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  • Rivotril
    / Roche


    Active Ingredient
    Clonazepam 2.5 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Oral Drops

    10 ml

    full basket chart 1909 18075

    Related information


    Dosage

    Standard dosage in Epilepsy: The dosage of Rivotril must be individually adjusted according to the patient’s clinical response, tolerance of the drug and the patient’s age. As a general rule, Rivotril is given as low-dose, single-drug therapy in new, non-therapy-resistant cases.
    A single oral dose of Rivotril begins to take effect within 30-60 minutes and remains effective for 6-8 hours in children and 8-12 hours in adults.
    Oral treatment: To avoid adverse reactions at the beginning of therapy, it is essential to start treatment with Rivotril at a low dose and increase the daily dose progressively until the maintenance dose suited to the individual patient has been reached. The initial dose for infants and children up to the age of 10 years (or up to 30 kg bodyweight) is 0.01-0.03 mg/kg daily given in 2-3 divided doses. The dose should be increased by no more than 0.25-0.5 mg every third day until either a daily maintenance dose of approximately 0.1 mg/kg of bodyweight daily has been reached or seizures are controlled or undesired effects preclude further increase. The daily maximum dose in children is 0.2 mg/kg of bodyweight and should not be exceeded. Rivotril should be given with a spoon and may be mixed with water, tea or fruit juice.
    Based on established dosages for children up to 10 years (see above) and those for adults (see below) the following can be recommended for children between 10 and 16 years: The initial dose is 1-1.5 mg/day given in 2-3 divided doses. The dose may be increased by 0.25-0.5 mg every third day until the individual maintenance dose (usually 3-6 mg/day) is reached. The initial dose for adults should not exceed 1.5 mg/day divided into 3 doses. The dose may be increased in increments of 0.5 mg every three days until either seizures are adequately controlled or undesired effects preclude any further increase. The maintenance dose must be individualized for each patient depending upon response. Usually a maintenance dose of 3-6 mg per day is sufficient. The maximum therapeutic dose for adults is 20 mg daily and should not be exceeded. The daily dose should be divided into 3 equal doses. If doses are not equally divided, the largest dose should be given before retiring. The maintenance dose level is best attained after 1-3 weeks of treatment. Once the maintenance dose level has been reached, the daily amount may be given in a single dose in the evening. Before adding Rivotril to an existing anticonvulsant regimen, it should be considered that the use of multiple anticonvulsants may result in an increase of undesired effects.
    Dosage in Panic Disorder
    Adults: The initial dose for adults with Panic Disorder is 0.25 mg twice daily (0.5 mg/day). An increase to 0.5 mg twice daily (1 mg/day) may be made after 3 days. Subsequent up-titration should be made at intervals of 3 days until Panic Disorder is controlled or until limited by side effects. The usual maintenance dose is 1 mg twice daily (2 mg/day). A maximum dose of 2 mg twice daily (4 mg/day) may be prescribed in exceptional cases. Once a stable dose is achieved, patients may switch to a once daily dose, usually taken at bedtime.
    There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it. Therefore, the physician who elects to use clonazepam for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. Treatment should be discontinued gradually, with down-titration of 0.25 mg every 3 days, until the drug is completely withdrawn.
    For full details see prescribing information.


    Indications

    Epilepsy, panic disorder.


    Contra-Indications

    Rivotril must not be used in patients with known hypersensitivity to benzodiazepines or any of the drug’s excipients or those with severe respiratory insufficiency or severe hepatic insufficiency. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.


    Special Precautions

    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) or with impairment of renal function. Concomitant use of alcohol / CNS depressants.
    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.
    Medical history of alcohol or drug abuse.
    Rivotril should be used with extreme caution in patients with a history of alcohol or drug abuse.
    For warnings related to the use in infants and small children see Pediatric Use.
    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
    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).
    Anticonvulsant drugs including Rivotril should not be discontinued abruptly in epileptic patients as this may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction or discontinuation arises, this should be done gradually.
    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.
    Porphyria: In patients with porphyria, clonazepam has to be used with care because it may have a porphyrogenic effect.
    For full details see prescribing information.


    Side Effects

    The adverse experiences for this product are provided separately for patients with seizure disorders and with panic disorder.
    Panic Disorder: Data from 3 placebo-controlled clinical trials including 477 patients on active treatment in total are presented in the table below. Adverse Events occurring in ≥ 5% of patients in at least one of the Active Treatment Groups are included. Table 1 Adverse Events Occurring in ≥ 5% of Patients in at least one of the Active Treatment Groups.
    For full details see prescribing information.


    Drug interactions

    Rivotril can be administered concurrently with one or more antiepileptic agents. But adding an extra drug to the patient’s regimen should involve a careful evaluation of the response to the treatment, because unwanted effects, such as sedation and apathy are more likely to occur. In such cases, the dosage of each drug must be adjusted to achieve the optimum desired effect.
    Pharmacokinetic Drug-Drug Interactions (DDI): The antiepileptic drugs phenytoin, phenobarbital, carbamazepine, and valproate may increase the clearance of clonazepam thereby decreasing the plasma concentrations of the latter during combined treatment.
    Clonazepam itself does not induce the enzymes responsible for its own metabolism. The selective serotonine reuptake inhibitors sertraline and fluoxetine do not affect the pharmacokinetics of clonazepam when administered concomitantly.
    Pharmacodynamic Drug-Drug Interactions (DDI):The combination of clonazepam with valproic acid may occasionally cause petit mal status epilepticus.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.
    Enhanced effects on sedation, respiration and hemodynamics may occur when Rivotril is co-administered with any centrally acting depressants including alcohol.
    Alcohol should be avoided in patients receiving Rivotril.
    See Overdose for warning of other central nervous system depressants, including alcohol.
    In combination therapy with centrally-acting medications, the dosage of each drug must be adjusted to achieve the optimum effect.


    Pregnancy and Lactation

    Pregnancy Labor & Drlivery: From preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations. 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. Under these circumstances, the drug should only be administered to pregnant women if the potential benefits outweigh the risk to the fetus.During pregnancy, Rivotril may be administered only if there is a compelling indication. Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heartbeat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feeding in the neonate. 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. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy.
    Nursing Mothers: Although the 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. If there is a compelling indication for Rivotril, breastfeeding should be discontinued.
    Pediatric Use: 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.


    Overdose

    Symptoms: 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 areflexia, apnea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.
    Treatment: Monitor the patient’s vital signs and institute 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. 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. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. 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.
    The benzodiazepine antagonist Anexate: (active ingredient: flumazenil) is not indicated in patients with epilepsy who have been treated with benzodiazepines. Antagonism of the benzodiazepine effect in such patients may provoke seizures.


    Manufacturer
    Roche S.P.A., Italy
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