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Pronunciation
(te MAZ e pam)
Generic Available (U.S.)
Yes
Controlled Substance
C-IV
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/UCM233806.pdf, must be dispensed with this medication.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Short-term treatment of insomnia
Use: Unlabeled
Treatment of anxiety
Pregnancy Risk Factor
X
Pregnancy Considerations
Adverse events were observed in animal reproduction studies. Although information specific to the use of temazepam has not been located, all benzodiazepines are assumed to cross the placenta. Teratogenic effects have been observed with some benzodiazepines; however, additional studies are needed. The incidence of premature birth and low birth weights may be increased following maternal use of benzodiazepines; hypoglycemia and respiratory problems in the neonate may occur following exposure late in pregnancy. Neonatal withdrawal symptoms may occur within days to weeks after birth and “floppy infant syndrome” (which also includes withdrawal symptoms) have been reported with some benzodiazepines. Use during pregnancy is contraindicated.
Lactation
Enters breast milk/use caution (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Information is available from a study conducted in 10 nursing women, <2 weeks postpartum. All women were given temazepam 10-20 mg at bedtime for ≥2 nights. Samples were obtained 10-21 hours after a dose. Temazepam was not found in the milk of nine mothers (maternal serum concentrations 8-59 mcg/L). Temazepam was detected in the milk of one patient whose serum concentration was 234 mcg/mL at ~14 hours after the dose; milk concentrations were 28 mcg/L (pre-feed) and 26 mcg/L (post-feed). Oxazepam concentrations were 9 mcg/mL in the maternal serum and below the limit of detection in breast milk. Adverse events were not noted in any nursing infants. Drowsiness, lethargy, or weight loss in nursing infants have been observed in case reports following maternal use of some benzodiazepines.
Contraindications
Hypersensitivity to temazepam or any component of the formulation (cross-sensitivity with other benzodiazepines may exist); narrow-angle glaucoma (not in product labeling, however, benzodiazepines are contraindicated); pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypersensitivity reactions: Postmarketing studies have indicated that the use of hypnotic/sedative agents for sleep has been associated with hypersensitivity reactions including anaphylaxis as well as angioedema.
• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.
• Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving; cooking and eating food, and making phone calls while asleep have also been noted.
Disease-related concerns:
• Depression: Use caution in patients with depression, particularly if suicidal risk may be present.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Impaired gag reflex: Use with caution in patients with an impaired gag reflex.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
Concurrent drug therapy issues:
• CNS depressants/psychoactive medications: Use with caution in patients receiving other CNS depressants or psychoactive medication; effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Debilitated patients: Use with caution in debilitated patients.
• Elderly: Due to increased sensitivity in this age group, smaller doses of benzodiazepines may be safer and as effective. Avoid using doses >15 mg daily of temazepam (Beers Criteria).
• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.
Other warnings/precautions:
• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.
• Hypnotic: Appropriate use: 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. A worsening of insomnia or the emergence of new abnormalities of thought or behavior may represent unrecognized psychiatric or medical illness and requires immediate and careful evaluation.
• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.
Adverse Reactions
1% to 10%:
Central nervous system: Anxiety, confusion, dizziness, drowsiness, euphoria, fatigue, hangover, headache, lethargy, vertigo
Dermatologic: Rash
Endocrine & metabolic: Libido decreased
Gastrointestinal: Diarrhea
Neuromuscular & skeletal: Dysarthria, weakness
Ocular: Blurred vision
Miscellaneous: Diaphoresis
<1%: Amnesia, anorexia, ataxia, back pain, blood dyscrasias, drug dependence, increased dreaming, menstrual irregularities, palpitation, paradoxical reactions, reflex slowing, tremor, vomiting
Postmarketing and/or case reports: Anaphylaxis, angioedema, complex sleep-related behavior (sleep-driving, cooking or eating food, making phone calls)
Metabolism/Transport Effects
Substrate of CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
CloZAPine: Benzodiazepines may enhance the adverse/toxic effect of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Fosphenytoin: Benzodiazepines may increase the serum concentration of Fosphenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification
OLANZapine: May enhance the adverse/toxic effect of Benzodiazepines. Management: Avoid concomitant use of parenteral benzodiazepines and IM olanzapine due to risks of additive adverse events (e.g., cardiorespiratory depression). Olanzapine prescribing information provides no specific recommendations regarding oral administration. Risk X: Avoid combination
Phenytoin: Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Serum levels may be increased by grapefruit juice.
Herb/Nutraceutical: St John's wort may decrease temazepam levels. Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Mechanism of Action
Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
Pharmacodynamics/Kinetics
Distribution: Vd: 1.4 L/kg
Protein binding: 96%
Metabolism: Hepatic
Half-life elimination: 9.5-12.4 hours
Time to peak, serum: 2-3 hours
Excretion: Urine (80% to 90% as inactive metabolites)
Dosage
Oral:
Adults: Usual dose: 15-30 mg at bedtime; some patients may respond to 7.5 mg in transient insomnia
Elderly or debilitated patients: Initial: 7.5 mg at bedtime
Monitoring Parameters
Respiratory and cardiovascular status
Reference Range
Therapeutic: 26 ng/mL after 24 hours
Patient Education
Drug may cause physical and/or psychological dependence. May take with food to decrease GI upset. While using this medication, do not use alcohol. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, lightheadedness, blurred vision, dry mouth, or GI discomfort. Report CNS changes (confusion, depression, increased sedation, excitation, headache, abnormal thinking, insomnia, or nightmares, memory impairment, impaired coordination), respiratory difficulty, persistent dizziness, alterations in normal gait, vision changes, or ineffectiveness of medication.
Geriatric Considerations
Because of its lack of active metabolites, temazepam could be considered in the elderly when a benzodiazepine hypnotic is indicated. Hypnotic use should be limited to 10-14 days. If insomnia persists, the patient should be evaluated for etiology.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria severity: High).
Additional Information
Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Anesthesia and Critical Care Concerns/Other Considerations
Chronic use of this agent may increase perioperative benzodiazepine dose needed to achieve desired effect. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Cardiovascular Considerations
Hypotension may result in orthostatic lightheadedness or syncope. Benzodiazepines, as a class, may depress respiration. These medications may often be prescribed for difficulty in sleeping but may exacerbate sleep-disordered breathing.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Comment
In 2007, the FDA requested that all manufacturers of sedative-hypnotic drug products revise labeling to include a greater emphasis on the risks of adverse effects. These risks include severe allergic reactions (anaphylaxis, angioedema) and complex sleep-related behaviors, which may include sleep-driving (driving while not fully awake and with no memory of the event), making phone calls, and preparing and eating food while asleep.
There are two subtypes of GABA receptors (GABA-A and GABA-B) and three different benzodiazepine receptors (Bz1, Bz2, and Bz3). Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors. The role of GABA-B receptors is unclear. Benzodiazepines have no specificity for benzodiazepine receptor subtypes.
Temazepam is a short half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance develops to the sedative, hypnotic, and anticonvulsant effects. It does not develop to the anxiolytic or skeletal muscle relaxing effects. Psychological and physical dependence may occur with prolonged use of benzodiazepines. The onset of withdrawal symptoms is usually seen on the first day without drug and lasts 5-7 days in patients receiving short half-life benzodiazepines, whereas, the onset occurs after 5 days with a duration of 10-14 days after abrupt discontinuance of long half-life benzodiazepines. Risk factors for abuse include personal or family history of substance abuse and personality disorder. Temazepam is slowly absorbed; undergoes phase II metabolism and, therefore, is less likely to be affected in patients with hepatic dysfunction.
Nursing: Physical Assessment/Monitoring
For short-term use. Assess for history of addiction; long-term use can result in dependence, abuse, or tolerance. For inpatient use, institute safety measures to prevent falls. For outpatients, monitor for CNS depression at beginning of therapy and periodically throughout.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 7.5 mg, 15 mg, 22.5 mg, 30 mg
Restoril™: 7.5 mg, 15 mg, 22.5 mg, 30 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Restoril)
7.5 mg (30): $348.76
15 mg (30): $368.93
22.5 mg (30): $348.75
30 mg (30): $348.76
Capsules (Temazepam)
7.5 mg (30): $155.99
15 mg (30): $12.99
22.5 mg (30): $199.98
30 mg (30): $14.99
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
Bergman U, Rosa FW, Baum C, et al, "Effects of Exposure to Benzodiazepine During Fetal Life," Lancet, 1992, 340(8821):694-6.
Divoll M, Greenblatt DJ, Harmatz JS, et al, “Effect of Age and Gender on Disposition of Temazepam,” J Pharm Sci, 1981, 70(10):1104-7.
Grahame-Smith DG, “Misuse of Temazepam,” BMJ, 1991, 302(6786):1210.
Ho PC, Triggs EJ, Heazlewood V, et al, “Determination of Nitrazepam and Temazepam in Plasma by High Performance Liquid Chromatography,” Ther Drug Monit, 1983, 5(3):303-7.
Iqbal MM, Sobhan T, Ryals T, et al, "Effects of Commonly Used Benzodiazepines on the Fetus, the Neonate, and the Nursing Infant," Psychiatr Serv, 2002, 53(1):39-49.
Klotz U and Kanto J, “Pharmacokinetics and Clinical Use of Flumazenil (Ro 15-1788),” Clin Pharmacokinet, 1988, 14(1):1-12.
Lebedevs TH, Wojnar-Horton RE, Yapp P, et al, "Excretion of Temazepam in Breast Milk," Br J Clin Pharmacol, 1992, 33(2):204-6.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Scharf MB, Berkowitz DV, and Brannen DE, “Effectiveness of Low-Dose Temazepam on Sleep Patterns in Geriatric Insomniac Subjects,” Consult Pharm, 1993, 8(12):1367-73.
Schutte-Rodin S, Broch L, Buysse D, et al, “Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults,” J Clin Sleep Med, 2008, 4(5):487-504.
Wikner BN, Stiller CO, Bergman U, et al, "Use of Benzodiazepines and Benzodiazepine Receptor Agonists During Pregnancy: Neonatal Outcome and Congenital Malformations," Pharmacoepidemiol Drug Saf, 2007, 16(11):1203-10.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
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