Rivotril 0.5mg Tablets

  • Name:

    Rivotril 0.5mg Tablets

  • Company:
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  • Active Ingredients:

    Clonazepam

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

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Roche Products (Ireland) Ltd

Roche Products (Ireland) Ltd

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Medicine Name Pulmozyme 2500 U/2.5ml Nebuliser Solution Active Ingredients Dornase Alfa
Medicine Name Rivotril 0.5mg Tablets Active Ingredients Clonazepam
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Medicine Name Roaccutane 20mg Soft Capsules Active Ingredients Isotretinoin
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1 - 0 of 10 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 10 September 2018 PIL

Reasons for updating

  • New individual PIL (was previously included in a combined PIL)
  • Change to section 6 - marketing authorisation holder
  • Change to date of revision

Updated on 10 September 2018 SmPC

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  • Change to section 7 - Marketing authorisation holder
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MAH Transfer from RPL to Roche Products (Ireland) Limited issue of new PA licence number(s)

Updated on 15 May 2018 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
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New Indication - The Rivotril CDS has been updated to be aligned with other Roche benzodiazepines CDS, ensuring consistent benzodiazepines class wording.

Updated on 24 April 2018 PIL

Reasons for updating

  • Change to Section 1 - what the product is
  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 5 - how to store or dispose
  • Change to section 6 - date of revision

Updated on 26 June 2015 SmPC

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  • New SmPC for new product

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 26 June 2015 SmPC

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  • Change to Section 4.8 – Undesirable effects - how to report a side effect
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 Underlined text has been added:

 

4.8 Undesirable effects

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 HPRA Pharmacovigilance,  Earlsfort Terrace, IRL – Dublin 2.  Tel: +353 1 6764971; Fax: +353 1 6762517, Website: www.hpra.ie; e-mail: medsafety@hpra.ie

 

10 DATE OF REVISION

19 June 2015

Updated on 24 June 2015 PIL

Reasons for updating

  • New PIL for new product

Updated on 24 June 2015 PIL

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 29 August 2013 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

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Underlined text = new text

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4.8         Undesirable effects

 

[ … ]

 

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 elderlyAn increased risk for falls and fractures has been reported in elderly benzodiazepine users.

 

[ … ]

 

 

10.         DATE OF REVISION OF THE TEXT

 

20 December 201216 August 2013

 

Updated on 23 August 2013 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 25 January 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to further information section
  • Change to date of revision

Updated on 2 January 2013 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

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Underlined text has been added, text with strike out deleted:

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Rivotril 0.5 mg Tablets:

Each tablet contains 500 micrograms (0.5 mg) clonazepam.

Excipients: Also contains 40 mg lactose monohydrate.

Rivotril 2 mg Tablets:

Each tablet contains 2 mg clonazepam.

Excipients: Also contains 121.5 mg lactose anhydrous.

For a full list of excipients, see section 6.1

4.3       Contraindications

 

Patients with known sensitivity to benzodiazepines or any of the drug’s excipients; acute pulmonary insufficiency, severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe hepatic insufficiency.

Rivotril must not be used in patients in a coma, or in patients known to be abusing pharmaceuticals, drugs or alcohol.

 

4.4       Special warnings and precautions for use

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications.  A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.  The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for clonazepam.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.  Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

 

Patients with a history of depression and/or suicide attempts should be kept under close supervision.

Rivotril should be used with caution in patients with chronic pulmonary insufficiency, or with impairment of renal or hepatic function, and in the elderly or the debilitated.  In these cases dosage should generally be reduced.

As with all other anti-epileptic drugs, treatment with Rivotril even if of short duration, must not be abruptly interrupted, but must be withdrawn by gradually reducing the dose in view of the risk of precipitating status epilepticus. In such cases a combination with other antiepileptics is indicated. This precaution must also be taken when withdrawing another drug while the patient is still receiving Rivotril therapy.

Prolonged use of benzodiazepines may result in dependence development with withdrawal symptoms on cessation of use.

Rivotril may be used only with particular caution in patients with spinal or cerebellar ataxia, in the event of acute intoxication with alcohol or drugs and in patients with severe liver damage (e.g. cirrhosis of the liver).

The concomitant use of Rivotril with alcohol or/and CNS depressants should be avoided. Such concomitant use has the potential to increase the clinical effects of Rivotril possibly including severe sedation, clinically relevant respiratory and/or cardio-vascular depression (see 4.5).

Rivotril should be used with extreme caution in patients with a history of alcohol or drug abuse.

In infants and small children Rivotril may cause increased production of saliva and bronchial secretion. Therefore special attention must be paid to maintaining patency of the airways.

The dosage of Rivotril must be carefully adjusted to individual requirements in patients with pre-existing disease of the respiratory system (e.g. chronic obstructive pulmonary disease) or liver and in patients undergoing treatment with other centrally acting medications or anticonvulsant (antiepileptic) agents (see section 4.5). Effects on the respiratory system may be aggravated by pre-existing airways obstruction or brain damage or if other medications which depress respiration have been given. As a rule, this effect can be avoided by careful adjustment of the dose to individual requirements.

            In patients with porphyria, clonazepam must be used with care because it may have a porphyrogenic effect.Clonazepam is considered to be probably nonporphyrinogenic, although there is some conflicting evidence. Therefore in patients with porphyria, clonazepam should be used with care.

Like all drugs of this type, Rivotril may, depending on dosage, administration and individual susceptibility, modify the patient’s reactions (e.g. driving ability, behaviour in traffic). (see 4.7)

As a general rule, epileptic patients are not allowed to drive. Even when adequately controlled on Rivotril, it should be remembered that any increase in dosage or alteration in timings of dosage may modify patients' reactions, depending on individual susceptibility.

In cases of loss or bereavement, psychological adjustment may be inhibited by benzodiazepines.

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

Dependence

Use of benzodiazepines may lead to the development of physical and psychicological dependence upon these products (see 4.8). In particular long-term or high-dose treatment, may lead to reversible disorders such as dysarthria, reduced coordination of movements and gait disorder (ataxia), nystagmus and vision (diplopia). Furthermore, the risk of anterograde amnesia, which may occur using benzodiazepines at therapeutic dosages, increases at higher dosages. Amnestic effects may be associated with inappropriate behaviour. With certain forms of epilepsy, an increase in the frequency of seizures (see 4.8) during long-term treatment is possible.

 

The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcoholism and/or drug abuse.

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. During long-term treatment, withdrawal symptoms may develop after a lengthy period of use, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued. The symptoms include tremor, sweating, agitation, sleep disturbances and anxiety, headaches, muscle pain, extreme anxiety, tension, restlessness, confusion, irritability and epileptic seizures which may be associated with the underlying disease. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact or hallucinations. Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should therefore be avoided and treatment - even if only of short duration - should be terminated by gradually reducing the daily dose. The risk of withdrawal symptoms is increased when benzodiazepines are used together with day-time sedatives (crossed tolerance).

 

4.5       Interaction with other medicinal products and other forms of interaction

Since alcohol can provoke epileptic seizures, irrespective of therapy, patients must under no circumstances drink alcohol while under treatment with antiepileptic drugs.  In combination with Rivotril, alcohol may modify the effects of the drug, compromise the success of therapy or give rise to unpredictable side-effects.

See section 4.9 Overdose for warning of other central nervous system depressants, including alcohol.

[…]

When Rivotril is used in conjunction with other anti-epileptic drugs, side-effects such as sedation and apathy and toxicity may be more evident, particularly with hydantoins or phenobarbital and combinations including them. In such cases, the dosage of each drug must be adjusted to achieve the optimum desired effect, particularly This requires extra care in adjusting dosage in the initial stages of treatment.  The combination of Rivotril and sodium valproate has, rarely, been associated with the development of absence status epilepticus.  Although some patients tolerate and benefit from this combination of drugs, this potential hazard should be borne in mind when its use is considered.

[…]

4.6       Fertility, pregnancy and lactation

 

Preclinical studies in animals have shown reproductive toxicity and from preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations (see section 5.3). From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens. However, it is difficult to determine from published epidemiological reports which drug or combination of drugs is responsible for defects in the newborn. The possibility also exists that other factors e.g. genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. Rivotril should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus.

During pregnancy, Rivotril may be administered only if there is a compelling indication. Rivotril has harmful pharmacological effects on pregnancy and the foetus/newborn child.  Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heart beat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feedingsucking in the neonate. Infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may have developed a physical dependence and may be at some risk for developing withdrawal symptoms in the post-natal period.  Therefore Rivotril should not be used in pregnancy unless clearly necessary. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy.  Rivotril should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus.

Although, tThe active ingredient of Rivotril has been found to pass into the maternal milk in small amounts only, mothers undergoing treatment with this drug should not breastfeed.  Therefore Rivotril should not be used in mothers who breastfeed unless clearly necessary. If there is a compelling indication for Rivotril, breastfeeding should be discontinued.

4.8       Undesirable effects

Dependence and withdrawal, (see 4.4).

Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products.  The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a medical history of alcoholism and/or drug abuse.

 

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.  During long-term treatment, withdrawal symptoms may develop, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued.  The symptoms include tremor, sweating, agitation, sleep disturbances and anxiety, headaches, muscle pain, extreme anxiety, tension, restlessness, confusion, irritability and epileptic seizures which may be associated with the underlying disease.  In severe cases the following symptoms may occur:  derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact or hallucinations.  Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should therefore be avoided and treatment - even if only of short duration - should be terminated by gradually reducing the daily dose.

Although Rivotril has been given uneventfully to patients with porphyria, rarely it may induce convulsions in these patients.

Paediatric population

For paediatric specific events please refer to the information listed under headings: Endocrine Disorders and Respiratory, Thoracic and Mediastinal System Disorders in section 4.8.

4.9       Overdose

As with other benzodiazepine drugs, overdosage should not present undue problems of management or threat to life.  Patients have recovered from overdoses in excess of 60 mg without special treatment. Severe somnolence with muscle hypotonia will be present. 

Symptoms

The symptoms of overdosage or intoxication vary greatly from person to person depending on age, bodyweight and individual response. Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Rivotril is seldom life-threatening if the drug is taken alone, but may lead to coma, areflexia, apnoea, hypotension and cardiorespiratory depression. Coma, if it occurs, usually lasts a few hours but in elderly people it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease.

Benzodiazepines potentiate the effects of other central nervous system depressants, including alcohol.

 

Management

1.      Maintain a clear airway and adequate ventilation if indicated.

2.      Supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.

1.            The benefit of gastric decontamination is uncertain.  Consider activated charcoal (50 g for an adult, 10-15 g for a child) in adults or children who have taken more than 0.4 mg/kg within 1 hour, provided they are not too drowsy.

1.            Gastric lavage is unnecessary if these drugs have been taken alone.

3.      Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients.

4.      In case of mixed ingestion gastric lavage may be considered, however not as a routine measure.

5.      Patients who are asymptomatic at 4 hours are unlikely to develop symptoms.

1.            Supportive measures as indicated by the patient’s clinical state.   In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.

6.      Flumazenil (Anexate), a benzodiazepine antagonist is available but should rarely be required. It has a short half-life (about an hour).If CNS depression is severe consider the use of flumazenil (Anexate®), a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil (Anexate®), for further information on the correct use of this drug. Flumazenil is NOT TO BE USED IN MIXED OVERDOSE OR AS A “DIAGNOSTIC TEST” (see separate prescribing information).

 Warning

The use of flumazenil is not indicatedrecommended in epileptic patients with epilepsy who have been receiving treated with benzodiazepines treatment for a prolonged period. Although flumazenil exerts a slight intrinsic anticonvulsant effect, its abrupt suppression of the protective effect of a benzodiazepine agonist can give rise to convulsions in epileptic patients.

 If excitation occurs, barbiturates should not be used.

 

10.                  DATE OF REVISION OF THE TEXT

 

23 November 201220 December 2012

 

 

Updated on 30 November 2012 SmPC

Reasons for updating

  • Change to section 6.4 - Special precautions for storage
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

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Update to Section 6.4 to explain why to store in original container “in order to protect from light”.

Updated on 4 April 2011 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may not be renewed (A)

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Underlined text has been added, text with strike through deleted:

 

4.4       Special warnings and precautions for use

 

[…]

 

Benzodiazepines Rivotril should be used with extreme caution in patients with a history of alcohol or drug abuse.

 

[…]

 

            In patients with porphyria, clonazepam must be used with care because it may have a porphyrogenic effect.

 

4.5       Interaction with other medicinal products and other forms of interaction

 

Since alcohol can provoke epileptic seizures, irrespective of therapy, patients  must under no circumstances drink alcohol while under treatment with antiepileptic drugs.  In combination with Rivotril, alcohol may modify the effects of the drug, compromise the success of therapy or give rise to unpredictable side-effects.

 

            Enhanced effects on sedation, respiration and haemodynamics may occur          when Rivitrol is co-administered with any centrally acting depressants e.g. alcohol, and other anticonvulsant (antiepileptic) agents, anaesthetics, hypnotics, psychoactive drugs and some analgesics as well as muscle relaxants and may result in mutual potentiation of drug effects.

 

In combination therapy with centrally-acting medications, the dosage of each      drug must be adjusted to achieve the optimum effect.

 

When Rivotril is used in conjunction with other anti-epileptic drugs, side-effects such as sedation and apathy, and toxicity may be more evident, particularly with hydantoins or phenobarbital and combinations including them. This requires extra care in adjusting dosage in the initial stages of treatment.  The combination of Rivotril and sodium valproate has, rarely, been associated with the development of absence status epilepticus.  Although some patients tolerate and benefit from this combination of drugs, this potential hazard should be borne in mind when its use is considered.

 

            The antiepileptic drugs phenytoin, phenobarbital, carbamazepine and valproate  may induce the metabolism of clonazepam causing higher clearance and lower increase the clearance of clonazepam thereby decreasing the plasma  concentrations of the latter during combined treatment.

 

In concurrent treatment with phenytoin or primidone a change, usually a rise, in the serum concentration of these two substances has occasionally been observed.

 

            Clonazepam itself does not induce the enzymes responsible for its own  metabolism.

 

 

The selective serotonin reuptake inhibitors sertraline and fluoxetine do not affect the pharmacokinetics of clonazepam when administered concomitantly.

 

Known inhibitors of hepatic enzymes, e.g. cimetidine, have been shown to reduce the clearance of benzodiazepines and may potentiate their action and known inducers of hepatic enzymes, e.g. rifampicin, may increase the clearance of benzodiazepines.

 

Concurrent use of Rivotril and other centrally acting medications, e.g. other anticonvulsant (antiepileptic) agents, anaesthetics, hypnotics, psychoactive drugs and some analgesics as well as muscle-relaxants may result in mutual potentiation of drug effects.  This is especially true in the presence of alcohol.  In combination therapy with centrally-acting medications, the dosage of each drug must be adjusted to achieve the optimum effect.

 

4.8       Undesirable effects

 

The side-effectsfollowing have been  observed: consist of fatigue, muscle weakness, dizziness, ataxia, light-headedness, somnolence, occasional muscular hypotonia and co-ordination disturbances.  Such effects are usually transitory and disappear spontaneously as treatment continues or with dosage reduction.  They tend to occur early in treatment and can be greatly reduced, if not avoided, by commencing with low dosages followed by progressive increases.

 

Poor concentration, restlessness, confusion and disorientation have been observed.  Anterograde amnesia may occur using benzodiazepines at therapeutic dosage, the risk increasing at higher dosages.  Amnestic effects may be associated with inappropriate behaviour.

 

Depression may occur in patients treated with Rivotril, but it may be also associated with the underlying disease.

 

In rare cases, urticaria, pruritus, transient hair loss, pigmentation changes, nausea, gastro-intestinal symptoms, headache, decrease in sexual drive (loss of libido), impotence and urinary incontinence may occur.  Isolated cases of reversible development of premature secondary sex characteristics in children (incomplete precocious puberty) have been reported.  Allergic reactions and a very few cases of anaphylaxis and angioedema have been reported to occur with benzodiazepines.

 

Particularly in long-term or high-dose treatment, reversible disorders such as a slowing or slurring of speech (dysarthria), reduced co-ordination of movements and gait (ataxia) and disorders of vision (double vision, nystagmus) may occur.

 

Rarely respiratory depression may occur with intravenous Rivotril, particularly if other depressant drugs have been administered.  As a rule, this effect can be avoided by careful adjustment of the dose in individual requirements.

 

Immune System Disorders

Allergic reactions and very few cases of anaphylaxis have been reported to occur with benzodiazepines.

 

Endocrine Disorders

Isolated cases of reversible development of premature secondary sex characteristics in children (incomplete precocious puberty) have been reported.

 

Psychiatric Disorders

Impaired concentration, restlessness, confusional state, disorientation have been observed. Depression may occur in patients treated with Rivotril, but it may be also associated with the underlying disease. The following paradoxical reactions have been observed: excitability, irritability, aggression, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares, vivid dreams and psychotic disorders and activation of new types of seizures may be precipitated. If these occur, the benefit of continuing the drug should be weighed against the adverse effect. The addition to the regimen of another suitable drug may be necessary or, in some cases, it may be advisable to discontinue Rivotril therapy. In rare cases loss of libido may occur.

 

Nervous System Disorders

Somnolence, slowed reaction, muscular hypotonia, dizziness, ataxia and co-ordination disturbance. These undesirable effects occur relatively frequently and are usually transient and generally disappear spontaneously in the course of the treatment or on reduction of the dosage. They can be partially prevented by increasing the dose slowly at the start of treatment.

 

Headache was observed in rare cases.

 

Particularly in long-term or high-dose treatment, reversible disorders such as dysarthria, reduced coordination of movements and gait disorder (ataxia) and nystagmus may occur. Anterograde amnesia may occur using benzodiazepines at therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour. With certain forms of epilepsy, an increase in the frequency of seizures during long-term treatment is possible.

 

Eye Disorders

Particularly in long-term or high-dose treatment, reversible disorders of vision (diplopia) may occur.

 

Cardiac Disorders

Cardiac failure including cardiac arrest has been reported.

 

Respiratory, Thoracic and Mediastinal System Disorders

Respiratory depression may occur, particularly on i.v. administration of clonazepam. This effect may be aggravated by pre-existing airways obstruction or brain damage or if other medications which depress respiration have been given. As a rule, this effect can be avoided by careful adjustment of the dose to individual requirements.

 

In infants and young children, particularly those with a degree of mental impairment, Rivotril may cause increased production of saliva or of bronchial secretion. Particular attention should therefore be paid to maintaining patency of the airways.

 

Gastrointestinal Disorders

The following effects have been reported in rare cases: nausea and gastrointestinal symptoms.

 

Skin and Subcutaneous Tissue Disorders

The following effects may occur in rare cases: urticaria, pruritus, rash, transient hairloss, pigmentation changes and angioedema.

 

Musculoskeletal and Connecting Tissue Disorders

Muscle weakness, this undesirable effect occurs relatively frequently and is usually transient and generally disappears spontaneously in the course of the treatment or on reduction of the dosage. It can be partially prevented by increasing the dose slowly at the start of treatment.

 

Renal and Urinary Disorders

In rare cases urinary incontinence may occur.

 

Reproductive System and Breast Disorders

In rare cases erectile dysfunction may occur.

 

General Disorders and Administration Site Conditions

Fatigue (tiredness, lassitude), this undesirable effect occurs relatively frequently and is usually transient and generally disappears spontaneously in the course of the treatment or on reduction of the dosage. It can be partially prevented by increasing the dose slowly at the start of treatment. Paradoxical reactions including irritability have been observed (see also psychiatric disorders).

 

Injury, Poisoning and Procedural Complications

An increased risk for falls and fractures has been reported in elderly benzodiazepine users.

 

Investigations

In rare cases decreased platelet count may occur. As with other benzodiazepines, isolated cases of blood dyscrasias and abnormal liver function tests have been reported.

 

Use of benzodiazepines may lead to the development of physical and psychological psychic dependence upon these products.  The risk of dependence increases with dose and duration of treatment; it is also greater and is particularly pronounced in predisposed patients with a medical history of alcoholism and/or drug abuse.

 

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms.  During long-term treatment, withdrawal symptoms may develop, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued.  The symptoms include tremor, sweating, agitation, sleep disturbances and anxiety, headaches, muscle pain, extreme anxiety, tension, restlessness, confusion, irritability and epileptic seizures which may be associated with the underlying disease.  In severe cases the following symptoms may occur:  derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact or hallucinations.  Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should therefore be avoided and treatment - even if only of short duration - should be terminated by gradually reducing the daily dose.

 

In infants and small children, and particularly those with a degree of mental impairment, Rivotril may give rise to salivary or bronchial hypersecretion with drooling.  Supervision of the airway may be required.

 

With certain forms of epilepsy, an increase in the frequency of seizures during long-term treatment is possible.

 

As with other benzodiazepines, isolated cases of blood dyscrasias and abnormal liver function tests have been reported.

 

Rivotril generally has a beneficial effect on behaviour disturbances in epileptic patients.  In certain cases, paradoxical effects such as aggressiveness, excitability, nervousness, hostility, anxiety, sleep disturbances, nightmares, vivid dreams, irritability, agitation, psychotic disorders and activation of new types of seizures may be precipitated.  If these occur, the benefit of continuing the drug should be weighed against the adverse effect.  The addition to the regimen of another suitable drug may be necessary or, in some cases, it may be advisable to discontinue Rivotril therapy.

 

Although Rivotril has been given uneventfully to patients with porphyria, rarely it may induce convulsions in these patients.

 

An increased risk of falls and fractures has been recorded in elderly benzodiazepine users.

 

5.1       Pharmacodynamic properties

 

Pharmacotherapeutic group: Benzodiazepine derivatives, ATC code: N03AE01

[…]

 

5.2       Pharmacokinetic properties

 

[…]

 

Within 4 - 10 days 50 - 70% of the total radioactivity of a radiolabeled oral dose of clonazepam is excreted in the urine and 10 - 30% in the faeces, almost exclusively in the form of free or conjugated metabolites.  Less than 0.5% appears as unchanged clonazepam in the urine.

 

Elimination

The elimination half-life is between 20 and 60 hours (mean 30 hours).

 

Within 4 - 10 days 50 - 70% of the total radioactivity of a radiolabeled oral dose of clonazepam is excreted in the urine and 10 - 30% in the faeces, almost exclusively in the form of free or conjugated metabolites.  Less than 0.5% appears as unchanged clonazepam in the urine.

[…]

 

6.6       Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

No special requirements.

 

Any unused product or waste material should be disposed of in accordance       with local requirements.

 

 

Updated on 1 April 2011 PIL

Reasons for updating

  • Change to side-effects

Updated on 4 December 2009 SmPC

Reasons for updating

  • Correction of spelling/typing errors

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typographical error corrected

Updated on 23 September 2009 PIL

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  • Change due to user-testing of patient information

Updated on 23 February 2009 SmPC

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  • Change to section 4.4 - Special warnings and precautions for use

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4.4       Special warnings and precautions for use

 

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications.  A meta-analysis of randomized placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.  The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for clonazepam.

 

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.  Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

 

Patients with a history of depression and/or suicide attempts should be kept under close supervision.

Patients with a history of depression and/or suicide attempts should be kept under close supervision.

 

Updated on 26 June 2008 SmPC

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  • Change to section 6.3 - Shelf life

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Change of shelf life 2mg: was 60months, now 3 years

Updated on 27 May 2008 PIL

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  • Change to packaging

Updated on 23 November 2007 PIL

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  • Improved electronic presentation

Updated on 23 November 2007 SmPC

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  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.9 - Overdose
  • Change to section 5.3 - Preclinical safety data

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4.5       Interaction with other medicinal products and other forms of interaction

The antiepileptic drugs phenytoin, phenobarbital, carbamazepine and valproate may induce the metabolism of clonazepam causing higher clearance and lower plasma concentrations of the latter during combined treatment.

 

The selective serotonin reuptake inhibitors sertraline and fluoxetine do not affect the pharmacokinetics of clonazepam when administered concomitantly.

 

In concurrent treatment with phenytoin or primidone, a change, usually a rise in the serum concentration of these two substances has occasionally been observed.

 

4.9       Overdose

Coma, hypotension and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone Overdose of Rivotril is seldom life-threatening if the drug is taken alone, but may lead to coma, areflexia, apnoea, hypotension and cardiorespiratory depression.

 

1.      Supportive measures as indicated by the patient’s clinical state.   In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects.

 

5.3       Preclinical safety data

 

In preclinical murine studies there was at least a two fold increase in teratogenic birth defects at dose levels of 3, 9 and 18 times the human therapeutic dose compared to the controls.

Carcinogenicity

No 2-year carcinogenicity studies have been conducted with clonazepam.  However, in an 18-month chronic study in rats no treatment-related histopathological changes were seen up to the highest tested dose of 300mg/kg/day.

 

Mutagenicity

Genotoxicity tests using bacterial systems with in vitro or host mediated metabolic activation did not indicate a genotoxic liability for clonazepam.

 

Impairment of Fertility

Studies assessing fertility and general reproductive performance in rats showed a reduced pregnancy rate and impaired pup survival at doses of 10 and 100mg/kg/day.

 

 

Teratogenicity

No adverse maternal or embryo-foetal effects were observed in either mice or rats following administration of oral clonazepam during organogenesis, at doses of up to 20 or 40mg/kg/day, respectively.

 

In several rabbit studies following doses of clonazepam of up to 20mg/kg/day, a low, non-dose-related incidence of a similar pattern of malformations (cleft palate, open eyelids, fused sternebrae and limb defects) was observed (see section 4.6 Pregnancy and Lactation).

 

Updated on 31 May 2007 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

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2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Rivotril Tablets 0.5mg:

Tablets containing clonazepam 500 micrograms.Each tablet contains 500 micrograms clonazepam.

 

Excipients: Also contains 40mg lactose monohydrate

 

Rivotril Tablets 2mg:

Tablets containing clonazepam 2mg.Each tablet contains 2mg clonazepam.

 

Excipients: Also contains 121.5mg lactose anhydrous.

 

For a full list of excipients, see section 6.1

 

3.         PHARMACEUTICAL FORM

 

The tablets can be broken into equal halves or quarters to facilitate dosing

 

4.4       Special warnings and precautions for use

 

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

 

4.8       Undesirable effects

 

An increased risk of falls and fractures has been recorded in elderly benzodiazepine users.

 

4.9       Overdose

 

As with other benzodiazepine drugs, overdosage should not present undue problems of management or threat to life.  Patients have recovered from overdoses in excess of 60mg without special treatment. Severe somnolence with muscle hypotonia will be present.  Treatment is symptomatic and may include the need to maintain an airway.  Gastric lavage may be useful if performed soon after ingestion.

 

 

Symptoms

The symptoms of overdosage or intoxication vary greatly from person to person depending on age, bodyweight and individual response.  They range from drowsiness and light-headedness to ataxia, somnolence and stupor, and finally to coma with respiratory depression and circulatory collapse.  Serious sequelae are rare unless other drugs or alcohol have been taken concomitantly.Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus.  Coma, hypotension and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone.  Coma usually lasts only a few hours but in elderly people it may be more protracted and cyclical.  Benzodiazepine respiratory depressant effects are more serious in patients with severe chronic obstructive airways disease.

 

Benzodiazepines potentiate the effects of other central nervous system depressants, including alcohol.

 

Management

In the management of overdose it should be borne in mind, that multiple agents may have been taken. In addition to monitoring of respiration, pulse rate and blood pressure, IV fluid replacement with general supportive measures is indicated.  Hypotension may be treated with sympathomimetic agents.

 

The value of dialysis has not been determined.

 

1.      Maintain a clear airway and adequate ventilation if indicated.

2.      The benefit of gastric decontamination is uncertain.  Consider activated charcoal (50g for an adult, 10-15g for a child) in adults or children who have taken more than 0.4mg/kg within 1 hour, provided they are not too drowsy.

3.      Gastric lavage is unnecessary if these drugs have been taken alone.

4.      Patients who are asymptomatic at 4 hours are unlikely to develop symptoms

5.      Supportive measures as indicated by the patient’s clinical state.

6.      Flumazenil (Anexate), a benzodiazepine antagonist is available but should rarely be required.  It has a short half-life (about an hour).  Flumazenil is NOT TO BE USED IN MIXED OVERDOSE OR AS A “DIAGNOSTIC TEST” (see separate prescribing information).

 

Overdosage in non-epileptic patients may be treated with flumazenil, a specific IV antidote for use in emergency situations.  Patients requiring such intervention should be monitored closely in hospital (see separate prescribing information).

 

9.6.6    Instructions for use and handlingSpecial precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

9.         date of first authorisation/renewal of authorisation

 

Date of first authorization:          1 April 1977/

 

Date of last renewal:                 1 April 20022007

 

            10.        DATE OF REVISION OF THE TEXT

 

September 2005March 2007

 

           

 

Updated on 31 May 2007 PIL

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 4 September 2006 PIL

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  • Change to marketing authorisation holder

Updated on 10 October 2005 SmPC

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  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 12 September 2005 PIL

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  • New PIL for medicines.ie

Updated on 18 May 2005 SmPC

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  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 6.1 - List of excipients
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may not be renewed (A)

Updated on 17 June 2003 SmPC

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  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may not be renewed (A)