Is any statin compatible with breast-feeding?/nStatin treatment has been withdrawn during pregnancy

Fråga: Is any statin compatible with breast-feeding?

Statin treatment has been withdrawn during pregnancy in a woman with familial hypercholesterolemia. The treating physician wants to reinstate the medication after the child is born.

Sammanfattning: Available data indicate that statins are excreted into milk and that the suckling infant may be exposed to drug amounts that are not negligible. Theoretically, statin exposure could have an inhibitory effect on cell growth in the exposed child, and use of these drugs cannot be recommended during breast-feeding. If breast-feeding is warranted, the possibility of postponing cholesterol-lowering treatment should be evaluated.

Svar: In the Swedish catalogue of approved medical products (Fass), it is stated that pravastatin passes into breast milk in amounts that could cause adverse effects in the suckling child. It is said to be unknown to what extent simvastatin, fluvastatin, atorvastatin and rosuvastatin is excreted into milk, and nursing is not recommended when taking these drugs (1).

A textbook on drug treatment and lactation states that pravastatin is excreted into breast milk in "small amounts" and that there is a potential risk of adverse effects in the nursed infant (2). According to the manufacturer, fluvastatin is also excreted into milk in concentrations twice as high as those in plasma (3). Although human data is absent, rat studies demonstrate excretion of atorvastatin into milk, resulting in a milk-plasma ratio of approximately 2 (4).

At steady-state, treatment with fluvastatin 40 mg BID results in a mean peak plasma concentration of 443 ug/L (5). Assuming a concentration in milk twice as high as that in plasma, a milk consumption of 150 mL/kg/day and a maternal weight of 60 kg, the maximum weight-adjusted dose of the infant would be 10 percent of the mother´s dose. The uncertainty regarding transfer of other statins into milk precludes quantitative estimations of exposure in suckling children.

Fluvastatin is completely absorbed, but undergoes extensive presystemic metabolism (6). However, it is not obvious to what extent the systemic concentrations are predictive of the pharmacological effects in the pre-systemically exposed liver, and it is not clear whether all metabolites are pharmacologically inactive. Statins block cholesterol synthesis by inhibiting the synthesis of a cholesterol precursor, mevalonic acid (7). This substance is essential for cell growth and an inhibitory effect of statins on e.g. leukemic cell growth has been demonstrated (7). Theoretically, inhibition of cell growth could have deleterious effects in growing children, and the mechanism has been implicated in statin-induced skeletal teratogenicity (7). Fass 2005 Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. P 1147. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. P 579. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2002. P 107. Barilla D, Prasad P, Hubert M, Gumbhir-Shah K. Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol. Biopharm Drug Dispos 2004; 25:51-9. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. F136-9. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. S37-41.