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Valg af anxiolytikum og amning


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Question

What is the benzodiazepine drug of choice during lactation?


Conclusion

The benzodiazepine of choice during lactation is oxazepam, as very small absolute amounts of drug is transferred to the suckling child. The lack of active metabolites and relatively short elimination also weigh in favourably. It is recommended to ingest an evening dose of oxazepam immediately after the evening breast feeding in order to minimize exposure.


Case description

A 36-year-old woman is breast feeding her seven-week-old child. She receives nortriptyline, but her treating psychiatrist would like to add a benzodiazepine due to anxiety.


Background information

Although oxazepam is excreted into the human milk (1), only two benzodiazepines result in a lower percentage of the weight-adjusted maternal dose being administered to the suckling infant through breast milk: oxazepam 0.9% – flunitrazepam 0.6% and midazolam 0.7% (2). However, since these drugs are strong hypnotics, they could not be used as anxiolytics necessitated by the patient in question. Oxazepam owes this advantageous position over the other benzodiazepine anxiolytics to the facts that it has no active metabolites and a relatively short elimination half-time (3).

 

In several clinical trials, performed in small number of patients, milk/plasma ratios for oxazepam have varied between 0.1 and 0.3 (3,4). The maximum concentration in milk and the corresponding maximum absolute dose for infant being 26 microgram/l and 4.0 microgram/kg/day, respectively (4).

 

In one reviewers opinion the limited distribution of benzodiazepines into the breast milk did not constitute a hazard to the breast fed infant (5). The position of the American Academy of Pediatrics Committee on Drugs is that the repeated use of benzodiazepines by nursing mothers is generally not recommended (6), since it can lead to accumulation of these drugs in the infants, which results in poor suckling, somnolence and loss of body weight (7). The WHO Working Group on Drugs and Human Lactation concludes that mothers receiving occasional small doses of the benzodiazepines can safely breast feed (3).

 

It should be stressed that the half-life of oxazepam is considerably prolonged (22 hours) in newborn due to the immaturity of the infants´ glucuronidation capacity (8). This increases the risk for accumulation in the infant, especially during long-term treatment and high doses. If given in the lowest possible dose, (ie. 10-15 mg at a maximum of three times a day) over a period as short as possible, oxazepam during lactation should be safely administered.


References

  1. Wretlind M. Excretion of oxazepam in breast milk. Eur J Clin Pharmacol. 1987;33(2):209-10.
  2. Speight TM, Holford NHG, editors. Avery’s Drug treatment. 4th edition. Auckland: Adis; 1997:1714-5.
  3. Oxazepam. REPROTOX(R) in Reprorisk System. Thomson MICROMEDEX, Greenwood Village, Colorado (Edition expires 04/12).
  4. Bennett PN (ed). Drugs and human lactation. 2nd ed. Amsterdam: Elsevier; 1996:471-2.
  5. McElhatton PR. The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994;8(6):461-75.
  6. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
  7. Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatr Serv. 2002;53(1):39-49.
  8. Yaffe JS, Aranda JV, editors. Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice. 3th ed. Philadelphia: : Lippincott Williams & Wilkins; 2004:34.


References Consulted

  • Speight TM, Holford NHG, editors. Avery´s Drug treatment. 4th ed. (1997).
  • Bloom FE et al (eds). Psychopharmacology. The fourth generation of progress (1995).
  • Laegemiddelinformationscentralen, CeKFO, Odense, Denmark.
  • Dollery C Sir editor. Therapeutic Drugs 2nd ed. (1999).
  • Laegemiddelkataloget. http://www.lk-online.dk
  • Danish Medicines Agency. Summary of product characteristics. www.dkma.dk
  • Dukes MNG, et al editor. Meyler´s Side effects of drugs. 14th ed. (2000).
  • Bennett PN (ed), Drugs and human lactation. 2nd ed. (1996).
  • Medline.
  • Drugline.
  • Davies DM et al, editors. Davie´s textbook of adverse drug reactions. 5th ed. (1998).
  • Goodman & Gillman´s. The Pharmacological Basis of Therapeutics 10th ed. (2001).
  • Janus. http://www.janusinfo.se
  • Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. (2002).
  • Micromedex.
  • RELIS database. http:/www.relis.no/database.

 

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