Lorazepam

RedPharm Inc.

FULL PRESCRIBING INFORMATION: CONTENTS*

• LORAZEPAM DESCRIPTION
• CLINICAL PHARMACOLOGY
• LORAZEPAM INDICATIONS AND USAGE
• LORAZEPAM CONTRAINDICATIONS
• WARNINGS
  • Physical and Psychological Dependence
• LORAZEPAM DOSAGE AND ADMINISTRATION
• HOW SUPPLIED

FULL PRESCRIBING INFORMATION

LORAZEPAM DESCRIPTION

Lorazepam, an antianxiety agent, has the chemical formula, 7-chloro-5-(o-chlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one:

C₁₅H₁₀Cl₂N₂O₂      MW: 321.16

Lorazepam, USP is a white or almost white crystalline powder almost insoluble in water. Each lorazepam tablet, to be taken orally, contains 0.5 mg, 1 mg, or 2 mg of lorazepam, USP. The inactive ingredients present are lactose monohydrate, microcrystalline cellulose, polacrilin potassium and sodium stearyl fumarate.

CLINICAL PHARMACOLOGY

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%. 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 6 months.

Studies comparing young and elderly subjects have shown that advancing age does not have a significant effect on the pharmacokinetics of lorazepam.

LORAZEPAM 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.

LORAZEPAM CONTRAINDICATIONS

Lorazepam tablets are contraindicated in patients with

• hypersensitivity to benzodiazepines or to any components of the formulation.
• acute narrow angle glaucoma.

WARNINGS

Preexisting depression may emerge or worsen during use of benzodiazepines including lorazepam. Lorazepam is not recommended for use in patients with a primary depressive disorder or psychosis.

Use of benzodiazepines, including lorazepam, both used alone and in combination with other CNS depressants, may lead to potentially fatal respiratory depression (see PRECAUTIONS: Clinically Significant Drug Interactions).

Use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence.

As with all patients on CNS depressant 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 diminished.

Physical and Psychological Dependence

The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence. The risk of dependence increases with higher doses and longer term use and is further increased in patients with a history of alcoholism or drug abuse or in patients with significant personality disorders. The dependence potential is reduced when lorazepam is used at the appropriate dose for short-term treatment. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving lorazepam or other psychotropic agents.

In general, benzodiazepines should be prescribed for short periods only (e.g., 2 to 4 weeks). Extension of the treatment period should not take place without reevaluation of the need for continued therapy. Continuous long-term use of product is not recommended. Withdrawal symptoms (e.g., rebound insomnia) can appear following cessation of recommended doses after as little as one week of therapy. Abrupt discontinuation of product should be avoided and a gradual dosage-tapering schedule followed after extended therapy.

Abrupt termination of treatment may be accompanied by withdrawal symptoms. Symptoms reported following discontinuation of benzodiazepines include headache, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, rebound phenomena, dysphoria, dizziness, derealization, depersonalization, hyperacusis, numbness/tingling of extremities, hypersensitivity to light, noise, and physical contact/perceptual changes, involuntary movements, nausea, vomiting, diarrhea, loss of appetite, hallucinations/delirium, convulsions/seizures, tremor, abdominal cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, vertigo, hyperreflexia, short-term memory loss, and hyperthermia. Convulsions/seizures may be more common in patients with preexisting seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.

There is evidence that tolerance develops to the sedative effects of benzodiazepines.

Lorazepam may have abuse potential, especially in patients with a history of drug and/or alcohol abuse.

LORAZEPAM 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 b.i.d. or t.i.d.

For insomnia due to anxiety or transient situational stress, a single daily dose of 2 mg 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.

HOW SUPPLIED

Lorazepam Tablets, USP are available containing 0.5 mg, 1 mg or 2 mg of lorazepam, USP.

The 0.5 mg tablet is a white to off-white round tablet debossed with M on one side of the tablet and 321 on the other side. They are available as follows:

NDC 0378-2321-01
bottles of 100 tablets

NDC 0378-2321-05
bottles of 500 tablets

NDC 0378-2321-10
bottles of 1000 tablets

The 1 mg tablet is a white to off-white round tablet debossed with MYLAN above the score and 457 below the score on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-2457-01
bottles of 100 tablets

NDC 0378-2457-05
bottles of 500 tablets

NDC 0378-2457-10
bottle of 1000 tablets

The 2 mg tablet is a white to off-white round tablet debossed with MYLAN above the score and 777 below the score on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-2777-01
bottles of 100 tablets

NDC 0378-2777-05
bottles of 500 tablets

NDC 0378-2777-10
bottles of 1000 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Mylan Pharmaceuticals Inc.
Morgantown, WV 26505

REVISED APRIL 2010
LORZ:R3

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