Diazepam (injection)
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chetan Lokhande, M.B.B.S [2]
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Overview
Diazepam (injection) is a general anesthetic that is FDA approved for the {{{indicationType}}} of alcohol withdrawal syndrome, anxiety, sedation, premedication before surgery, endoscopic procedures and cardioversion, seizure, refractory, increased frequency, seizure adjunct, skeletal muscle spasm; adjunct, skeletal muscle spasm - tetanus, status epilepticus.. Common adverse reactions include cardiovascular: hypotension, dermatologic: rash (3%, rectal gel ), gastrointestinal: diarrhea (4%, rectal gel ), musculoskeletal: muscle weakness, neurologic: ataxia, incoordination (3%, rectal gel ), somnolence, psychiatric: euphoria (3%, rectal gel )respiratory: respiratory depression, other: fatigue.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Alcohol withdrawal syndrome: initial, 10 mg IM or IV; may give 5 to 10 mg in 3 to 4 hr if necessary.
- Alcohol withdrawal syndrome: initial, 10 mg ORALLY 3 to 4 times in first 24 hr, then 5 mg ORALLY 3 to 4 times daily as needed.
- Anxiety: 2 to 10 mg ORALLY 2 to 4 times a day depending on symptom severity.
- Anxiety: 2 to 10 mg IM or IV every 3 to 4 hr if needed depending on symptom severity.
- Sedation, Premedication before surgery, endoscopic procedures and cardioversion: preoperative medication, 10 mg IM before surgery [2]
Sedation, Premedication before surgery, endoscopic procedures and cardioversion: endoscopic procedure, 10 mg or less IV immediately prior to procedure; MAX 20 mg OR 5 to 10 mg IM 30 min prior to procedure.
- Sedation, Premedication before surgery, endoscopic procedures and cardioversion: cardioversion, 5 to 15 mg IV 5 to 10 min prior to procedure.
- Sedation for a mechanically ventilated patient, Intensive care unit: 0.03 to 0.1 mg/kg every 0.5 to 6 hr IV as needed.
- Seizure, Refractory, increased frequency: 0.2 mg/kg gel RECTALLY, may repeat in 4 to 12 hr if necessary; may use for up to 1 episode/5 days or 5 episodes/mo.
- Seizure; Adjunct: 2 to 10 mg ORALLY 2 to 4 times daily.
- Seizure; Adjunct: severe, recurrent; initial, 5 to 10 mg IV every 10 to 15 min as necessary up to a MAX dose of 30 mg; may repeat in 2 to 4 hr if needed.
- Seizure; Adjunct: initial, 0.2 mg/kg RECTALLY (rounded up to available rectal dose available available), may repeat in 4 to 12 hours, no more than 1 episode every 5 days, and 5 episodes per month.
- Skeletal muscle spasm; Adjunct: 2 to 10 mg ORALLY 3 to 4 times a day.
- Skeletal muscle spasm; Adjunct: initial, 5 to 10 mg IM or IV, then repeat in 3 to 4 hr if needed.
- Skeletal muscle spasm - Tetanus: initial, 5 to 10 mg IM or IV, then repeat in 3 to 4 hr if needed; larger doses may be required for tetanus.
- Status epilepticus: initial, 5 to 10 mg IV every 10 to 15 min up to a MAX dose of 30 mg; may repeat in 2 to 4 hr if needed.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
- Anesthesia; Adjunct.
- Benzodiazepine withdrawal.
- Sedation for a mechanically ventilated patient, Intensive care unit.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Diazepam in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
- Safety and effectiveness not established in children less than 6 months of age.
- Anxiety: initial, 1 to 2.5 mg ORALLY 3 to 4 times daily; increase gradually as needed.
- Seizure, Refractory, increased frequency: 2 to 5 yr, 0.5 mg/kg gel RECTALLY, may repeat in 4 to 12 hr if necessary; may use for up to 1 episode/5 days or 5 episodes/mo.
- Seizure, Refractory, increased frequency: 6 to 11 yr, 0.3 mg/kg gel RECTALLY, may repeat in 4 to 12 hr if necessary; may use for up to 1 episode/5 days or 5 episodes/mo.
- Seizure, Refractory, increased frequency: 12 yr and older, 0.2 mg/kg gel RECTALLY, may repeat in 4 to 12 hr if necessary; may use for up to 1 episode/5 days or 5 episodes/mo.
- Seizure; Adjunct: 6 mo or older, initial, 1 to 2.5 mg ORALLY 3 to 4 times daily, may increase gradually as needed.
- Seizure; Adjunct: severe, recurrent; 30 days to 5 yr of age, 0.2 to 0.5 mg IV slowly (preferred) OR IM every 2 to 5 min up to a MAX of 5 mg.
- Seizure; Adjunct: severe, recurrent; 5 yr and older, 1 mg IV slowly (preferred) OR IM every 2 to 5 min up to MAX of 10 mg; repeat in 2 to 4 hr if necessary.
- Seizure; Adjunct: 2 to 5 years, initial, 0.5 mg/kg RECTALLY (rounded up to the manufactured unit dose available), may repeat in 4 to 12 hours, no more than 1 episode every 5 days, and 5 episodes per month.
- Seizure; Adjunct: 6 to 11 years, initial, 0.3 mg/kg RECTALLY (rounded up to the manufactured unit dose available), may repeat in 4 to 12 hours, no more than 1 episode every 5 days, and 5 episodes per month.
- Seizure; Adjunct: 12 years and older, initial, 0.2 mg/kg RECTALLY (rounded up to the manufactured unit dose available), may repeat in 4 to 12 hours, no more than 1 episode every 5 days, and 5 episodes per month.
- Skeletal muscle spasm; Adjunct: 6 mo or older, initial, 1 to 2.5 mg ORALLY 3 to 4 times daily, may increase gradually as needed.
- Skeletal muscle spasm - Tetanus: spasms due to tetanus, over 30 days to 5 yr, 1 to 2 mg IM OR IV, repeat every 3 to 4 hr as necessary.
- Skeletal muscle spasm - Tetanus: spasms due to tetanus, 5 yr and older, 5 to 10 mg IM OR IV, repeat every 3 to 4 hr as necessary.
- Status epilepticus: 30 days to 5 yr of age, 0.2 to 0.5 mg IV slowly (preferred) OR IM every 2 to 5 min up to a MAX of 5 mg.
- Status epilepticus: 5 yr and older, 1 mg IV slowly (preferred) OR IM every 2 to 5 min up to MAX of 10 mg; repeat in 2 to 4 hr if necessary.
- Status epilepticus: infants and children, 0.1 mg/kg up to a MAX of 0.3 mg/kg IV every 2 min; do not exceed a total dose of 5 mg in children aged 30 days to 5 yr OR a total dose of 10 mg in children aged 5 yr or older.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Diazepam in pediatric patients.
Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Diazepam in pediatric patients.
Contraindications
Valium is 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. Valium 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
Valium is not recommended in the treatment of psychotic patients and should not be employed instead of appropriate treatment.
Since Valium has a central nervous system depressant effect, patients should be advised against the simultaneous ingestion of alcohol and other CNS-depressant drugs during Valium therapy.
As with other agents that have anticonvulsant activity, when Valium 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 Valium in such cases may also be associated with a temporary increase in the frequency and/or severity of seizures.
Adverse Reactions
Clinical Trials Experience
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 Valium 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.
Postmarketing Experience
Injury, Poisoning and Procedural Complications
There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcohol), and in the elderly.
Drug Interactions
Centrally Acting Agents
If Valium is to be combined with other centrally acting agents careful consideration should be given to the pharmacology of the agents employed particularly with compounds that may potentiate or be potentiated by the action of Valium, such as phenothiazines, antipsychotics, anxiolytics/sedatives, hypnotics, anticonvulsants, narcotic analgesics, anesthetics, sedative antihistamines, narcotics, barbiturates, MAO inhibitors and other antidepressants.
Alcohol
Concomitant use with alcohol is not recommended due to enhancement of the sedative effect.
Antacids
Diazepam peak concentrations are 30% lower when antacids are administered concurrently. However, there is no effect on the extent of absorption. The lower peak concentrations appear due to a slower rate of absorption, with the time required to achieve peak concentrations on average 20 - 25 minutes greater in the presence of antacids. However, this difference was not statistically significant.
Compounds Which Inhibit Certain Hepatic Enzymes
There is a potentially relevant interaction between diazepam and compounds which inhibit certain hepatic enzymes (particularly cytochrome P450 3A and 2C19). Data indicate that these compounds influence the pharmacokinetics of diazepam and may lead to increased and prolonged sedation. At present, this reaction is known to occur with cimetidine, ketoconazole, fluvoxamine, fluoxetine, and omeprazole.
Phenytoin
There have also been reports that the metabolic elimination of phenytoin is decreased by diazepam.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): D An increased risk of congenital malformations and other developmental abnormalities associated with the use of benzodiazepine drugs during pregnancy has been suggested. There may also be non-teratogenic risks associated with the use of benzodiazepines during pregnancy. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy. In addition, children born to mothers receiving benzodiazepines on a regular basis late in pregnancy may be at some risk of experiencing withdrawal symptoms during the postnatal period.
Diazepam has been shown to be teratogenic in mice and hamsters when given orally at daily doses of 100 mg/kg or greater (approximately eight times the maximum recommended human dose [MRHD=1 mg/kg/day] or greater on a mg/m2 basis). Cleft palate and encephalopathy are the most common and consistently reported malformations produced in these species by administration of high, maternally toxic doses of diazepam during organogenesis. Rodent studies have indicated that prenatal exposure to diazepam doses similar to those used clinically can produce long-term changes in cellular immune responses, brain neurochemistry, and behavior.
In general, the use of diazepam in women of childbearing potential, and more specifically during known pregnancy, should be considered only when the clinical situation warrants the risk to the fetus. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Patients should also be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Diazepam (injection) in women who are pregnant.
Labor and Delivery
Special care must be taken when Valium is used during labor and delivery, as high single doses may produce irregularities in the fetal heart rate and hypotonia, poor sucking, hypothermia, and moderate respiratory depression in the neonates. With newborn infants it must be remembered that the enzyme system involved in the breakdown of the drug is not yet fully developed (especially in premature infants).
Nursing Mothers
Diazepam passes into breast milk. Breastfeeding is therefore not recommended in patients receiving Valium.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 6 months have not been established.
Geriatic Use
In elderly patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (2 mg to 2.5 mg once or twice daily, initially to be increased gradually as needed and tolerated).
Extensive accumulation of diazepam and its major metabolite, desmethyldiazepam, has been noted following chronic administration of diazepam in healthy elderly male subjects. Metabolites of this drug are known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender
There is no FDA guidance on the use of Diazepam (injection) with respect to specific gender populations.
Race
There is no FDA guidance on the use of Diazepam (injection) with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Diazepam (injection) in patients with renal impairment.
Hepatic Impairment
Decreases in clearance and protein binding, and increases in volume of distribution and half-life have been reported in patients with cirrhosis. In such patients, a 2- to 5- fold increase in mean half-life has been reported. Delayed elimination has also been reported for the active metabolite desmethyldiazepam. Benzodiazepines are commonly implicated in hepatic encephalopathy. Increases in half-life have also been reported in hepatic fibrosis and in both acute and chronic hepatitis (see CLINICAL PHARMACOLOGY: Pharmacokinetics in Special Populations: Hepatic Insufficiency ).
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Diazepam (injection) in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Diazepam (injection) in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Diazepam (injection) Administration in the drug label.
Monitoring
There is limited information regarding Diazepam (injection) Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Diazepam (injection) and IV administrations.
Overdosage
There is limited information regarding Diazepam (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Diazepam (injection) Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Diazepam (injection) Mechanism of Action in the drug label.
Structure
There is limited information regarding Diazepam (injection) Structure in the drug label.
Pharmacodynamics
There is limited information regarding Diazepam (injection) Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Diazepam (injection) Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Diazepam (injection) Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Diazepam (injection) Clinical Studies in the drug label.
How Supplied
There is limited information regarding Diazepam (injection) How Supplied in the drug label.
Storage
There is limited information regarding Diazepam (injection) Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Diazepam (injection) Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Diazepam interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Diazepam (injection) Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Diazepam (injection) Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
Synonyms / Brand Names: DAP, Methyldiazepinone, Alboral, Aliseum, Alupram, Amiprol, An-Ding, Ansiolin, Ansiolisina, Apaurin, Apo-Diazepam, Apozepam, Armonil, Assival, Atensine, Atilen, Bensedin, Bialzepam, Calmocitene, Calmpose, Cercine, Ceregulart, Condition, Diacepan, Dialag, Dialar, Diapam, Diastat, Diazemuls, Diazemulus, Diazepam Intensol, Diazepan, Diazetard, Dienpax, Dipam, Dipezona, Dizac, Domalium, Duksen, Duxen, E-Pam, Eridan, Eurosan, Evacalm, Faustan, Faustan, Freudal, Frustan, Gewacalm, Gihitan, Kabivitrum, Kiatrium, LA III, La-Iii, Lamra, Lembrol, Levium, Liberetas, Mandrozep, Morosan, Neurolytril, Noan, Novazam, Novo-Dipam, Paceum, Pacitran, Paranten, Paxate, Paxel, Plidan, Pms-Diazepam, Pro-Pam, Q-Pam, Q-Pam Relanium, Quetinil, Quiatril, Quievita, Relaminal, Relanium, Renborin, Ruhsitus, Saromet, Sedapam, Sedipam, Seduksen, Seduxen, Serenack, Serenamin, Serenzin, Servizepam, Setonil, Sibazon, Sibazone, Solis, Sonacon, Stesolid, Stesolin, Tensopam, Tranimul, Tranqdyn, Tranquase, Tranquirit, Tranquo-Puren, Tranquo-Tablinen, Umbrium, Unisedil, Usempax Ap, Valaxona, Valeo, Valiquid, Valitran, Valium, Valrelease, Vatran, Velium, Vival, Vivol, Zetran, Zipan