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Previous version: Excipients: lactose monohydrate
New version: Excipient: lactose
Previous version: Paediatric use
New version: Children and adolescents (less than 18 years of age):
Previous version: Second and third trimesters of pregnancy (see section 4.6).
New version: Second and third trimesters of pregnancy (see sections 4.4 and 4.6).
- In section 4.4
- Paragraph Renal impairment
Previous version: Impairment of renal function
New version: Renal impairment
- Paragraph Hypersensitivity/Angioedema
This paragraph has been added: “Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan, or ultrasound or at surgery and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.”
- Paragraph Neutropenia/Agranulocytosis/Thrombocytopenia/Anaemia:
This sentence has been added at the end: “(e.g. sore throat, fever)”.
1/ Previous version: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril. Patients at risk for the development of hyperkalaemia include those with renal insufficiency, uncontrolled diabetes mellitus, or those using concomitant potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). If concomitant use of the above-mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended.
New version: Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including perindopril. Risk factors for the development of hyperkalemia include those with renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene, or amiloride), potassium supplements or potassium-containing salt substitutes; or those patients taking other drugs associated with increases in serum potassium (e.g. heparin). The use of potassium supplements, potassiumsparing diuretics, or potassium-containing salt substitutes particularly in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalemia can cause serious, sometimes fatal arrhythmias. If concomitant use of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium (see section 4.5).
2/ The following paragraph has been added:
“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 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 (see sections 4.3 and 4.6).”
· In section 4.5
o Paragraph Non-steroidal anti-inflammatory medicinal products (NSAIDs) including aspirin ≥ 3 g/day:
1/ Previous version: The administration of a non-steroidal anti-inflammatory drug may reduce the antihypertensive effect of ACE inhibitors. Additionally, NSAIDs and ACE inhibitors exert an additive effect on the increase in serum potassium and may result in a deterioration of renal function. These effects are usually reversible. Rarely, acute renal failure may occur, especially in patients with compromised renal function such as those who are elderly or dehydrated.
New version: 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. 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.
2/ The following paragraph has been added:
“Gold:
Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including perindopril.”
Previous version: COVERSYL ARGININE should not be used during the first trimester of pregnancy. When a pregnancy is planned or confirmed, the switch to an alternative treatment should be initiated as soon as possible. Controlled studies with ACE inhibitors have not been done in humans, but in a limited number of cases with first trimester exposure there do not appear to have been any malformations consistent with human fetotoxicity as described below.
Perindopril is contraindicated during the second and third trimesters of pregnancy.
Prolonged ACE inhibitor exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, retardation of skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).
Should exposure to perindopril have occurred from the second trimester of pregnancy, an ultrasound check of renal function and the skull is recommended.
New version:
Pregnancy:
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 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).
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 inhibitor 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.
Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foeto-toxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3). Should exposure to ACE inhibitor 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 also sections 4.3 and 4.4).
Lactation:
Because no information is available regarding the use of COVERSYL ARGININE during breast-feeding, COVERSYL ARGININE is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Previous version: No studies on the effects on the ability to drive and use machines have been performed.
When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.
New version:
COVERSYL ARGININE has no direct influence on the ability to drive and use machines but individual reactions related to low blood pressure may occur in some patients, particularly at the start of treatment or in combination with another antihypertensive medication.
As a result the ability to drive or operate machinery may be impaired.
1/ New version: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); not known (cannot be estimated from the available data).
2/ These following paragraph have been added;
“Metabolism and nutrition disorders:
Not known : hypoglycaemia (see sections 4.4 and 4.5).”
Vascular disorders:
“Not known: vasculitis.”
E numbers have been removed for each concerned excipient
Date of revision has been updated
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