NDC 52584-213 Diazepam

Diazepam

NDC Product Code 52584-213

NDC 52584-213-12

Package Description: 1 VIAL, MULTI-DOSE in 1 BAG > 10 mL in 1 VIAL, MULTI-DOSE

NDC Product Information

Diazepam with NDC 52584-213 is a a human prescription drug product labeled by General Injectables And Vaccines, Inc.. The generic name of Diazepam is diazepam. The product's dosage form is injection, solution and is administered via intramuscular; intravenous form.

Labeler Name: General Injectables And Vaccines, Inc.

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

DEA Schedule: Schedule IV (CIV) Substances What is the Drug Enforcement Administration (DEA) CIV Schedule?
The controlled substances in the CIV schedule have an abuse potential and dependence liability less than those listed in CIII and have an accepted medical use in the United States.

Diazepam Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • DIAZEPAM 5 mg/mL

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Benzodiazepine - [EPC] (Established Pharmacologic Class)
  • Benzodiazepines - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: General Injectables And Vaccines, Inc.
Labeler Code: 52584
FDA Application Number: ANDA071583 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 08-27-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Diazepam Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Description

Diazepam Injection, USP is a sterile, nonpyrogenic solution
intended for intramuscular or intravenous administration. Each milliliter (mL)
contains 5 mg diazepam; 40% propylene glycol; 10% alcohol; 5% sodium benzoate
and benzoic acid added as buffers; and 1.5% benzyl alcohol added as a
preservative. pH 6.6 (6.2 to 6.9). Note: Solution may appear colorless to light
yellow.Diazepam is a benzodiazepine derivative chemically designated as
7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one. It is a
colorless crystalline compound, insoluble in water, with the following molecular
structure:

Clinical Pharmacology

In animals, diazepam appears to act on parts of the limbic system, the thalamus
and hypothalamus, and induces calming effects. Diazepam, unlike chlorpromazine
and reserpine, has no demonstrable peripheral autonomic blocking action, nor
does it produce extrapyramidal side effects; however, animals treated with
diazepam do have a transient ataxia at higher doses. Diazepam was found to have
transient cardiovascular depressor effects in dogs. Long-term experiments in
rats revealed no disturbances of endocrine function. Injections into animals
have produced localized irritation of tissue surrounding injection sites and
some thickening of veins after intravenous use.

Indications And Usage Section

Diazepam is 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.As an adjunct prior to endoscopic procedures if apprehension, anxiety or
acute stress reactions are present, and to diminish the patient’s recall of the
procedures. (See WARNINGS.)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; stiff-man syndrome; and
tetanus.Diazepam is a useful adjunct in status epilepticus and severe recurrent
convulsive seizures.Diazepam is a useful premedication (the I.M. route is preferred) for relief
of anxiety and tension in patients who are to undergo surgical procedures.
Intravenously, prior to cardioversion for the relief of anxiety and tension and
to diminish the patient’s recall of the procedure.

Contraindications Section

Diazepam is contraindicated in patients with a known hypersensitivity to this
drug; acute narrow angle glaucoma; and open angle glaucoma unless patients are
receiving appropriate therapy.

Warnings

When used intravenously, the following
procedures should be undertaken to reduce the possibility of venous thrombosis,
phlebitis, local irritation, swelling, and, rarely, vascular impairment; the
solution should be injected slowly, taking at least one minute for each 5 mg (1
mL) given; do not use small veins, such as those on the dorsum of the hand or
wrist; extreme care should be taken to avoid intra-arterial administration or
extravasation.Do not mix or dilute diazepam with other solutions or
drugs in syringe or infusion container. If it is not feasible to administer
diazepam directly I.V., it may be injected slowly through the infusion tubing as
close as possible to the vein insertion.Extreme care must be used in administering Diazepam Injection, particularly
by the I.V. route, to the elderly, to very ill patients and to those with
limited pulmonary reserve because of the possibility that apnea and/or cardiac
arrest may occur. Concomitant use of barbiturates, alcohol or other central
nervous system depressants increases depression with increased risk of apnea.
Resuscitative equipment including that necessary to support respiration should
be readily available.When diazepam is used with a narcotic analgesic, the dosage of the narcotic
should be reduced by at least one-third and administered in small increments. In
some cases the use of a narcotic may not be necessary.Diazepam Injection should not be administered to patients in shock, coma, or
in acute alcoholic intoxication with depression of vital signs. As is true of
most CNS-acting drugs, patients receiving diazepam should be cautioned against
engaging inhazardous occupations requiring complete mental alertness, such as
operating machinery or driving a motor vehicle.Tonic status epilepticus has been precipitated in patients treated with I.V.
diazepam for petit mal status or petit mal variant status.Usage in Pregnancy:An increased risk of congenital malformations associated
with the use of minor tranquilizers (diazepam, meprobamate and chlordiazepoxide)
during the first trimester of pregnancy has been suggested in several studies.
Because use of these drugs is rarely a matter of urgency, their use 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
during therapy or intend to become pregnant they should communicate with their
physicians about the desirability of discontinuing the drug.In humans, measurable amounts of diazepam were found in maternal and cord
blood, indicating placental transfer of the drug. Until additional information
is available, diazepam injection is not recommended for obstetrical use.Pediatric Use:Efficacy and safety of parenteral diazepam has not been established in the
neonate (30 days or less of age).Prolonged central nervous system depression has been observed in neonates,
apparently due to inability to biotransform diazepam into inactive
metabolites.In pediatric use, in order to obtain maximal clinical effect with the minimum
amount of drug and thus to reduce the risk of hazardous side effects, such as
apnea or prolonged periods of somnolence, it is recommended that the drug be
given slowly over a three-minute period in a dosage not to exceed 0.25 mg/kg.
After an interval of 15 to 30 minutes the initial dosage can be safely repeated.
If, however, relief of symptoms is not obtained after a third administration,
adjunctive therapy appropriate to the condition being treated is
recommended.Withdrawal symptoms of the barbiturate type have occurred after the
discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).Benzyl alcohol has been reported to be associated with a fatal gasping
syndrome in premature infants.

Precautions

Although seizures may be brought under control promptly, a significant proportion of patients experience a return to seizure activity, presumably due to the short-lived effect of diazepam after I.V. administration. The physician should be prepared to re-administer the drug. However, diazepam is not recommended for maintenance, and once seizures are brought under control, consideration should be given to the administration of agents useful in longer term control of seizures.If diazepam is to be combined with other psychotropic agents or anticonvulsant drugs, careful consideration should be given to the pharmacology of the agents to be employed—particularly with known compounds which may potentiate the action of diazepam, such as phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants. In highly anxious patients with evidence of accompanying depression, particularly those who may have suicidal tendencies, protective measures may be necessary. The usual precautions in treating patients with impaired hepatic function should be observed. Metabolites of diazepam are excreted by the kidney; to avoid their excess accumulation, caution should be exercised in the administration to patients with compromised kidney function.Since an increase in cough reflex and laryngospasm may occur with peroral endoscopic procedures, the use of a topical anesthetic agent and the availability of necessary countermeasures are recommended.Propylene glycol toxicity has been reported in patients treated with diazepam injection at doses significantly greater than recommended. In these cases, diazepam was being used to treat alcohol withdrawal symptoms at doses greater than 900 mg/day. Propylene glycol toxicity can cause acute tubular necrosis (which can progress to multi-organ failure), mental status changes, hypotension, seizures, and cardiac arrhythmias. Patients at high risk for propylene glycol toxicity include those with renal dysfunction, hepatic dysfunction, impaired alcohol hydrogenase enzymes, or other comorbidities (such as a history of alcoholism).Until additional information is available, diazepam injection is not recommended for obstetrical use.Diazepam injection has produced hypotension or muscular weakness in some patients particularly when used with narcotics, barbiturates or alcohol. Lower doses (usually 2 mg to 5 mg) should be used for elderly and debilitated patients.The clearance of diazepam and certain other benzodiazepines can be delayed in association with cimetidine administration. The clinical significance of this is unclear.

Adverse Reactions

Side effects most commonly reported were drowsiness, fatigue and
ataxia; venous thrombosis and phlebitis at the site of injection. Other adverse
reactions less frequently reported include: CNS: confusion, depression, dysarthria, headache,
hypoactivity, slurred speech, syncope, tremor, vertigo. G.I.: constipation, nausea. G.U.: incontinence, changes in libido, urinary retention.
Cardiovascular : bradycardia, cardiovascular
collapse, hypotension. EENT: blurred vision,
diplopia, nystagmus. Skin: urticaria, skin rash.
Other: hiccups, changes in salivation, neutropenia,
jaundice. Paradoxical reactions such as acute hyperexcited states, anxiety,
hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances
and stimulation have been reported; should these occur, use of the drug should
be discontinued. 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.In peroral endoscopic procedures, coughing, depressed respiration, dyspnea,
hyperventilation, laryngospasm and pain in throat or chest have been
reported.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 Section

Diazepam Injection is classified by the Drug Enforcement
Administration as a schedule IV controlled substance.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 diazepam. 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. 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.

Dosage And Administration

Dosage should be individualized for maximum beneficial effect. The usual recommended dose in older children and adults ranges from 2 mg to 20 mg I.M. or I.V., depending on the indication and its severity. In some conditions, e.g., tetanus, larger doses may be required. (See dosage for specific indications.) In acute conditions the injection may be repeated within one hour although an interval of 3 to 4 hours is usually satisfactory. Lower doses (usually 2 mg to 5 mg) and slow increase in dosage should be used for elderly or debilitated patients and when other sedative drugs are administered. (See WARNINGS and ADVERSE REACTIONS.)For dosage in infants above the age of 30 days and children, see the specific indications below. When intravenous use is indicated, facilities for respiratory assistance should be readily available.Intramuscular: Diazepam Injection, USP should be injected deeply into the muscle.Intravenous use: (See WARNINGS, particularly for use in children.) The solution should be injected slowly, taking at least one minute for each 5 mg (1 mL) given. Do not use small veins, such as those on the dorsum of the hand or wrist. Extreme care should be taken to avoid intra-arterial administration or extravasation.Do not mix or dilute diazepam with other solutions or drugs in syringe or infusion flask. If it is not feasible to administer diazepam directly I.V., it may be injected slowly through the infusion tubing as close as possible to the vein insertion.Once the acute symptomatology has been properly controlled with diazepam injection, the patient may be placed on oral therapy with diazepam if further treatment is required.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit (see PRECAUTIONS). NOTE: Solution may appear colorless to light yellow.

Management Of Overdosage

Manifestations of diazepam overdosage include somnolence, confusion, coma, and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal. General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value.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 CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.

How Supplied

Diazepam Injection, USP  is supplied as follows10 mL multiple dose vials containing 50 mg (5 mg/mL)Box of 10  NDC 0409-3213-12Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from light.

Animal Pharmacology

Oral LD50 of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. Intraperitoneal administration of 400 mg/kg to a monkey resulted in death on the sixth day.Reproduction Studies: A series of rat reproduction studies was performed with diazepam in oral doses of 1, 10, 80 and 100 mg/kg given for periods ranging from 60−228 days prior to mating. At 100 mg/kg there was a decrease in the number of pregnancies and surviving offspring in these rats. These effects may be attributable to prolonged sedative activity, resulting in lack of interest in mating and lessened maternal nursing and care of the young. Neonatal survival of rats at doses lower than 100 mg/kg was within normal limits. Several neonates, both controls and experimentals, in these rat reproduction studies showed skeletal or other defects. Further studies in rats at doses up to and including 80 mg/kg/day did not reveal significant teratological effects on the offspring. Rabbits were maintained on doses of 1, 2, 5 and 8 mg/kg from day 6 through day 18 of gestation. No adverse effects on reproduction and no teratological changes were noted.Revised: 2/2014EN-3481Hospira, Inc., Lake Forest, IL 60045 USA

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