Lorazepam - Lorazepam tablet prescribing information
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS
- Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for 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 (see WARNINGS and PRECAUTIONS ).
- The use of benzodiazepines, including lorazepam tablets, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing lorazepam tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see WARNINGS ).
- The continued use of benzodiazepines, including lorazepam tablets, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of lorazepam tablets after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam tablets or reduce the dosage (DOSAGE AND ADMINISTRATION and WARNINGS ).
INDICATIONS AND USAGE
Lorazepam tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
The effectiveness of lorazepam tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
DOSAGE AND ADMINISTRATION
Lorazepam tablets are administered orally. For optimal results, dose, frequency of administration, and duration of therapy should be individualized according to patient response. To facilitate this, 0.5 mg, 1 mg, and 2 mg tablets are available.
The usual range is 2 to 6 mg/day given in divided doses, the largest dose being taken before bedtime, but the daily dosage may vary from 1 to 10 mg/day.
For anxiety, most patients require an initial dose of 2 to 3 mg/day given two times a day or three times a day.
For insomnia due to anxiety or transient situational stress, a single daily dose of 2 to 4 mg may be given, usually at bedtime.
For elderly or debilitated patients, an initial dosage of 1 to 2 mg/day in divided doses is recommended, to be adjusted as needed and tolerated.
The dosage of lorazepam tablets should be increased gradually when needed to help avoid adverse effects. When higher dosage is indicated, the evening dose should be increased before the daytime doses.
Discontinuation or Dosage Reduction of Lorazepam Tablets
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue lorazepam tablets or reduce the dosage. If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. Subsequently decrease the dosage more slowly (see WARNINGS: Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE: Dependence ).
CONTRAINDICATIONS
Lorazepam tablets are contraindicated in patients with:
- hypersensitivity to benzodiazepines or to any components of the formulation.
- acute narrow-angle glaucoma.
ADVERSE REACTIONS
Most adverse reactions to benzodiazepines, including CNS effects and respiratory depression, are dose dependent, with more severe effects occurring with high doses.
In a sample of about 3500 patients treated for anxiety, the most frequent adverse reaction to lorazepam tablets was sedation (15.9%), followed by dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). The incidence of sedation and unsteadiness increased with age.
Other adverse reactions to benzodiazepines, including lorazepam are fatigue, drowsiness, amnesia, memory impairment, confusion, disorientation, depression, unmasking of depression, disinhibition, euphoria, suicidal ideation/attempt, ataxia, asthenia, extrapyramidal symptoms, convulsions/seizures, tremor, vertigo, eye function/visual disturbance (including diplopia and blurred vision), dysarthria/slurred speech, change in libido, impotence, decreased orgasm; headache, coma; respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease; gastrointestinal symptoms including nausea, change in appetite, constipation, jaundice, increase in bilirubin, increase in liver transaminases, increase in alkaline phosphatase; hypersensitivity reactions, anaphylactoid reactions; dermatological symptoms, allergic skin reactions, alopecia; syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia; thrombocytopenia, agranulocytosis, pancytopenia; hypothermia; and autonomic manifestations.
Paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. Small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by lorazepam tablets.
To report SUSPECTED ADVERSE REACTIONS, contact Chartwell RX, LLC. at 1-845-232-1683 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
DESCRIPTION
Lorazepam Tablets, USP, an antianxiety agent, has the chemical formula, 7-Chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy-2 H -1,4-benzodiazepin-2-one:
C 15 H 10 Cl 2 N 2 O 2 MW: 321.16
It is a white or almost white crystalline powder almost insoluble in water. Each Lorazepam Tablet, USP, to be taken orally, contains 0.5 mg, 1 mg, or 2 mg of Lorazepam, USP. The inactive ingredients present are croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate and tribasic calcium phosphate.
CLINICAL PHARMACOLOGY
Studies in healthy volunteers show that in single high doses lorazepam tablets have a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular systems.
Lorazepam tablets are readily absorbed with an absolute bioavailability of 90%. Peak concentrations in plasma occur approximately 2 hours following administration. The peak plasma level of lorazepam from a 2 mg dose is approximately 20 ng/mL.
The mean half-life of unconjugated lorazepam in human plasma is about 12 hours and for its major metabolite, lorazepam glucuronide, about 18 hours. At clinically relevant concentrations, lorazepam is approximately 85% bound to plasma proteins. Lorazepam tablets are rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine. Lorazepam glucuronide has no demonstrable central nervous system (CNS) activity in animals.
The plasma levels of lorazepam are proportional to the dose given. There is no evidence of accumulation of lorazepam on administration up to 6 months.
Studies comparing young and elderly subjects have shown that advancing age does not have a significant effect on the pharmacokinetics of lorazepam. However, in one study involving single intravenous doses of 1.5 to 3 mg of Ativan 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.
HOW SUPPLIED
Lorazepam Tablets, USP are available containing 0.5 mg, 1 mg or 2 mg of Lorazepam, USP.
The 0.5 mg tablets are white to off white, round shaped tablets, debossed on one side with “ CE ” and “ 228 ” and plain on other side. They are available as follows:
NDC 62135-861-01
bottles of 100 tablets
The 1 mg tablets are white to off white, round scored tablets, debossed on one side with “ CE ” and “ 229 ” and plain on other side. They are available as follows:
NDC 62135-862-01
bottles of 100 tablets
The 2 mg tablets are white to off white, round scored tablets, debossed on one side with “ CE ” and “ 230 ” and plain on other side. They are available as follows:
NDC 62135-863-01
bottles of 100 tablets
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Manufactured for:
Chartwell RX, LLC
Congers, NY 10920
L72197
Rev. 11/2024
PHARMACIST: Dispense a Medication Guide with each prescription.
Print Medication Guide at: www.chartwellpharma.com/medguides .
