The following text is complete prescribing information based on official labeling in effect June 2000.
Each mL contains 5 mg diazepam compounded with 40% propylene glycol, 10% ethyl alcohol, 5% sodium benzoate and benzoic acid as buffers, and 1.5% benzyl alcohol as preservative.
Diazepam is a benzodiazepine derivative developed through original Roche research. 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.
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.
Valium 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, Valium 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 .)
Valium 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.
Valium Injection is a useful adjunct in status epilepticus and severe recurrent convulsive seizures.
Valium is a useful premedication (the IM 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' recall of the procedure.
Valium 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.
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 1 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 Valium with other solutions or drugs in syringe or infusion flask. If it is not feasible to administer Valium directly IV, it may be injected slowly through the infusion tubing as close as possible to the vein insertion.
Extreme care must be used in administering Valium Injection, particularly by the IV 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 Valium 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.
Valium 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 Valium 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 IV Valium 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, Valium Injection is not recommended for obstetrical use.
Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).
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 Valium after IV administration. The physician should be prepared to readminister the drug. However, Valium 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 Valium 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 Valium, 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 Valium 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.
Valium 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 Valium and certain other benzodiazepines can be delayed in association with Tagamet (cimetidine) administration. The clinical significance of this is unclear.
Pediatric Use: Safety and effectiveness in pediatric patients below the age of 30 days have not been established.
Prolonged central nervous system depression has been observed in neonates, apparently due to inability to biotransform Valium into inactive metabolites.
In pediatric use, 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 slowly over a 3-minute period in a dosage not to exceed 0.25 mg/kg. After an interval of 15 to 30 minutes the initial dosage can be safely repeated. If, however, relief of symptoms is not obtained after a third administration, adjunctive therapy appropriate to the condition being treated is recommended.
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. GI: constipation, nausea. GU: 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 Valium 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.
Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of diazepam. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (eg, dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving diazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.
Dosage should be individualized for maximum beneficial effect. The usual recommended dose in adults ranges from 2 mg to 20 mg IM or IV, depending on the indication and its severity. In some conditions, eg, tetanus, larger doses may be required. (See dosage for specific indications.) In acute conditions the injection may be repeated within 1 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 and ADVERSE REACTIONS ).
For dosage in pediatric patients above the age of 30 days, see the specific indications below. When intravenous use is indicated, facilities for respiratory assistance should be readily available.
Intramuscular: Valium Injection should be injected deeply into the muscle.
Intravenous Use: (See and PRECAUTIONS : Pediatric Use .) The solution should be injected slowly, taking at least 1 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 Valium with other solutions or drugs in syringe or infusion flask. If it is not feasible to administer Valium directly IV, it may be injected slowly through the infusion tubing as close as possible to the vein insertion.
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Once the acute symptomatology has been properly controlled with Valium Injection, the patient may be placed on oral therapy with Valium if further treatment is required.
Manifestations of Valium 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® (levarterenol) or Aramine (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 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 in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, and PRECAUTIONS, should be consulted prior to use.
Vials, 10 mL, boxes of 1 (NDC 0004-1932-09). Tel-E-Ject ® (disposable syringes), 2 mL, boxes of 10 (NDC 0004-1933-06).
Oral LD 50 of diazepam is 720 mg/kg in mice and 1240 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.
Distributed by Roche Laboratories Inc, Nutley, NJ 07110
Revised: March 1999