Temazepam

Indications

• FDA-approved for short-term treatment of insomnia in adults, generally 7-10 days, with reassessment required if use extends beyond 2-3 weeks.
• Its 8-15 hour half-life targets sleep maintenance and early morning awakening better than zaleplon or sublingual zolpidem.
• Off-label as a benzodiazepine option in patients with hepatic impairment who need short-term sedation, since clearance is glucuronidation only.
• Off-label for anxiety-associated insomnia, though a scheduled daytime anxiolytic or an antidepressant is the more durable strategy.
• Cognitive behavioral therapy for insomnia is first line per the American Academy of Sleep Medicine, with hypnotics as adjunct or second line.
• Not indicated for chronic insomnia maintenance, transient jet lag, or as a substitute for treating sleep apnea or restless legs.

Mechanism of action

• Positive allosteric modulator at the GABA-A benzodiazepine site, increasing chloride channel opening frequency and promoting sleep onset and maintenance.
• Non-selective alpha subunit binding means sedation comes packaged with amnesia, muscle relaxation and next-day psychomotor impairment.
• Suppresses slow wave sleep and REM to a modest degree while increasing stage 2 sleep, so sleep architecture is altered rather than normalized.
• Slower absorption than zolpidem means it is better at holding sleep through the night than at shortening time to sleep onset.
• Chronic nightly use downregulates GABA-A receptors, producing tolerance to the hypnotic effect and rebound insomnia on withdrawal.

Pharmacokinetics

• Well absorbed orally with peak concentrations at 1.2-1.6 hours; a high-fat meal delays absorption and can blunt the hypnotic effect.
• Mean elimination half-life is about 11 hours, long enough to carry residual sedation into the morning in sensitive or older patients.
• Conjugated directly by glucuronidation to an inactive O-conjugate and excreted renally; there are no active metabolites.
• Because it bypasses hepatic oxidation entirely, it is not meaningfully affected by CYP3A4 inhibitors or inducers.
• Along with lorazepam and oxazepam it is one of three benzodiazepines preferred in cirrhosis and in older adults on this pharmacokinetic basis.

Dosing

• Adults: 15 mg PO at bedtime, taken 30 minutes before sleep with at least 7-8 hours available before the next required activity.
• The full labeled range is 7.5-30 mg; many patients respond to 7.5 mg, and 30 mg should be reserved for clear inadequate response.
• Older adults or debilitated patients: start at 7.5 mg and titrate only if needed, since half-life and impairment both lengthen with age.
• No renal or hepatic dose adjustment is formally required, which is part of why this agent is chosen when liver function is poor.
• Limit continuous use to 7-10 nights where possible; if used nightly for weeks, taper by 25 percent every 1-2 weeks rather than stopping outright.
• Available only as oral capsules in 7.5, 15, 22.5 and 30 mg strengths; there is no liquid or parenteral formulation.

Adverse effects

• Drowsiness in about 9 percent, headache 8 percent, fatigue 5 percent, dizziness 5 percent, nervousness and lethargy each around 5 percent.
• Next-morning residual sedation and impaired driving, which is the practical limit on dosing and the reason to insist on a full sleep opportunity.
• Anterograde amnesia for events after dosing, including nocturnal awakenings, phone calls and conversations the patient will not recall.
• Falls, hip fracture, confusion and delirium in older adults; nocturnal ambulation while impaired is the specific mechanism of harm.
• Respiratory depression and death with opioids or alcohol, and worsening of untreated obstructive sleep apnea and hypoventilation.
• Rebound insomnia and anxiety on discontinuation, and after prolonged use full withdrawal with tremor, agitation and seizure risk.

Monitoring

• Confirm and treat contributors before prescribing: sleep apnea, restless legs, alcohol use, pain, nocturia and untreated mood disorder.
• Reassess sleep response, next-day sedation and continued need within 7-10 days rather than issuing automatic refills.
• Ask directly about falls, nocturnal confusion, sleepwalking and any amnesia for nighttime events at each follow-up.
• Check the prescription monitoring program and screen for substance use disorder before starting and periodically during therapy.
• No routine laboratory monitoring is required; consider a sleep study when apnea is suspected or hypnotic response is poor.

Interactions

• Additive respiratory depression and death with opioids, the basis of the boxed warning; avoid the combination whenever an alternative exists.
• Alcohol, sedating antihistamines, gabapentinoids, antipsychotics and other hypnotics all compound sedation and next-day impairment.
• Unaffected by CYP inhibitors and inducers, so it is a reasonable hypnotic in patients on ritonavir, carbamazepine or rifampin.
• Probenecid and valproate inhibit glucuronidation and may modestly increase exposure; reduce the dose if sedation is excessive.
• Contraindicated in pregnancy, in known benzodiazepine hypersensitivity, and to be avoided in untreated severe sleep apnea.

Special populations

• Pregnancy: the label lists pregnancy as a contraindication, citing fetal harm; screen for pregnancy before prescribing to patients who may conceive.
• Lactation: excreted into breast milk; monitor the infant for sedation and poor feeding, or choose a non-drug approach to insomnia.
• Pediatrics: safety and effectiveness under age 18 are not established, and hypnotics are rarely appropriate in pediatric insomnia.
• Older adults: the AGS Beers Criteria advise avoiding benzodiazepines, but if one is used temazepam at 7.5 mg is among the least problematic.
• Hepatic and renal impairment: no formal dose adjustment; glucuronidation is relatively preserved in cirrhosis, unlike oxidative clearance.

Clinical pearls

• One of three benzodiazepines that skip hepatic oxidation, with lorazepam and oxazepam.
• Half-life is long enough to hold sleep but also long enough to impair the morning commute.
• Contraindicated in pregnancy on the label; confirm pregnancy status before you prescribe.