Lectopam - Product Information
|Class:||Anxiolytics, sedatives, and hypnotics|
|Ingredients:||Iron oxide red, Lactose monohydrate, Magnesium stearate, Microcrystalline cellulose, Talc, Indigotine aluminum lake, Iron oxide yellow|
Summary Product Information
|Route of Administration||Dosage Form / Strength||Nonmedicinal Ingredients|
|Oral||Tablets, 3 mg and 6 mg||Tablets 3 mg: iron oxide red, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc.
Tablets 6 mg: indigotine aluminum lake, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc.
Indications and Clinical Use
LECTOPAM (bromazepam) is useful for the short-term, symptomatic relief of manifestations of excessive anxiety in patients with anxiety neurosis.
Elderly and debilitated patients are especially susceptible to dose-related adverse events and a reduced dose is recommended (see WARNINGS AND PRECAUTIONS, Special Populations, Geriatrics and DOSAGE AND ADMINISTRATION, Elderly and Debilitated Patients).
LECTOPAM is not recommended for children under 18 years of age (see WARNINGS AND PRECAUTIONS, Special Populations, Pediatrics).
- Patients who are hypersensitive to other benzodiazepines, this drug or to any ingredient in the formulation or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
- Myasthenia gravis
- Severe hepatic insufficiency
- Severe respiratory insufficiency
- Sleep apnea syndrome
- Narrow angle glaucoma
Warnings and Precautions
Benzodiazepines are only indicated when the anxiety disorder is severe, disabling or subjecting the individual to extreme distress.
LECTOPAM (bromazepam) is not recommended for use in patients with depressive disorders or psychosis.
Anterograde amnesia may occur with therapeutic doses of benzodiazepines and may be associated with inappropriate behaviour, the risk increasing with higher doses, (see ADVERSE REACTIONS).
Concomitant use of alcohol / CNS depressants
The concomitant use of LECTOPAM with alcohol and/or CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of LECTOPAM possibly including severe sedation, clinically relevant respiratory and/or cardiovascular depression (see DRUG INTERACTIONS).
Patients should be advised against the concurrent use of alcohol and other CNS depressant drugs.
Medical History of Alcohol or Drug Abuse
LECTOPAM should be used with extreme caution in patients with a medical history of alcohol or drug abuse.
Benzodiazepines have produced habituation, dependence and withdrawal symptoms similar to those noted with barbiturates and alcohol. The risk of dependence increases with dose and duration, and is greater in patients with a medical history of alcohol and drug).
Dependence Liability and Withdrawal
With long-term LECTOPAM treatment at the therapeutic doses, development of physical and psychic dependence may occur. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. The possibility that such effects may also occur following short-term use, especially at high doses, or if the daily dose is reduced rapidly or abruptly discontinued, should be considered. Symptoms of withdrawal include irritability, nervousness, insomnia, agitation, tremors, convulsions, diarrhea, abdominal cramps, vomiting, sweating, memory impairment, headache, muscle pain, extreme anxiety, tension, restlessness, and confusion. In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations, or epileptic seizures. Since these symptoms are similar to those for which the patient is being treated, it may appear that he/she has suffered a relapse upon discontinuation of the drug. Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should be avoided and treatment - even if only of short duration - should be terminated by gradually reducing the daily dose.
Some loss of response to the effects of LECTOPAM may develop after repeated use for a prolonged time.
Lactose monohydrate is a non-medicinal ingredient in LECTOPAM. Therefore, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Driving and Hazardous Activities
Since bromazepam has a central nervous system depressant effect, patients should be warned against driving, operating dangerous machinery, or engaging in other hazardous activities requiring mental alertness and physical coordination. Sedation, amnesia and impaired muscular function may adversely affect the ability to drive or operate machinery. This effect is increased if the patient has had alcohol.
Driving, operating machinery and other hazardous activities should be avoided altogether or at least during the first few days of treatment. The decision on this question rests with the patient’s physician and should be based on the patient’s response to treatment and the dosage involved.
They also should be warned against the concomitant use of alcohol and other CNS depressant drugs.
Mental and Emotional Disorders
It should be recognized that suicidal tendencies may be present in patients with emotional disorders and that protective measures and appropriate treatment may be necessary and should be instituted without delay.
Since excitement and other paradoxical reactions can result from the use of anxiolytic sedatives in psychotic patients, bromazepam should not be used in ambulatory patients suspected of having psychotic tendencies.
As with other benzodiazepines, bromazepam should not be used in individuals with physiological anxiety or normal stresses of daily living, but only in the presence of disabling manifestations of an appropriate pathological anxiety disorder.
These drugs are not effective in patients with characterological and personality disorders or those with obsessive-compulsive disorders. Bromazepam is also not recommended for management of depressive or psychotic disorders. Benzodiazepines should not be used to treat anxiety associated with depression, as suicide may be precipitated in these patients.
Respiratory depression may occur following administration of LECTOPAM. This effect may be aggravated by pre-existing airway obstruction or brain damage or if other medications which depress respiration have been given. As a rule, this effect can be avoided by careful adjustment of the dose to individual requirements.
LECTOPAM should be used with caution in patients with chronic respiratory diseases (see CONTRAINDICATIONS).
Falls and fractures
There have been reports of falls and fractures among benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
The safety of use of bromazepam in pregnancy has not been established. Therefore, bromazepam should not be used during pregnancy. Several studies have suggested an increased risk of congenital malformations (e.g., congenital malformations of the heart, cleft lip and/or palate) associated with the use of the benzodiazepines chlordiazepoxide and diazepam, and meprobamate, during the first trimester of pregnancies. Since bromazepam is also a benzodiazepine derivative, its administration is rarely justified in women of childbearing potential. Administration of bromazepam during the last three months of pregnancy or during labour is allowed only in the event of a strict medical indication, when the expected benefits to the patient outweigh the possible risks to the fetus. Due to the pharmacological action of the product, effects such as irregular heartbeat in the unborn child, hypothermia, hypotonia, moderate respiratory depression, and poor feeding in the neonate can be expected. Moreover, infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. If the drug is prescribed to a woman of childbearing potential, she should be warned to consult her physician regarding discontinuation of the drug if she plans to become or suspects that she is pregnant.
Bromazepam and its metabolites are probably excreted in human milk. Therefore, this drug should not be given to nursing mothers.
Because of the lack of sufficient clinical experience, bromazepam is not recommended for use in patients less than 18 years of age.
Elderly and debilitated patients, or those with organic brain syndrome, have been found to be prone to CNS depression after even low doses of benzodiazepines. Therefore, medication should be initiated in these patients with very low initial doses, and increments should be made gradually, depending on the response of the patient, in order to avoid over sedation or neurological impairment (see DOSAGE AND ADMINISTRATION).
There is an increased risk for falls and fractures among elderly and debilitated benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages).
Impaired Hepatic or Renal Function
In patients with impaired hepatic or renal function, it is recommended to initiate therapy, if necessary, at a very low dose and to increase the dosage only to the extent that such an increase is compatible with the degree of residual function of these organs. Such patients should be followed closely and have periodic laboratory assessments.
Monitoring and Laboratory Tests
If bromazepam should be administered for repeated cycles of therapy, periodic blood counts and liver function tests are advisable.
Adverse Drug Reaction Overview
Most Frequent Adverse Reactions
The most frequently reported adverse reactions with LECTOPAM (bromazepam) are related to CNS effects and include drowsiness, ataxia and dizziness. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.
Serious and Important Adverse Reactions
There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
Allergic reactions and a very few cases of anaphylaxis have been reported to occur with benzodiazepines.
Release of hostility and other paradoxical reactions such as irritability, excitability, restlessness, agitation, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur with the use of benzodiazepines. They are more likely to occur in children and elderly patients than in other patients. If these occur, use of the drug should be discontinued.
Anterograde amnesia may occur using therapeutic doses of benzodiazepines, the risk increasing with higher doses. Effects of anterograde amnesia may be associated with inappropriate behaviour.
Chronic use (even at therapeutic doses) may lead to the development of physical and psychic drug dependence: discontinuation of therapy may result in withdrawal or rebound phenomena (see WARNINGS and PRECAUTIONS).
Abuse of benzodiazepines has been reported.
Post-Market Adverse Drug Reactions
Other side effects which can occur, listed by body systems, include the following:
Cardiovascular System: Cardiac failure including cardiac arrest; hypotension, palpitations, tachycardia.
Digestive System: Dry mouth, nausea, non-specific gastrointestinal disturbances, vomiting.
Hemic and Lymphatic System: Decreased hemoglobin and hematocrit, increased and decreased WBC.
Metabolic and Nutritional Disorders: increased and decreased blood sugar levels, elevations of alkaline phosphatase, bilirubin, SGOT, SGPT.
Musculoskeletal System: Muscle weakness, muscle spasm.
Nervous System: Drowsiness, headache, dizziness, decreased alertness, ataxia, fatigue, seizures, confusional state, emotional disorder, depression, euphoria, change in libido.
Respiratory Disorders: Respiratory depression.
Skin and Subcutaneous Tissue Disorders Appendages: Pruritus, rash.
Special Senses: Diplopia, blurred vision.
Urogenital System: Incontinence.
Injury, Poisoning and Procedural Complications: There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
Pharmacokinetic Drug-Drug Interaction (DDI)
The specific enzymes involved in the metabolism of bromazepam have not been fully elucidated. There is a possibility that compounds which inhibit key oxidative hepatic enzymes may enhance the activity of benzodiazepines. Co-administration of cimetidine, a multi-CYP inhibitor, and possibly propranolol may prolong the elimination half-life of bromazepam through a substantially reduced clearance (with cimetidine reduction by 50%). Combined administration with fluvoxamine, an inhibitor of CYP1A2, results in significantly increased bromazepam exposure (2.4-fold increase in AUC) and elimination half-life (1.9-fold).
Bromazepam at therapeutic doses does not change the pharmacokinetics of co-administered antipyrine, a substrate of several CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP3A4).
Pharmacodynamic Drug-Drug Interaction (DDI)
Enhanced effects on sedation, respiration and hemodynamics may occur when LECTOPAM is co-administered with any centrally acting depressants including alcohol, narcotics, narcotic analgesics, barbiturates, non-barbiturate hypnotics, antihistamines, phenothiazines, thioxanthenes, butyrophenones classes of antipsychotics, anxiolytics/sedatives, anesthetics, monoamine oxidase inhibitors, tricyclic antidepressants and anticonvulsants (see WARNINGS AND PRECAUTIONS, Concomitant use of alcohol / CNS depressants, and OVERDOSAGE sections).
In the case of narcotic analgesics enhancement of euphoria may also occur, leading to an increase in psychic dependence. Because of the enhancement of effects that might occur, patients should be advised against the simultaneous use of other CNS depressant drugs and should be cautioned not to take alcohol during the administration of bromazepam.
The concomitant use of LECTOPAM with alcohol should be avoided. Such concomitant use has the potential to increase the clinical effects of LECTOPAM possibly including severe sedation, clinically relevant respiratory and/or cardiovascular depression (see WARNINGS AND PRECAUTIONS, Concomitant use of alcohol / CNS depressants, and OVERDOSAGE sections).
Dosage and Administration
Patients should be evaluated carefully at the start of treatment in order to minimize the dosage and/or the frequency of administration and to prevent overdose due to accumulation.
The dosage of LECTOPAM (bromazepam) must be individualized and carefully titrated in order to avoid excessive sedation or mental and motor impairment. Short course of treatment should usually be the rule for the symptomatic relief of excessive anxiety and the initial course of treatment should not last longer than one week without reassessment of the need for a limited extension. If necessary, drug dosage can be adjusted after one week of treatment. Initially, not more than one week’s supply of the drug should be provided and automatic prescription renewals should not be allowed. Subsequent prescriptions, when required, should be limited to a short course of therapy.
It may be useful to inform the patient when treatment is started that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. It is important that the patient should be aware of the possibility of rebound phenomena that may occur while the drug is being discontinued.
Recommended Dose and Dosage Adjustment
Usual Adult Dosage
The recommended initial adult daily dosage is 6 to 18 mg in equally divided doses, depending on the severity of symptoms and response of the patient. Treatment should be initiated by lower doses and adjusted as necessary. The optimal dosage may range from 6 to 30 mg daily in individual patients, in divided doses. There is limited experience with higher doses up to 60 mg daily.
Elderly and Debilitated Patients
The initial daily dose in these patients should not exceed 3 mg in divided doses. This dosage can be carefully adjusted, depending on tolerance and response of the patient (see WARNINGS AND PRECAUTIONS, Special Populations, Geriatrics; ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions).
|For management of a suspected drug overdose, contact your regional Poison Control Centre.|
Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of LECTOPAM is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.
Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.
In managing overdosage, consider the possibility of multiple drug involvement.
Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.
Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. Induction of vomiting is not generally recommended.
As in overdosage with other benzodiazepines, dialysis is of no known value in bromazepam overdosage.
If CNS depression is severe consider the use of flumazenil, a benzodiazepine receptor antagonist. The following should be kept in mind when flumazenil is used in the treatment of benzodiazepine overdosage:
- Flumazenil should only be administered under closely monitored conditions. In view of the short half-life (about 1 hour) and duration of action of flumazenil, and the possible need for repeat doses, the patient should be closely monitored until all possible central benzodiazepine effects (e.g., resedation) have subsided.
- Particular caution is necessary when using flumazenil in cases of multiple drug overdosage, since the toxic effects (cardiac arrhythmias and/or convulsions) of other psychotropic drugs, especially cyclic antidepressants, may increase as the effects of benzodiazepines subside. Flumazenil is contraindicated in patients who are showing signs of serious cyclic antidepressant overdose.
The benzodiazepine receptor antagonist flumazenil is not indicated in patients with epilepsy who have been treated with benzodiazepines. Antagonism of the benzodiazepine effect in such patients may provoke seizures.
Refer to the product monograph for flumazenil for further information on the correct use of this drug.
Action and Clinical Pharmacology
The absolute bioavailability of unchanged, orally administered bromazepam is 60%, and peak blood levels are achieved within 2 hours after administration.
Food may decrease the bioavailability of bromazepam.
On average, 70% of bromazepam is bound to plasma proteins.
Bromazepam is extensively metabolized in the liver. Bromazepam is metabolized, at least in part, through cytochrome P450 (CYP450). However, the specific CYP isozymes involved have not been identified. Nevertheless, the observations that a strong CYP3A4 inhibitor (itraconazole) and a moderate CYP2C9 inhibitor (fluconazole) had no effect on the pharmacokinetics of bromazepam suggest that these isozymes are not involved to a major extent. The pronounced interaction with fluvoxamine points to co-involvement of CYP1A2 (see DRUG INTERACTIONS, Drug-Drug Interactions).
Bromazepam has an elimination half-life of approximately 20 hours (the half-life may be longer in elderly patients). Over a 72-hour interval, 69% of a 12 mg oral dose was recovered in the urine, in the form of conjugated 3-hydroxybromazepam and conjugated 2-(2-amino-5-bromo-3-hydroxybenzoyl)-pyridine.
Special Populations and Conditions
Elderly and Debilitated Patients
Elderly patients may have significantly higher peak concentrations, a smaller volume of distribution, increased serum free fraction, lower clearance and hence also a prolonged elimination half-life of bromazepam. This indicates that steady-state concentrations of bromazepam at any given dosing rate will be on average nearly twice as high in an elderly subject as compared to a younger individual (see DOSAGE AND ADMINISTRATION: Recommended Dose and Dosage Adjustment, Elderly and Debilitated Patients).
Storage and Stability
Keep LECTOPAM in a cool dry place stored at room temperature (15-30°C).
Special Handling Instructions
Keep this medicine out of sight and reach of children.
Dosage Forms, Composition and Packaging
LECTOPAM (bromazepam) is available as 3 mg (pale red in colour, slightly speckled, cylindrical and biplane in shape, single scored on one side and engraved with ROCHE over 3 on the other side) and 6 mg (greenish-grey to greyish-green in colour, slightly speckled, cylindrical and biplane in shape, single scored on one side and engraved with ROCHE over 6 on the other side) tablets in PVC blister packs. There are 10 tablets per blister card and 10 blister cards per carton, for a total of 100 tablets per unit.
The non-medicinal ingredients are as follows:
Tablets 3 mg: iron oxide red, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc.
Tablets 6 mg: indigotine aluminum lake, iron oxide yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, talc.