Embedded Files
Pharmacologic Category
Dosing: Adult
Anxiety: Oral: Initial: 6 to 18 mg/day in equally divided doses. Initial course of treatment should not last longer than 1 week without reassessment of the need for a limited extension. Optimal dosage range: 6 to 30 mg/day. Limited experience with doses up to 60 mg/day.
Debilitated patients: Oral: Initial dose: 3 mg/day in divided doses; may adjust dose cautiously based on response and tolerance
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing: Geriatric
Anxiety: Oral: Initial dose: 3 mg/day in divided doses; may adjust dose cautiously based on response and tolerance
Dosing: Renal Impairment: Adult
There are no dosage adjustments provided in the manufacturer’s labeling; initiate therapy conservatively and titrate cautiously.
Dosing: Hepatic Impairment: Adult
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling; initiate therapy conservatively and titrate cautiously.
Severe impairment: Use is contraindicated.
Use: Labeled Indications
Note: Not approved in the US.
Anxiety: Short-term, symptomatic treatment of severe anxiety
Administration: Oral
May be administered with or without food.
Storage/Stability
Store at room temperature of 15°C to 30°C (59°F to 86°F).
Medication Safety Issues
Geriatric Patients: High-Risk Medication:
International issues:
Contraindications
Hypersensitivity to bromazepam, other benzodiazepines, or any component of the formulation; myasthenia gravis; narrow-angle glaucoma; severe hepatic impairment; severe respiratory disease; sleep apnea
Warnings/Precautions
Concerns related to adverse effects:
• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; effects may be potentiated by other CNS depressants, psychoactive medication, or ethanol. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines; risk may be increased in adolescent/pediatric patients, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders (Mancuso 2004).
• Sleep-related activities: Hazardous sleep-related activities such as sleep-driving, cooking and eating food, and making phone calls while asleep have been noted with benzodiazepines (Dolder 2008).
Disease-related concerns:
• Depression: Use is not recommended in patients with depressive disorders or psychosis.
• 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 mild or moderate hepatic impairment; dose adjustment may be necessary. Use is contraindicated in severe hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; dose adjustment may be necessary.
• Respiratory disease: May cause respiratory depression; use with caution particularly in patients with preexisting or chronic respiratory disease and concomitantly with other respiratory depressive agents. Use is contraindicated with severe disease.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; may experience greater adverse effects. Limit dose to smallest effective amount and increase gradually and as tolerated to avoid adverse reactions.
• Elderly patients: Use with caution in elderly patients; may experience greater adverse effects. Limit dose to smallest effective amount and increase gradually and as tolerated to avoid adverse reactions. Elderly patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in elderly dementia patients (Jennum 2015; Saarelainen 2018).
• Fall risk: Use with extreme caution in patients who are at risk of falls (elderly); benzodiazepines have been associated with falls and traumatic injury (Nelson 1999).
Dosage form specific issues:
• Lactose: May contain lactose; do not use with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndromes.
Concurrent drug therapy issues:
• Concomitant use with opioids: [Canadian Boxed Warning]: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of bromazepam than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking bromazepam, prescribe a lower initial dose of the opioid and titrate based upon clinical response.
Other warnings/precautions:
• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties.
• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation, large decreases in dose, or when changing to a benzodiazepine with a shorter half-life. 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.
Pregnancy Considerations
Adverse events were observed in animal reproduction studies. Benzodiazepines have the potential to cause harm to the fetus. An increased risk of fetal malformations may be associated with first trimester exposure (malformations of the heart, cleft lip/palate). Maternal use later in pregnancy may be associated with adverse events in the fetus (irregular heart beat) and neonate (hypothermia, hypotonia, respiratory depression, poor feeding, withdrawal).
Breast-Feeding Considerations
Bromazepam and metabolites are expected to be found in breast milk, therefore, use while breast-feeding is not recommended by the manufacturer. Drowsiness, lethargy, or weight loss in nursing infants have been observed in case reports following maternal use of some benzodiazepines (Iqbal, 2002).
Adverse Reactions
Frequency not defined: Central nervous system: Ataxia, dizziness, drowsiness, drug abuse
<1%, postmarketing, and/or case reports: Abnormal dreams, anxiety, blurred vision, cardiac failure, change in libido, confusion, decreased hematocrit, decreased hemoglobin, decreased serum glucose, decreased white blood cell count, depression, diplopia, disorientation, emotional disturbance, euphoria, fatigue, gastrointestinal distress, headache, hyperactivity, hypotension, impaired consciousness, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin, increased serum glucose, leukocytosis, mood changes, muscle spasm, myasthenia, nausea, nervousness, palpitations, pruritus, respiratory depression, seizure, skin rash, tachycardia, urinary incontinence, vomiting, xerostomia
Allergy and Idiosyncratic Reactions
Toxicology
Metabolism/Transport Effects
Substrate of CYP1A2 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Drug Interactions Open Interactions
Abametapir: May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Bromazepam. 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. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Bromazepam. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Bromazepam. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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 (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. 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
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Melatonin: May enhance the sedative effect of Benzodiazepines. Risk C: Monitor therapy
Methadone: Benzodiazepines may enhance the CNS depressant effect of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. Risk D: Consider therapy modification
Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: Benzodiazepines may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification
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
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Teduglutide: May increase the serum concentration of Benzodiazepines. Risk C: Monitor therapy
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Theophylline Derivatives: May diminish the therapeutic effect of Benzodiazepines. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Genes of Interest
Monitoring Parameters
Respiratory, cardiovascular, and mental status; periodic CBC and liver function tests
Product Availability
Not available in the US
Dosage Forms: Canada
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Lectopam: 3 mg [DSC]
Lectopam: 6 mg [DSC] [contains fd&c blue #2 aluminum lake]
Generic: 1.5 mg, 3 mg, 6 mg
Anatomic Therapeutic Chemical (ATC) Classification
- N05BA08
Generic Available (US)
May be product dependent
Mechanism of Action
Benzodiazepines bind 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. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors (Brunton, 2011).
Pharmacodynamics/Kinetics
Absorption: Food may significantly decrease absorption (decreased Cmax and AUC). Time to peak and half-life do not appear to be affected (Fujii 1990).
Distribution: Vd: ~50 L
Protein binding: 70%
Metabolism: Hepatic via hydroxylation and glucuronidation
Bioavailability: 60%
Half-life elimination: 20 hours (may be prolonged in the elderly)
Time to peak, serum: ≤2 hours
Excretion: Urine (69% as metabolites 3-hydroxybromazepam and 2-[2-amino-5-bromo-3-hydroxybenzoyl]-pyridine)
Local Anesthetic/Vasoconstrictor Precautions
No information available to require special precautions
Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Effects on Bleeding
No information available to require special precautions
Related Information
References
2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694. doi: 10.1111/jgs.15767.[PubMed 30693946]
Bromazepam [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; September 2019.
Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill Medical; 2011.
Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs. 2008;22(12):1021-1036.[PubMed 18998740 ]
Fujii J, Inotsume N, and Nakano M, “Effect of Food on the Bioavailability of Bromazepam Following Oral Administration in Healthy Volunteers,” J Pharmacobiodyn, 1990, 13(5):269-71.[PubMed 2273442]
Iqbal MM, Sobhan T, and Ryals T, "Effects of Commonly Used Benzodiazepines on the Fetus, the Neonate, and the Nursing Infant," Psychiatr Serv, 2002, 53(1):39-49.[PubMed 11773648]
Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. doi: 10.1016/j.euroneuro.2015.08.014.[PubMed 26342397]
Kirschberg O, Saers T, Krakamp B, et al, “Chemical Gastritis After Chronic Bromazepam Intake: A Case Report,” BMC Gastroenterol, 2010, 10:84.[PubMed 20667143]
Lectopam (bromazepam) [product monograph]. Mississauga, Ontario, Canada: Hoffman-La Roche Limited; September 2018.
Lexotan (bromazepam) [product information]. Dee Why NSW, Australia: Roche Products PTY Limited; October 2012.
Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004;24(9):1177-1185.[PubMed 15460178 ]
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.[PubMed 12628894]
Nelson J, Chouinard G. Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound, and withdrawal. Canadian Society for Clinical Pharmacology. Can J Clin Pharmacol. 1999;6(2):69-83.[PubMed 10519733 ]
Saarelainen L, Tolppanen AM, Koponen M, et al. Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study. Int J Geriatr Psychiatry. 2018;33(4):583-590. doi: 10.1002/gps.4821.[PubMed 29143367]
Brand Names: International
Akamon (JO, MT, MY, TR, TW); Anxyl (LB); Brazepam (ZA); Bromam (DK); Bromatop (BE); Bromazanil (LU); Bromaze (ZA); Bromazepam-Eurogenerics (LU); Bromazin (TW); Bromidem (LU); Bropam (EG); Calmepam (EG); Creosedin (AR); Finaten (AR); Lekotam (HR, SI); Lexatin (ES); Lexaurin (CZ, HR); Lexavrin (SK); Lexilium (CY, HR); Lexomil (FR, VN); Lexopam (BH, EG, JO); Lexotan (AU, BD, BE, BG, BR, DK, EC, HK, IE, IS, IT, LU, MT, MX, MY, PE, PH, PL, PT, PY, SG, TW, UY, VN, ZA); Lexotanil (AE, AR, AT, BH, CH, CL, CY, GR, JO, KW, LB, LK, LT, LV, NL, PK, QA, SA, TR, VE); Lexotanol (EE); Lexzepam (ID); Nervan (VE); Notorium (MT); Octanyl (CO, EC, UY); Otedram (MX); Quietiline (FR); Rem (BD); Sedam (PL); Seniran (JP); Somalium (BR); Tenil (BD); Tredum (PY); Zepam (BD)
Last Updated 10/14/20
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