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 molecular formula is C16H13ClN2O and the molecular weight is 284.74. The structural formula is as follows:
Diazepam is available for oral administration as tablets containing 2 mg, 5 mg or 10 mg diazepam, USP. In addition to the active ingredient diazepam, each tablet contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch (corn) and sodium lauryl sulfate. The following coloring agents are employed:
2 mg – none
5 mg – FD&C Yellow No.6 Aluminum Lake
10 mg – FD&C Blue No. 1 Aluminum Lake and D&C Yellow No. 10 Aluminum Lake.
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 AND USAGE
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 tablets may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis.
Diazepam tablets are 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 tablets may be used adjunctively in convulsive disorders, although it has not proved useful as the sole therapy.
The effectiveness of diazepam 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.
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Diazepam tablets are contraindicated in patients with a known hypersensitivity to diazepam 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.
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 that 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.
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
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.
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.
DOSAGE AND ADMINISTRATION
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.
USUAL DAILY DOSE:
| Management of Anxiety Disorders and Relief of Symptoms of Anxiety
|| Depending upon severity of symptoms—2 mg to 10 mg, 2 to 4 times daily
| Symptomatic Relief in Acute Alcohol Withdrawal
|| 10 mg, 3 or 4 times during the first 24 hours, reducing to 5 mg, 3 or 4 times daily as needed
| Adjunctively for Relief of Skeletal Muscle Spasm
|| 2 mg to 10 mg, 3 or 4 times daily
| Adjunctively in Convulsive Disorders
|| 2 mg to 10 mg, 2 to 4 times daily
| Geriatric Patients, or in the presence of debilitating disease
|| 2 mg to 2.5 mg, 1 or 2 times daily initially; increase gradually as needed and tolerated
| Because of varied responses to CNS-acting drugs, initiate therapy with lowest dose and increase as required. Not for use in pediatric patients under 6 months
|| 1 mg to 2.5 mg, 3 or 4 times daily initially; increase gradually as needed and tolerated
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Diazepam Tablets, USP are available containing 2 mg, 5 mg or 10 mg of diazepam, USP.
The 2 mg tablets are white, round, scored tablets debossed with MYLAN over 271 on one side and the other side being scored.
The 5 mg tablets are orange, round, scored tablets debossed with MYLAN over 345 on one side and the other side being scored. They are available as follows:
blistercards of 30 tablets
The 10 mg tablets are green, round, scored tablets debossed with MYLAN over 477 on one side and the other side being scored.
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 U.S.A.
REVISED SEPTEMBER 2015
PRINCIPAL DISPLAY PANEL – 5 mg
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4