DIAZEPAM Injection, USP Rx only
5 mg/mL
Fliptop Vial
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND
ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory
depression, coma, and death (see WARNINGS).
Reserve concomitant prescribing of these drugs in patients for whom alternative treatment
options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation (see
WARNINGS and PRECAUTIONS).
The use of benzodiazepines, including diazepam, exposes users to risks of abuse, misuse, and
addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly
involve concomitant use of other medications, alcohol, and/or illicit substances, which is
associated with an increased frequency of serious adverse outcomes. Before prescribing
diazepam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction
(see WARNINGS).
The continued use of benzodiazepines may lead to clinically significant physical dependence.
The risks of dependence and withdrawal increase with longer treatment duration and higher
daily dose. Although diazepam is indicated only for intermittent use (see INDICATIONS AND
USAGE and DOSAGE AND ADMINISTRATION), if used more frequently than
recommended, abrupt discontinuation or rapid dosage reduction of diazepam may precipitate
acute withdrawal reactions, which can be life-threatening. For patients using diazepam more
frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper
to discontinue diazepam (see WARNINGS).
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 a
molecular weight of 284.74 and with the following molecular structure:
Page 1 of 13
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.
Population PK analysis in 87 pediatric patients 0.4 – 17.8 years of age with status epilepticus showed that,
after initial dosing, the median plasma half-life was 0.5 hours and the median terminal elimination plasma
half-life was 18 to 25 hours.
INDICATIONS AND USAGE
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 Injection is a useful adjunct in status epilepticus.
Diazepam is a useful premedication (the intramuscular 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
Diazepam Injection 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
Risks from Concomitant Use with Opioids
Concomitant use of benzodiazepines, including diazepam, and opioids may result in profound sedation,
respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of
benzodiazepines and opioids in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and
benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a
decision is made to prescribe diazepam concomitantly with opioids, prescribe the lowest effective dosages
Page 2 of 13
and minimum durations of concomitant use, and follow patients closely for signs and symptoms of
respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory
depression and sedation when diazepam is used with opioids (see PRECAUTIONS: Drug Interactions).
Abuse, Misuse, and Addiction
The use of benzodiazepines, including diazepam, exposes users to the risks of abuse, misuse, and
addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not
always) involve the use of doses greater than the maximum recommended dosage and commonly involve
concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an
increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death
(see DRUG ABUSE AND DEPENDENCE: Abuse).
Before prescribing diazepam and throughout treatment, assess each patient’s risk for abuse, misuse,
and addiction. Use of diazepam, particularly in patients at elevated risk, necessitates counseling about the
risks and proper use of diazepam along with monitoring for signs and symptoms of abuse, misuse, and
addiction. Do not exceed the recommended dosing frequency; avoid or minimize concomitant use of CNS
depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics,
stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is
suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.
Dependence and Withdrawal Reactions After Use of Diazepam More Frequently Than
Recommended
For patients using diazepam more frequently than recommended, to reduce the risk of withdrawal
reactions, use a gradual taper to discontinue diazepam (a patient-specific plan should be used to taper the
dose).
Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or
rapid dosage reduction include those who take higher dosages, and those who have had longer durations
of use.
Acute Withdrawal Reactions
The continued use of benzodiazepines, including diazepam may lead to clinically significant physical
dependence. Although diazepam is indicated only for intermittent use (see INDICATIONS AND
USAGE and DOSAGE AND ADMINISTRATION), if used more frequently than recommended, abrupt
discontinuation or rapid dosage reduction of diazepam or administration of flumazenil (a benzodiazepine
antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see
DRUG ABUSE AND DEPENDENCE: Dependence).
Protracted Withdrawal Syndrome
In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal
symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE;
Dependence).
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 except for treatment of
status epilepticus in children (see DOSAGE AND ADMINISTRATION); 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.
Page 3 of 13
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 intravenous., 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 intravenous 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 in hazardous occupations requiring complete mental
alertness, such as operating machinery or driving a motor vehicle.
Tonic status epilepticus has been precipitated in patients treated with intravenous diazepam for petit
mal status or petit mal variant status.
Neonatal Sedation and Withdrawal Syndrome
Use of Diazepam injection late in pregnancy can result in sedation (respiratory depression, lethargy,
hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable
crying, and feeding difficulties) in the neonate (see PRECAUTIONS: Pregnancy). Monitor neonates
exposed to Diazepam injection during pregnancy or labor for signs of sedation and monitor neonates
exposed to Diazepam injection during pregnancy for signs of withdrawal; manage these neonates
accordingly.
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 for the treatment of status epilepticus, 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 as a slow intravenous push
over 1 minute (see DOSAGE AND ADMINISTRATION). The safety and tolerability of the
recommended dosage regimen is supported by a randomized, double-blind study that included
162 pediatric patients ages 3 months to 17 years who received intravenous diazepam for the treatment of
status epilepticus. In this study, 16% of pediatric patients who received diazepam experienced severe or
life-threatening respiratory depression.
Benzyl alcohol has been reported to be associated with a fatal gasping syndrome in premature infants.
PRECAUTIONS
General
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 intravenous
administration. The physician should be prepared to readminister 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.
Page 4 of 13
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 is associated with an
anion gap metabolic acidosis, serum hyperosmolality, and increased lactate. 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 dehydrogenase enzymes, or other
comorbidities (such as a history of alcoholism). Until additional information is available, diazepam
injection is not recommended for obstetrical use. Lower doses (usually 2 mg to 5 mg) should be used for
elderly and debilitated patients.
Risks from Concomitant Use with Opioids
Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation
when diazepam is used with opioids and not to use such drugs concomitantly unless supervised by a
health care provider. Advise patients not to drive or operate heavy machinery until the effects of
concomitant use with the opioid have been determined (see WARNINGS: Risks from Concomitant Use
with Opioids and PRECAUTIONS: Drug Interactions).
Abuse, Misuse, and Addiction
Inform patients that the use of diazepam more frequently than recommended, even at recommended
dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death,
especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or
illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and
addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal
of unused drug (see WARNINGS and DRUG ABUSE AND DEPENDENCE).
Withdrawal Reactions
Inform patients that use of diazepam more frequently than recommended may lead to clinically significant
physical dependence and that abrupt discontinuation or rapid dosage reduction of diazepam may
precipitate acute withdrawal reactions, which can be life-threatening. Inform patients that in some cases,
patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal
symptoms lasting weeks to more than 12 months (see WARNINGS and DRUG ABUSE AND
DEPENDENCE).
Pregnancy
Advise pregnant females that use of Diazepam Injection late in pregnancy can result in sedation
(respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability,
restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see WARNINGS;
Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Pregnancy). Instruct patients to
inform their healthcare provider if they are pregnant.
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women
exposed to Diazepam Injection during pregnancy (see PRECAUTIONS: Pregnancy).
Page 5 of 13
Nursing
Advise patients that breastfeeding is not recommended during treatment with Diazepam Injection (see
PRECAUTIONS; Nursing Mothers).
Drug Interactions
The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because
of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at
GABA
A
sites and opioids interact primarily at mµ receptors. When benzodiazepines and opioids are
combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression
exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor
patients closely for respiratory depression and sedation.
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.
Diazepam injection has produced hypotension or muscular weakness in some patients particularly when
used with narcotics, barbiturates or alcohol.
The clearance of diazepam and certain other benzodiazepines can be delayed in association with
cimetidine administration. The clinical significance of this is unclear.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs,
such as Diazepam injection, during pregnancy. Healthcare providers are encouraged to recommend that
pregnant patient taking Diazepam injection enroll in the NAAED Pregnancy Registry by calling 1-888-
233-2334 or online at http://www.aedpregnancyregistry.org/.
Risk Summary
Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience
symptoms of sedation and/or neonatal withdrawal (see WARNINGS: Neonatal Sedation and
Withdrawal Syndrome, and PRECAUTIONS: Clinical Considerations). Available data from
published observational studies of pregnant women exposed to benzodiazepines do not report a clear
association with benzodiazepines and major birth defects (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All
pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general
population, the estimated risk of major birth defects and of miscarriage in clinically recognized
pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in
neonates. Monitor neonates exposed to Diazepam injection during pregnancy or labor for signs of
Page 6 of 13
sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to
Diazepam injection during pregnancy for signs of withdrawal. Manage these neonates accordingly (see
WARNINGS: Neonatal Sedation and Withdrawal Syndrome).
Data
Human Data
Published data from observational studies on the use of benzodiazepines during pregnancy do not report a
clear association with benzodiazepines and major birth defects.
Although early studies reported an increased risk of congenital malformations with diazepam and
chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-
control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding
exposures to alcohol, tobacco and other medications, have not confirmed these findings.
Animal Data
Diazepam has been shown to produce increased incidences of fetal malformations in mice and hamsters
when given orally at single doses of 100 mg/kg or greater (approximately 20 times the maximum
recommended adult dose [0.4 mg/kg/day] or greater on a mg/m
2
basis). Cleft palate and exencephaly are
the most common and consistently reported malformations produced in these species by administration of
high, maternally-toxic doses of diazepam during organogenesis. In published animal studies,
administration of benzodiazepines or other drugs that enhance GABAergic inhibition to neonatal rats has
been reported to result in widespread apoptotic neurodegeneration in the developing brain at plasma
concentrations relevant for seizure control in humans. The window of vulnerability to these changes in
rats (postnatal days 0-14) includes a period of brain development that takes place during the third
trimester of pregnancy in humans.
Nursing Mothers
Risk Summary
Diazepam is present in breastmilk. There are reports of sedation, poor feeding and poor weight gain in
infants exposed to benzodiazepines through breast milk. There are no data on the effects of diazepam on
milk production. The developmental and health benefits of breastfeeding should be considered along with
the mother's clinical need for Diazepam injection and any potential adverse effects on the breastfed infant
from Diazepam injection or from the underlying maternal condition.
Clinical Considerations
Infants exposed to Diazepam injection through breast milk should be monitored for sedation, poor feeding
and poor weight gain.
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 [including respiratory depression (see WARNINGS: Pediatric Use)],
dysarthria, headache, hypoactivity, slurred speech, syncope, tremor, vertigo.
G.I.: constipation, nausea.
G.U.: incontinence, changes in libido, urinary retention.
Page 7 of 13
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
Controlled Substance
Diazepam Injection is a schedule IV controlled substance.
Abuse
Diazepam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is
the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological
effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other
than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of
behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug,
difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a
higher priority to drug use than other activities and obligations), and possible tolerance or physical
dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of
their medication. Abuse and misuse of benzodiazepines may lead to addiction.
Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the
maximum recommended dosage and commonly involve concomitant use of other medications, alcohol,
and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes,
including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals
who abuse drugs and other substances, and by individuals with addictive disorders (see WARNINGS:
Abuse, Misuse, and Addiction).
The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal
pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition,
disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle
pain, slurred speech, tremors, and vertigo.
The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse:
delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death
is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants
such as opioids and alcohol).
Dependence
Physical Dependence After Use of Diazepam More Frequently Than Recommended
Diazepam may produce physical dependence if used more frequently than recommended. Physical
dependence is a state that develops as a result of physiological adaptation in response to repeated drug
use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose
Page 8 of 13
reduction of a drug. Although diazepam is indicated only for intermittent use (see INDICATIONS AND
USAGE and DOSAGE AND ADMINISTRATION), if used more frequently than recommended, abrupt
discontinuation or rapid dosage reduction or administration of flumazenil, a benzodiazepine antagonist,
may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at
an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage
reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who
have had longer durations of use (see WARNINGS: Dependence and Withdrawal Reactions).
For patients using diazepam more frequently than recommended, to reduce the risk of withdrawal
reactions, use a gradual taper to discontinue diazepam (see WARNINGS: Dependence and Withdrawal
Reactions).
Acute Withdrawal Signs and Symptoms
Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal
involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness,
fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased
appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle
pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute
withdrawal signs and symptoms, including life-threatening reactions, have included catatonia,
convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.
Protracted Withdrawal Syndrome
Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive
impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle
twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine
withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there
may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation
of symptoms for which the benzodiazepine was being used.
Tolerance
Tolerance to diazepam may develop after use more frequently than recommended. Tolerance is a
physiological state characterized by a reduced response to a drug after repeated administration (i.e., a
higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Tolerance to the therapeutic effect of benzodiazepines may develop; however, little tolerance develops to
the amnestic reactions and other cognitive impairments caused by benzodiazepines.
OVERDOSAGE
Overdosage of benzodiazepines is characterized by central nervous system depression ranging from
drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria,
lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory
reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness,
excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory
depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants
(including alcohol and opioids) may be fatal (see WARNINGS: Abuse, Misuse, and Addiction).
Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern
that additional drugs and/or alcohol are involved in the overdosage.
Page 9 of 13
In managing benzodiazepine overdosage, employ general supportive measures, including intravenous
fluids and airway maintenance. Flumazenil, a specific benzodiazepine receptor antagonist indicated for
the complete or partial reversal of the sedative effects of benzodiazepines in the management of
benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly
in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic
antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of
withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is
contraindicated in patients who have received a benzodiazepine for control of a potentially
life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be
used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See
the flumazenil injection Prescribing Information.
Consider contacting a poison center (1-800-222-1222), poisoncontrol.org, or a medical toxicologist for
additional overdosage management recommendations.
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 intramuscular or intravenous, 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 should be injected deeply into the muscle.
Intravenous Use: For the treatment of status epilepticus in children, the solution should be injected
slowly, taking one minute for administration (see WARNINGS, particularly for use in children.). For
other indications, 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 intravenous., it may be injected slowly through the infusion
tubing as close as possible to the vein insertion.
INDICATION
Moderate Anxiety Disorders
and Symptoms of Anxiety
USUAL ADULT DOSAGE
2 mg to 5 mg, intramuscular
or intravenous. Repeat in 3 to
4 hours, if necessary.
DOSAGE RANGE IN
CHILDREN
(Intravenous administration
should be made slowly)
Severe Anxiety Disorders
and Symptoms of Anxiety
5 mg to 10 mg, intramuscular
or intravenous. Repeat in 3 to
4 hours, if necessary.
Page 10 of 13
INDICATION USUAL ADULT DOSAGE
DOSAGE RANGE IN
CHILDREN
(Intravenous administration
should be made slowly)
Acute Alcohol Withdrawal:
As an aid in symptomatic
relief of acute agitation,
tremor, impending or acute
delirium tremens and
hallucinosis.
10 mg, intramuscular or
intravenous. initially, then
5 mg to 10 mg in 3 to 4 hours,
if necessary.
Endoscopic Procedures:
Adjunctively, if
apprehension, anxiety or
acute stress reaction are
present prior to endoscopic
procedures. Dosage of
narcotics should be reduced
by at least a third and in
some cases may be omitted.
See PRECAUTIONS for
peroral procedures.
Titrate intravenous. dosage to
desired sedative response,
such as slurring of speech,
with slow administration
immediately prior to the
procedure. Generally 10 mg or
less is adequate, but up to
20 mg intravenous. may be
given, particularly when
concomitant narcotics are
omitted. If intravenous cannot
be used, 5 mg to 10 mg
intramuscular approximately
30 minutes prior to the
procedure.
Muscle Spasm: Associated
with local pathology,
cerebral palsy, athetosis,
stiff-man syndrome or
tetanus.
5 mg to 10 mg, intramuscular
or intravenous initially, then
5 mg to 10 mg in 3 to 4 hours,
if necessary. For tetanus,
larger doses may be required.
For tetanus in infants over
30 days of age, 1 mg to 2 mg
intramuscular or intravenous,
slowly, repeated every 3 to 4
hours as necessary. In children
5 years or older, 5 mg to
10 mg repeated every 3 to
4 hours may be required to
control tetanus spasms.
Respiratory assistance should
be available.
Page 11 of 13
Unit
of
Sale Concentration
NDC 0409-3213-12
-
dose Fliptop Vials
50
(5
mg/10 mL
mg/mL)
INDICATION USUAL ADULT DOSAGE
DOSAGE RANGE IN
CHILDREN
(Intravenous administration
should be made slowly)
Status Epilepticus: In the
convulsing patient, the
intravenous route is by far
preferred. This injection
should be administered
slowly. However, if
intravenous administration
is impossible, the
intramuscular route may be
used.
5 mg to 10 mg initially
(intravenous preferred). This
injection may be repeated if
necessary at 10 to 15 minute
intervals up to a maximum
dose of 30 mg.
If necessary, therapy with
diazepam may be repeated in
2 to 4 hours; however,
residual active metabolites
may persist, and
readministration should be
made with this consideration.
Extreme caution must be
exercised with individuals
with chronic lung disease or
unstable cardiovascular status.
Children 3 months up to
17 years of age with status
epilepticus:
First dose: 0.2 mg/kg
(maximum 8 mg) by slow
intravenous push (one minute
in duration).
Second dose (if necessary;
5 minutes after the first dose):
0.1 mg/kg (maximum 4 mg)
by slow intravenous push (one
minute in duration).
EEG monitoring of the seizure
may be helpful.
Preoperative Medication:
To relieve anxiety and
tension. (If atropine,
scopolamine or other
premedications are desired,
they must be administered
in separate syringes.)
10 mg, intramuscular
(preferred route), before
surgery.
Cardioversion: To relieve
anxiety and tension and to
reduce recall of procedure.
5 mg to 15 mg, intravenous,
within 5 to 10 minutes prior to
the procedure.
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.
NOTE: Solution may appear colorless to light yellow.
HOW SUPPLIED
Diazepam Injection, USP is supplied as follows:
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of 13
Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
Protect from light.
ANIMAL PHARMACOLOGY
Oral LD
50
of diazepam is 720 mg/kg in mice and 1,240 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 to 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.
CAUTION: Federal (USA) law prohibits dispensing without prescription.
This product’s labeling may have been updated. For the most recent prescribing information, please visit
www.pfizer.com.
Distributed by Hospira, Inc., Lake Forest, IL 60045 USA
LAB-0837-7.0
Revised: April 2023
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