Clonazepam oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of clonazepam.
Drugs List
Therapeutic Indications
Uses
Treatment of all forms of epilepsy
Treatment of myoclonus and associated abnormal movements
All clinical forms of epileptic disease and seizures in infants, children and adults, especially absence seizures (petit mal) including atypical absence; primary or secondarily generalised tonic-clonic (grand mal), tonic or clonic seizures; partial (focal) seizures with elementary or complex symptomatology; various forms of myoclonic seizures, myoclonus and associated abnormal movements.
Dosage
Treatment should be started at the lowest possible dose. The dose may then be increased progressively until a suitable maintenance dose for the patient has been found. The maintenance dose must be determined according to clinical response and tolerance.
The daily dose should be divided in to 3 or 4 equal doses, if doses are not equally divided, the largest dose should be administered before retiring. Once the maintenance dose has been reached, it may be given as a single dose in the evening.
Adults
Initial dosage should not exceed 1mg/day administered at night. This can then be increased over 2 to 4 weeks to the usual maintenance dose which normally falls within the range 4 to 8mg daily in divided doses.
If necessary larger doses of up to 20mg per day in divided doses may be administered at the discretion of the physician.
Elderly
It is recommended that the initial dosage of clonazepam should not exceed 0.5mg per day, as the elderly are particularly sensitive to the effects of centrally depressant drugs and may experience confusion.
This can then be increased over 2 to 4 weeks to the usual maintenance dose which normally falls within the range 4 to 8mg daily in divided doses.
If necessary larger doses of up to 20mg per day in divided doses may be administered at the discretion of the physician.
Children
Children 12 to 18 years
(See Dosage; Adult)
Children 5 to 12 years
Initially 500micrograms at night for 4 nights, increased over 2 to 4 weeks to usual maintenance dose of 3 to 6mg at night (may be given in 3 divided doses if necessary)
Children 1 to 5 years
Initially 250micrograms at night for 4 nights, increased over 2 to 4 weeks to usual maintenance dose of 1 to 3mg at night (may be given in 3 divided doses if necessary)
Children 1 month to 1 year
Initially 250micrograms at night for 4 nights, increased over 2 to 4 weeks to usual maintenance dose of 500micrograms to 1mg at night (may be given in 3 divided doses if necessary)
In some forms of childhood epilepsy, certain patients may cease to be adequately controlled by clonazepam. Control may be re-established by increasing the dose, or interrupting treatment with clonazepam for 2 or 3 weeks. During the interruption of therapy, careful observation and other drugs may be needed.
Additional Dosage Information
If status epilepticus occurs in a patient receiving oral clonazepam, intravenous clonazepam may still control the seizures.
Before adding clonazepam to an existing anticonvulsant regimen, it should be considered that the use of multiple anticonvulsants may result in an increase of undesired effects.
Combinations of more than one antiepileptic drug is a common practice in the treatment of epilepsy. The dosage of each drug may require adjustment in order to obtain the optimum effect.
Contraindications
Drug intoxication
Acute respiratory impairment
Coma
Myasthenia gravis
Severe hepatic impairment
Severe respiratory depression
Sleep apnoea
Precautions and Warnings
Debilitation
Elderly
Suicidal ideation
Brain damage
Breastfeeding
Cerebellar ataxia
Chronic respiratory impairment
Depression
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatic cirrhosis
History of alcohol abuse
History of drug misuse
Lactose intolerance
Mild hepatic impairment
Porphyria
Pregnancy
Pulmonary disease
Renal impairment
Spinal ataxia
Patients at risk of suicide should be closely supervised
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
Consider prescribing by manufacturer to ensure seizure control maintenance
Folic acid 5mg daily required pre-conception to end of 1st trimester
Some formulations contain lactose
Some formulations may contain alcohol
A patent airway and adequate oxygenation must be maintained
Monitor for signs of suicide ideation or behaviour
Amnesia may occur
May cause dependence
Psychological adjustment may be impaired in loss or bereavement
Abrupt withdrawal may precipitate status epilepticus
Avoid abrupt withdrawal
Reduce dose in elderly
Start treatment at lowest recommended dose
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Alcohol may enhance side effects
Advise patient/carers to report signs of suicide ideation or behaviour
Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour; available data suggest that the increased risk applies to all antiepileptics and is seen as early as one week after starting treatment.
The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.
Prolonged use may result in dependence development and withdrawal symptoms on cessation of use.
Avoid abrupt withdrawal, as this may precipitate status epilepticus. This also applies to withdrawing another drug while the patient is still receiving clonazepam therapy.
A patent airway and adequate oxygenation must be maintained, especially in infants and small children where clonazepam may cause an increase in saliva and bronchial secretion.
The dosage of clonazepam must be titrated to individual requirements in patients with pre-existing disease of the respiratory system (e.g. COPD) or liver and in patients undergoing treatment with other centrally acting medications or anticonvulsant (antiepileptic) agents.
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. This effect can be avoided by careful adjustment of the dose to individual requirements.
Pregnancy and Lactation
Pregnancy
Use clonazepam with caution during pregnancy.
The manufacturer recommends that clonazepam should only be administered during pregnancy if the potential benefits outweigh the risks. Preclinical studies in animals have shown reproductive toxicity. From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens.
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 suckling in the neonate. Schaefer (2015) concludes that low doses of clonazepam are permitted, even during the first trimester. Exposure to benzodiazepines is not an indication for termination, but abuse or long term treatment with high doses during organogenesis should warrant a detailed foetal anatomical ultrasound examination. If exposure occurs during later pregnancy, observation of foetal motor patterns should be performed by ultrasound.
Infants born to mothers who took benzodiazepines chronically during the later stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the post-natal period. This is particularly likely following long-term treatment, particularly in the third trimester. The neonate should be observed closely for neonatal respiratory depression during the first days of life, especially following administration of high doses shortly before or during delivery.
Adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of inadequate seizure control may be more detrimental to the foetus than the use of antiepileptic drugs. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.
Lactation
Use clonazepam with caution during breastfeeding.
The manufacturer does not recommend using clonazepam during breastfeeding. Clonazepam is excreted into maternal milk in small amounts. LactMed (2021) states that if clonazepam is required, it is not a reason to discontinue breastfeeding, but notes that the infant should be monitored for drowsiness, adequate weight gain and developmental milestones, especially in younger, exclusively breastfed infants. If excessive sedation occurs, the infant's serum concentration should be monitored.
Schaefer (2015) concludes that antiepileptic therapy with clonazepam should be critically evaluated on an individual basis, and the infant observed for weak suck, vomiting and tiredness. If there is a suspicion of side effects, the infant's serum concentration should be determined. Consider adding formula in order to reduce the drug transfer via the mother's milk or wean the baby. Anticonvulsive combination therapy with clonazepam is not compatible with breastfeeding.
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving. When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them. It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1.The medicine has been prescribed to treat a medical or dental problem and 2.The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine and 3.The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk
Counselling
Patients should be advised to avoid driving, operating machinery and hazardous activities altogether, or at least for the first few days of treatment, as clonazepam may slow reactions. This effect is aggravated by alcohol.
Patients should be advised that any changes in dosage or in the timing of administration may alter their reactions.
Warn patients that they should not drink alcohol while receiving treatment as alcohol can provoke epileptic seizures, modify the effect of clonazepam, compromise the effect of the treatment or give rise to unpredictable side-effects.
Patients should be advised to consult their physician if they are planning a pregnancy, and consider taking folic acid 5mg daily before conception, and continue throughout the first trimester.
Patients and caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour, and the need to seek medical advice immediately if they present.
Advise patient not to use products containing St John's Wort with clonazepam.
Side Effects
Activation of new seizure types
Agitation
Allergic reaction
Altered liver function tests
Anaphylaxis
Angioedema
Anterograde amnesia
Anxiety
Apnoea
Ataxia
Behavioural disturbances
Blood dyscrasias
Bronchial hypersecretion (children)
Cardiac arrest
Cardiac failure
Changes in libido
Confusion
Convulsions
Delayed reactions
Dependence
Depression
Diplopia
Disorientation
Dizziness
Drooling
Drowsiness
Dysarthria
Erectile dysfunction
Excitability
Falls
Fatigue
Fractures
Gastro-intestinal symptoms
Hair loss (transient)
Headache
Hypersalivation (children)
Hypotension
Impaired co-ordination
Impaired concentration
Impotence
Incomplete precocious puberty
Increased hostility and aggression (paradoxical)
Irritability
Light-headedness
Muscle hypotonia
Muscle weakness
Nausea
Nervousness
Nightmares
Nystagmus
Pruritus
Psychiatric disorders
Rash
Reduced platelet count
Respiratory depression
Restlessness
Seizure frequency increased
Skin pigmentation changes
Sleep disturbances
Somnolence
Suicidal ideation
Urinary incontinence
Urinary retention
Urticaria
Visual disturbances
Vivid dreams
Withdrawal symptoms
Withdrawal Symptoms and Signs
Abrupt termination of treatment will lead to withdrawal symptoms. During long term treatment, withdrawal symptoms may occur, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued. Withdrawal symptoms include:
tremor
sweating
agitation
sleep disturbances
anxiety
headache
muscle pain
tension
restlessness
confusion
irritability
epileptic seizures
In severe cases the following may occur:
derealisation
depersonalisation
hyperacusis
numbness and tingling of the extremities
hypersensitivity to light, noise or physical contact
hallucinations
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: August 2014
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Summary of Product Characteristics: Clonazepam 1mg tablets. Neuraxpharm UK Ltd. Revised February 2022.
Summary of Product Characteristics: Rivotril Tablets. Roche Products Ltd. Revised January 2013.
Clinical Knowledge Summaries - Pre-conception - advice and management - Management
How do I manage women who are taking AEDs who are pregnant or planning pregnancy?
Available at: https://cks.nice.org.uk/epilepsy#!scenariorecommendation:8
Last accessed: July 21, 2014
Clinical Knowledge Summaries - Epilepsy - Management
Scenario: Epilepsy - pregnancy planning
Available at: https://cks.nice.org.uk/epilepsy#!scenariorecommendation:8
Last accessed: July 21, 2014
Clinical Knowledge Summaries - Epilepsy - Management
Risks to the fetus from antiepileptic drugs
Available at: https://cks.nice.org.uk/epilepsy#!scenarioclarification:3
Last accessed: July 21, 2014
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015
MHRA Drug Safety Update Vol 2, Issue 1, August 2008
Antiepileptics: risk of suicidal thoughts and behaviour
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON023078
Last accessed: July 21, 2014
NICE clinical guideline 20 - The epilepsies, October 2008
Available at: www.nice.org.uk/nicemedia/pdf/CG020NICEguideline.pdf
Last accessed: July 21, 2014
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 June 2022
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Clonazepam. Last revised: 16 August 2021
Last accessed: 21 June 2022
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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