Summary of Use during Lactation

Clorazepate is excreted into breastmilk and appears to accumulate in the serum of breastfed infants. Because the half-life of clorazepate and its active metabolite are long, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Other agents may be preferred, especially while nursing a newborn or preterm infant. If clorazepate is used, monitor the infant for sedation, poor feeding and poor weight gain.

Drug Levels

Clorazepate is a prodrug of nordiazepam (desmethyldiazepam) which is the primary active metabolite of diazepam.

Maternal Levels. After a single 20 mg intramuscular dose of clorazepate in 7 women, milk nordiazepam levels ranged from 7.5 to 15.5 mcg/L at 2 days after the dose and 6 to 12 mcg/L at 4 days after the dose.[1]

Infant Levels. Nordiazepam has been found in infants' serum in levels higher than milk levels, indicating accumulation, and only slightly lower than adult therapeutic levels after diazepam use by the mother.[2,3]

After a single 20 mg intramuscular dose of clorazepate in 7 women, serum levels of their breastfed infants ranged from trace levels in 5 of the infants to 4 and 7.5 mcg/L in the others on the second day after the dose. On the fourth day after the dose, infant serum levels was a trace amounts in one and ranged from 4 to 8.5 mcg/L in the others, indicating accumulation in infant serum.[1]

Effects in Breastfed Infants

Sedation in infants has been reported during maternal use of diazepam which has nordiazepam as its active metabolite.[3,4] Concern has also been expressed that nordiazepam may compete with bilirubin for hepatic glucuronide conjugation in the neonate.[2]

Effects on Lactation and Breastmilk

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

Alternate Drugs to Consider

(Sedative) Lorazepam, Oxazepam (Seizure Disorder) Carbamazepine, Divalproex, Gabapentin, Lamotrigine, Oxcarbazepine, Phenytoin, Valproic Acid

References

1.

Rey E, Giraux P, d'Athis P, et al. Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam into the feto-placental unit and in the neonate. Eur J Clin Pharmacol. 1979;15:181–5. [PubMed: 37090]

2.

Erkkola R, Kanto J. Diazepam and breast-feeding. Lancet. 1972;299:1235–6. [Letter] [PubMed: 4113217]

3.

Wesson DR, Camber S, Harkey M, et al. Diazepam and desmethyldiazepam in breast milk. J Psychoactive Drugs. 1985;17:55–6. [PubMed: 3920372]

4.

Patrick MJ, Tilstone WJ, Reavey P. Diazepam and breast-feeding. Lancet. 1972;299:542–3. [Letter] [PubMed: 4110044]

Substance Name

Clorazepate

CAS Registry Number

57109-90-7

Drug Class

Breast Feeding

Lactation

Milk, Human

Hypnotics and Sedatives

Anti-Anxiety Agents

Benzodiazepines