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Zolpidem (Ambien ®)
Hypnotic. Non-benzodiazepine of the imidazopyridine class, shares some of the pharmacological properties
of the benzodiazepines. Molecular weight:764.88
Reproductive studies conducted in rats and rabbits
showed no teratogenic effects after zolpidem administration. In rats and rabbits no fetal toxicity was noted at 5 times
and 7 times the maximum human
dose (on a mg/m 2 basis) respectively. [1]
In rats, adverse maternal and fetal effects occurred at 20 and 100 mg
base/kg and included dose-related maternal lethargy and ataxia and a
dose-related trend to incomplete ossification of fetal skull bones. In
rabbits there was an
increase in postimplantation fetal loss and underossification of sternebrae
in viable fetuses at the dose of 16 mg base/kg. These fetal findings in
rabbits are often secondary to reductions in maternal weight gain [1].
One case report suggests zolpidem crosses the human placenta [8].
Although animal studies have been reassuring data on the use of zolpidem
during human pregnancy is minimal. In one observational study from England first trimester exposure in 18 pregnancies (including one set of twins)
resulted in delivery of 11 normal infants and two spontaneous abortions. Six
women chose to have elective abortions
[2].
BREAST FEEDING: Excretion of zolpidem into human milk
appeared to be very low (less than
0.02% of the total administered dose) in a study of five lactating women
treated with a single 20 mg dose of zolpidem. The milk:plasma ratio was 0.13 at 3 hours [3]. The American Academy of Pediatrics considers zolpidem to be compatible with breastfeeding [4].
NEONATAL SIDE EFFECTS:
Although withdrawal may occur with excessive doses of zolpidem, the incidence of rebound insomnia or withdrawal symptoms after discontinuation
of the drug when it is given as recommended appears to be much lower than
that of benzodiazepines [5-7]. Nonetheless children born of mothers taking
sedative/hypnotic drugs may be at some risk for withdrawal symptoms from the
drug during the postnatal period. In addition, neonatal flaccidity has been
reported in infants born of mothers who received sedative/hypnotic drugs
during pregnancy. [1]
SEARCH LITERATURE
1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR;
2004: 3008
2. Wilton LV, Pearce GL, Martin RM et al: The outcomes of pregnancy women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 105:882-889, 1998.
MEDLINE
3. Pons G, et al., Zolpidem excretion in breast milk. Eur J Clin Pharmacol. 1989;37:245-8.
MEDLINE
4. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108:776-89.
5. Aragona M.Abuse, dependence, and epileptic seizures after zolpidem withdrawal:
review and case report.Clin Neuropharmacol. 2000;23:281-3.
MEDLINE
6. Hajak G, et al., Abuse and dependence potential for the
non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case
reports and epidemiological data.Addiction. 2003;98:1371-8
MEDLINE
7. Holm KJ and Goa KL.Zolpidem: an update of its pharmacology,
therapeutic efficacy and tolerability in the treatment of insomnia. Drugs. 2000;59:865-89.
MEDLINE
8. Askew JP.Zolpidem addiction in a pregnant woman with a history of second-trimester bleeding.Pharmacotherapy. 2007 Feb;27(2):306-8.PMID: 17253922
Created: 11/30/2002
Update: 12/26/2003
Update: 1/12/2009
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