Nadolol

Summary of Use during Lactation

Because of its relatively extensive excretion into breastmilk and its renal excretion, other beta-adrenergic blocking drugs are preferred to nadolol, especially while nursing a newborn or preterm infant.

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 25% protein binding, 70% renal excretion and long half-life, nadolol presents a high risk for accumulation in infants, especially neonates. It is estimated that a fully breastfed infant would receive about 5.1% of the maternal weight-adjusted dosage of nadolol.[2]

Maternal Levels. One mother received nadolol 20 mg daily during gestation for hypertension, with the last dose taken 20 hours before delivery. A single sample of breastmilk obtained 38 hours postpartum (58 hours after the last dose) was 146 mcg/L.[3]

After oral doses of 80 mg daily in 12 women, peak nadolol levels occurred in milk at an average of 6 hours after the dose, compared to peak serum levels at 2.7 hours. Serum and milk half-lives were both about 22 hours. Steady-state milk levels occurred after 3 days of therapy; peak milk levels averaged 443 mcg/L and the mean milk levels averaged 357 mcg/L. None of the infants were breastfed.[4,5]

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

Effects in Breastfed Infants

Relevant published information on nadolol was not found as of the revision date. A study of mothers taking beta-blockers during nursing found a numerically, but not statistically significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated. None of the mothers were taking nadolol.[6]

A prospective study of pregnant patients taking a beta-blocker asked mothers to complete a questionnaire about postpartum breastfeeding and any side effects in their breastfed infants. Two mothers reported taking nadolol in unreported dosages while breastfeeding. Neither reported any adverse reactions in their breastfed infants; both had breastfed during nadolol therapy in a previous pregnancy.[7]

Effects on Lactation and Breastmilk

Relevant published information on the effects of beta-blockade or nadolol 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

Propranolol, Labetalol, Metoprolol

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. [PubMed: 2878668]

2.

Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk: Clinical pharmacokinetic considerations. Clin Pharmacokinet 1988;14:217-40. [PubMed: 3292101]

3.

Fox RE, Marx C, Stark AR. Neonatal effects of maternal nadolol therapy. Am J Obstet Gynecol 1985;152:1045-6. [PubMed: 4025452]

4.

Devlin RG, Duchin KL, Fleiss PM. Nadolol in human serum and breast milk. Br J Clin Pharmacol 1981;12:393-6. [PMC free article: PMC1401819] [PubMed: 6117304]

5.

Devlin RG, Fleiss PM. Nadolol excretion in human milk. Clin Pharmacol Ther 1981;29:240. doi:10.1038/clpt.1981.37 [CrossRef]

6.

Ho TK, Moretti ME, Schaeffer JK, et al. Maternal beta-blocker usage and breast feeding in the neonate. Pediatr Res 1999;45 (4, pt. 2):67A. doi:10.1203/00006450-199904020-00402 [CrossRef]

7.

Freppel R, Gaboriau L, Richardson M, et al. Beta-blockers and breastfeeding: A real-life prospective study. Eur J Clin Pharmacol 2024. [PubMed: 39259357]

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. [PubMed: 556882]

Substance Name

Nadolol

CAS Registry Number

42200-33-9

Drug Class

Breast Feeding

Lactation

Milk, Human

Antihypertensive Agents

Adrenergic Beta-Antagonists

Antiarrhythmics