cSPC Changes, Zestril range

Section 2

Text change to second paragraph, now reads,

“For a full list of excipients, see section 6.1.”

Section 4.4

Sub heading Pregnancy and lactation has been changed to “Pregnancy”.  Second paragraph of this sub heading is deleted.

Section 4.5

Sub heading on NSAIDs now updated, reads as,

“Non-steroidal anti-inflammatory medicinal products (NSAIDs) including acetylsalicylic acid ³ 3 g/day

When ACE-inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. Concomitant use of ACE-inhibitors and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor pre-existing renal function. These effects are usually reversible. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.”

Section 4.9

Minor change to second paragraph, now reads as,

“The recommended treatment of overdose is intravenous infusion of normal saline solution. 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 Zestril (e.g. emesis, gastric lavage, administration of absorbents and sodium sulphate). Zestril may be removed from the general circulation by haemodialysis (see section 4.4). Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored frequently.”

Section 9

Date of first authorisation: 8 June 2000

Date of first renewal: 1 August 2010

Section 10

20 September 2010

Zestril range cSPC Changes

Section 4.2

Inclusion of sub-section after ‘Dosage adjustment in renal impairment’ sub-section, reads as,

“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.”

Inclusion of sub-section after ‘Renal complications of diabetes mellitus’ sub-section, reads as,

“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). Zestril is not recommended in children in other indications than hypertension.

Zestril 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).”

Section 4.8

Inclusion of final paragraph, reads as,

“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

Inclusion of 2 final paragraphs, reads as,

“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 Zestril once a day, and patients who weighed 50 kg or more received either 1.25 mg, 5 mg or 40 mg of Zestril once a day. At the end of 2 weeks, Zestril 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 randomised to placebo than it did in patients who were randomised to remain on the middle and high doses of Zestril. The dose-dependent antihypertensive effect of Zestril was consistent across several demographic subgroups: age, Tanner stage, gender, and race.”

Section 5.2

Inclusion of sub-section ‘Paediatrics’ after sub-section ‘Heart failure’, reads as,

“Paediatrics

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 C_max values in children in this study were consistent with those observed in adults.”

Section 10, date of revision of the text

20 August 2010

cSPC changes – Zestril 2.5mg, 5mg, 10mg & 20mg

Section 6.5

Additional text throughout section, now reads,

“2.5 mg Tablets: Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of 14, 20, 28, 30, 50, 84, 100 and 400 tablets.

Aluminium/PVC-PVDC or Aluminium/PVC foil blister calendar packs of 14, 28 and 84 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

5 mg Tablets: Aluminium/PVC-PVDC, Aluminium/PVC or

Aluminium/Aluminium foil blister packs of 14, 20, 28, 28x1, 30, 42, 50, 56, 60, 84, 98, 100, 400 and 500 tablets.

Aluminium/PVC-PVDC, Aluminium/PVC or

Aluminium/Aluminium foil blister calendar packs of 14, 28, 42, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

10 mg Tablets: Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of

14, 20, 28, 30, 50, 56, 84, 98, 100 and 400 tablets.

Aluminium/PVC-PVDC or Aluminium/PVC foil blister calendar packs of

14, 28, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

20 mg Tablets: Aluminium/PVC-PVDC, Aluminium/PVC or Aluminium/Aluminium foil blister packs of 14, 20, 28, 30, 42, 50, 56, 56x1 60, 84, 98, 100, 400 and 500 tablets.

Aluminium/PVC-PVDC, Aluminium/PVC or Aluminium/Aluminium foil blister calendar packs of 14, 28, 42, 56, 84 and 98 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

Not all pack sizes may be marketed.”

Section 10

12 August 2010

Zestril cSPC changes

Section 4.8

Under heading, ‘Nervous system and psychiatric disorders’, ‘rare’, now reads,

“mental confusion, olfactory disturbance”

Under  heading, ‘Endocrine disorders’, now reads,

“frequency    

not known:         inappropriate antidiuretic hormone secretion.”

Section 6.1

Now reads,

“Mannitol

Calcium Hydrogen Phosphate dihydrate

Red Iron Oxide, in all strengths except the 2.5 mg (E172)

Maize Starch

Pregelatinised Starch

Magnesium Stearate”

Section 10

4 March 2010

Zestril SPC Changes

Section 3

New text:

“2.5 mg tablets: round, white, uncoated, biconvex tablet with “♥ 2.5” on one side and plain on the other side. Diameter 6 mm.

5 mg tablets: round, pink, uncoated, biconvex tablet with “♥ 5” on one side and bisected on the other side. Diameter 6 mm.

The tablet can be divided into equal halves.

10 mg tablets: round, pink, uncoated, biconvex tablet with “♥ 10” on one side and plain on the other side. Diameter 8 mm.

20 mg tablets: round, brownish-red, uncoated, biconvex tablet with “♥ 20” on one side and plain on the other side. Diameter 8 mm.”

Section 4.4

Final paragraph, additional text at end of last sentence,

“(see section 4.6).”

Section 4.6

Additional final paragraph,

“Lactation

Because no information is available regarding the use of Zestril during breast-feeding, Zestril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.”

Section 10

1 October 2009

Section 4.8

First paragraph, additional wording after the word, frequencies, “Very common (³1/10), common (³1/100 to <1/10), uncommon (³1/1,000 to <1/100), rare (³1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).”

Additional wording under heading, Nervous system and psychiatric disorders,

“frequency    

not known:        depressive symptoms, syncope.”

Additional wording under heading, Skin and subcutaneous tissue disorders, uncommon

“rash, pruritus, hypersensitivity/angioneurotic oedema: angioneurotic oedema of the face, extremities, lips, tongue, glottis, and/or larynx (see section 4.4)”

 
Deletion of wording in rare, remaining text being, “urticaria, alopecia, psoriasis”.

Section 4.3

Change of text to 4^th bullet point

Second or and third trimesters of pregnancy (see sections 4.4 and 4.6).

Section 4.4

Additional new text at end of section

Pregnancy and lactation

Pregnancy: ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).

Lisinopril should not be used during the first trimester of pregnancy. Zestril is contraindicated in the second and third trimesters of pregnancy (see section 4.3). When pregnancy is detected, lisinopril treatment should discontinue as soon as possible (see section 4.6).

Section 4.5

New additional text

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.

Section 4.6

New text

The use of ACE inhibitors is not recommended during the first trimester of pregnancy (see section 4.4).The use of ACE inhibitors is contra-indicated during the second and third trimester of pregnancy (see sections 4.3 and 4.4).

Replacement text

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitors therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an

established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

ACE inhibitors therapy exposure during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3).

Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy,ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension (see sections 4.3 and 4.4).

Lactation information remains the same.

Section 4.8

Additional very rare side effect under the heading Skin and subcutaneous tissue disorders ‘cutaneous pseudolymphoma’

Section 10

Revision date of text: 8 October 2008

Section 6.3
4 years.2.5 mg: 24 months.

2.5 mg tablets:Do not store above 25°C

2.5 mg Tablets: Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of 14, 20, 28, 30, 50, 84, 100 and 400 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

5 mg Tablets: Aluminium/PVC-PVDC, Aluminium/PVC or

Aluminium/Aluminium foil blister packs of 14, 20, 28, 28x1, 30, 42, 50, 56, 60, 84, 98, 100, 400 and 500 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

10 mg Tablets: Aluminium/PVC-PVDC or Aluminium/PVC foil blister packs of

14, 20, 28, 30, 50, 56, 84, 98, 100 and 400 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

20 mg Tablets: Aluminium/PVC-PVDC, Aluminium/PVC or Aluminium/Aluminium foil blister packs of 14, 20, 28, 30, 42, 50, 56, 56x1 60, 84, 98, 100, 400 and 500 tablets.

HDPE bottle packs of 20, 30, 50, 100 and 400 tablets.

Not all pack sizes may be marketed.2.5 mg, 5 mg, 10 mg and 20 mg: Blister Packs of 28 or 84 tablets.

Not all pack sizes may be marketed.


Section 10
Date changed to 28th January 2008

Section 6.2

Current text: None known

New text: Not applicable

Section 6.6

Current text: No special instructions

New text: No special requirements.

Section 10

New revision date of text: 14 February 2007