Features
The symptoms of Sibazon solution for injections 0,5% overdose are mainly an intensification of the therapeutic effects (ataxia, drowsiness, dysarthria, sedation, muscle weakness, profound sleep, hypotension, bradycardia, nystagmus) or paradoxical excitation. In most cases only observation of vital functions is required.
Extreme overdosage may lead to coma, areflexia, cardiorespiratory depression and apnoea, requiring appropriate countermeasures (ventilation, cardiovascular support). Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease. Severe effects in overdose also include rhabdomyolysis and hypothermia.
Management
Maintain a clear airway and adequate ventilation.
Consider activated charcoal (50g for an adult, 1g/kg for a child) in adults who have taken more than 100mg or children who have taken more than 1mg/kg within one hour, provided they are not too drowsy.
Monitoring level of consciousness, respiratory rate, pulse oximetry and blood pressure in symptomatic patients.
Consider arterial blood gas analysis in patients who have a reduced level of consciousness (GCS < 8; AVPU scale P or U) or have reduced oxygen saturations on pulse oximetry.
Correct hypotension by raising the foot of the bed and by giving an appropriate fluid challenge. Where hypotension is thought mainly due to decreased systemic vascular resistance, drugs with alpha-adrenergic activity such as noradrenaline or high dose dopamine (10-30 micrograms/kg/min) may be beneficial. The dose of inotrope should be titrated against blood pressure.
If severe hypotension persists despite the above measures, then central venous pressure monitoring should be considered.
Supportive measures are indicated depending on the patient's clinical state.
Benzodiazepines are not significantly removed from the body by dialysis.
Flumazenil, a benzodiazepine antagonist, is not advised as a routine diagnostic test in patients with reduced conscious level. It may sometimes be used as an alternative to ventilation in children who are naive to benzodiazepines, or in patients with COPD to avoid the need for ventilation. It is not necessary or appropriate in cases of poisoning to fully reverse the benzodiazepine effect. Flumazenil has a short half-life (about an hour) and in this situation an infusion may therefore be required. Flumazenil is contraindicated when patients have ingested multiple medicines, especially after co-ingestion of a benzodiazepine and a tricyclic antidepressant or any other drug that causes seizures. This is because the benzodiazepine may be suppressing seizures induced by the second drug; its antagonism by flumazenil can reveal severe status epilepticus that is very difficult to control.
Contraindications to the use of flumazenil include features suggestive of a tricyclic antidepressant ingestion including a wide QRS, or large pupils. Use in patients postcardiac arrest is also contraindicated.
It should be used with caution in patients with a history of seizures, head injury, or chronic benzodiazepine use.
Occasionally a respirator may be required but generally few problems are encountered, although behavioral changes are likely in children.
If excitation occurs, barbiturates should not be used.
Effects of overdose are more severe when taken with centrally-acting drugs, especially alcohol, and in the absence of supportive measures, may prove fatal.
Sibazon solution for injections 0,5% is contra-indicated for patients with:
-
- Phobic or obsessional states; chronic psychosis, hyperkinesis (paradoxical reactions may occur).
- Acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency (ventilatory failure may be exacerbated).
- Myasthenia gravis (condition may be exacerbated).
- Sleep apnoea (condition may be exacerbated).
- Severe hepatic insufficiency (elimination half-life of Sibazon solution for injections 0,5% may be prolonged).
- Acute porphyria.
- Sibazon solution for injections 0,5% should not be used as monotherapy in patients with depression or those with anxiety and depression as suicide may be precipitated in such patients.
- Planning a pregnancy.
None known.
Drowsiness, numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or double vision predominantly occur at the start of therapy but usually disappear with repeated administration. Among elderly patients there may be confusion conditions at high dose levels. There is an increased risk of falls and associated fractures in elderly patients using benzodiazepines.
Increased salivary and bronchial secretion has been reported, in particular in children.
Amnesia
Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour.
Dependence
Chronic use (even at therapeutic doses) may lead to the development of physical and psychic dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena. Abuse of benzodiazepines has been reported.
The frequencies of adverse events are ranked according to the following:
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).
| System Organ Class | Frequency | Undesirable effects |
| Blood and lymphatic system disorders | Rare | Blood dyscrasias |
| Very rare | Leukopenia | |
| Immune system disorders | Very rare | Anaphylaxis. |
| Psychiatric disorders | Common | Confusion. |
| Rare | Psychiatric and paradoxical reactions such as excitation, restlessness, agitation, irritability, aggressiveness, delusion, rages, hallucinations, psychoses, memory loss, nightmares, inappropriate behaviour and other adverse behavioural effects.a Emotional poverty, decreased alertness and depression.b | |
| Nervous system disorders | Very common | Drowsiness. |
| Common | Ataxia, impaired motor ability, tremor. | |
| Uncommon | Anterograde amnesia.c Concentration difficulties, balance disorders, dizziness, headache, slurred speech. | |
| Rare | Unconsciousness, insomnia, dysarthria. | |
| Eye disorders | Not known | Reversible disorders of vision: blurred vision, diplopia, nystagmus. |
| Cardiac disorders | Rare | Bradycardia, heart failure including cardiac arrest. |
| Vascular disorders | Rare | Hypotension, syncope. |
| Respiratory, thoracic and mediastinal disorders | Uncommon | Respiratory depression. |
| Rare | Respiratory arrest, increased bronchial secretion. | |
| Not Known | Apnoea | |
| Gastrointestinal disorders | Uncommon | Gastrointestinal disorders (nausea, vomiting, constipation, diarrhoea), increased salivary secretion. |
| Rare | Dry mouth, increased appetite. | |
| Hepatobiliary disorders | Rare | Jaundice, changes of hepatic parameters (elevation of ALT, AST, alkaline phosphatase). |
| Skin and subcutaneous tissue disorders | Uncommon | Allergic skin reactions (itching, erythema, rash). |
| Musculoskeletal and connective tissue disorders | Uncommon | Myasthenia. |
| Renal and urinary disorders | Rare | Urinary retention, incontinence. |
| Reproductive system and breast disorders | Rare | Gynaecomastia, impotence, increased or reduced libido. |
| General disorders and administration site conditions | Common | Fatigue, withdrawal symptoms (anxiety, panic, palpitations, sweating, tremor, gastrointestinal disorders, irritability, aggression, disrupted sensory perception, muscle spasms, general malaise, loss of appetite, paranoid psychosis, delirium and epileptic attacks).d |
| Investigations | Very rare | Elevation of transaminases. |
a Known to occur when using benzodiazepines or benzodiazepine-like agents. These reactions may be quite severe. They are more likely to occur in children and the elderly. Sibazon solution for injections 0,5% should be discontinued if such symptoms occur.
b Pre-existing depression may be unmasked during benzodiazepine use.
c May occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour.
d The likelihood and degree of severity of withdrawal symptoms is dependent on the duration of treatment, dose level and degree of dependency.
Reporting of suspected adverse reactions
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; website: www.mhra.gov.uk/yellowcard
Not applicable.
Sibazon solution for injections 0,5% has potent anxiolytic, anticonvulsant and central muscle-relaxing properties; these effects are probably mediated through special areas in the CNS. It also has uses in pre-operative medication and is used in the treatment of skeletal-muscle spasm, and the associated pain.
The main uses are:
Adults:
1) The short term relief (14 days) only of anxiety which is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness.
The use of benzodiazepines to treat short-term anxiety is considered to be inappropriate.
2) Cerebral palsy.
3) Muscle spasm; as an adjunct to the control of muscle spasm in tetanus.
4) As an adjunct to the management of certain types of epilepsy (e.g. myoclonus).
5) Symptomatic treatment of acute alcohol withdrawal.
6) As oral premedication for the nervous dental patient.
Paediatric population:
1) Control of tension and irritability in cerebral spasticity in selected cases.
2) Oral premedication.
ATC code: N05B A01
Pharmacotherapeutic group: Sibazon solution for injections 0,5% is a benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant and amnesic properties.
Absorption
Sibazon solution for injections 0,5% is readily and completely absorbed from the GI tract.
Distribution
Peak plasma concentration occurring within 30-90 minutes of oral administration; the rate of absorption is age related and tends to be delayed in the elderly. Sibazon solution for injections 0,5% crosses the blood-brain barrier and is highly lipid soluble. Sibazon solution for injections 0,5% is very extensively bound to plasma proteins.
Sibazon solution for injections 0,5% and its metabolites cross the placental barrier and are excreted in breast milk.
Biotransformation
It has a biphasic half-life with an initial rapid distribution phase followed by a prolonged terminal elimination phase of 1-2 days; its action is further prolonged by the even longer half-life of 2-5 days of its active principle metabolite, desmethylSibazon solution for injections 0,5%, the relative proportion of which increases in the body on long-term administration.
Sibazon solution for injections 0,5% is extensively metabolised in the liver and, in addition to desmethylSibazon solution for injections 0,5%, its active metabolites include oxazepam and temazepam.
The half-life of Sibazon solution for injections 0,5% is prolonged in neonates, in the elderly and in patients with kidney or liver disease.
Elimination
It is excreted in the urine, mainly in the form of its metabolites, either free or in conjugated forms.
- The concomitant use of Sibazon solution for injections 0,5% with alcohol and/or CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Sibazon solution for injections 0,5% possibly including severe sedation, clinically relevant respiratory and/or cardio-vascular depression.
Duration of Treatment - The duration of treatment should be as short as possible depending on the indication, but should not exceed 4 weeks including tapering off process. Treatment should not continue beyond 4 weeks without re-evaluation of the patient's condition. The patient must be evaluated after a period of no more than 4 weeks and then regularly thereafter in order to assess the need for continued treatment, especially if the patient is free of symptoms. In general, treatment must not last any longer than 8-12 weeks, including the tapering off process. Extension beyond these periods should not take place without re-evaluation of the situation.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. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimizing anxiety over such symptoms should they occur while Sibazon solution for injections 0,5% is being discontinued.
There are indications that, in the case of benzodiazepines with a long duration of action such as Sibazon solution for injections 0,5%, withdrawal phenomena can become manifest between doses, 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.Dependence and Withdrawal - Withdrawal symptoms occur with benzodiazepines following normal therapeutic doses given for short periods of time.
As sudden discontinuation of benzodiazepines may result in convulsions, particular care should be taken in patients with epilepsy, other patients who have had a history of seizures or in alcohol or drug dependants. Discontinuation should be gradual in order to minimise the risk of withdrawal symptoms.
Use of Sibazon solution for injections 0,5% may lead to the development of physical and psychic dependence. The risk of dependence increases with the dose and duration of treatment, and in patients with a history of alcoholism and drug abuse or in patients with marked personality disorders. Regular monitoring in such patients is essential, routine repeat prescriptions should be avoided and treatment should be withdrawn gradually.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.Rebound insomnia and anxiety: a transient syndrome whereby the symptoms that led to treatment with Sibazon solution for injections 0,5% may recur in an enhanced form on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.
- Tolerance - Limits of tolerance in patients with organic cerebral changes (particularly arteriosclerosis) or cardiorespiratory insufficiency may be very wide; care must be taken in adapting the dosage with such patients.
Some loss of efficacy to the hypnotic effects of Sibazon solution for injections 0,5% may develop after repeated use for a few weeks.
- Benzodiazepines are not indicated to treat patients with severe hepatic insufficiency as they may precipitate encephalopathy. In patients with chronic hepatic disease dosage may need to be reduced.
- The usual precautions in treating patients with impaired renal function should be observed. In renal failure, the half-life of Sibazon solution for injections 0,5% is not clinically significantly changed, and dose adjustment is usually not necessary.
- Alcohol should be avoided during treatment with Sibazon solution for injections 0,5% (additive CNS depression).
- Amnesia: Sibazon solution for injections 0,5% may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have uninterrupted sleep of 7-8 hours. Amnestic effects may be associated with inappropriate behaviour.
Anterograde amnesia may occur even if benzodiazepines are used within the normal dose range, though this is seen in particular at high dose levels.
- In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.
- History of alcohol or drug abuse (as these are patients predisposed to habituation and dependence).
- Depression or anxiety associated with depression. Benzodiazepines should not be used alone in the treatment of depression or anxiety associated with depression as suicide may be precipitated in such patients.
- Hypoalbuminaemia (may predispose the patient to higher incidence of sedative side effects).
- Extreme caution should be used in prescribing Sibazon solution for injections 0,5% to patients with personality disorders.
Specific patient groups
Paediatric population
Benzodiazepines should not be given to children without careful assessment of the need to do so; the duration of treatment must be kept to a minimum. Safety and effectiveness of Sibazon solution for injections 0,5% in paediatric patients below the age of 6 months have not been established.
Elderly and debilitated patients
Should be given a reduced dose. Due to the myorelaxant effect there is a risk of falls and consequently hip fractures in the elderly.
Psychiatric and 'paradoxical' reactions
Paradoxical reactions (such as restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects) have been reported from the use of benzodiazepines.
Such reactions are possibly seen more often in the treatment of children and elderly patients and should result in the discontinuation of treatment.
Potentially suicidal individuals should not have access to large amounts of Sibazon solution for injections 0,5% due to the risk of overdosing.
Excipients
Sibazon solution for injections 0,5% Oral solution contains Sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Sibazon solution for injections 0,5% oral solution contains 2.500mg of Propyl parahydroxybenzoate (E216) per 5ml solution and 5.000mg of Methyl parahydroxybenzoate (E218) per 5ml solution. May cause allergic reactions (possibly delayed).
Sibazon solution for injections 0,5% oral solution contains 0.63g of glycerol per 5ml solution. May cause headache, stomach upset and diarrhoea in doses higher than 31mg.
Sedation, amnesia, impaired concentration and impaired muscular function may adversely effect the ability to drive or to use machines. If insufficient sleep duration occurs, the likelihood of impaired alertness may be increased (see also Interactions). Patients should be warned that effects on the central nervous system may persist into the day after administration even after a single dose.
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:
- The medicine is likely to affect your ability to drive
- Do not drive until you know how the medicine affects you
- It is an offence to drive while under the influence of this medicine
- However, you would not be committing an offence (called 'statutory defence') if:
- The medicine has been prescribed to treat a medical or dental problem and
- You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
- It was not affecting your ability to drive safely
Posology
As an anxiolytic, the lowest effective dose should be employed; dosage regimes should not exceed beyond 14 days. Patients who have received benzodiazepines for a long time may require an extended withdrawal period. Long-term chronic use is not recommended.
Adults:
Anxiety states, obsessive-compulsive neuroses, and other psychiatric disorders: 2-30mg daily in divided doses.
Insomnia associated with anxiety: 5-30mg before retiring.
Cerebral palsy: 2-60mg daily in divided doses.
Upper motor neuronic spasticity: 5-60mg daily in divided doses.
Muscle spasm of varied aetiology, fibrositis, cervical spondylosis: 2-15mg daily in divided doses.
Adjunct to the management of some types of epilepsy: Premedication: 2-60mg daily in divided doses. Adults: 5-20mg and children: 2-10mg.
Alcohol withdrawal: 5-20mg, repeated if necessary in 2 to 4 hours.
Oral premedication in dental patients: 5mg the night before, 5mg on waking and 5mg two hours before the appointment.
Paediatric population:
Conditions associated with muscle spasm: Control of tension and irritability in spasticity in selected cases; 2-40mg daily in divided doses. As an adjunct to the control of muscle spasm in tetanus; as for adults.
Spastic children with minimal brain damage: 2-40mg daily in divided doses.
Elderly and debilitated patients:
Doses should not exceed half the above recommended adult doses.
Method of administration
For oral administration.
Not applicable.
Administrative data
