2.1 Therapeutic Indication(s): Anxiety, tension and other somatic or psychiatric complaints associated with the anxiety syndrome. Adjunctive use for treatment of anxiety or excitation associated with psychiatric disorders, such as mood disorders or schizophrenia. Benzodiazepines are only indicated when the disorder is severe, disabling or subjecting the individual to extreme distress.
Central nervous system (CNS)
Dosage and Administration Standard dosage: Average dosing for outpatient therapy: 1.5â€“3 mg up to three times daily. Severe cases, especially in hospital: 6â€“12 mg two or three times daily. These amounts are general recommendations, and dosage should be individually determined. Treatment of outpatients should begin with low doses, gradually increasing to the optimum level. The duration of treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in case the patient is symptom-free. The overall treatment generally should not be more than 8â€“12 weeks, including a tapering-off process. In certain cases extension beyond the maximum treatment period may be necessary: if so, it should not take place without re-evaluation of the patientâ€™s status with special expertise. Special Dosage Instructions: LexotanilÂ® is usually not indicated in children, but if the physician feels LexotanilÂ® treatment is appropriate, then the dose should be adjusted to their low body weight (about 0.1â€“0.3 mg/kg body weight). Elderly patients (see Pharmacokinetics in Special Populations) and those with impaired hepatic function require lower doses because of individual variations in sensitivity and pharmacokinetics.
Contraindications: LexotanilÂ® must not be administered to patients with known hypersensitivity to benzodiazepines, severe respiratory insufficiency, severe hepatic insufficiency (benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may cause encephalopathy) or sleep apnea syndrome.
Undesirable Effects Post Marketing: LexotanilÂ® is well tolerated in therapeutic doses. The following undesirable effects may occur: Psychiatric Disorders: Confusional state, emotional disorder. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Libido disorders have been reported occasionally. Depression: Pre-existing depression may be unmasked during benzodiazepine use. Paradoxical reactions such as restlessness, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur with benzodiazepines or benzodiazepine-like agents (see 2.4.2 Drug Abuse and Dependence). Should this occur, the use of the drug should be discontinued. They are more likely to occur in children and elderly patients than in other patients. Dependence: 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 2.4.1 General [Warnings and Precautions] and 2.4.2 Drug Abuse and Dependence). Abuse of benzodiazepines has been reported. Nervous System Disorders: Drowsiness, headache, dizziness, decreased alertness, ataxia. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration. Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour. Eye Disorders: Diplopia, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration. Gastrointestinal Disorders: Gastrointestinal disorders have been reported occasionally. Skin and Subcutaneous Tissue Disorders: Skin reactions have been reported occasionally. Musculoskeletal and Connective Tissue Disorders: Muscle weakness, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration. General Disorders and Administration Site Conditions: Fatigue, this phenomenon occurs predominantly at the start of therapy and usually disappears with repeated administration. 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. Respiratory Disorders: Respiratory depression. Cardiac Disorders: Cardiac failure including cardiac arrest Ability to Drive and Use Machines Sedation, amnesia and impaired muscular function may adversely affect the ability to drive or to use machinery. This effect is increased if the patient has taken alcohol.
Use in Special Populations Pregnancy: The safety of bromazepam for use in human pregnancy has not been established. A review of spontaneously reported adverse drug events shows no greater incidence than would be anticipated from a similar untreated population. An increased risk of congenital malformations associated with the use of minor tranquilisers (diazepam, meprobamate and chlordiazepoxide) during the first trimester of pregnancy has been suggested in several studies. Bromazepam should be avoided during pregnancy unless there is no safer alternative. If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspects that she is pregnant. Administration of bromazepam during the last three months of pregnancy or during labour is allowed only in the event of a strict medical indication as, due to the pharmacological action of the product, effects on the neonate can be expected, such as hypothermia, hypotonia and moderate respiratory depression. Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. Labour and Delivery: See Pregnancy. Nursing Mothers: As benzodiazepines pass into breast milk, nursing mothers should not take LexotanilÂ®. Pediatric Use: See Special Dosage Instructions. Geriatric Use: See also Special Dosage Instructions Undesirable Effects and Pharmacokinetics in Special Populations. Hepatic Impairment: See Special Dosage Instructions.
2.4 Warnings and Precautions 2.4.1 General: Amnesia: Benzodiazepines may induce anterograde amnesia. Anterograde amnesia may occur using higher therapeutic dosages (documented at 6 mg), the risk increasing at higher dosages. Duration of treatment: 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 (see 2.4.2 Drug Abuse and Dependence). General precautions: Concomitant use of alcohol/CNS depressants: The concomitant use of LexotanilÂ® with alcohol or/ and central nervous system (CNS) depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of LexotanilÂ® possibly including severe sedation, clinically relevant respiratory and/or cardiovascular depression (see 2.4.4 Interactions with other Medicinal Products and other Forms of Interaction). Medical history of alcohol or drug abuse: LexotanilÂ® should be used with extreme caution in patients with a medical history of alcohol or drug abuse. The patient should be checked regularly at the start of treatment in order to minimise the dosage and/or the frequency of administration and to prevent overdose due to accumulation. When benzodiazepines are used, withdrawal symptoms may develop when changing to a benzodiazepine with a considerably shorter elimination half-life (see 2.4.2 Drug Abuse and Dependence). Tolerance: Some loss of response to the effects of LexotanilÂ® may develop after repeated use for a prolonged time. Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). Benzodiazepines are not recommended for the primary treatment of psychotic illness. Specific patient groups: In patients with myasthenia gravis who are prescribed LexotanilÂ®, care should be taken on account of pre-existing muscle weakness. Particular care is required in patients with chronic respiratory insufficiency due to the risk of respiratory depression. If containing lactose, patients with rare hereditary problems of galactose intolerance (the Lapp lactase deficiency or glucose-galactose malabsorption) should not take this medicine.
PHARMACEUTICAL PARTICULARS Storage: This medicine should not be used after the expiry date (EXP) shown on the pack. Protect from light. Store in a dry place below 35 degree celcius.