AQUMELDI Orodispersible tablet Ref.[51538] Active ingredients: Enalapril

AQUMELDI should be initiated by a physician experienced in the treatment of paediatric patients with heart failure.

Posology

Starting/test dose

0.01 to 0.04 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 5^th 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 5^th percentile enalapril should be stopped and appropriate clinical care given.

Target/maintenance dose

0.15 to 0.3 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.

• If systolic blood pressure (SBP) is greater than or equal to the 5^th percentile and serum creatinine is no more than 1.5 × baseline, consider enalapril dose up-titration.
• If SBP is below the 5^th percentile and serum creatinine is more than 2 × baseline, enalapril should be stopped.
• If systolic blood pressure is below the 5^th percentile and serum creatinine is between 1.5 and 2 × baseline, enalapril dose should be titrated down.
• If SBP is above the 5^th percentile and serum creatinine is more than 2 × baseline, enalapril dose should be titrated down.
• If systolic blood pressure is greater than or equal to the 5^th percentile and serum creatinine is between 1.5 to 2 × baseline the enalapril should be continued at the same dose.

At any stage if potassium ≥5.5 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. If potassium is repeatedly above 5.5 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.

Special populations

Renal impairment

Special precautions should be followed in patients with impaired renal function (see section 4.3 and 4.4):

• Enalapril is contraindicated in paediatric patients with glomerular filtration rate (GFR) <30 ml/min/1.73 m² (see section 4.3).
• GFR ≥50 ml/min/1.73 m²: Dose adjustment not required.
• GFR ≥30-<50 ml/min/1.73 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. Treatment of children below the age of 1 month with hepatic impairment is not recommended (see section 4.4).

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.

Method of administration

For oral use only. Place on the tongue or in the buccal cavity and allow to disperse.

AQUMELDI can be taken with or without meals.

For instructions on administering starting doses <0.25 mg and in case of feeding tube administration, see section 6.6.

Limited data are available for overdose of enalapril in adults and there is no specific data in children. The most prominent features of overdose reported to date are marked hypotension, beginning some six hours after ingestion of tablets, concomitant with blockade of the renin-angiotensin system, and stupor. Symptoms associated with overdose of ACE inhibitors may include circulatory shock, electrolyte disturbances, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, and cough. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively.

The recommended treatment of overdose is intravenous infusion of sodium chloride 9 mg/ml (0.9%) solution for injection. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. If ingestion is recent, take measures aimed at eliminating enalapril maleate (e.g., emesis, gastric lavage, administration of absorbents, and sodium sulfate). Enalapril may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapyresistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.

2 years.

After first opening, use within 100 days.

Do not store above 25°C. Store in the original package in order to protect from moisture.

High density polyethylene bottle with polypropylene cap (equipped with a child-resistant, tamper evident closure system and an integrated silica desiccant) and one scoop to allow extraction of the tablets from the bottle.

AQUMELDI is provided in bottles of 50, 100 or 200 tablets, each.

Not all pack sizes may be marketed.

The first time the bottle is opened, the seal needs to be broken:

• Hold the bottle firmly with one hand.
• With the other hand: push down firmly whilst twisting the cap anti-clockwise.
• Continue turning until the seal is broken.

Due to the small size of the orodispersible tablets, use the scoop provided in the pack to facilitate extraction from the bottle. As much as possible, avoid touching the tablets with your hands.

Administration of doses <0.25 mg

Where the starting dose is less than 0.25 mg, a lower dose can be achieved by placing one 0.25 mg tablet in a 10 ml oral syringe, adding tap water to the 10 ml graduation, rolling the syringe for 3 minutes to fully disperse the tablet, and administering the required volume to the patient (1 ml will contain 0.025 mg enalapril, 4 mL will contain 0.1 mg enalapril). Sterile water should be used in children under 6 months. After full dispersion of the orodispersible tablet in the oral syringe, the required volume should be used immediately.

Administration via enteral tube

Some patients may require administration via an enteral feeding tube. AQUMELDI rapidly disperses in tap water and can be administered once dispersed. Sterile water should be used in children under 6 months. AQUMELDI should only be dispersed in water by rolling or mixing for 3 minutes in a syringe. A maximum of four orodispersible tablets can be dispersed in 1 ml at any one time. If the child is given the medicinal product through a feeding tube, flush the tube with at least 3 ml of water after you have given the medicinal product.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.