Status EpilepticusLorazepam Injection is indicated for the treatment of status epilepticus.PreanestheticLorazepam Injection is indicated in adult patients for preanesthetic medication, producing sedation (sleepiness or drowsiness), relief of anxiety, and a decreased ability to recall events related to the day of surgery.It is most useful in those patients who are anxious about their surgical procedure and who would prefer to have diminished recall of the events of the day of surgery (see “PRECAUTIONS”- Information for Patients).
Lorazepam Injection is contraindicated in patients with a known sensitivity to benzodiazepines or its vehicle (polyethylene glycol, propylene glycol, and benzyl alcohol), in patients with acute narrow-angle glaucoma, or in patients with sleep apnea syndrome.
It is also contraindicated in patients with severe respiratory insufficiency, except in those patients requiring relief of anxiety and/or diminished recall of events while being mechanically ventilated.The use of Lorazepam Injection intra-arterially is contraindicated because, as with other injectable benzodiazepines, inadvertent intra-arterial injection may produce arteriospasm resulting in gangrene which may require amputation (see “WARNINGS”).
Use in Status EpilepticusManagement of Status Epilepticus Status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, if inadequately treated. The treatment of status, however, requires far more than the administration of an anticonvulsant agent.
It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required.
Ventilatory support must be readily available.
The use of benzodiazepines, like Lorazepam Injection, is ordinarily only one step of a complex and sustained intervention which may require additional interventions (e.g., concomitant intravenous administration of phenytoin).
Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected.
Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy. Any health care professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus.
A comprehensive review of the considerations critical to the informed and prudent management of status epilepticus cannot be provided in drug product labeling.
The archival medical literature contains many informative references on the management of status epilepticus, among them the report of the working group on status epilepticus of the Epilepsy Foundation of America “Treatment of Convulsive Status Epilepticus” (JAMA 1993; 270:854-859).
As noted in the report just cited, it may be useful to consult with a neurologist if a patient fails to respond (e.g., fails to regain consciousness). For the treatment of status epilepticus, the usual recommended dose of Lorazepam Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older.
If seizures cease, no additional Lorazepam Injection is required.
If seizures continue or recur after a 10- to 15- minute observation period, an additional 4 mg intravenous dose may be slowly administered.
Experience with furtherdoses of lorazepam is very limited. The usual precautions in treating status epilepticus should be employed. An intravenous infusion should be started, vital signs should be monitored, an unobstructed airway should be maintained, and artificial ventilation equipment should be available.Respiratory DepressionThe most important risk associated with the use of Lorazepam Injection in status epilepticus is respiratory depression.
Accordingly, airway patency must be assured and respiration monitored closely. Ventilatory support should be given as required.Excessive SedationBecause of its prolonged duration of action, the prescriber should be alert to the possibility, especially when multiple doses have been given, that the sedative effects of lorazepam may add to the impairment of consciousness seen in the post-ictal state.Preanesthetic UseAIRWAY OBSTRUCTION MAY OCCUR IN HEAVILY SEDATED PATIENTS. INTRAVENOUS LORAZEPAM AT ANY DOSE, WHEN GIVEN EITHER ALONE OR IN COMBINATION WITH OTHER DRUGS ADMINISTERED DURING ANESTHESIA, MAY PRODUCE HEAVY SEDATION; THEREFORE, EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY AND TO SUPPORT RESPIRATION/VENTILATION SHOULD BE AVAILABLE. As is true of similar CNS-acting drugs, the decision as to when patients who have received injectable lorazepam,particularly on an outpatient basis, may again operate machinery, drive a motor vehicle, or engage in hazardous or other activities requiring attention and coordination must be individualized.
It is recommended that no patient engage in such activities for a period of 24 to 48 hours or until the effects of the drug, such as drowsiness, have subsided, whichever is longer.
Impairment of performance may persist for greater intervals because of extremes of age, concomitant use of other drugs, stress of surgery, or the general condition of the patient. Clinical trials have shown that patients over the age of 50 years may have a more profound and prolonged sedation with intravenous lorazepam (see also “DOSAGE AND ADMINISTRATION”-Preanesthetic). As with all central-nervous-system depressant drugs, care should be exercised in patients given injectable lorazepam as premature ambulation may result in injury from falling. There is no added beneficial effect to the addition of scopolamine to injectable lorazepam, and their combined effect may result in an increased incidence of sedation, hallucination, and irrational behavior.General (All Uses)PRIOR TO INTRAVENOUS USE, LORAZEPAM INJECTION MUST BE DILUTED WITH AN EQUAL AMOUNT OF COMPATIBLE DILUENT (SEE “DOSAGE AND ADMINISTRATION”).
INTRAVENOUS INJECTION SHOULD BE MADE SLOWLY AND WITH REPEATED ASPIRATION. CARE SHOULD BE TAKEN TO DETERMINE THAT ANY INJECTION WILL NOT BE INTRA-ARTERIAL AND THAT PERIVASCULAR EXTRAVASATION WILL NOT TAKE PLACE.
IN THE EVENT THAT A PATIENT COMPLAINS OF PAIN DURING INTENDED INTRAVENOUS INJECTION OF LORAZEPAM INJECTION, THE INJECTION SHOULD BE STOPPED IMMEDIATELY TO DETERMINE IF INTRA-ARTERIAL OR PERIVASCULAR EXTRAVASATION HAS TAKEN PLACE. Since the liver is the most likely site of conjugation of lorazepam and since excretion of conjugated lorazepam (glucuronide) is a renal function, this drug is not recommended for use in patients with hepatic and/or renal failure.
Lorazepam should be used with caution in patients with mild-to-moderate hepatic or renal disease (see “DOSAGE AND ADMINISTRATION”).PregnancyLORAZEPAM MAY CAUSE FETAL DAMAGE WHEN ADMINISTERED TO PREGNANT WOMEN.
Ordinarily, Lorazepam Injection should not be used during pregnancy except in serious or life-threatening conditions where safer drugs cannot be used or are ineffective.
Status epilepticus may represent such a serious and life-threatening condition. An increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam, and meprobamate) during the first trimester of pregnancy has been suggested in several studies.
In humans, blood levels obtained from umbilical cord blood indicate placental transfer of lorazepam and lorazepam glucuronide. Reproductive studies in animals were performed in mice, rats, and two strains of rabbits.
Occasional anomalies (reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia) were seen in drug-treated rabbits without relationship to dosage. Although all of these anomalies were not present in the concurrent control group, they have been reported to occur randomly in historical controls.
At doses of 40 mg/kg orally or 4 mg/kg intravenously and higher, there was evidence of fetal resorption and increased fetal loss in rabbits which was not seen at lower doses. The possibility that a woman of childbearing potential may be pregnant at the time of therapy should be considered. There are insufficient data regarding obstetrical safety of parenteral lorazepam, including use in cesarean section. Such use, therefore, is not recommended.Endoscopic ProceduresThere are insufficient data to support the use of Lorazepam Injection for outpatient endoscopic procedures.Inpatient endoscopic procedures require adequate recovery room observation time. When Lorazepam Injection is used for peroral endoscopic procedures; adequate topical or regional anesthesia is recommended to minimize reflex activity associated with such procedures.