Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Genus Pharmaceuticals Holding Limited, T/A Genus Pharmaceuticals, Linthwaite, Huddersfield, HD7 5QH, UK
Patients should be advised that since their tolerance for other CNS depressants will be diminished in the presence of lormetazepam, these substances should either be avoided or taken in reduced dosage. Lormetazepam may enhance the sedative effects of alcohol. Since this affects the ability to drive or use machinery, alcohol should be avoided while taking lormetazepam.
Due to the potential adverse reactions including ataxia, muscle weakness, dizziness, drowsiness and fatigue (see Section 4.8), Benzodiazepines may be associated with an increased risk of falling especially in elderly patients. As a result, caution should be exercised particularly when getting up at night. The elderly should receive a reduced dose (see section 4.2).
Lormetazepam is not intended for the primary treatment of psychotic illness or depressive disorders, and should not be used alone to treat depressed patients with associated insomnia. The use of benzodiazepines may have a disinhibiting effect and may release suicidal tendencies in depressed patients. Therefore, large quantities of lormetazepam should not be prescribed to these patients.
Pre-existing depression may emerge during benzodiazepine use.
The use of benzodiazepines may lead to physical and psychological dependence. The risk of dependence on lormetazepam is low when used at the recommended dose and duration, but increased with higher doses and longer term use. The risk of dependence is further increased 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.
Dependence may lead to withdrawal symptoms, especially if treatment is discontinued abruptly (see 4.8 Undesirable effects). Therefore, the drug should always be discontinued gradually.
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.
Abuse of benzodiazepines has been reported.
Some loss of efficacy to the hypnotic effects of short-acting benzodiazepines may develop after repeated use for a few weeks.
Caution should be used in the treatment of patients with acute narrow-angle glaucoma.
Insomnia 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 a more specific treatment.
Patients with impaired renal or hepatic function 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 haematology and liver-function assessments are recommended where repeated courses of treatment are considered clinically necessary.
Transient anterograde amnesia or memory impairment has been reported in association with the use of benzodiazepines. This condition, which may be associated with inappropriate behaviour, usually occurs several hours after ingestion. Therefore, 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).
Paradoxical reactions have been occasionally reported during benzodiazepines use. Such reactions are more likely to occur in children and the elderly. Should these occur, use of the drug should be discontinued (see 4.8 Undesirable Effects).
Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
Concomitant use of lormetazepam 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 lormetazepam with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe lormetazepam 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).
The benzodiazepines, including lormetazepam produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression e.g., alcohol, barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants, and anaesthetics.
When taken with muscle relaxants, the overall muscle-relaxing effect may be increased (accumulative) therefore caution is advised, especially in elderly patients and at higher doses (risk of falling, see Section 4.4).
Concomitant use of alcohol is not recommended. The sedative effects may be enhanced when lormetazepam is used in combination with alcohol. This will affect the ability to drive or use machines.
An enhancement of the euphoria induced by narcotic analgesics may occur with benzodiazepine use, leading to an increase in psychological dependence.
Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines. To a lesser degree this also applies to benzodiazepines which are metabolised only by conjugation.
Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lormetazepam.
Enhanced hypotensive effects may occur when lormetazepam is given to patients treated with antihypertensive agents.
The concomitant use of sedative medicines such as benzodiazepines or related drugs such as lormetazepam 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).
Benzodiazepines should not be used during pregnancy, especially during the first and last trimesters. Benzodiazepines may cause foetal damage when administered to pregnant women.
If the drug is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the drug if she intends to become, or suspects that she is, pregnant.
There is a possibility that infants born to mothers who take benzodiazepines chronically during the later stages of pregnancy may develop physical dependence. Infants of mothers who ingested benzodiazepines for several weeks or more preceding delivery have been reported to have withdrawal symptoms during the postnatal period. Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnoea, feeding problems, and impaired metabolic response to cold stress have been reported in neonates born of mothers who have received benzodiazepines during the late phase of pregnancy or at delivery.
Since limited data indicates that a small proportion of parent drug and its conjugate is excreted in breast milk, lormetazepam should not be given to breast-feeding women. Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines.
Sedation, amnesia, dizziness and impaired muscular function may adversely affect the ability to drive or use machines. If insufficient sleep occurs, the likelihood of impaired alertness may be increased (see also Interactions).
This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:
Adverse reactions, when they occur, are usually observed at the beginning of therapy and generally decrease in severity or disappear with continued use or upon decreasing the dose.
Most frequently reported adverse reactions associated with benzodiazepines include daytime drowsiness, dizziness, muscle weakness and ataxia.
Adverse reactions are listed by frequency: common (>1/100, <1/10); uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000); very rare (<1/10,000).
Very rare: Thrombocytopenia, leucopenia, agranulocytosis, pancytopenia
Very rare: Hypersensitivity including anaphylaxis/anaphylactoid reactions
Very rare: Inappropriate antidiuretic hormone secretion, hyponatraemia
Rare: Confusion, depression and unmasking of depression, numbed emotions, disinhibition, euphoria, appetite changes, sleep disturbance, change in libido, decreased orgasm
Unknown: Dependence, Suicidal ideation/attempt
Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, delusion, rage, insomnia, nightmares, hallucinations, psychoses, sexual arousal, and inappropriate behaviour have been occasionally reported during use.
Very common: Daytime drowsiness, sedation
Common: Dizziness, ataxia
Rare: headache, reduced alertness, dysarthria/slurred speech, transient anterograde amnesia or memory impairment
Very rare: Tremor, extrapyramidal reactions, Coma (see 4.9 Overdose)
Rare: Visual disturbances (diplopia, blurred vision)
Rare: Hypotension (see 4.4 Special warnings and precautions)
Rare: Apnoea, worsening of sleep apnoea, worsening of obstructive pulmonary disease.
Respiratory depression (see 4.9 Overdose)
Rare: Nausea, constipation, salivation changes
Rare: Abnormal liver function test values (increases in bilirubin, transaminases, alkaline phosphatase), jaundice
Rare: Rash, allergic dermatitis
Common: Muscle weakness
Rare: Impotence
Common: Asthenia, fatigue
Very rare: Hypothermia
Drug withdrawal symptoms (see 4.4 Special warnings and precautions)
Symptoms reported following discontinuation of benzodiazepines include headaches, muscle pain, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, and the occurrence of “rebound” phenomena whereby 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.
In severe cases the following symptoms may occur: derealisation; depersonalisation; hyperacusis; tinnitus; numbness and tingling of the extremities; hypersensitivity to light, noise, and physical contact; involuntary movements; hyperreflexia, tremor, nausea, vomiting; diarrhoea, abdominal cramps, loss of appetite, agitation, palpitations, tachycardia, panic attacks, vertigo, short-term memory loss, hallucinations/delirium; catatonia; hyperthermia, convulsions. Convulsions 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.
Not known: Fall
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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for ‘MHRA Yellow Card’ in the Google Play or Apple App Store.
None known.
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