C10AA03

Hydrophilic statin ^{(Pan 1991)}, which acts by reducing hepatic cholesterol synthesis. Indicated in the treatment of primary, hetero- and homozygous familial hypercholesterolemia (FH) and combined familial hyperlipemia. Authorized use from 8 years of age. Oral administration in a daily dose.

Its pharmacokinetic data (large volume of distribution, high molecular weight, acidic pKa, hydrophilicity, and rapid clearance) explain the null or negligible passage into breast milk observed. ^{(Saito 2022, Pan 1988)}

The negligible secretion into breast milk, known for pravastatin ^{(Pan 1988)} and rosuvastatin ^{(Lwin 2018, Schutte 2013)} and presumed for the other statins, is very unlikely to alter the lipid composition of breast milk and decrease its cholesterol concentration.

Its low oral bioavailability makes it difficult to pass into infant plasma from ingested breast milk, except in premature infants and the immediate neonatal period where there may be increased intestinal permeability.

There are no published data to indicate that statins taken by the mother during breastfeeding are harmful to the nursing infant. ^{(Holmsen 2017)}

Mothers homozygous for FH took statins during 18 pregnancies and 11 breastfeedings of 3 to 9 months duration. The infants had no developmental or school learning problems. ^{(Botha 2018)}

Expert authors consider safe or probably compatible or of minimal risk the use of statins, especially the hydrophilic ones rosuvastatin or pravastatin, during pregnancy and/or breastfeeding. ^{(Hale, Botha 2018, Holmsen 2017, Amir 2011)}

Breastfeeding has a cardioprotective effect, with reduced risk of myocardial infarction and hypertension, improved blood glucose control and lipid profile, and reduced risk of type 2 diabetes , which is particularly important for women with FH and their infants. ^{(Holmsen 2017)}

The health benefits of a woman with FH continuing to breastfeed while using a statin outweigh the low risk to the child. It is safe and beneficial for children of women with FH to breastfeed while the mother is receiving adequate treatment with a statin, preferably rosuvastatin. ^{(Holmsen 2017)}

Other authors advise postponing statin treatment from 3 months before pregnancy and until breastfeeding ends or is not exclusive ^{(FDA 2021, Shala 2020, Lawrence 2016 p 393)}. Except in severe forms of hypercholesterolemia ^{(Moss 2018)}, postponing drug treatment for a few months is not likely to alter the long-term outcome of the disease in the mother. ^{(FDA 2021)}

One hundred and two women affected by FH stopped taking statins for a mean of 2.3 years (range 0 to 14 years) for the times of pregnancy and breastfeeding without it being known whether this increased the risk of cardiovascular disease ^{(Klevmoen 2021)}. It is known that hypercholesterolemia maintained during pregnancy in a woman with FH increases the risk of atherosclerosis in the child ^{(Napoli 1999)}, that these women develop very high cholesterol levels during this period ^{(Holmsen 2017, Avis 2009)} and that there is an increase in the thickness of the arterial intima media during pregnancy in women with FH. ^{(Kusters 2010)}

It is advisable to follow a lipid-lowering diet and exercise.

Cholesterol levels are normally increased (by 40%) during pregnancy and lactation in healthy women ^{(Lawrence 2016 p590)}. Breast milk cholesterol is synthesized in the mammary gland and its concentration in breast milk varies from 30 mg/dL in colostrum to 10 - 20 mg/dL in mature milk.^{(Lawrence 2016 p98, 105 & 767)}

Cholesterol concentration is greatly increased (up to 3-fold) in the milk of lactating mothers affected with familial hypercholesterolemia in homozygous form ^{(Holmsen 2017, Tsang 1978)}. Statin treatment would, at most, reduce it to normal levels. ^{(Holmsen 2017)}

Cholesterol is necessary for the development of brain tissue, myelination of nerves and is the basis of many enzymes. Breastfed infants have higher plasma cholesterol levels than those fed artificial formulas and this would protect them against the consequences of hypercholesterolemia in adulthood. ^{(Lawrence 2016 p108)}

Infants fed formula substitutes ("artificial milks") do not receive cholesterol in their diet, as these products do not contain cholesterol^{(Lawrence 2016 p 109 and 215)}. The amount of cholesterol in breast milk that would remain after the hypothetical cholesterol reduction produced by the statins taken by the mother would still be much higher than that provided by artificial formulas. ^{(Holmsen 2017)}

In conclusion, it seems wise to advise mothers with severe FH to continue statins during lactation. Mothers without FH and with moderately high cholesterol levels can discontinue statins during the lactation period by monitoring their low density lipoproteins (LDL) levels.

For considerations on the appropriateness of lipid-lowering treatment during lactation see Maternal hyperlipidemia, hypercholesterolemia, hypertriglyceridemia.

See below the information of this related product:

• Maternal Hyperlipidemia, Hypercholesterolemia, Hypertriglyceridemia (Safe substance and/or breastfeeding is the best option.)