Also known as Betimol, Blocadren, Timolol anhydrous, Timololo, Timololum

A propanolamine derivative and a non-selective beta-adrenergic antagonist with antihypertensive property. Timolol competitively binds to beta-1-adrenergic receptors in the heart and vascular smooth muscle and beta-2-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in beta-adrenergic stimulation. Beta-1-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta-2-blockade results in an increase in peripheral vascular resistance. The ultimate results include vasodilation, and negative chronotropic and inotropic cardiac effects. In addition, timolol reduces intra-ocular pressure possibly by decreasing aqueous humor production by reduction of blood flow to the ciliary processes and cAMP synthesis.

Originator: NCI Thesaurus | Source: The website of the National Cancer Institute (http://www.cancer.gov)

Can I take Timolol while breastfeeding?

Because of the variability in excretion of timolol into breastmilk and minimal reported experience during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.

Ophthalmic use of timolol by the mother should pose little risk to the breastfed infant. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

Drug levels

The excretion of beta-adrenergic blocking drugs into breastmilk is largely determined by their protein binding. Those with low binding are more extensively excreted into breastmilk.[1] Accumulation of the drugs in the infant is related to the fraction excreted in urine. With less than 10% protein binding, 20% renal excretion and a relatively short half-life, timolol presents a moderate risk for accumulation in infants, especially neonates.

Maternal Levels. Timolol was measured in milk during the use of ophthalmic drops twice daily in one eye. Although the time of the previous dose was not stated, a predose milk level of 0.5 mcg/L was measured. One and one-half hours after a single drop of 0.5% timolol maleate, the milk level was 5.6 mcg/L. The authors estimated that use of 0.5% timolol drops in one eye twice daily gave the infant 0.63% of a cardiac dose and treatment of both eyes would be 1.25% of a cardiac dose.[2]

A 32-year-old woman was using ophthalmic drops containing 0.5% timolol and 0.2% brimonidine twice daily in the right eye for 6 months. Four milk samples were collected over 6 days, but the times with respect to dosages or nursing were not reported. Milk timolol concentrations ranged from 0 to 0.37 mcg/L. The authors estimated that the maximum dose that a fully breastfed infant would obtain would be 123 ng/kg daily or 0.012% of the weight-adjusted maternal dosage. If the mother had been applying the medication to both eyes, these values would be approximately doubled.[3]

Nine women taking oral timolol 5 mg three times a day had a mean milk timolol level of 15.9 mcg/L (range 2 to 55 mcg/L). In 4 women taking 10 mg three times a day, the mean milk timolol levels was 41 mcg/L (range 7 to 88 mcg/L). The time after the dose when milk was sampled was not stated. In these cases it was estimated that a fully breastfed infant would receive between 0.96 to 1.2% of the maternal weight-adjusted dosage.[4]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

The excretion of beta-adrenergic blocking drugs into breastmilk is largely determined by their protein binding. Those with low binding are more extensively excreted into breastmilk.[1] Accumulation of the drugs in the infant is related to the fraction excreted in urine. With less than 10% protein binding, 20% renal excretion and a relatively short half-life, timolol presents a moderate risk for accumulation in infants, especially neonates.

Maternal Levels. Timolol was measured in milk during the use of ophthalmic drops twice daily in one eye. Although the time of the previous dose was not stated, a predose milk level of 0.5 mcg/L was measured. One and one-half hours after a single drop of 0.5% timolol maleate, the milk level was 5.6 mcg/L. The authors estimated that use of 0.5% timolol drops in one eye twice daily gave the infant 0.63% of a cardiac dose and treatment of both eyes would be 1.25% of a cardiac dose.[2]

A 32-year-old woman was using ophthalmic drops containing 0.5% timolol and 0.2% brimonidine twice daily in the right eye for 6 months. Four milk samples were collected over 6 days, but the times with respect to dosages or nursing were not reported. Milk timolol concentrations ranged from 0 to 0.37 mcg/L. The authors estimated that the maximum dose that a fully breastfed infant would obtain would be 123 ng/kg daily or 0.012% of the weight-adjusted maternal dosage. If the mother had been applying the medication to both eyes, these values would be approximately doubled.[3]

Nine women taking oral timolol 5 mg three times a day had a mean milk timolol level of 15.9 mcg/L (range 2 to 55 mcg/L). In 4 women taking 10 mg three times a day, the mean milk timolol levels was 41 mcg/L (range 7 to 88 mcg/L). The time after the dose when milk was sampled was not stated. In these cases it was estimated that a fully breastfed infant would receive between 0.96 to 1.2% of the maternal weight-adjusted dosage.[4]

Infant Levels. Relevant published information was not found as of the revision date.

Possible effects on lactation

Relevant published information on the effects of beta-blockade or timolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol.[8]

Alternate drugs to consider

Labetalol, Levobunolol, Metipranolol, Metoprolol, Propranolol

References

1. Riant P, Urien S, Albengres E et al. High plasma protein binding as a parameter in the selection of betablockers for lactating women. Biochem Pharmacol. 1986;35:4579-81. PMID: 2878668

2. Lustgarten JS, Podos SM. Topical timolol and the nursing mother. Arch Ophthalmol. 1983;101:1381-2. PMID: 6615302

3. Madadi P, Koren G, Freeman DJ et al. Timolol concentrations in breast milk of a woman treated for glaucoma: calculation of neonatal exposure. J Glaucoma. 2008;17:329-31. PMID: 18552619

4. Fidler J, Smith V, de Swiet M. Excretion of oxprenolol and timolol in breast milk. Br J Obstet Gynaecol. 1983;90:961-5. PMID: 6626493

5. Boutroy MJ, Bianchetti G, Dubruc C et al. To nurse when receiving acebutolol: is it dangerous for the neonate? Eur J Clin Pharmacol. 1986;30:737-9. PMID: 3770068

6. Schimmel MS, Eidelman AI, Wilschanski MA et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr. 1989;114:476-8. PMID: 2921694

7. Johnson SM, Martinez M, Freedman S. Management of glaucoma in pregnancy and lactation. Surv Ophthalmol. 2001;45:449-54. PMID: 11274697

8. Board JA, Fierro RJ, Wasserman AJ et al. Effects of alpha- and beta-adrenergic blocking agents on serum prolactin levels in women with hyperprolactinemia and galactorrhea. Am J Obstet Gynecol. 1977;127:285-7. PMID: 556882

Last Revision Date

20150310

Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

Source: LactMed – National Library of Medicine (NLM)

3D Model of the Timolol molecule

MolView – data visualization platform