Source: Υπουργείο Υγείας (CY) Revision Year: 2019 Publisher: Medochemie Iberia, S.A., Rua Jose Maria Nicolau, no 6, 7oB, São Domingos de Benfica, Lisboa 1500 662, Portugal
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Temelor should not be administered intra-arterially. As with other injectable benzodiazepines, an intraarterial injection may cause arterial spasm that causes gangrene and may require amputation.
Temelor is also contraindicated in patients with:
Temelor is contraindicated in children under 12 years of age.
For intravenous use, lorazepam should be diluted with an equal amount of a compatible diluent (see section 6.6).
Intravenous administration should be performed slowly and repeatedly.
One should ensure that the injection does not occur intra-arterially and no perivascular extravasation occurs.
Tolerance for alcohol and other CNS depressants will be diminished in the presence of lorazepam, therefore patients should be advised to either avoid Temelor or use a reduced dose.
Alcoholic beverages should not be used for at least 24 to 48 hours after receiving Temelor, due to the general additive depressant effect of benzodiazepines on central nervous system.
It is recommended that patients treated with lorazepam, remain under observation for 24 hours after administration of the last dose.
If lorazepam is used for short-term procedures on an outpatient basis, the patient must be accompanied by a responsible adult at the time of discharge.
Patients should be warned not to drive vehicles or take activities requiring attention for 24-48 hours after administration.
A reduction in performance may persist for extended periods due to patient’s high age, concomitant use of other drugs, stress due to surgery, or the general condition of the patient. Patients should also be warned that premature walking (within 8 hours after lorazepam administration) may lead to injury due to traps.
There are insufficient data to warrant the use of lorazepam in endoscopic procedures in ambulatory patients. If these procedures are performed in hospitalized patients, adequate observation in a recovery room is necessary and the pharyngeal reflex activity must be reduced by local anesthesia, prior to the endoscopic procedure.
There are no data that can justify the use of lorazepam in coma or shock.
Concomitant use of scopolamine is not recommended because this combination may lead to an increased incidence of sedation, hallucinations and irrational behavior.
Concomitant use of lorazepam and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe lorazepam concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2).
The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers (where applicable) to be aware of these symptoms (see section 4.5).
Caution is required when administering lorazepam to patients with status epilepticus, especially patients who have received other central nervous system depressants or patients who are severely ill.
The possibility of respiratory depression or partial respiratory tract obstruction should be considered. Adequate resuscitation equipment must be available.
Lorazepam is not intended for primary treatment of psychotic illness or depressive disorders, and should not be used as a monotherapy in depressed patients.
Benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients.
There are no data to support a long term use of lorazepam.
Some patients have developed blood dyscrasia during the treatment with benzodiazepines; in some, an increase in the hepatic enzyme values was observed.
If prolonged treatment is considered clinically necessary, regular blood and hepatic function tests are recommended.
Prolonged treatment with benzodiazepines should be gradually reduced.
As with any premedication, extreme caution is required when administering lorazepam in elderly or severely ill patients and patients with limited lung retention (COPD, sleep apnoea syndrome), due to the possibility of apnea and/or hypoxic heart failure. Resuscitation equipment for ventilation assistance must be readily available.
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).
Patients with impaired renal or hepatic function should be closely monitored and the dosage should be carefully adjusted according to their reactions. Lower doses may be sufficient in these patients. The same precautions apply to elderly or debilitated patients and patients with chronic respiratory insufficiency.
Lorazepam is not recommended for use in patients with renal insufficiency. If lorazepam is used in patients with mild to moderate hepatic or renal disease, the lowest effective dose should be used as the duration of the effect may be prolonged in those circumstances.
Caution is required in the treatment of patients with acute narrow-angle glaucoma.
Anxiety can be a symptom of various other conditions. It should be taken into account that the patient complaint may be related to an underlying physical or psychiatric condition for which more specific treatment is available.
During treatment with benzodiazepines, paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, despair, anger attacks, nightmares, hallucinations, psychoses and inappropriate behavior were occasionally reported. Such reactions are more likely to occur in children and in the elderly. Should these occur, use of the drug should be discontinued.
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.
In rats treated with lorazepam for more than one year at a dose of 6 mg/kg/day, an esophagus dilatation was observed. The dose without effect was 1.25 mg/kg/day (approximately 6 times the maximum therapeutic dose in humans, which is 10 mg/day). The effect was only reversible if treatment was discontinued within two months after this phenomenon was first observed. The clinical significance of this is not clear. However, with long-term use of lorazepam and in geriatric patients, caution is necessary and frequent control of symptoms of a proximal gastrointestinal disorder is required. The use of lorazepam for prolonged periods is not recommended.
Benzodiazepines can cause anterograde amnesia. This usually occurs several hours after ingestion. Therefore, in order to reduce the risk, patients should be able to sleep continuously for 7/8 hours (see also section 4.8).
The use of lorazepam is contraindicated in children under 12 years (see section 4.3). After administration of lorazepam especially in neonates with very low birth weight, epileptic seizures and myoclonus were reported.
There are no clinical data with regard to abuse or dependence. However, based upon experience with oral benzodiazepines, physicians should be aware that repeated administration of lorazepam over a long period of time may lead to physical and/or psychological dependence.
The risk increases with higher doses and longer-term use and is further increased in patients with a history of alcoholism or drug abuse.
In case of physical dependence, abrupt discontinuation of treatment may be associated with withdrawal symptoms. Symptoms reported following discontinuation of oral benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating and rebound symptoms in which the symptoms that gave rise to benzodiazepine treatment increased return. It may be difficult to distinguish these symptoms from the original symptoms for which the product was prescribed.
In severe cases, the following symptoms may occur: derealisation, depersonalisation, hyperacusis, tinnitus, numbness and tingling of the extremities, sensitivity to light, noise and physical contact, involuntary movements, vomiting, hallucinations and convulsions. Convulsions may occur more frequently in patients with pre-existing convulsive disease or in patients using other drugs that reduce the convulsion threshold, such as antidepressants.
Withdrawal symptoms, and especially the more severe ones, occur more frequently in patients treated with high doses over a long period of time. However, withdrawal symptoms are also reported after discontinuation of treatment with benzodiazepines in therapeutic doses, especially if the treatment is abruptly discontinued. Since the risk of withdrawal symptoms/rebound phenomena is greater if the treatment is abruptly stopped, it should be gradually decreased.
This medicine contains 21 mg benzyl alcohol in each 1 ml of solution for injection.
Benzyl alcohol may cause allergic reactions.
High volumes should be used with caution and only if necessary, especially pregnant or breast‑feeding women or in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).
This medicine contains 840 mg propylene glycol in each 1 ml of solution for injection.
Benzodiazepines, including lorazepam, produce additive CNS depressant effects when co-administered with other agents such as alcohol, barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants and anesthetics.
Concomitant use with alcohol is not recommended.
Cases of apnea, coma, bradycardia, cardiac arrest and death have been reported with concomitant use of lorazepam and haloperidol.
Concomitant use of scopolamine showed an increased incidence of sedation, hallucinations and irrational behavior.
Concomitant use of clozapine and lorazepam may cause marked sedation, excessive salivation and ataxia.
Valproate may inhibit the glucuronidation of lorazepam (increased serum levels: increased risk of drowsiness).
Probenecid increases the half-life of lorazepam and reduces the clearance due to inhibition of glucuronidation.
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as lorazepam with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section 4.4).
No interactions with laboratory tests were observed or reported.
There are insufficient data on the use of lorazepam during pregnancy. When lorazepam is administered during pregnancy, hypothermia, respiratory depression and hypotonia (Floppy Infant Syndrome) may occur as a result of the pharmacological action of lorazepam in the newborn child. In case of prolonged use, withdrawal symptoms may occur in the child.
Animal experimental studies do not indicate direct or indirect harmful effects for pregnancy, embryodevelopmental development, labor or postnatal development.
Temelor should only be used during pregnancy if strictly necessary for a period as short as possible and at the lowest possible dose.
Lorazepam passes in small amounts into breast milk. During Temelor use, breastfeeding is not recommended.
There are no data on possible effects of parenterally administered lorazepam on female fertility.
Like all patients who use central nervous system inhibitors, patients who use lorazepam should be warned that they should not operate dangerous machines or drive vehicles until they are not sleepy or dizzy. Patients should be advised not to drive vehicles or take activities requiring attention during 24 to 48 hours after lorazepam administration. A reduction of performance may persist for prolonged periods due to the patient’s high age, concomitant use of other agents, stress due to surgery or the general condition of the patient.
Side effects are usually observed at the beginning of treatment. They generally become less severe or disappear with continuation of treatment or reduction of the dose.
The reported incidents depend on the dose, route of administration and concomitant use of other drugs that suppress the central nervous system.
The following side effects have been observed with the following frequencies: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency group, adverse reactions are ranked by decreasing seriousness.
| System Organ Class | Very Common (≥1/10) | Common (≥1/100 to <1/10) | Uncommon (≥1/1,000 to <1/100) | Rare (≥1/10,000 to <1/1,000) |
|---|---|---|---|---|
| Blood and lymphatic system disorders | Blood dyscrasia | |||
| Psychiatric disorders | Confusion, depression, emotional flattening, sleep disorders, change in libido | Temporary anterograde amnesia or memory disorder, paradoxical reactions* | ||
| Nervous system disorders | Sedation, drowsiness, dizziness, ataxia | Headache, decreased alertness | ||
| Eye disorders | Visual disturbances, diplopia | |||
| Vascular disorders | Hypotension, | |||
| Gastrointestinal disorders | Nausea, gastrointestinal symptoms. | |||
| Hepatobiliary disorders | Abnormal liver function tests | |||
| Skin and subcutaneous tissue disorders | Allergic skin reactions. | |||
| Musculoskeletal and connective tissue disorders | Muscle weakness | |||
| General disorders and administration site conditions | Fatigue |
* During treatment with benzodiazepines, paradoxical reactions such as agitation, nervousness, irritability, aggressiveness, despair, anger attacks, nightmares, hallucinations, psychosis and inappropriate behaviour have been occasionally reported. Such reactions are more likely to occur in children and in the elderly.
After intramuscular administration: pain, burning sensation and redness at the site of injection were reported. Following intravenous administration: local phlebitis, pain immediately after the injection and redness observed during a 24-hour observation period.
1.6% of patients reported pain immediately after injection, while 0.5% of patients reported pain 24 hours after injection.
An intra-arterial injection may lead to arterial spasm, possibly resulting in gangrene for which amputation may be necessary (see section 4.3).
A certain loss of efficacy of the sedative and hypnotic effect of benzodiazepines may occur after repeated use for several weeks.
Tolerance for the effects of benzodiazepines may occur after repeated use.
Pre-existing depression can be manifested when using benzodiazepines.
In patients with severe sedation, partial respiratory tract obstruction may occur. Intravenous administration of lorazepam, alone and in a higher dose than recommended or in the recommended dose together with other agents used during anesthesia, may cause severe sedation.
Therefore, the necessary equipment for keeping the airways open and supporting the respiration/ventilation must be available and should be used if necessary.
Anterograde amnesia may occur with the use of therapeutic doses of lorazepam, the risk increasing at higher doses. Amnestic effects may be accompanied by inappropriate behavior (see also section 4.4).
During lorazepam administration, propylene glycol toxicity (e.g., lactate acidosis, hyperosmolality, hypotension) has been rarely reported.
Other symptoms of propylene glycol toxicity are non-responsiveness, tachypnoea, tachycardia, diaphoresis and central nervous system toxicity, including epileptic seizures and intraventricular haemorrhage. Such symptoms may be expected in patients with renal insufficiency and in children (see also section 4.4).
The use of lorazepam, (also in therapeutic doses) may lead to physical dependence. Symptoms reported after discontinuation of benzodiazepine treatment include: headache, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating and rebound symptoms, with the symptoms leading to the treatment with benzodiazepines to a greater extent recurrence. It may be difficult to distinguish these symptoms from the original symptoms for which the product was indicated.
In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, tinnitus, numbness and tingling of the extremities, sensitivity to light, sound and physical contact, involuntary movements, vomiting, hallucinations and convulsions.
Convulsions/seizures may be more common in patients with pre-existing seizure disorders or who are taking other drugs that lower the convulsive threshold such as antidepressants.
Convulsions may occur more frequently in patients with a history of convulsions or in patients using other drugs that reduce the convulsion threshold, such as antidepressants.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via ADR Reporting, Website: www.medicinesauthority.gov.mt/adrportal.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products other than those mentioned in section 4.
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