| Update to SPC and PIL following EU paediatric work-sharing procedure.
Under Section 4.2 the following wording has been added:
Use in Hypertensive Paediatric Patients aged 6-16 years
The recommended initial dose is 2.5 mg once daily in patients 20 to <50 kg, and 5 mg once daily in patients ≥50 kg. The dosage should be individually adjusted to a maximum of 20 mg daily in patients weighing 20 to <50 kg, and 40 mg in patients ≥50 kg. Doses above 0.61 mg/kg (or in excess of 40 mg) have not been studied in paediatric patients (see section 5.1). In children with decreased renal function, a lower starting dose or increased dosing interval should be considered.
And:
Paediatric Use
There is limited efficacy and safety experience in hypertensive children >6 years old, but no experience in other indications (see section 5.1). Lisinopril is not recommended in children in other indications than hypertension.
Lisinopril is not recommended in children below the age of 6, or in children with severe renal impairment (GFR <30ml/min/1.73m2) (see section 5.2).
Under section 4.5 the following text has been added:
Gold
Nitritoid reactions (symptoms of vasodilatation including flushing, nausea, dizziness and hypotension, which can be very severe) following injectable gold (for example, sodium aurothiomalate) have been reported more frequently in patients receiving ACE inhibitor therapy.
Under section 4.8 and Nervous system and psychiatric disorders the following side effect has been added:
frequency unknown: depressive symptoms, syncope
And under Skin and subcutaneous tissue disorders, cutaneous psudolymphoma has been added under very rare.
Following text has also been added under section 4.8:
Safety data from clinical studies suggest that lisinopril is generally well tolerated in hypertensive paediatric patients, and that the safety profile in this age group is comparable to that seen in adults.
Section 5.1 has been changed to include the following text:
In a clinical study involving 115 paediatric patients with hypertension, aged 6-16 years, patients who weighed less than 50 kg received either 0.625 mg, 2.5 mg or 20 mg of lisinopril once a day, and patients who weighed 50 kg or more received either 1.25 mg, 5 mg or 40 mg of lisinopril once a day. At the end of 2 weeks, lisinopril administered once daily lowered trough blood pressure in a dose-dependent manner with a consistent antihypertensive efficacy demonstrated at doses greater than 1.25 mg.
This effect was confirmed in a withdrawal phase, where the diastolic pressure rose by about 9 mm Hg more in patients randomized to placebo than it did in patients who were randomized to remain on the middle and high doses of lisinopril. The dose-dependent antihypertensive effect of lisinopril was consistent across several demographic subgroups: age, Tanner stage, gender, and race.
Under section 5.2 the following pharmacokinetic information has been added:
The pharmacokinetic profile of lisinopril was studied in 29 paediatric hypertensive patients, aged between 6 and 16 years, with a GFR above 30 ml/min/1.73m2. After doses of 0.1 to 0.2 mg/kg, steady state peak plasma concentrations of lisinopril occurred within 6 hours, and the extent of absorption based on urinary recovery was about 28%.
These values are similar to those obtained previously in adults. AUC and Cmax values in children in this study were consistent with those observed in adults.
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