clorazepate

Contraindicated in:

Hypersensitivity;
Cross-sensitivity with other benzodiazepines may occur;
Pre-existing CNS depression;
Severe uncontrolled pain;
Angle-closure glaucoma;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

All patients (may ↑ risk of suicidal thoughts/behaviors);
Hepatic impairment;
Patients who may be suicidal or have been addicted to drugs in the past;
Severe pulmonary disease;
Geri: Appears on Beers list. ↑ risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. If possible, avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

EENT: blurred vision

GI: constipation, diarrhea, nausea, vomiting

Neuro: dizziness, drowsiness, lethargy, ataxia, depression, hangover, headache, paradoxical excitation, slurred speech, SUICIDAL THOUGHTS

Resp: RESPIRATORY DEPRESSION

Misc: physical dependence, psychological dependence, tolerance

Interactions ⬆ ⬇

Drug-drug:

Use with opioids or other CNS depressants, including otherbenzodiazepines, non-benzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Cimetidine, hormonal contraceptives, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propranolol, or valproic acid may ↓metabolism of clorazepate, ↑ its actions.
May ↓ efficacy of levodopa.
Rifampin or barbiturates may ↓ metabolism and ↓ effectiveness of clorazepate.
Sedative effects may be ↓ by theophylline.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile↑ CNS depression.

Availability ⬆ ⬇

(Generic available)

Tablets: 3.75 mg; 7.5 mg; 15 mg

Route/Dosage ⬆ ⬇

Prescribe largest dose at bedtime to avoid daytime sedation. Can be used on prn basis for anxiety
PO (Adults ): Anxiety: 7.5–15 mg 2–4 times daily or 15 mg at bedtime initially. Alcohol withdrawal: 30 mg initially, then 15 mg 2–4 times daily on 1st day, then gradually ↓ over subsequent days.
PO (Adults and Children >12 yr): Anticonvulsant: 7.5 mg 3 times daily; may ↑ by no more than 7.5 mg/day at weekly intervals (daily dose not to exceed 90 mg).
PO Geriatric Patients ): Anxiety: 7.5 mg 1–2 times daily; may be ↑.
PO (Children 9–12 yr): Anticonvulsant: 7.5 mg twice daily initially, may ↑ by no more than 7.5 mg/wk (not to exceed 60 mg/day).

US Brand Names ⬆ ⬇

~~Gen-XENE,~~ ~~Tranxene T-Tab~~

Action ⬆ ⬇

Acts at many levels in the CNS to produce anxiolytic effect and CNS depression (by stimulating inhibitory GABA receptors).
Produces skeletal muscle relaxation (by inhibiting spinal polysynaptic afferent pathways).
Also has anticonvulsant effect (enhances presynaptic inhibition).

Therapeutic effects:

Relief of anxiety.
Sedation.
Prevention of seizures.

Classifications ⬆ ⬇

Therapeutic Classification: anticonvulsants, sedative/hypnotics

Pharmacologic Classification: benzodiazepines

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed from the GI tract as desmethyldiazepam.

Distribution: Widely distributed.

Metabolism/Excretion: Metabolized by the liver; some conversion to active compounds.

Half-Life: 48 hr.

Contr. Subst. Schedule ⬆ ⬇

Time/Action Profile ⬆ ⬇

(sedation)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 hr	1–2 hr	up to 24 hr‡

‡May last longer in geriatric patients.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed, not to skip or double up on missed doses. Abrupt withdrawal may cause status epilepticus, tremors, nausea, vomiting, and abdominal and muscle cramps. Instruct patient to read the Medication Guide before starting and with each Rx refill, changes may occur.
- Advise patient that clorazepate is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
- May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to drug is known. Instruct patient and family how to reduce falls risk at home.
- Caution patient to avoid alcohol or other CNS depressants, including opioids, concurrently with this medication, may cause respiratory depression and overdose. Advise patient to consult health care professional prior to taking OTC or herbal products.
- Instruct patient and family to notify health care professional of unusual tiredness, bleeding, sore throat, fever, clay-colored stools, yellowing of skin, or behavioral changes. Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
- May cause fetal harm. Advise females of reproductive potential to contact health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Monitor infants exposed to clorazepate during 2nd and 3rd trimester or immediately prior to or during childbirth for decreased fetal movement and/or fetal heart rate variability, “floppy infant syndrome,” dependence, sedation (respiratory depression, lethargy, hypotonia) and symptoms of withdrawal (hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, vomiting, restlessness, inconsolable crying, and feeding difficulties); may occur shortly after delivery up to 3 wk after birth. Monitor breastfed infants for sedation, poor sucking, poor feeding and poor weight gain. Encourage pregnant patients to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.
- Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
- Emphasize the importance of follow-up exams to determine effectiveness of the medication.
Seizures: Patients on anticonvulsant therapy should carry identification describing disease process and medication regimen at all times.

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Indications ⬇

Contraind./Precautions ⬆ ⬇