RIAMEC

· Treatment of hypertension.

· Cardiovascular prevention: reduction of cardiovascular morbidity and mortality in patients with:

o manifest atherothrombotic cardiovascular disease (history of coronary heart disease or stroke, or peripheral vascular disease) or

o diabetes with at least one cardiovascular risk factor (see section 5.1).

· Treatment of nephropathy.

o incipient glomerular diabetic nephropathy, as defined by the presence of microalbuminuria.

o manifest glomerular diabetic nephropathy, as defined by macroproteinuria in patients with at least one cardiovascular risk factor (see section 5.1).

o manifest glomerular non-diabetic nephropathy, as defined by macroproteinuria ≥ 3 g/day (see section 5.1).

· Treatment of symptomatic heart failure.

· Secondary prevention following acute myocardial infarction: reduction of mortality in the acute phase of myocardial infarction in patients with clinical signs of heart failure, starting > 48 hours after the myocardial infarction.

Pregnancy

RAMIPRIL ZENTIVA is not recommended during the 1st trimester of pregnancy (see section 4.4.) and is contraindicated in the 2nd and 3rd trimesters of pregnancy (see section 4.3).

Available epidemiological data concerning the risk of malformation after exposure to ACE inhibitors in the 1st trimester of pregnancy do not allow for a conclusion. However, a small increase in the risk of congenital malformations cannot be excluded.

Unless ACE inhibitor treatment is considered essential, it is recommended to modify the antihypertensive treatment of patients planning a pregnancy to a medication having an established safety profile during pregnancy. In case of diagnosis of pregnancy, ACE inhibitor treatment must be stopped immediately, and if necessary an alternative treatment will be started.

Exposure to ACE inhibitors during the 2nd and 3rd trimesters of pregnancy is known to cause fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of skull bones) and toxicity in the newborn (renal failure, hypotension, hyperkalemia) (see section 5.3 "Preclinical safety data").

In case of exposure to an ACE inhibitor from the 2nd trimester of pregnancy, it is recommended to perform a fetal ultrasound in order to check renal function and the bones of the skull vault.

Newborns of mothers treated with ACE inhibitors must be closely monitored to look for any sign of hypotension, oliguria and hyperkalemia (see also sections 4.3 and 4.4).

Breastfeeding

Due to the insufficiency of available information on the use of RAMIPRIL ZENTIVA during breastfeeding (see section 5.2), RAMIPRIL ZENTIVA is not recommended. It is preferable to use other treatments having a well established safety profile during breastfeeding, particularly in the newborn or the premature infant.

Some side effects (for example, symptoms of reduced blood pressure such as dizziness) may impair the patient's ability to concentrate and react, and therefore constitute a risk in situations where these abilities are of particular importance (such as driving a vehicle or using a machine).

This may occur particularly at the start of treatment, or when replacing other treatments. After the first dose or subsequent dose increases, it is not recommended to drive or use machines for several hours.

Summary of the safety profile

The tolerability profile of ramipril includes a persistent dry cough and reactions due to hypotension. Serious adverse reactions include angioedema, hyperkalaemia, impairment of renal or hepatic function, pancreatitis, severe skin reactions and neutropenia/agranulocytosis.

Summary table of adverse reactions

The frequency of adverse reactions is defined according to the following convention:

Very frequent (≥ 1/10); frequent (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10000 to < 1/1000); very rare (< 1/10000), of unknown frequency (cannot be estimated from the available data).

Within each frequency group, adverse effects are presented in descending order of severity.

Paediatric population

The tolerability of ramipril was monitored in 325 children and adolescents aged 2 to 16 years, during 2 clinical trials. While the nature and severity of adverse effects appear similar to those in adults, the frequency of the following adverse effects is higher in children:

· Tachycardia, nasal congestion and rhinitis, "common" (≥ 1/100 to < 1/10) in the paediatric population and "uncommon" (≥ 1/1000 to < 1/100) in the adult population.

· Conjunctivitis "common" (≥ 1/100 to < 1/10) in the paediatric population, and "rare" (≥ 1/10 000 to < 1/1000) in the adult population.

· Tremors and urticaria "uncommon" (≥ 1/1000 to < 1/100) in the paediatric population, and "rare" (≥ 1/10 000 to < 1/1000) in the adult population.

The overall tolerability profile of ramipril in the paediatric population does not differ significantly from that in the adult population.

Reporting of suspected adverse effects

Reporting of suspected adverse effects after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals report any suspected adverse effect via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and the network of Regional Pharmacovigilance Centres - Website: www.signalement-sante.gouv.fr .