T LOR

A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent. [PubChem]

T LOR (T LOR) is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

The effectiveness of T LOR (T LOR) in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

T LOR injection is used before certain medical procedures, such as surgery, to relieve anxiety. When T LOR is used before surgery, the patient will not remember some of the details about the procedure. T LOR is also used to treat certain convulsive (seizure) disorders, such as epilepsy.

T LOR is a benzodiazepine. Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants, which are medicines that slow down the nervous system.

T LOR is available only with your doctor's prescription.

T LOR must never be used without individualization of dosage particularly when used with other medications capable of producing central-nervous-system depression.

EQUIPMENT NECESSARY TO MAINTAIN A PATENT AIRWAY SHOULD BE IMMEDIATELY AVAILABLE PRIOR TO INTRAVENOUS ADMINISTRATION OF T LOR.

Status Epilepticus

General Advice

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 T LOR Injection, is ordinarily only an initial 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).

Intravenous Injection

For the treatment of status epilepticus, the usual recommended dose of T LOR Injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional T LOR 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 further doses of T LOR 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.

Intramuscular Injection

IM T LOR is not preferred in the treatment of status epilepticus because therapeutic T LOR levels may not be reached as quickly as with IV administration. However, when an intravenous port is not available, the IM route may prove useful.

Pediatric

The safety of T LOR in pediatric patients has not been established.

Preanesthetic

Intramuscular Injection

For the designated indications as a premedicant, the usual recommended dose of T LOR for intramuscular injection is 0.05 mg/kg up to a maximum of 4 mg. As with all premedicant drugs, the dose should be individualized. Doses of other central-nervous-system-depressant drugs ordinarily should be reduced. For optimum effect, measured as lack of recall, intramuscular T LOR should be administered at least 2 hours before the anticipated operative procedure. Narcotic analgesics should be administered at their usual preoperative time.

There are insufficient data to support efficacy or make dosage recommendations for intramuscular T LOR in patients less than 18 years of age; therefore, such use is not recommended.

Intravenous Injection

For the primary purpose of sedation and relief of anxiety, the usual recommended initial dose of T LOR for intravenous injection is 2 mg total, or 0.02 mg/lb (0.044 mg/kg), whichever is smaller. This dose will suffice for sedating most adult patients and ordinarily should not be exceeded in patients over 50 years of age. In those patients in whom a greater likelihood of lack of recall for perioperative events would be beneficial, larger doses as high as 0.05 mg/kg up to a total of 4 mg may be administered. Doses of other injectable central-nervous-system-depressant drugs ordinarily should be reduced. For optimum effect, measured as lack of recall, intravenous T LOR should be administered 15 to 20 minutes before the anticipated operative procedure.

There are insufficient data to support efficacy or make dosage recommendations for intravenous T LOR in patients less than 18 years of age; therefore, such use is not recommended.

Dose Administration In Special Populations

Elderly Patients and Patients With Hepatic Disease

No dosage adjustments are needed in elderly patients and in patients with hepatic disease.

Patients With Renal Disease

For acute dose administration, adjustment is not needed for patients with renal disease. However, in patients with renal disease, caution should be exercised if frequent doses are given over relatively short periods of time.

Dose Adjustment Due to Drug Interactions

The dose of T LOR should be reduced by 50% when coadministered with probenecid or valproate.

It may be necessary to increase the dose of T LOR in female patients who are concomitantly taking oral contraceptives.

Administration

When given intramuscularly, T LOR Injection, undiluted, should be injected deep in the muscle mass.

Injectable T LOR can be used with atropine sulfate, narcotic analgesics, other parenterally used analgesics, commonly used anesthetics, and muscle relaxants.

Immediately prior to intravenous use, T LOR Injection must be diluted with an equal volume of compatible solution. Contents should be mixed thoroughly by gently inverting the container repeatedly until a homogenous solution results. Do not shake vigorously, as this will result in air entrapment. When properly diluted, the drug may be injected directly into a vein or into the tubing of an existing intravenous infusion. The rate of injection should not exceed 2.0 mg per minute.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if solution is discolored or contains a precipitate.

T LOR Injection is compatible for dilution purposes with the following solutions: Sterile Water for Injection, USP; Sodium Chloride Injection, USP; 5% Dextrose Injection, USP.

How supplied

T LOR (T LOR) Injection is available in the following dosage strengths in single-dose and multiple-dose vials:

2 mg per mL

NDC 60977-112-01, 25 x 1 mL vial,

NDC 60977-112-02, 10 x 10 mL vial

4 mg per mL

NDC 60977-113-01, 25 x 1 mL vial,

NDC 60977-113-02, 10 x 10 mL vial

For IM or IV injection.

Store in a refrigerator.

PROTECT FROM LIGHT.

Use carton to protect contents from light.

Manufactured by : Baxter Healthcare Corporation, Deerfield, IL 60015 USA, For Product Inquiry 1 800 ANA DRUG (1-800-262-3784).

See also:
What is the most important information I should know about T LOR?

Do not use this medication if you are allergic to T LOR or to other benzodiazepines, such as alprazolam (Xanax), chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), or oxazepam (Serax).

This medication can cause birth defects in an unborn baby. Do not use T LOR if you are pregnant.

Before taking T LOR, tell your doctor if you have any breathing problems, glaucoma, kidney or liver disease, or a history of depression, suicidal thoughts, or addiction to drugs or alcohol.

Do not drink alcohol while taking T LOR. This medication can increase the effects of alcohol.

Avoid using other medicines that make you sleepy. They can add to sleepiness caused by T LOR.

T LOR may be habit-forming and should be used only by the person it was prescribed for. T LOR should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

It is dangerous to try and purchase T LOR on the Internet or from vendors outside of the United States. Medications distributed from Internet sales may contain dangerous ingredients, or may not be distributed by a licensed pharmacy. Samples of T LOR purchased on the Internet have been found to contain haloperidol (Haldol), a potent antipsychotic drug with dangerous side effects. For more information, contact the U.S. Food and Drug Administration (FDA) or visit www.fda.gov/buyonlineguide.

Use T LOR solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• T LOR solution is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using T LOR solution at home, a health care provider will teach you how to use it. Be sure you understand how to use T LOR solution. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use T LOR solution if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• T LOR solution should not be injected into an artery because serious side effects may occur.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of T LOR solution, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use T LOR solution.

Use: Labeled Indications

Anxiety (oral): Management of anxiety disorders or short-term (≤4 months) relief of anxiety.

Procedural anxiety, premedication (injection): Anesthesia premedication in adults to relieve anxiety or to produce amnesia (diminish recall) or sedation.

Status epilepticus (injection): Treatment of status epilepticus. May be used off label for acute seizures that have not yet progressed to status epilepticus.

Off Label Uses

Akathisia, antipsychotic-induced

Data from a limited number of open-label clinical trials suggest that T LOR may be beneficial for the treatment of patients with antipsychotic-induced akathisia.

See also:
What other drugs will affect T LOR?

T LOR Injection, like other injectable benzodiazepines, produces additive depression of the central nervous system when administered with other CNS depressants such as ethyl alcohol, phenothiazines, barbiturates, MAO inhibitors, and other antidepressants.

When scopolamine is used concomitantly with injectable T LOR, an increased incidence of sedation, hallucinations and irrational behavior has been observed.

There have been rare reports of significant respiratory depression, stupor and/or hypotension with the concomitant use of loxapine and T LOR.

Marked sedation, excessive salivation, ataxia, and, rarely, death have been reported with the concomitant use of clozapine and T LOR.

Apnea, coma, bradycardia, arrhythmia, heart arrest, and death have been reported with the concomitant use of haloperidol and T LOR.

The risk of using T LOR in combination with scopolamine, loxapine, clozapine, haloperidol, or other CNS-depressant drugs has not been systematically evaluated. Therefore, caution is advised if the concomitant administration of T LOR and these drugs is required.

Concurrent administration of any of the following drugs with T LOR had no effect on the pharmacokinetics of T LOR: metoprolol, cimetidine, ranitidine, disulfiram, propranolol, metronidazole, and propoxyphene. No change in T LOR dosage is necessary when concomitantly given with any of these drugs.

T LOR-Valproate Interaction

Concurrent administration of T LOR (2 mg intravenously) with valproate (250 mg twice daily orally for 3 days) to 6 healthy male subjects resulted in decreased total clearance of T LOR by 40% and decreased formation rate of T LOR glucuronide by 55%, as compared with T LOR administered alone. Accordingly, T LOR plasma concentrations were about two-fold higher for at least 12 hours post-dose administration during valproate treatment. T LOR dosage should be reduced to 50% of the normal adult dose when this drug combination is prescribed in patients.

T LOR-Oral Contraceptive Steroids Interaction

Coadministration of T LOR (2 mg intravenously) with oral contraceptive steroids (norethindrone acetate, 1 mg, and ethinyl estradiol, 50 μg, for at least 6 months) to healthy females (n=7) was associated with a 55% decrease in half-life, a 50% increase in the volume of distribution, thereby resulting in an almost 3.7-fold increase in total clearance of T LOR as compared with control healthy females (n=8). It may be necessary to increase the dose of T LOR in female patients who are concomitantly taking oral contraceptives.

T LOR-Probenecid Interaction

Concurrent administration of T LOR (2 mg intravenously) with probenecid (500 mg orally every 6 hours) to 9 healthy volunteers resulted in a prolongation of T LOR half-life by 130% and a decrease in its total clearance by 45%. No change in volume of distribution was noted during probenecid co-treatment. T LOR dosage needs to be reduced by 50% when coadministered with probenecid.

Drug/Laboratory Test Interactions

No laboratory test abnormalities were identified when T LOR was given alone or concomitantly with another drug, such as narcotic analgesics, inhalation anesthetics, scopolamine, atropine, and a variety of tranquilizing agents.

See also:
What are the possible side effects of T LOR?

Status Epilepticus

The most important adverse clinical event caused by the use of T LOR Injection is respiratory depression.

The adverse clinical events most commonly observed with the use of T LOR Injection in clinical trials evaluating its use in status epilepticus were hypotension, somnolence, and respiratory failure.

Incidence in Controlled Clinical Trials

All adverse events were recorded during the trials by the clinical investigators using terminology of their own choosing. Similar types of events were grouped into standardized categories using modified COSTART dictionary terminology. These categories are used in the table and listings below with the frequencies representing the proportion of individuals exposed to T LOR Injection or to comparative therapy.

The prescriber should be aware that these figures cannot be used to predict the frequency of adverse events in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigators involving different treatment, uses, or investigators. An inspection of these frequencies, however, does provide the prescribing physician with one basis to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied.

Commonly Observed Adverse Events in a Controlled Dose-Comparison Clinical Trial

Table 1 lists the treatment-emergent adverse events that occurred in the patients treated with T LOR Injection in a dose-comparison trial of T LOR 1 mg, 2 mg, and 4 mg.

TABLE 1: NUMBER (%) OF STUDY EVENTS IN A DOSE COMPARISON CLINICAL TRIAL

These trials were not designed or intended to demonstrate the comparative safety of the two treatments.

The overall adverse experience profile for T LOR was similar between women and men. There are insufficient data to support a statement regarding the distribution of adverse events by race. Generally, age greater than 65 years may be associated with a greater incidence of central-nervous-system depression and more respiratory depression.

Other Events Observed During the Pre-Marketing Evaluation of T LOR Injection for the Treatment of Status Epilepticus

T LOR Injection, active comparators, and T LOR Injection in combination with a comparator were administered to 488 individuals during controlled and open-label clinical trials. Because of reenrollments, these 488 patients participated in a total of 521 patient-episodes. T LOR Injection alone was given in 69% of these patient-episodes (n=360). The safety information below is based on data available from 326 of these patient-episodes in which T LOR Injection was given alone.

All adverse events that were seen once are listed, except those already included in previous listings (Table 1 and Table 2).

Study events were classified by body system in descending frequency by using the following definitions: frequent adverse events were those that occurred in at least 1/100 individuals; infrequent study events were those that occurred in 1/100 to 1/1000 individuals.

Frequent and Infrequent Study Events

Body as a Whole - Infrequent: asthenia, chills, headache, infection.

Digestive System - Infrequent: abnormal liver function test, increased salivation, nausea, vomiting.

Metabolic and Nutritional - Infrequent: acidosis, alkaline phosphatase increased.

Nervous System - Infrequent: agitation, ataxia, brain edema, coma, confusion, convulsion, hallucinations, myoclonus, stupor, thinking abnormal, tremor.

Respiratory System - Frequent: apnea; Infrequent: hyperventilation, hypoventilation, respiratory disorder.

Terms Not Classifiable - Infrequent: injection site reaction.

Urogenital System - Infrequent: cystitis.

Preanesthetic

Central Nervous System

The most frequent adverse drug event reported with injectable T LOR is centralnervous- system depression. The incidence varied from one study to another, depending on the dosage, route of administration, use of other central-nervous-system depressants, and the investigator's opinion concerning the degree and duration of desired sedation. Excessive sleepiness and drowsiness were the most common consequences of CNS depression. This interfered with patient cooperation in approximately 6% (25/446) of patients undergoing regional anesthesia, causing difficulty in assessing levels of anesthesia. Patients over 50 years of age had a higher incidence of excessive sleepiness or drowsiness when compared with those under 50 (21/106 versus 24/245) when T LOR was given intravenously. On rare occasion (3/1580) the patient was unable to give personal identification in the operating room on arrival, and one patient fell when attempting premature ambulation in the postoperative period.

Symptoms such as restlessness, confusion, depression, crying, sobbing, and delirium occurred in about 1.3% (20/1580). One patient injured himself by picking at his incision during the immediate postoperative period.

Hallucinations were present in about 1% (14/1580) of patients and were visual and self-limiting.

An occasional patient complained of dizziness, diplopia and/or blurred vision. Depressed hearing was infrequently reported during the peak-effect period.

An occasional patient had a prolonged recovery room stay, either because of excessive sleepiness or because of some form of inappropriate behavior. The latter was seen most commonly when scopolamine was given concomitantly as a premedicant. Limited information derived from patients who were discharged the day after receiving injectable T LOR showed one patient complained of some unsteadiness of gait and a reduced ability to perform complex mental functions. Enhanced sensitivity to alcoholic beverages has been reported more than 24 hours after receiving injectable T LOR, similar to experience with other benzodiazepines.

Local Effects

Intramuscular injection of T LOR has resulted in pain at the injection site, a sensation of burning, or observed redness in the same area in a very variable incidence from one study to another. The overall incidence of pain and burning in patients was about 17% (146/859) in the immediate postinjection period and about 1.4% (12/859) at the 24-hour observation time. Reactions at the injection site (redness) occurred in approximately 2% (17/859) in the immediate postinjection period and were present 24 hours later in about 0.8% (7/859).

Intravenous administration of T LOR resulted in painful responses in 13/771 patients or approximately 1.6% in the immediate postinjection period, and 24 hours later 4/771 patients or about 0.5% still complained of pain. Redness did not occur immediately following intravenous injection but was noted in 19/771 patients at the 24-hour observation period. This incidence is similar to that observed with an intravenous infusion before T LOR is given. Intra-arterial injection may produce arteriospasm resulting in gangrene which may require amputation.

Cardiovascular System

Hypertension (0.1%) and hypotension (0.1%) have occasionally been observed after patients have received injectable T LOR.

Respiratory System

Five patients (5/446) who underwent regional anesthesia were observed to have airway obstruction. This was believed due to excessive sleepiness at the time of the procedure and resulted in temporary hypoventilation. In this instance, appropriate airway management may become necessary.

Other Adverse Experiences

Skin rash, nausea and vomiting have occasionally been noted in patients who have received injectable T LOR combined with other drugs during anesthesia and surgery.

Paradoxical Reactions

As with all benzodiazepines, paradoxical reactions such as stimulation, mania, irritability, restlessness, agitation, aggression, psychosis, hostility, rage, or hallucinations may occur in rare instances and in an unpredictable fashion. In these instances, further use of the drug in these patients should be considered with caution.

Postmarketing Reports

Voluntary reports of other adverse events temporally associated with the use of T LOR (T LOR) Injection that have been received since market introduction and that may have no causal relationship with the use of T LOR Injection include the following: acute brain syndrome, aggravation of pheochromocytoma, amnesia, apnea/respiratory arrest, arrhythmia, bradycardia, brain edema, coagulation disorder, coma, convulsion, gastrointestinal hemorrhage, heart arrest/failure, heart block, liver damage, lung edema, lung hemorrhage, nervousness, neuroleptic malignant syndrome, paralysis, pericardial effusion, pneumothorax, pulmonary hypertension, tachycardia, thrombocytopenia, urinary incontinence, ventricular arrhythmia.

Fatalities also have been reported, usually in patients on concomitant medications (e.g., respiratory depressants) and/or with other medical conditions (e.g., obstructive sleep apnea).

Drug Abuse And Dependence

Controlled Substance Class

T LOR is a controlled substance in Schedule IV.

Abuse And Physical And Psychological Dependence

As with other benzodiazepines, T LOR Injection has a potential for abuse and may lead to dependence. Physicians should be aware that repeated doses over a prolonged period of time may result in physical and psychological dependence and withdrawal symptoms, following abrupt discontinuance, similar in character to those noted with barbiturates and alcohol.