Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Drugline nr 20096

Publicerat 2003-06-02

Question

Is glaucoma treatment with locally administered dipivefrin, dorzolamide, timolol or latanoprost compatible with breast-feeding?

A 30-year-old woman with severe glaucoma is now pregnant. She has been successfully treated with timolol eye-drops for several years. However, with timolol treatment, caution is advised towards the end of pregnancy because of the possible risk of fetal bradykardia.

Answer

No information regarding breast-feeding and the epinephrine prodrug dipivefrin was found in Drugline, Medline or standard pharmacological literature. However, with the total daily dose of dipivefrine being at most 0.2 mg, the half-life of the derivative epinehrine being very short and the oral absorption of epinephrine negligable, the maternal use of dipivefrine eye-drops must be considered safe for the nursing infant (1).

According to the manufacturer, local administration of the beta-blocker timolol causes milk levels high enough to cause pharmacological effects in the suckling child (1). With systemic treatment with timolol (15-30 mg/d) to nursing mothers, the maximum observed milk level was 41 ug/L. This would theoretically expose the child to a weight adjusted daily dose corresponding to 3.3 percent of the mother´s, which is considered safe in healthy infants (3). In the only published case of timolol milk transfer in a woman treated with timolol eye drops (0.5 mg/d), the peak concentrations in milk was much lower, 5.6 ug/L (3).

Regarding the carbonic anhydrase inhibitor dorzolamide, the manufacturer states that data concerning the compatibility with breast-feeding is missing (1). For another carbonic anhydrase inhibitor, acetazolamide, passage to the milk is low and the exposure to the child negligible (2). Based on structural similarity, one textbook extrapolates these findings to other substances of the same group and states that use of carbonic anhydrase inhibitors for glaucoma is acceptable in nursing mothers (2). Dorzolamide has a very long terminal half-life of four months, which could be a reason to avoid it in a nursing mother.

The prostaglandin F2-analogue latanoprost is, according to the manufacturer, contraindicated in nursing mothers. The reason for this is allegedly that it passes over to the milk (1). However, one textbook points out that no negative effects have been reported in suckling children exposed to latanoprost and suggests that it could be used in nursing women with severe glaucoma, as long as the child is carefully observed (2). As possible long term effects of this drug is unknown, we would still not recommend this drug during breast-feeding.

Conclusion

Milk transfer data from one nursing mother using timolol eye drops suggests that the drug is compatible with breast-feeding, since the exposure to the infant is very low. The use of dipivefrin can also be considered safe, as dipivefrin is hydrolysed to epinephrine, which is not absorbed orally. There is no data regarding milk transfer of dorzolamide. One textbook states that the drug is compatible with breast-feeding, based on structural similarity with another safe drug of the same class. Information on latanoprost is sparse. It passes over to milk in unknown amounts. The possible effect any of these ocular prepations on the production of breast milk has not been considered in this document.

Lindh J
Böttiger Y

References

  1. FASS 2003, p. 1538-9, p. 259-60, p. 1623-4
  2. Schaefer C, editor. Drugs during pregnancy and lactation. Handbook of prescription drugs and comparative risk assessment. Amsterdam: Elsevier; 2001. p. 276, 280, 288-9.
  3. Bennett PN (ed), Drugs and human lactation. 2nd ed. Amsterdam: Elsevier; 1996. p. 265-6.

Senast ändrad 2018-09-20