INEGY /

Prevention of cardiovascular events

EZETIMIBE/SIMVASTATINE ARROW is indicated to reduce the risk of cardiovascular events (see section 5.1) in patients with coronary artery disease and a history of acute coronary syndrome (ACS), previously treated or not with a statin.

Hypercholesterolaemia

EZETIMIBE/SIMVASTATINE ARROW is indicated as an adjunct to diet in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia when the use of a combination is appropriate:

· patients not adequately controlled by a statin alone;

· patients already receiving a statin and ezetimibe.

Homozygous familial hypercholesterolaemia (HFHo)

EZETIMIBE/SIMVASTATINE ARROW is indicated as an adjunct to diet in patients with HFHo. These patients may also receive adjuvant treatments (example: LDL apheresis).

Pregnancy

Atherosclerosis is a chronic disease, and in general, stopping lipid-lowering drugs during pregnancy should have little impact on the long-term risk associated with primary hypercholesterolemia.

ezetimibe/simvastatin combination

EZETIMIBE/SIMVASTATINE ARROW is contraindicated during pregnancy. No clinical data are available on the use of the ezetimibe/simvastatin combination during pregnancy. Animal studies on the use of the combination have shown reproductive toxicity (see section 5.3).

Simvastatin

Safety of use has not been established in pregnant women. No controlled clinical studies of simvastatin have been conducted in pregnant women. Rare cases of congenital anomalies have been reported following intrauterine exposure to HMG-CoA réductase inhibitors. However, upon analysis of approximately 200 prospectively followed pregnancies exposed during the first trimester to simvastatin or another closely related HMG-CoA réductase inhibitor, the incidence of congenital anomalies was comparable to that observed in the general population. The number of pregnancies was statistically sufficient to exclude a ≥ 2,5-fold increase in congenital anomalies compared to the baseline incidence.

Although there is no evidence that the incidence of congenital anomalies in the offspring of patients taking simvastatin or another closely related HMG-CoA reductase inhibitor differs from that observed in the general population, maternal treatment with simvastatin may reduce fetal mevalonate levels, which is a precursor to cholesterol biosynthesis. For this reason, EZETIMIBE/SIMVASTATINE ARROW should not be used in pregnant women, women wishing to become pregnant or who think they may be pregnant. Treatment with EZETIMIBE/SIMVASTATINE ARROW should be discontinued during the duration of pregnancy or until it has been established that the woman is not pregnant (see section 4.3).

Ezetimibe

No clinical data are available on the use of ezetimibe during pregnancy.

Breastfeeding

EZETIMIBE/SIMVASTATINE ARROW is contraindicated during breastfeeding. Studies conducted in rats have shown that ezetimibe is excreted in breast milk. No data exist on the secretion of the active substances of the ezetimibe/simvastatin combination into breast milk in women (see section 4.3).

Fertility

Ezetimibe

No clinical data are available on the effect of ezetimibe on human fertility. Ezetimibe has had no effect on the fertility of male or female rats (see section 5.3).

Simvastatin

No clinical data are available on the effect of simvastatin on human fertility. Simvastatin has had no effect on the fertility of male and female rats (see section 5.3).

The effects on the ability to drive vehicles and use machines have not been studied. However, when driving vehicles or using machines, account must be taken of the fact that dizziness has been reported.