Diazepam

Product Type: HUMAN PRESCRIPTION DRUG

Route: INTRAMUSCULAR

Dosage Form:

NDC: 11704-600

Application: NDA020124

Effective: 20231218

INDICATIONS Diazepam is indicated for the management of anxiety disorders 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. Note: Because the autoinjector provides a minimum dose of 10 mg diazepam, it should not be used to treat individuals with mild and moderate degrees of anxiety and anxiety related disorders that would ordinarily be managed with intramuscular doses of less than 10 mg. 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 and severe recurrent convulsive seizures. Diazepam is useful premedication for relief of anxiety and tension in patients who are to undergo surgical procedures.

DOSAGE AND ADMINISTRATION (INTRAMUSCULAR ONLY) Administration of the Diazepam Autoinjector 1. Pull off gray safety cap 2. Place Black end on mid outer thigh 3. Push hard until injector functions 4. Withdraw after 10 seconds Dosage Caution: Because the autoinjector automatically delivers a fixed dose of 10 mg of diazepam, it cannot be used in situations requiring lower total doses or those in which small incremental increases of diazepam are required. The usual recommended dose in older children and adults ranges from 10 mg to 20 mg I.M. depending on the indication and its severity. The cumulative total dose and individual maximum dose for intramuscular administration will vary with the specific indication (See dosage for specific indications). Intramuscular When instructions are followed properly the Diazepam Autoinjector injects deeply into the muscle. Intravenous Use The Diazepam Autoinjector is not designed or intended for intravenous use. Severe Anxiety Disorders and Symptoms of Anxiety Usual Adult Dosage: 10 mg, I. M. Repeat in 3 to 4 hours, if necessary. Acute Alcohol Withdrawal As an aid in symptomatic relief of acute agitation, tremor, impending or acute delirium tremens and hallucinosis. Usual Adult Dosage: 10 mg, I. M. initially, then 10 mg in 3 to 4 hours, if necessary. Endoscopic procedures Adjunctively, if apprehension, anxiety or acute stress reactions 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. Usual Adult Dosage: 10 mg I. M., approximately 30 minutes prior to the procedure. Muscle Spasm Associated with local pathology, cerebral palsy, athetosis, stiff-man syndrome or tetanus. Usual Adult Dosage: 10 mg, I. M., initially, then 10 mg in 3 to 4 hours, if necessary. For tetanus, larger doses may be required. Status Epilepticus and Severe Recurrent Convulsive Seizures In the convulsing patient, the I.V. route is preferred. However, if conditions preclude intravenous administration, the I.M. route may be used. Usual Adult Dosage: 10 mg, initially. 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 re-administration should be made with this consideration. Extreme caution must be exercised with individuals with chronic lung disease or unstable cardiovascular status. Preoperative Medication To relieve anxiety and tension. (if atropine, scopolamine or other premedications are desired, they must be administered in separate syringes). Usual Adult Dosage: 10 mg, I.M. (preferred route), before surgery. General 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 the solution and container permit.

CONTRAINDICATIONS INTRAVENOUS ADMINISTRATION OF DIAZEPAM WITH THE AUTOINJECTOR IS CONTRAINDICATED. 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 Diazepam Autoinjector is to be administered only by the intramuscular (I.M.) route. 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 for 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 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 ). Abuse, Misuse, and Addiction The use of benzodiazepines, including Diazepam injection, 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, that 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 injection and throughout treatment, assess each patient's risk for abuse, misuse, and addiction. Use of Diazepam injection, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of Diazepam injection 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 injection More Frequently Than Recommended For patients using Diazepam injection more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue Diazepam injection (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 may lead to clinically significant physical dependence. Although Diazepam injection 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 injection, 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 ). Respiratory and Central Nervous System Depression Extreme care must be used in administering injectable diazepam 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 (see PRECAUTIONS ) . 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. Use in Patients with Petit Mal Status Tonic status epilepticus has been precipitated in patients treated with I.V. 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.

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.