Diazepam Injection

This medication is given by injection into a vein or deep into a muscle as directed by your doctor. Giving the medication too fast can cause heart problems. If giving this medication into a vein, inject it slowly into a large vein because the medication is very irritating to the vein. Do not inject this medication into an artery or into the skin.This medication may be available in a vial, ampule, pre-filled syringe, or pre-filled syringe with autoinjector. The autoinjector automatically delivers a dose of 10 milligrams deep into the muscle. It cannot be used when a lower dose is needed. Do not use the autoinjector for injecting into a vein.Dosage is based on your medical condition, age, and response to treatment. You will be closely monitored for several hours after receiving this medication. If your doctor orders you to continue to receive this medication, you should be switched to a form that can be taken by mouth as soon as possible.If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.This medication may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as shakiness, trouble sleeping, muscle cramps, vomiting, sweating, seizures, mental/mood changes such as anxiety/agitation) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.Rarely, abnormal drug-seeking behavior (addiction) is possible with this medication. Do not increase your dose, take it more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.When used for an extended time, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: fluvoxamine, kava, phenytoin, sodium oxybate.Other medications can affect the removal of diazepam from your body, which may affect how diazepam works. Examples include cimetidine, ketoconazole, omeprazole, among others.Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, clozapine, risperidone, amitriptyline, trazodone, MAO inhibitors such as phenelzine). Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain ingredients that may cause drowsiness. Ask your pharmacist about using those products safely.This medication contains a small amount of alcohol. Tell your doctor if you are taking drugs such as disulfiram or metronidazole that can cause an unpleasant reaction when combined with alcohol.

If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: extreme drowsiness/dizziness, confusion, slow/shallow breathing, loss of consciousness.

Each mL of this sterile injection contains 5 mg diazepam compounded with 40% propylene glycol, 10% alcohol, 5% sodium benzoate and benzoic acid as buffers, and 1.5% benzyl alcohol as preservative.

Diazepam is a benzodiazepine derivative. Chemically, diazepam is 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one. It is a colorless crystalline compound, insoluble in water and has a molecular weight of 284.74. The solution is clear, colorless to slightly yellow.

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.

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 IV 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.

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.

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 Tagamet® (cimetidine) administration. The clinical significance of this is unclear.

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 Levophed® (norepinephrine bitartrate) or Aramine (metaraminol). Dialysis is of a 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 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 cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.

Do not use if solution is darker than slightly yellow or contains a precipitate.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Protect from light.

To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.

Oral LD50 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.

Revised: 12/2015

Hospira, Inc., Lake Forest, IL 60045 USA

DIAZEPAM   Diazepam Injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:52584-273(NDC:0409-1273) Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule CIV

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Diazepam (Diazepam) Diazepam 5 mg  in 1 mL

Packaging # Item Code Package Description 1 NDC:52584-273-32 1 CARTRIDGE in 1 BAG 1 2 mL in 1 CARTRIDGE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA072079 06/01/2010

Labeler - General Injectables and Vaccines, Inc. (108250663)

Revised: 08/2017   General Injectables and Vaccines, Inc.