, 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. concomitant use with cimetidine the clearance of diazepam and certain other benzodiazepines can be delayed in association with tagamet (cimetidine) administration. the clinical significance of this is unclear.

r 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.

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, 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 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. 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.

xiety 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. 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 benzodiazapine 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 airways, 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 in cyclic antidepressant overdosage. the complete flumazenil package insert including contraindications, warnings, and precautions should be consulted prior to use.

ance. 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.

, 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. concomitant use with cimetidine the clearance of diazepam and certain other benzodiazepines can be delayed in association with tagamet (cimetidine) administration. the clinical significance of this is unclear.

tor is 100% of that obtained from the syringe. in addition, the mean c max value from the autoinjector was 314 ng/ml (c.v. = 18.7%, range 185 to 439 ng/ml) and 48.6 ng/ml (c.v.= 19.8%, range 29.4 to 69.7 ng/ml) for diazepam and desmethyldiazepam, respectively, while the syringe gave corresponding values of 287 ng/ml (c.v. = 18.9%, range 174 to 378 ng/ml) and 47.2 ng/ml (c.v. = 19.4%, range 33.1 to 61.2 ng/ml) for diazepam and desmethyldiazepam, respectively. the corresponding mean t max values were 1.47 hours (c.v. = 69.9%, range 0.8 to 6 hours) and 61.0 hours (c.v. = 56.8%, range 24 to 144 hours) for diazepam and desmethyldiazepam for the autoinjector whereas the syringe gave values of 1.31 hours (c.v. = 32%, range 0.7 to 2.0 hours) and 54.5 hours (c.v. = 47.3%, range 12 to 96 hours) for diazepam and desmethyldiazepam, respectively.

of 1.31 hours (c.v. = 32%, range 0.7 to 2.0 hours) and 54.5 hours (c.v. = 47.3%, range 12 to 96 hours) for diazepam and desmethyldiazepam, respectively.