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]

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.[7]

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. Abstract. 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–Abstract 385. [CrossRef]

7.

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

Antihypertensive Agents

Adrenergic Beta-Antagonists

Antiarrhythmics