Lorazepam is conjugated by the liver via UDP-glucuronosyltransferase (UGT) to lorazepam glucuronide, an inactive metabolite. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. Dosage generally produces some amnesia of short-term memory. Lorazepam first became available in the US in 1977 by Wyeth Pharmaceuticals. Acceptable storage information for all products for which storage is recommended at temperatures below room temperature (20-25 C [68-77 F]) was compiled and arranged in tabular format. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. American Society of Health-System Pharmacists 2022. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Lorazepam Intensol Oral Concentrate, USP, CIV Rx Only - DailyMed McMullan JT et. If used together, a reduction in the dose of one or both drugs may be needed. Store at cold temperature. Drug concentrations were determined in a central laboratory by high-performance liquid chromatography. Initiate extended-release (ER) dosing with the total daily dose of lorazepam PO once daily in the morning. American Journal of Emergency Medicine. Long-Term Stability of Lorazepam in Sodium Chloride 0.9% - PubMed 3 repeated excursions of 24 hours at 25C. However, in one study involving single intravenous doses of 1.5 mg to 3 mg of lorazepam injection, mean total body clearance of lorazepam decreased by 20% in 15 elderly subjects of 60 to 84 years of age compared to that in 15 younger subjects of 19 to 38 years of age. Store in a dry place. Avoid use of benzodiazepines in older adults with the following due to the potential for symptom exacerbation or adverse effects: delirium (new-onset or worsening delirium), dementia (adverse CNS effects), and history of falls/fractures (ataxia, impaired psychomotor function, syncope, and additional falls). Aripiprazole: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of aripiprazole and benzodiazepines. Valerian, Valeriana officinalis: (Major) Any substances that act on the CNS, including psychoactive drugs and drugs used as anesthetic adjuvants (e.g., barbiturates, benzodiazepines), may theoretically interact with valerian, Valeriana officinalis. Amgen 800-772-6436 Formoterol (Foradil) Prior to dispensing, refrigerate at 36 to 46 F (2 to 8C). Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. Pimozide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines. Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone, dehydroepiandrosterone, DHEA may inhibit the metabolism of benzodiazepines (e.g., alprazolam, estazolam, midazolam) which undergo CYP3A4-mediated metabolism. NICHD DASH - Eunice Kennedy Shriver National Institute of Child Health document.write(new Date().getFullYear()) PDR, LLC. Am J Hosp Pharm. Butabarbital: (Moderate) Additive CNS and/or respiratory depression may occur with concurrent use. Use caution with this combination. Safety and efficacy have not been established. There are exceptions that may warrant the use of an anxiolytic such as a long-acting benzodiazepine for withdrawal from a short-acting benzodiazepine, use for neuromuscular syndromes (e.g., tardive dyskinesia, restless legs syndrome, seizure disorder, cerebral palsy), or end of life care. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Clonazepam: 18-50 hours. In postmarketing experience, overdose with lorazepam has occurred predominantly in combination with alcohol and/or other drugs. 2 mg PO every 8 hours on days 1 and 2, then 1 mg PO every 8 hours on day 3, then 1 mg PO every 12 hours on day 4, and then 1 mg PO once daily at bedtime on day 5. No patient should get out of bed unassisted within 8 hours of lorazepam injection. A reduction in dose of the CNS depressant may be needed in some cases. Crystallization was also detected after 7 days in syringes at room temperature, 3 days in bottles at 5 3C, and 2 days in bottles at room temperature. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Butalbital; Acetaminophen: (Moderate) Additive CNS and/or respiratory depression may occur with concurrent use. Educate patients about the risks and symptoms of respiratory depression and sedation. DISCONTINUATION: To discontinue, gradually taper the dose. PDF USP Compounding Standards and Beyond-Use Dates (BUDs) *CRT (controlled room temperature) One of the most significant changes to the chapter is the inability to extend BUDs beyond those in Table . Nalbuphine: (Major) Concomitant use of mixed opiate agonists/antagonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and lorazepam. Promethazine; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of respiratory depression and sedation. If used with a benzodiazepine, droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect. Ramelteon: (Moderate) Ramelteon is a sleep-promoting agent; therefore, additive pharmacodynamic effects are possible when combining ramelteon with benzodiazepines or other miscellaneous anxiolytics, sedatives, and hypnotics. Use caution with this combination. Guanabenz can potentiate the effects of CNS depressants such as benzodiazepines, when administered concomitantly. Although all of these anomalies were not present in the concurrent control group, they have been reported to occur randomly in historical controls. The duration of the sedative effect is approximately 6 to 12 hours for most patients. Several benzodiazepines, including clonazepam, oxazepam, flurazepam, diazepam, clobazam, flunitrazepam, and lorazepam have been implicated in these reactions. Educate patients about the risks and symptoms of respiratory depression and sedation. Lorazepam in excreted in the urine primarily as the inactive glucuronide metabolite; lorazepam also undergoes enterohepatic recirculation. Accessibility To discourage abuse, the smallest appropriate quantity of the benzodiazepine should be prescribed, and proper disposal instructions for unused drug should be given to patients. 4.2 Posology and method of administration. The aim of this review was to build upon previous literature describing the maximum duration for which refrigerated medications can tolerate room temperature excursions while maintaining stability and potency. Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation. when stored at room temperature (22C), the mean lorazepam concentration on day 91 was Clinicians should be aware that the use of flumazenil may increase the risk of seizures, particularly in long-term users of benzodiazepines. official website and that any information you provide is encrypted If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. The peak plasma level of lorazepam from a 2 mg dose is approximately 20 ng/mL. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Concentration as a function of MKT was analyzed by linear regression. Educate patients about the risks and symptoms of respiratory depression and sedation. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. US-based MDs, DOs, NPs and PAs in full-time patient practice can register for free on PDR.net. Lorazepam (Oral Route) Side Effects - Mayo Clinic Eszopiclone: (Moderate) Concomitant administration of benzodiazepines with eszopiclone can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Lorazepam is an UGT substrate and ombitasvir is an UGT inhibitor. Administer the morning after the day of discontinuation of a lorazepam immediate-release (IR) product. Off-label information indicates unopened bottle stable when maintained at continuous room temperature 77 o F for 12 months. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. Methohexital: (Moderate) Additive CNS and/or respiratory depression may occur with concurrent use. Air Med J. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. It may be appropriate to delay certain procedures if doing so will not jeopardize the health of the child and/or mother. Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking a mixed opiate agonist/antagonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Room-temperature storage of medications labeled for refrigeration. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. Dilutions not prepared in a sterile environment should not be stored; discard immediately. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. Lorazepam is an UGT substrate and pibrentasvir is an UGT inhibitor. General supportive and symptomatic measures are recommended; vital signs must be monitored and the patient closely observed. Do not administer lorazepam injection by intra-arterial injection since arteriospasm can occur which may cause tissue damage and/or gangrene.Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Pre-existing depression may emerge or worsen during use of benzodiazepines including lorazepam. When higher dosage is indicated, the evening dose should be increased before the daytime doses. 2007 Aug 15;64(16):1711-5. doi: 10.2146/ajhp060262. Add the minimum volume of sterile water necessary for tablet dispersion. An initial infusion rate of 0.025 to 0.05 mg/kg/hour IV is recommended by some experts. Educate patients about the risks and symptoms of respiratory depression and sedation. The mean half-life of unconjugated lorazepam in human plasma is about 12 hours and for its major metabolite, lorazepam glucuronide, about 18 hours. Extension of Expiration Time for Lorazepam Injection at Room Temperature The need for indefinite continuation of lorazepam (e.g., seizure disorder) should be based on confirmation of the condition being treated and its potential cause(s). 1981; 38:879-81. ativan storage - Patient Medications - allnurses MeSH Specific maximum dosage information not available; the dose required is dependent on route of administration, indication, and clinical response.1 to 11 years: Safety and efficacy have not been established. Refrigerate at 2 to 8C (36 to 46F), Dispense only in the bottle and only with. Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Participants in Cohort 1 received lorazepam 0.1 mg/kg up to a maximum dose of 4 mg/kg. Immediate-release Formulations (e.g., tablets)When given in unequal doses, give the largest dose before bedtime. Store at cold temperature. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. In patients treated with methadone for opioid use disorder, cessation of benzodiazepines or other CNS depressants is preferred in most cases. Reproductive studies in animals were performed in mice, rats, and two strains of rabbits. Use lorazepam with caution in patients with a history of alcoholism or substance abuse due to the potential for psychological dependence. Reduce injectable buprenorphine dose by 1/2, and for the buprenorphine transdermal patch, start therapy with the 5 mcg/hour patch. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers Hosp Pharm. Initiation of sleep induction or maintenance medication should be preceded or accompanied by non-pharmacologic interventions and maximized treatment of underlying conditions (if applicable). In general, all benzodiazepines increase the risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults. It appears glucuronide conjugation of lorazepam is increased in the presence of combined hormonal oral contraceptives; the clinical significance of this interaction is not determined. Continuous IV InfusionNOTE: Lorazepam is not FDA-approved for administration by continuous IV infusion.Use of glass or polyolefin containers is recommended; polypropylene syringes have also been used. In one study of elderly volunteers, half of the patients received DHEA 200 mg/day PO for 2 weeks, followed by a single dose of triazolam 0.25 mg. Triazolam clearance was reduced by close to 30% in the DHEA-pretreated patients vs. the control group; however, the effect of DHEA on CYP3A4 metabolism appeared to vary widely among subjects. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. (e.g., validated stability-indicating assays, release testing for sterility, endotoxins, container-closure integrity, particulate matter, and additionally personnel and environmental monitoring) that . Use caution with this combination. Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. At least one case of sudden death was reported following intravenous administration of lorazepam to a patient receiving clozapine. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Chlorpheniramine; Pseudoephedrine: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Vancomycin: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. In older pediatric patients, the daily dosage for anxiety disorders is typically divided into 2 to 3 doses and should not exceed 10 mg/day in those 12 years and older. Educate patients about the risks and symptoms of respiratory depression and sedation. Because lorazepam can cause drowsiness and a decreased level of consciousness, there is a higher risk of falls, particularly in the elderly, with the potential for subsequent severe injuries. Lorazepam Injection, USP - Stability Stored Above Recommended Temperatures [provided document]. to a friend, relative, colleague or yourself. coma / Early / 0.1-1.2seizures / Delayed / 0-1.0apnea / Delayed / 1.0muscle paralysis / Delayed / Incidence not knownsuicidal ideation / Delayed / Incidence not knownneuroleptic malignant syndrome-like symptoms / Delayed / Incidence not knownpulmonary edema / Early / Incidence not knownrespiratory arrest / Rapid / Incidence not knownpulmonary hypertension / Delayed / Incidence not knownpneumothorax / Early / Incidence not knownGI bleeding / Delayed / Incidence not knowntissue necrosis / Early / Incidence not knownrenal tubular necrosis / Delayed / Incidence not knownSIADH / Delayed / Incidence not knownlactic acidosis / Delayed / Incidence not knownanaphylactoid reactions / Rapid / Incidence not knownpericardial effusion / Delayed / Incidence not knownheart failure / Delayed / Incidence not knowncardiac arrest / Early / Incidence not knownbradycardia / Rapid / Incidence not knownAV block / Early / Incidence not knownhearing loss / Delayed / Incidence not knownpancytopenia / Delayed / Incidence not knownagranulocytosis / Delayed / Incidence not knowncoagulopathy / Delayed / Incidence not knownneonatal respiratory depression / Rapid / Incidence not knownneonatal abstinence syndrome / Early / Incidence not known, erythema / Early / 2.0-2.4hypotension / Rapid / 0.1-2.4confusion / Early / 0.1-1.3depression / Delayed / 1.3-1.3delirium / Early / 1.3-1.3hypoventilation / Rapid / 0.1-1.2ataxia / Delayed / 0.1-1.0hallucinations / Early / 0.1-1.0elevated hepatic enzymes / Delayed / 0-1.0cystitis / Delayed / 0-1.0metabolic acidosis / Delayed / 0-1.0dysarthria / Delayed / Incidence not knowneuphoria / Early / Incidence not knownamnesia / Delayed / Incidence not knownmemory impairment / Delayed / Incidence not knownpsychosis / Early / Incidence not knownhostility / Early / Incidence not knownmania / Early / Incidence not knownhyperreflexia / Delayed / Incidence not knownrespiratory depression / Rapid / Incidence not knownhypoxia / Early / Incidence not knownmyoclonia / Delayed / Incidence not knownjaundice / Delayed / Incidence not knownhyperbilirubinemia / Delayed / Incidence not knownconstipation / Delayed / Incidence not knownhyponatremia / Delayed / Incidence not knownurinary incontinence / Early / Incidence not knownimpotence (erectile dysfunction) / Delayed / Incidence not knownsinus tachycardia / Rapid / Incidence not knownhypertension / Early / Incidence not knownblurred vision / Early / Incidence not knownleukopenia / Delayed / Incidence not knownthrombocytopenia / Delayed / Incidence not knowntolerance / Delayed / Incidence not knownpsychological dependence / Delayed / Incidence not knownwithdrawal / Early / Incidence not knownphysiological dependence / Delayed / Incidence not known, injection site reaction / Rapid / 0.5-17.0drowsiness / Early / 1.5-15.9dizziness / Early / 6.9-6.9weakness / Early / 4.2-4.2restlessness / Early / 1.3-1.3headache / Early / 0.1-1.2asthenia / Delayed / 0.1-1.0agitation / Early / 0.1-1.0tremor / Early / 0.1-1.0hyperventilation / Early / 0.1-1.0nausea / Early / 0-1.0hypersalivation / Early / 0.1-1.0vomiting / Early / 0-1.0infection / Delayed / 0-1.0chills / Rapid / 0-1.0vertigo / Early / Incidence not knownfatigue / Early / Incidence not knowninsomnia / Early / Incidence not knownanxiety / Delayed / Incidence not knownnightmares / Early / Incidence not knownirritability / Delayed / Incidence not knownhyperactivity / Early / Incidence not knowndiarrhea / Early / Incidence not knownhypothermia / Delayed / Incidence not knownlibido decrease / Delayed / Incidence not knownorgasm dysfunction / Delayed / Incidence not knownrash / Early / Incidence not knownalopecia / Delayed / Incidence not knowndiplopia / Early / Incidence not known. doi: 10.1093/ajhp/zxab297. Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. An official website of the United States government. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night. Teduglutide has direct effects on the gut that may increase benzodiazepine exposure by improving oral absorption. Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Avoid lorazepam extended-release capsules and utilize lorazepam immediate-release dosage forms that can be easily titrated. Consider the benefits of appropriate anesthesia in young children against the potential risks, especially for procedures that may last more than 3 hours or if multiple procedures are required during the first 3 years of life. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. See our toolbox, Medication Storage: Maintaining the Cold Chain, for helpful storage tips and other resources. Risperidone: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics. Avoid opiate cough medications in patients taking benzodiazepines. Allowable room temperature excursions for refrigerated medications: A Dexbrompheniramine; Pseudoephedrine: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Find patient medical information for Lorazepam Intensol oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Coadministration of lorazepam with probenecid may cause a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. Liquid (solution): Store in a refrigerator. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. Caution should be used when vigabatrin is given in combination with benzodiazepines. Ibuprofen; Oxycodone: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. Educate patients about the risks and symptoms of respiratory depression and sedation. Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and benzodiazepines. Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Store tablets at controlled room temperature (59 to 86F). If hydrocodone is initiated in a patient taking a benzodiazepine, reduce initial dosage and titrate to clinical response; for hydrocodone extended-release products, initiate hydrocodone at 20% to 30% of the usual dosage. If the sleep agent is used routinely and is beyond the manufacturer's recommendations for duration of use, the facility should attempt a quarterly taper, unless clinically contraindicated as defined in the OBRA guidelines.
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