Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Use of benzodiazepines, including lorazepam, may lead to potentially fatal respiratory depression.

Severe anaphylactic/anaphylactoid reactions have been reported with the use of benzodiazepines.
Cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of benzodiazepines. Some patients taking benzodiazepines have had additional symptoms such as dyspnoea, throat closing, or nausea and vomiting. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with a benzodiazepine should not be rechallenged with the drug.

Lorazepam should be used with caution in patients with compromised respiratory function (e.g., COPD).

Patients should be advised that since their tolerance for alcohol and other CNS depressants will be diminished in the presence of lorazepam, these substances should either be avoided or taken in reduced dosage.

Anxiety may be a symptom of several other disorders. The possibility should be considered that the complaint may be related to an underlying physical or psychiatric disorder for which there is more specific treatment.

Abuse of benzodiazepines has been reported, especially in patients with a history of drug and/or alcohol abuse.

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required.

Tolerance

Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.

There is evidence that tolerance develops to the sedative effects of benzodiazepines.

Dependence
The use of benzodiazepines may lead to physical and psychological dependence. The risk of dependence on lorazepam is low when used at the recommended dose and duration, but increases with higher doses and longer term use. The risk of dependence increases with dose and duration of treatment and is also greater in patients with a history of alcoholism or drug abuse, or in patients with significant personality disorders. Therefore, use in individuals with a history of alcoholism or drug abuse should be avoided.
Withdrawal Reactions

Dependence may lead to withdrawal symptoms, especially if treatment is discontinued abruptly.
Therefore, the drug should always be discontinued gradually.

Withdrawal symptoms can appear following cessation of recommended doses after as little as one week of therapy.

Abrupt discontinuation or rapid dosage reduction of lorazepam after continued use may precipitate withdrawal reactions, which can be life-threatening. These can range from mild dysphoria and insomnia to a major syndrome which may include abdominal and muscle cramps, vomiting, sweating, tremor, and convulsions. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.
Convulsions/seizures may occur more often in patients with preexisting seizure disorders or in patients who take other drugs that lower the convulsive threshold, such as antidepressants.

The following symptoms have also been described: headache, anxiety, tension, restlessness, confusion and irritability, dizziness, dysphoria, derealisation, depersonalisation, hyperacusis, tinnitus, numbness and tingling of the extremities, hypersensitivity to light, noise, and physical contact/perceptual changes, involuntary movements, nausea, diarrhoea, loss of appetite, panic attacks, myalgia/muscle pain, agitation, palpitations, tachycardia, vertigo, hyperreflexia, short-term memory loss and hyperthermia.

Occurrence of "rebound" phenomena: The symptoms that led to treatment with benzodiazepines recur in an enhanced form. These symptoms may be difficult to distinguish from the original symptoms for which the drug was prescribed.

Drug Abuse

Lorazepam has abuse potential. Patients with particular risk include those with a history of drug and/ or alcohol abuse.
Drug abuse is a known risk for benzodiazepines, and patients should be monitored accordingly when receiving lorazepam. Benzodiazepines may be subject to diversion. There have been reports of overdose related deaths when benzodiazepines are abused with other CNS depressants including opioids, other benzodiazepines, alcohol and/or illicit substances. These risks should be considered when prescribing or dispensing lorazepam. To reduce these risks the lowest effective dose should be used, and patients should be advised on the proper storage and disposal of unused drug to prevent diversion (e.g. through friends and relatives).

Duration

Treatment should be as short as possible. Generally, the duration of treatment varies from a few days to 4 weeks including the tapering off process.

It may be useful to inform the patient that treatment will be of limited duration and that it will be discontinued gradually. The patient should also be made aware of the possibility of "rebound" phenomena to minimise anxiety should they occur.

There are indications that, in the case of benzodiazepines with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.

When benzodiazepines with a long duration of action are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms may develop.

Amnesia

Transient anterograde amnesia or memory impairment has been reported in association with the use of benzodiazepines. This effect may be advantageous when Ativan is used as a premedicant. However, if Ativan is used for insomnia due to anxiety, patients should ensure that they will be able to have a period of uninterrupted sleep which is sufficient to allow dissipation of drug effect (e.g., 7-8 hours).

Psychiatric and paradoxical reactions

Paradoxical reactions have been occasionally reported during benzodiazepine use (see section 4.8).
Such reactions may be more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued.
Specific patient groups

Lorivan is not intended for the primary treatment of psychotic illness or depressive disorders, and should not be used alone to treat depressed patients. The use of benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients. Therefore, large quantities of Lorivan should not be prescribed to these patients. The use of benzodiazepines in these patients should not be used without adequate antidepressant therapy.

Pre-existing depression may emerge during benzodiazepine use.
Caution should be used in the treatment of patients with acute narrow-angle glaucoma.

Patients with impaired renal function or mild to moderate hepatic insufficiency should be monitored frequently and have their dosage adjusted carefully according to patient response. Lower doses may be sufficient in these patients. The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency.

As with all CNS-depressants, the use of benzodiazepines may precipitate encephalopathy in patients with severe hepatic insufficiency. Therefore, use in these patients is contraindicated.

Some patients taking benzodiazepines have developed a blood dyscrasia, and some have had elevations in liver enzymes. Periodic haematologic and liver-function assessments are recommended where repeated courses of treatment are considered clinically necessary.

Although hypotension has occurred only rarely, benzodiazepines should be administered with caution to patients in whom a drop in blood pressure might lead to cardiovascular or cerebrovascular complications. This is particularly important in elderly patients. Elderly patients should be warned of the risk of falls due to the myorelaxant effect of lorazepam.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose- galactose malabsorption should not take this medicine.

Elderly patients
Lorazepam should be used with caution in elderly due to the risk of sedation and/or musculoskeletal weakness that can increase the risk of falls, with serious consequences in this population. Elderly patients should be given a reduced dose (see section 4.2 Posology).

Effects on Driving

4.7 Effects on ability to drive and use machines

Sedation, amnesia, impaired concentration and impaired muscular function may adversely affect the ability to drive or to use machines. If insufficient sleep occurs, the likelihood of impaired alertness may be increased (see section 4.5). Patients should be warned not to operate dangerous machinery or motor vehicles if any of these effects occur.