COSYREL

Pregnancy

Based on existing data concerning single components, COSIMPREL is not recommended during the 1st trimester of pregnancy and is contraindicated during the 2nd and 3rd trimesters of pregnancy.

Bisoprolol

Bisoprolol possesses pharmacological properties likely to lead to harmful effects on pregnancy and/or the foetus/newborn (a decrease in placental perfusion associated with growth retardation, intrauterine deaths, abortions or preterm labour, and adverse effects (for example hypoglycemia and bradycardia) may occur in the foetus and the newborn). If beta-blocker treatment is necessary, selective beta-1 agents should be preferred.

Bisoprolol should not be used during pregnancy except if necessary. If bisoprolol treatment proves necessary, uteroplacental blood flow and foetal growth must be monitored. In case of harmful effects on pregnancy or on the foetus, an alternative treatment should be considered. The newborn must be subject to close monitoring. Symptoms of hypoglycemia and bradycardia generally appear within the first 3 days of life.

Périndopril

The use of ACE inhibitors is not recommended during the 1st trimester of pregnancy (see section 4.4). The use of ACE inhibitors is contraindicated in the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

Available epidemiological data concerning the risk of teratogenicity 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 that patients planning a pregnancy modify their antihypertensive treatment to a medication with a well-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 foetotoxicity (decrease in renal function, oligohydramnios, delayed ossification of skull bones) and toxicity in the newborn (renal failure, hypotension, hyperkalaemia) (see section 5.3). In case of exposure to an ACE inhibitor from the 2nd trimester of pregnancy, it is recommended to perform a foetal ultrasound to check renal function and the bones of the skull vault. Newborns of mothers treated with ACE inhibitors must be monitored for blood pressure (see sections 4.3 and 4.4).

Breastfeeding

COSIMPREL is not recommended during breastfeeding.

The excretion of bisoprolol in breast milk is unknown. Consequently, breastfeeding is not recommended during the administration of bisoprolol.

Due to the absence of available information on the use of périndopril during breastfeeding, it is not recommended. It is preferable to use other treatments having a well-established safety profile during breastfeeding, particularly for the newborn or the premature infant.

Fertility

No data on fertility is available regarding the use of COSIMPREL.

COSIMPREL has no direct influence on the ability to drive vehicles and use machines, but sensations of dizziness or fatigue related to a drop in blood pressure may occur in some patients, particularly at the beginning or in case of a change in treatment, as well as in case of association with alcohol.

Consequently, the ability to drive vehicles or use machines may be decreased.

Summary of the safety profile

The most frequent adverse effects of bisoprolol are: headache, dizziness, worsening of heart failure, hypotension, sensation of cold in the extremities, nausea, vomiting, abdominal pain, diarrhoea, constipation, asthenia and fatigue.

The most frequently reported adverse effects in clinical trials and observed with perindopril are: headache, vertigo, dizziness, paraesthesia, visual disturbances, tinnitus, hypotension, cough, dyspnoea, nausea, vomiting, abdominal pain, diarrhoea, constipation, dysgeusia, dyspepsia, rash, pruritus, muscle cramps and asthenia.

Table of adverse effects

The following adverse effects have been observed during clinical trials and/or post-marketing use of bisoprolol and perindopril taken separately and are classified according to the MedDRA system organ class and by frequency.

Very common ( ³ 1/10); common ( ³ 1/100, < 1/10); uncommon ( ³ 1/1 000, < 1/100); rare ( ³ 1/10 000, < 1/1000); very rare (< 1/10 000), not known frequency (cannot be estimated from the available data).

*Frequency estimated from clinical trial data for adverse reactions reported post-marketing (spontaneous notifications).

**These symptoms occur particularly at the beginning of treatment. They are generally mild and disappear within 1 to 2 weeks.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicine is important. It allows for continuous monitoring of the benefit/risk ratio of the medicine. Healthcare professionals report any suspected adverse reaction via the national reporting system: French National Agency for Medicines and Health Products Safety (ANSM) and network of Regional Pharmacovigilance Centres – Website: https://signalement.social-sante.gouv.fr