FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.
Product Label Table of Contents
Lorazepam, an antianxiety agent, has the chemical formula, (±)-7-Chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:
It is a nearly white powder almost insoluble in water. Each lorazepam tablet, to
be taken orally, contains 0.5 mg, 1 mg or 2 mg of lorazepam. This product
contains the following inactive ingredients: lactose, magnesium stearate,
microcrystalline cellulose and polacrilin potassium.
Studies in healthy volunteers show that in single high doses
lorazepam has a tranquilizing action on the central nervous system with no
appreciable effect on the respiratory or cardiovascular systems.
Lorazepam is readily absorbed with an absolute bioavailability of 90 percent.
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 is rapidly conjugated at its 3-hydroxy group into
lorazepam glucuronide which is then excreted in the urine. Lorazepam glucuronide
has no demonstrable 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 six months.
Studies comparing young and elderly subjects have shown that the
pharmacokinetics of lorazepam remain unaltered with advancing age.
Indications And Usage
Lorazepam is 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 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.
Lorazepam is contraindicated in patients with known sensitivity to the
benzodiazepines or with acute narrow-angle glaucoma.
Lorazepam is not recommended for use in patients with a primary depressive
disorder of psychosis. As with all patients on CNS-acting drugs, patients
receiving lorazepam should be warned not to operate dangerous machinery or motor
vehicles and that their tolerance for alcohol and other CNS depressants will be
In patients with depression accompanying anxiety, a possibility
for suicide should be borne in mind.
For elderly or debilitated patients, the initial daily dosage should not
exceed 2 mg in order to avoid oversedation.
Lorazepam dosage should be terminated gradually, since abrupt withdrawal of
any antianxiety agent may result in symptoms similar to those for which patients
are being treated: anxiety, agitation, irritability, tension, insomnia, and
The usual precautions for treating patients with impaired renal or hepatic
function should be observed.
In patients where gastrointestinal or cardiovascular disorders coexist with
anxiety, it should be noted that lorazepam has not been shown to be of
significant benefit in treating the gastrointestinal or cardiovascular
Esophageal dilation occurred in rats treated with lorazepam for more than one
year at 6 mg/kg/day. The no-effect dose was 1.25 mg/kg/day (approximately 6
times the maximum human therapeutic dose of 10 mg per day). The effect was
reversible only when the treatment was withdrawn within two months of first
observation of the phenomenon. The clinical significance of this is unknown.
However, use of lorazepam for prolonged periods and in geriatric patients
requires caution and there should be frequent monitoring for symptoms of upper
Safety and effectiveness of lorazepam in children of less than 12 years have
not been established.INFORMATION FOR PATIENTS
To assure the safe and effective use of lorazepam, patients
should be informed that, since benzodiazepines may produce psychological and
physical dependence, it is advisable that they consult with their physician
before either increasing the dose or abruptly discontinuing this drug.ESSENTIAL LABORATORY TESTS
Some patients on lorazepam have developed leukopenia, and some
have had elevations of LDH. As with other benzodiazepines, periodic blood counts
and liver-function tests are recommended for patients on long-term
therapy.CLINICALLY SIGNIFICANT DRUG INTERACTIONS
The benzodiazepines, including lorazepam, produce CNS-depressant
effects when administered with such medications as barbiturates or
alcohol.CARCINOGENESIS AND MUTAGENESIS
No evidence of carcinogenic potential emerged in rats during an
18-month study with lorazepam. No studies regarding mutagenesis have been
Reproductive studies in animals were performed in mice, rats, and
two strains of rabbits. Occasional anomalies (reduction of tarsals, tibia,
metatarsals, malrotated limbs, gastroschisis, malformed skull, and
microphthalmia) were seen in drug-treated rabbits without relationship to
dosage. Although all of these anomalies were not present in the concurrent
control group, they have been reported to occur randomly in historical controls.
At doses of 40 mg/kg and higher, there was evidence of fetal resorption and
increased fetal loss in rabbits which was not seen at lower doses.
The clinical significance of the above findings is not known. However, an
increased risk of congenital malformations associated with the use of minor
tranquilizers (chlordiazepoxide, diazepam, and meprobamate) during the first
trimester of pregnancy has been suggested in several studies. Because the use of
these drugs is rarely a matter of urgency, the use of lorazepam during this
period should almost always be avoided. The possibility that a woman of
childbearing potential may be pregnant at the time of institution of therapy
should be considered. Patients should be advised that if they become pregnant,
they should communicate with their physician about the desirability of
discontinuing the drug.
In humans, blood levels obtained from umbilical cord blood indicate placental
transfer of lorazepam and lorazepam glucuronide.NURSING MOTHERS
It is not known whether oral lorazepam is excreted in human milk
like the other benzodiazepine tranquilizers. As a general rule, nursing should
not be undertaken while a patient is on a drug since many drugs are excreted in
Adverse reactions, if they occur, are usually observed at the
beginning of therapy and generally disappear on continued medication or upon
decreasing the dose. In a sample of about 3,500 anxious patients, the most
frequent adverse reaction to lorazepam is sedation (15.9%), followed by
dizziness (6.9%), weakness (4.2%), and unsteadiness (3.4%). Less frequent
adverse reactions are disorientation, depression, nausea, change in appetite,
headache, sleep disturbance, agitation, dermatological symptoms, eye-function
disturbance, together with various gastrointestinal symptoms and autonomic
manifestations. The incidence of sedation and unsteadiness increased with
Small decreases in blood pressure have been noted but are not clinically
significant, probably being related to the relief of anxiety produced by
Transient amnesia or memory impairment has been reported in association with
the use of benzodiazepines.
Drug Abuse And Dependence
Withdrawal symptoms, similar in character to those noted with
barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps,
vomiting, and sweating), have occurred following abrupt discontinuance of
lorazepam. The more severe withdrawal symptoms have usually been limited to
those patients who received excessive doses over an extended period of time.
Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been
reported following abrupt discontinuance of benzodiazepines taken continuously
at therapeutic levels for several months. Consequently, after extended therapy,
abrupt discontinuation should generally be avoided and a gradual dosage-tapering
schedule followed. Addiction-prone individuals (such as drug addicts or
alcoholics) should be under careful surveillance when receiving lorazepam or
other psychotropic agents because of the predisposition of such patients to
habituation and dependence.
Lorazepam tablets are classified by the Drug Enforcement Administration as a
Schedule IV controlled substance.
In the management of overdosage with any drug, it should be borne
in mind that multiple agents may have been taken.
Manifestations of lorazepam overdosage include somnolence, confusion, and
coma. Induced vomiting and/or gastric lavage should be undertaken, followed by
general supportive care, monitoring of vital signs, and close observation of the
patient. Hypotension, though unlikely, usually may be controlled with
norepinephrine bitartrate injection. The usefulness of dialysis has not been
Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for
the complete or partial reversal of the sedative effects of benzodiazepines and
may be used in situations when an overdose with a benzodiazepine is known or
suspected. Prior to the administration of flumazenil, necessary measures should
be instituted to secure airway, ventilation, and intravenous access. Flumazenil
is intended as an adjunct to, not as a substitute for, proper management of
benzodiazepine overdose. Patients treated with flumazenil should be monitored
for re-sedation, respiratory depression, and other residual benzodiazepine
effects for an appropriate period after treatment. 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. The complete flumazenil package insert including
PRECAUTIONS should be consulted prior to use.
Dosage And Administration
Lorazepam is 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
For anxiety, most patients require an initial dose of 2 to 3 mg/day given
b.i.d. or t.i.d.
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 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.
Lorazepam tablets are available in the following dosage
0.5 mg: white, scored, round flat faced beveled edge, debossed with 240 over 0.5 on one side and WATSON on the other side, supplied in:
|Bottles of 10||NDC 54868-2145-0|
|Bottles of 20||NDC 54868-2145-2|
|Bottles of 30||NDC 54868-2145-3|
|Bottles of 50||NDC 54868-2145-5|
|Bottles of 60||NDC 54868-2145-6|
|Bottles of 90||NDC 54868-2145-9|
|Bottles of 100||NDC 54868-2145-4|
1 mg: white, scored, round flat faced beveled edge, debossed with 241 over 1 on one side and WATSON on the other side, supplied in:
|Bottles of 03||NDC 54868-1338-6|
|Bottles of 10||NDC 54868-1338-7|
|Bottles of 15||NDC 54868-1338-0|
|Bottles of 20||NDC 54868-1338-1|
|Bottles of 30||NDC 54868-1338-3|
|Bottles of 60||NDC 54868-1338-4|
|Bottles of 90||NDC 54868-1338-8|
|Bottles of 100||NDC 54868-1338-2|
|Bottles of 120||NDC 54868-1338-9|
2 mg: white, scored, round flat faced beveled edge, debossed with 242 over 2 on one side and WATSON on the other side, supplied in:
|Bottles of 30||NDC 54868-0061-3|
|Bottles of 60||NDC 54868-0061-5|
|Bottles of 90||NDC 54868-0061-4|
|Bottles of 100||NDC 54868-0061-2|
|Bottles of 120||NDC 54868-0061-6|
Store at controlled room temperature 15°-30°C (59°-86°F). [See USP.]
Dispense in a tight, light-resistant container as defined in the USP.
Watson Laboratories, Inc.
Corona, CA 92880
Rev: February 2004
Repackaging and Relabeling by:
Physicians Total Care, Inc.
Tulsa, OK 74146
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