IRVECOR

Pregnancy

Irbesartan and amlodipine

There is limited data on the use of APREXEVO in pregnant women. No reproductive toxicity studies in animals have been performed with APREXEVO.

As for irbesartan (see details below), the use of APREXEVO is not recommended during the first trimester of pregnancy (see section 4.4). The use of APREXEVO is contraindicated during the second and third trimesters of pregnancy (see section 4.3).

Irbesartan

The available epidemiological data regarding the risk of teratogenicity after exposure to ACE inhibitors during the first trimester of pregnancy does not allow for a conclusion. However, a slight increase in risk cannot be excluded. There is no controlled epidemiological study available regarding the use of AIIRA in the 1 trimester of pregnancy, however a risk similar to ACE inhibitors could exist for this class. Unless continued treatment with AIIRA is considered essential, it is recommended to change the antihypertensive treatment in patients planning a pregnancy to an antihypertensive treatment with an established safety profile during pregnancy. When pregnancy is diagnosed, treatment with AIIRA should be stopped immediately and, if appropriate, alternative treatment should be started.

Based on post-marketing experience, AIIRA treatments induce foetotoxicity in humans (decreased renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalaemia) when administered during the 2nd and 3rd trimester of pregnancy. Studies in animals have shown reproductive toxicity (see section 5.3).

In case of exposure to AIIRA from the second trimester of pregnancy, it is recommended to perform a foetal ultrasound to check renal function and skull bones. Infants born to mothers treated with AIIRA should be closely monitored for hypotension.

Amlodipine

The safety of amlodipine during pregnancy has not been established. Studies in animals have shown reproductive toxicity at high doses (see section 5.3). The use of amlodipine in monotherapy during pregnancy is only recommended if no safer alternative is available and when the disease itself poses greater risks for the mother and the foetus.

Breastfeeding

Irbesartan and amlodipine

No information is available regarding the use of APREXEVO during breastfeeding. As for irbesartan and amlodipine (see details below), a decision must be made whether to discontinue breastfeeding or to discontinue treatment taking into account the benefit of breastfeeding for the child against the benefit of treatment for the woman.

Irbesartan

As no information is available regarding the use of irbesartan during breastfeeding, this medicine is not recommended. Alternative treatments with better established safety profiles during breastfeeding are advised, especially when breastfeeding a newborn or preterm infant.

It is unknown whether irbesartan or its metabolites are excreted in human milk.

Available pharmacodynamic and toxicological data in rats have shown that irbesartan and its metabolites are excreted in milk (see section 5.3).

Amlodipine

Amlodipine is excreted in human milk. The proportion of the maternal dose received by the infant has been estimated with an interquartile range of 3 to 7 %, with a maximum of 15 %. The effect of amlodipine on infants is unknown. A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with amlodipine should be made taking into account the benefit of breastfeeding to the child and the benefit of amlodipine therapy to the mother.

Fertility

Irbesartan and amlodipine

No fertility toxicity studies in animals have been performed with APREXEVO.

Irbesartan

Irbesartan had no effect on the fertility of treated rats and their offspring up to the dose levels inducing the first signs of parental toxicity (see section 5.3).

Amlodipine

Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated by calcium channel blockers. Clinical data are insufficient regarding the potential effect of amlodipine on fertility. In a rat study, adverse effects were observed on male fertility (see section 5.3).

When driving vehicles or using machines, it should be taken into account that sensations of dizziness or fatigue may occasionally occur during treatment of hypertension.

Amlodipine may have a minor or moderate influence on the ability to drive vehicles and use machines. If patients treated with amlodipine present sensations of dizziness, headaches, fatigue or nausea, their reaction capacity may be impaired.