COSYREL

Pregnancy

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

Bisoprolol

Bisoprolol has pharmacological properties that may cause harmful effects on pregnancy and/or the fetus/newborn (a decrease in placental perfusion associated with growth retardation, intrauterine death, abortion or early labor, and adverse effects (e.g. hypoglycemia and bradycardia) may occur in the fetus and newborn). If treatment with beta-blockers is necessary, selective beta-1 agents should be preferred.

Bisoprolol should not be used during pregnancy unless necessary. If treatment with bisoprolol is considered necessary, uterine-placental blood flow and fetal growth should be monitored. In case of harmful effects on pregnancy or the fetus, an alternative treatment should be considered. The newborn must be closely monitored. Symptoms of hypoglycemia and bradycardia generally appear within the first 3 days of life.

Perindopril

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 during the 2nd and 3rd trimesters of pregnancy (see sections 4.3 and 4.4).

The available epidemiological data regarding 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 treatment with ACE inhibitors is considered essential, it is recommended that patients planning a pregnancy change their antihypertensive treatment to a medicine with a well-established safety profile during pregnancy.

In case of pregnancy diagnosis, treatment with ACE inhibitors 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 induce fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia) (see section 5.3). In case of exposure to an ACE inhibitor from the 2nd trimester of pregnancy, it is recommended to perform a fetal 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 into breast milk is unknown. Therefore, breastfeeding is not recommended during the administration of bisoprolol.

Due to the lack of information available on the use of perindopril during breastfeeding, it is not recommended. It is preferable to use other treatments with a well-established safety profile during breastfeeding, particularly for the newborn or preterm 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, diarrhea, constipation, asthenia and fatigue.

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

Table of adverse effects

The following adverse effects were observed during clinical trials and/or post-marketing use of bisoprolol and périndopril taken separately and are classified according to the MedDRA classification by system organ class and based on their frequency.

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

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

**These symptoms appear more particularly at the start of treatment. They are generally mild and disappear in 1 to 2 weeks.

Reporting of suspected adverse effects

Reporting suspected adverse effects after medicinal product authorization is important. It allows for 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: https://signalement.social-sante.gouv.fr