treated with enalapril under strict monitoring. 4). Children less than 30 days of age Treatment of infants < 30 days of age should only be conducted with rigorous monitoring, including blood pressure, serum potassium levels and renal function.

2%). Tabulated list of adverse drug reactions Children The adverse reaction frequency listed in Table 1 is derived from the clinical studies in children receiving AQUMELDI for heart failure. In total 86 children in these studies received enalapril for up to 1 year; as such the data are limited.

The adverse reactions are listed below by SOC (system organ class) and by frequency, most frequent reactions first, with the following guidelines: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 1. List of adverse reactions in children with heart failure. Adults Enalapril tablets have been evaluated for safety in more than 10 000 adult patients and in controlled clinical studies involving 2 314 hypertensive patients and 363 patients with congestive heart failure.

Adverse reactions and frequency in the adult population is listed in Table 2. Table 2. List of adverse reactions in the adult population Adverse reactions Frequency Blood and lymphatic system disorders Aplastic anaemia Uncommon Haemolytic anaemia Uncommon Anaemia Uncommon Bone marrow depression Rare Neutropenia Rare Agranulocytosis Rare Pancytopenia Rare Thrombocytopenia Rare Adverse reactions Frequency Nervous system disorders Dizziness postural Common Vascular disorders Hypotension Common Respiratory, thoracic and mediastinal disorders Cough Common Gastrointestinal disorders Vomiting Common Investigations Hyperkalaemia Common Microalbuminuria Common Adverse reactions Frequency Lymphadenopathy Rare Haemoglobin decreased Rare Haematocrit decreased Rare Immune system disorders Angioedema Common Autoimmune diseases Rare Endocrine disorders Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Unknown Metabolism and nutrition disorders Hypoglycaemia Uncommon Psychiatric disorders Depression Common Confusion Uncommon Nervousness Uncommon Insomnia Uncommon Abnormal dreams Rare Sleep disorders Rare Nervous system disorders Dizziness Very common Headache Common Syncope Common Taste alteration Common Paraesthesia Uncommon Somnolence Uncommon Vertigo Uncommon Eye disorders Blurred vision Very common Ear and labyrinth disorders Tinnitus Uncommon Cardiac disorders Chest pain Common Rhythm disturbances Common Angina pectoris Common Tachycardia Common Myocardial infarction Uncommon Cerebrovascular accident Uncommon Palpitations Uncommon Vascular disorders Hypotension Common Orthostatic hypotension Uncommon Flushing Uncommon Raynaud’s phenomenon Rare Respiratory, thoracic and mediastinal disorders Cough Very common Dyspnoea Common Asthma Uncommon Bronchospasm Uncommon Sore throat Uncommon Rhinorrhoea Uncommon Hoarseness Uncommon Pulmonary infiltrates Rare Adverse reactions Frequency Allergic alveolitis Rare Eosinophilic pneumonia Rare Rhinitis Rare Gastrointestinal disorders Nausea Very common Diarrhoea Common Abdominal pain Common Vomiting Common Ileus Uncommon Pancreatitis Uncommon Peptic ulcer Uncommon Constipation Uncommon Anorexia Uncommon Gastric irritation Uncommon Dyspepsia Uncommon Dry mouth Uncommon Stomatitis Rare Aphthous ulceration Rare Glossitis Rare Intestinal angioedema Very rare Hepatobiliary disorders Hepatic failure Rare Cholestasis Rare Hepatitis Rare Skin and subcutaneous tissue disorders Rash Common Pruritis Uncommon Diaphoresis Uncommon Alopecia Uncommon Erythema multiforme Rare Stevens-Johnson syndrome Rare Exfoliative dermatitis Rare Toxic epidermal necrolysis Rare Pemphigus Rare Erythroderma Rare Severe skin reactions* Unknown Hypersensitivity reactions Unknown Musculoskeletal and connective tissue disorders Muscle cramps Uncommon Renal and urinary disorders Renal failure Uncommon Renal dysfunction Uncommon Proteinuria Uncommon Oliguria Rare Reproductive system and breast disorder Impotence Uncommon Gynaecomastia Rare General disorders and administration site conditions Aesthenia Very common Fatigue Common Fever Uncommon Malaise Uncommon Adverse reactions Frequency Investigations Hyperkalaemia Common Microalbuminuria Common Increased serum creatinine Common Increased blood urea Uncommon Hyponatraemia Uncommon Increased liver enzymes Rare Increased serum bilirubin Rare * A symptom complex has been reported which may include some or all of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive ANA, elevated ESR, eosinophilia, and leucocytosis.

Symptomatic hypotension In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment.

In these patients, therapy should be started under medical supervision and the patients should be followed closely whenever the dose of AQUMELDI and/or diuretic is adjusted. Similar considerations may apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with AQUMELDI. This effect is anticipated, and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose and/or discontinuation of the diuretic and/or AQUMELDI may be necessary.

9%) solution for injection. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion. Aortic or mitral valve stenosis/hypertrophic cardiomyopathy As with all vasodilators, ACE inhibitors should be given with caution in patients with left ventricular valvular and outflow tract obstruction and avoided in cases of cardiogenic shock and haemodynamically significant obstruction.

Renal impairment Renal failure has been reported in association with enalapril and has been seen mainly in patients with severe heart failure or underlying renal disease, including renal artery stenosis. 8). Some hypertensive patients, with no apparent pre-existing renal disease have developed increases in blood urea and creatinine when enalapril has been given concurrently with a diuretic.

1 or any other angiotensin converting enzyme inhibitor (ACEi). • History of angioedema associated with previous ACE inhibitor therapy. • Hereditary or idiopathic angioedema. 6). 1). • Combination with sacubitril/valsartan (a medicinal product containing a neprilysin inhibitor) due to the increased risk of angioedema.

5). 2).