Diazepam, Tablets USP C-IV, Revised: June 2008, Rx only, 173018

DESCRIPTION

id: 74657305-bf93-43b7-8ec5-d379c6d00a9f
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Diazepam is a benzodiazepine derivative. The chemical name of diazepam is 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one. It is a colorless to light yellow crystalline compound, insoluble in water. The empirical formula is C₁₆H₁₃ClN₂O and the molecular weight is 284.75. The structural formula is as follows: Diazepam is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg diazepam. In addition to the active ingredient diazepam, each tablet contains the following inactive ingredients: anhydrous lactose, magnesium stearate and microcrystalline cellulose. Diazepam Tablets USP 5 mg also contain D&C Yellow No. 10. Diazepam Tablets USP 10 mg also contain FD&C Blue No. 1.

CLINICAL PHARMACOLOGY

id: 11eb573d-2dd0-4140-8915-865475d966e7
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle-relaxant, anticonvulsant and amnestic effects. Most of these effects are thought to result from a facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system.

INDICATIONS

id: 103fc3b3-1496-4c53-9406-88d85e448981
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Diazepam Tablets USP are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. In acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Diazepam is a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology (such as inflammation of the muscles or joints, or secondary to trauma); spasticity caused by upper motor neuron disorders (such as cerebral palsy and paraplegia); athetosis; and stiff-man syndrome. Oral diazepam may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy. The effectiveness of diazepam 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.

CONTRAINDICATIONS

id: 75dd0663-fea8-4191-b809-2317059adb33
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Diazepam Tablets USP are contraindicated in patients with a known hypersensitivity to this drug and, because of lack of sufficient clinical experience, in pediatric patients under 6 months of age. Diazepam is also contraindicated in patients with myasthenia gravis, severe respiratory insufficiency, severe hepatic insufficiency, and sleep apnea syndrome. It may be used in patients with open-angle glaucoma who are receiving appropriate therapy, but is contraindicated in acute narrow-angle glaucoma.

WARNINGS

id: a8bde028-1748-48b9-9dd1-f6085751ba59
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

Diazepam is not recommended in the treatment of psychotic patients and should not be employed instead of appropriate treatment. Since diazepam has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during diazepam therapy. As with other agents which have anticonvulsant activity, when diazepam is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. Abrupt withdrawal of diazepam in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures.

ADVERSE REACTIONS

id: d8edd9ec-a523-4bf8-9541-8315815e0dbd
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Side effects most commonly reported were drowsiness, fatigue, muscle weakness, and ataxia. The following have also been reported:
Central Nervous System:
confusion, depression, dysarthria, headache, slurred speech, tremor, vertigo
Gastrointestinal System:
constipation, nausea, gastrointestinal disturbances
Special Senses:
blurred vision, diplopia, dizziness
Cardiovascular System:
hypotension
Psychiatric and Paradoxical Reactions:
stimulation, restlessness, acute hyperexcited states, anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, delusions, increased muscle spasticity, insomnia, sleep disturbances, and nightmares. Inappropriate behavior and other adverse behavioral effects have been reported when using benzodiazepines. Should these occur, use of the drug should be discontinued. They are more likely to occur in children and in the elderly.
Urogenital System:
incontinence, changes in libido, urinary retention
Skin and Appendages:
skin reactions
Laboratories:
elevated transaminases and alkaline phosphatase
Other:
changes in salivation, including dry mouth, hypersalivation Antegrade amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behavior. Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance. Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy.

DRUG ABUSE AND DEPENDENCE

id: e339e317-8bf4-4d30-88a2-57aaaaca8f8a
displayName: DRUG ABUSE AND DEPENDENCE SECTION
FDA Article Code: 42227-9

Diazepam is subject to Schedule IV control under the Controlled Substances Act of 1970. Abuse and dependence of benzodiazepines have been reported. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence. Once physical dependence to benzodiazepines has developed, termination of treatment will be accompanied by withdrawal symptoms. The risk is more pronounced in patients on long-term therapy. Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuance of diazepam. These withdrawal symptoms may consist of tremor, abdominal and muscle cramps, vomiting, sweating, headache, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures. The more severe withdrawal symptoms have usually been limited to those patients who had 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. Chronic use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena.
Rebound Anxiety:
 A transient syndrome whereby the symptoms that led to treatment with diazepam recur in an enhanced form. This may occur upon discontinuation of treatment. It may be accompanied by other reactions including mood changes, anxiety, and restlessness. Since the risk of withdrawal phenomena and rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage be decreased gradually.

OVERDOSAGE

id: 330b0912-ae5f-4897-acde-9b970f98661e
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Overdose of benzodiazepines is usually manifested by central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, confusion, and lethargy. In more serious cases, symptoms may include ataxia, diminished reflexes, hypotonia, hypotension, respiratory depression, coma (rarely), and death (very rarely). Overdose of benzodiazepines in combination with other CNS depressants (including alcohol) may be fatal and should be closely monitored. Management of Overdosage Following overdose with oral benzodiazepines, general supportive measures should be employed including the monitoring of respiration, pulse, and blood pressure. Vomiting should be induced (within 1 hour) if the patient is conscious. Gastric lavage should be undertaken with the airway protected if the patient is unconscious. Intravenous fluids should be administered. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Special attention should be paid to respiratory and cardiac function in intensive care. General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Should hypotension develop, treatment may include intravenous fluid therapy, repositioning, judicious use of vasopressors appropriate to the clinical situation, if indicated, and other appropriate countermeasures. Dialysis is of limited value. As with the management of intentional overdosage with any drug, it should be considered that multiple agents may have been ingested. 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 resedation, 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. Caution should be observed in the use of flumazenil in epileptic patients treated with benzodiazepines. The complete flumazenil package insert, including
CONTRAINDICATIONS  , WARNINGS , and PRECAUTIONS , should be consulted prior to use. Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE ).

DOSAGE AND ADMINISTRATION

id: 58e4c5f1-fdc9-47c6-a5e2-37d491437181
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Dosage should be individualized for maximum beneficial effect. While the usual daily dosages given below will meet the needs of most patients, there will be some who may require higher doses. In such cases dosage should be increased cautiously to avoid adverse effects.

HOW SUPPLIED

id: 2f0d44a4-1d8a-457b-b9f7-62b996600b0d
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Diazepam Tablets USP 2 mg are scored, round, white tablets imprinted DAN 5621 and 2. Diazepam Tablets USP 5 mg are scored, round, yellow tablets imprinted DAN 5619 and 5. Diazepam Tablets USP 10 mg are scored, round, blue tablets imprinted DAN 5620 and 10. Dispense in tight, light-resistant container with child-resistant closure. Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Manufactured by:
Watson Laboratories, Inc.Corona, CA 92880 USA Distributed by:
Watson Pharma, Inc.Corona, CA 92880 USA Revised: June 2008 0608B 173018

Image of 5 mg Label

id: 2bc3fecc-7a6d-4bcb-bc93-aff485190643
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Image of 10mg Label

id: d505c10f-aed0-4550-bd2f-5ac6f1761887
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4