4/10/05njm

Q. Can we use Zolpidem for relaxation in pregnancy?

A. Yes, we use Zolpidem for relaxation in pregnancy. Here are more
details

Zolpidem is in the hypnotic, nonbenzodiazepine category for short-term
treatment of insomnia. Zolpidem has a favorable pharmacodynamic profile
for use in pregnancy and is Risk Factor Class B (show Table I below).
Avoid alcohol and other CNS depressants while taking this medication;
for fastest onset, take on an empty stomach; may cause drowsiness.

Zolpidem is rapidly absorbed and has an onset of action is 30 minutes
with a duration of 6-8 hours. In some centers, the P + T Committee has
approached the maternity providers to change to a Zolpidem-like product
to avoid using barbiturate products which may have more abuse potential.

Zolpidem is structurally dissimilar to benzodiazepine, however, has much
or all of its actions explained by its effects on benzodiazepine (BZD)
receptors, especially the omega-1 receptor (with a high affinity ratio
of the alpha 1/alpha 5 subunits); retains hypnotic and much of the
anxiolytic properties of the BZD, but has reduced effects on skeletal
muscle and seizure threshold.

#2

**A. What is the current status of Therapeutic rest in prolonged latent
phase of labor?**

Q. There is little new data. Common treatment modalities include
therapeutic rest; therapeutic rest, oxytocin, amniotomy; and cervical
ripening.

For today's discussion, therapeutic rest involves administration of
parenteral analgesics to relieve the patient\'s discomfort and allow for
progression of labor while she rests or sleeps. Subcutaneous morphine
(0.15 mg/kg) or other narcotic analgesics have been used in the past,
but the efficacy of these agents as pain relievers as opposed to
sedatives has been disputed (Koontz) . Approximately 85 percent of women
treated with this regimen will wake up in the active phase of labor, 10
percent will not be in labor (suggesting a diagnosis of false labor),
and 5 percent will have a persistent dysfunctional pattern

Please see a more complete discussion of prolonged latent phase of
labor. (see References below)

**Resources:**

**Zolpidem: Drug information**

<http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/283657&type=A&selectedTitle=1~10>

**Zolpidem: Patient drug information: UpToDate**

<http://www.uptodateonline.com/application/topic.asp?r=/application/topic.asp&file=labordel/7208&type=A&selectedTitle=1~3&app=utdol>

**Prolonged latent phase of labor: UpToDate**

[[http://www.uptodateonline.com/application/topic.asp?file=labordel/7208&type=A&selectedTitle=1\~3]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=labordel/7208&type=A&selectedTitle=1~3)

**Abnormal labor: Protraction and arrest disorders**

<http://www.uptodateonline.com/application/topic.asp?file=labordel/4449>

**Active management of labor**

<http://www.uptodateonline.com/application/topic.asp?file=labordel/2820>

Koontz WL; Bishop EH. Management of the latent phase of labor. Clin
Obstet Gynecol 1982 Mar;25(1):111-4.

1\. Iatrogenic causes of prolonged latent phase such as sedation,
narcotic analgesia, and epidural anesthesia should be avoided during the
latent phase. 2. Cesarean delivery is not appropriate management solely
for failure to progress in latent phase. 3. Multiparas in latent phase
with favorable cervices should be treated with oxytocin stimulation. 4.
Multiparas with unfavorable cervices and most nulliparas should be
treated with therapeutic rest when they become exhausted during a long
latent phase, without regard to an arbitrary time table. 5.
Characteristics of latent phase in induced labors are undefined. 6.
Management of latent phase in the presence of ruptured membranes should
take into consideration the total clinical picture, including
gestational age, presentation, and risk of infection and other pertinent
factors.

**Other Zolpidem Information**

**DOSING: ADULTS**\
Insomnia: Oral: 10 mg immediately before bedtime; maximum: 10 mg
(duration of therapy should be limited to 7-10 days)

**DOSING: ELDERLY** --- 5 mg immediately before bedtime

**DOSING: RENAL IMPAIRMENT** --- Not dialyzable

**DOSING: HEPATIC IMPAIRMENT** --- Decrease dose to 5 mg.

**DOSAGE FORMS**\
Tablet, as tartrate: 5 mg, 10 mg\
  Ambien® PAK™ \[dose pack\]: 5 mg (30s), 10 mg (30s)

**GENERIC EQUIVALENT AVAILABLE** --- No

**ADMINISTRATION** --- Ingest immediately before bedtime due to rapid
onset of action

**LACTATION** --- Enters breast milk/use caution (AAP rates
\"compatible\")

**PHARMACODYNAMICS / KINETICS**\
Onset of action: 30 minutes

Duration: 6-8 hours

Absorption: Rapid

Distribution: Very low amounts enter breast milk

Protein binding: 92%

Metabolism: Hepatic to inactive metabolites

Half-life elimination: 2-2.6 hours; Cirrhosis: Up to 9.9 hours

**USE** --- Short-term treatment of insomnia

**ADVERSE REACTIONS SIGNIFICANT**\
1% to 10%:\
  Cardiovascular: Palpitations\
  Central nervous system: Headache, drowsiness, dizziness, lethargy,
lightheadedness, depression, abnormal dreams, amnesia\
  Dermatologic: Rash\
  Gastrointestinal: Nausea, diarrhea, xerostomia, constipation\
  Respiratory: Sinusitis, pharyngitis

\<1% (Limited to important or life-threatening): Confusion, depression,
falls, impaired concentration, manic reaction, tremor, vomiting

**CONTRAINDICATIONS** --- Hypersensitivity to zolpidem or any component
of the formulation

**WARNINGS / PRECAUTIONS** --- Should be used only after evaluation of
potential causes of sleep disturbance. Failure of sleep disturbance to
resolve after 7-10 days may indicate psychiatric or medical illness. Use
with caution in patients with depression. Behavioral changes have been
associated with sedative-hypnotics. Causes CNS depression, which may
impair physical and mental capabilities. Effects with other sedative
drugs or ethanol may be potentiated. Closely monitor elderly or
debilitated patients for impaired cognitive or motor performance; not
recommended for use in children \<18 years of age. Avoid use in patients
with sleep apnea or a history of sedative-hypnotic abuse.

**RESTRICTIONS** --- C-IV

**DRUG INTERACTIONS** --- Substrate of CYP1A2 (minor), 2C8/9 (minor),
2C19 (minor), 2D6 (minor), 3A4 (major)

Antipsychotics: Sedative effects may be additive with antipsychotics,
including phenothiazines; monitor for increased effect

CNS depressants: Sedative effects may be additive with other CNS
depressants; monitor for increased effect; includes barbiturates,
benzodiazepines, narcotic analgesics, ethanol, and other sedative agents

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of
zolpidem. Example inducers include aminoglutethimide, carbamazepine,
nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of zolpidem. Example
inhibitors include azole antifungals, ciprofloxacin, clarithromycin,
diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone,
nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

SSRIs: Sertraline and fluoxetine (to a lesser extent) have been
demonstrated to increase zaleplon levels; pharmacodynamic effects were
not significantly changed; monitor

**ETHANOL / NUTRITION / HERB INTERACTIONS**\
Ethanol: Avoid ethanol (may increase CNS depression).

Herb/Nutraceutical: St John\'s wort may decrease zolpidem levels. Avoid
valerian, St John\'s wort, kava kava, gotu kola (may increase CNS
depression).

**PRICING** --- (data from drugstore.com)\
Tablets (Ambien)\
  5 mg (30): \$65.99\
  10 mg (30): \$81.99

**MONITORING PARAMETERS** --- Daytime alertness; respiratory and cardiac
status

**REFERENCE RANGE** --- 80-150 ng/mL

**TOXICOLOGY / OVERDOSE COMPREHENSIVE** --- Symptoms include coma and
hypotension. Treatment for overdose is supportive. Rarely is mechanical
ventilation required. Flumazenil has been shown to selectively block
binding to CNS receptors, resulting in reversal of CNS depression but
not always respiratory depression.

Table I: Pregnancy Ratings for Drugs

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