Can a patient take temazepam (a benzodiazepine) with alprazolam (a benzodiazepine) together?

Combining Temazepam and Alprazolam: Strong Recommendation Against

No, a patient should not take temazepam and alprazolam together—this combination carries serious risks of respiratory depression, oversedation, and death that far outweigh any potential benefits. 1, 2

Critical Safety Concerns

Life-Threatening Respiratory Effects

• The FDA has issued a black box warning specifically about combining benzodiazepines with other CNS depressants, citing risks of slowed or difficult breathing and death 2
• When benzodiazepines are combined with other sedatives in clinical studies, hypoxemia occurred in 92% of subjects and apnea occurred in 50%, demonstrating dangerous synergistic respiratory effects 1, 3
• Studies have identified a 3- to 10-fold higher risk of death when benzodiazepines and similar sedative-hypnotics are prescribed together compared to either agent alone 1

Explicit Guideline Prohibition

• The American Academy of Sleep Medicine explicitly states that clinicians should avoid prescribing benzodiazepines concurrently with other CNS depressants whenever possible, as both cause central nervous system depression and can decrease respiratory drive 1
• If temazepam is to be combined with other drugs having known hypnotic properties or CNS-depressant effects, consideration should be given to potential additive effects, with the FDA label warning about synergistic effects 2

Additional Risks Beyond Respiratory Depression

Oversedation and Falls

• The risk of oversedation, dizziness, confusion, and ataxia increases substantially with larger doses or combinations of benzodiazepines, particularly in elderly and debilitated patients 2
• Because temazepam causes drowsiness and decreased level of consciousness, patients (particularly the elderly) are at higher risk of falls, which is compounded when combined with another benzodiazepine 2

Complex Sleep Behaviors

• Both medications can cause "sleep-driving" and other complex behaviors (preparing food, making phone calls, having sex) while not fully awake, with no memory of the event 2
• The use of alcohol and other CNS depressants with temazepam appears to increase the risk of such behaviors, and this applies to combining it with alprazolam 2

Cognitive and Psychomotor Impairment

• Benzodiazepines cause reduced lane control, increased reaction times, reduced hand-eye coordination, and cognitive impairment that can exceed that seen with 0.05 g% ethanol 4
• Combining two benzodiazepines would amplify these effects significantly 4

Safe Alternatives

If Both Medications Are Currently Prescribed

• Taper one medication immediately under close medical supervision 1
• The American Academy of Sleep Medicine recommends sedating antidepressants as first-line add-on therapy instead of benzodiazepines for insomnia management, with options including trazodone, mirtazapine, and doxepin 1
• Cognitive behavioral therapy for insomnia (CBT-I) should be added to any pharmacologic regimen, as it improves sleep onset latency, wake after sleep onset, and sleep efficiency 1

Brief Overlap During Transition (If Absolutely Unavoidable)

• If there is an unavoidable brief overlap during medication transition, use the lowest effective doses and limit duration to 24-48 hours maximum 3
• Monitor closely for respiratory depression with pulse oximetry and cardiorespiratory monitoring 3
• Observe for progressive sedation, which often precedes respiratory depression 3
• Ensure naloxone is immediately available, though it will not reverse benzodiazepine effects 3

High-Risk Populations Requiring Extra Caution

• Patients with baseline respiratory compromise (chronic obstructive pulmonary disease, sleep apnea) should absolutely avoid this combination 3, 2
• Elderly patients require dose reductions by 50% or more if any benzodiazepine is used, and combining two is particularly dangerous 3, 2
• Patients with limited cardiopulmonary reserve are more susceptible to respiratory depression 1

Clinical Bottom Line

The combination of temazepam and alprazolam represents a dangerous polypharmacy practice with no legitimate clinical indication. 1, 2 Both are benzodiazepines acting on the same GABA receptors, providing redundant mechanisms with compounded toxicity rather than complementary benefits 5, 6. One medication should be discontinued, with preference for maintaining the agent that best addresses the patient's primary indication (temazepam for sleep maintenance, alprazolam for anxiety), while implementing non-pharmacologic interventions and considering safer alternatives 1.