Lonazem Tablets 0.5mg - 1mg - 2mg
Seizure Disorders,Panic Disorder
Composition
Each tablet contains: (0.5 mg – 1mg – 2 mg) of clonazepam
Excipients: corn starch, lactose anhydrous, magnesium stearate and microcrystalline Cellulose.
Colorants: 0.5 mg ‐ D&C yellow No. 10 aluminum lake.
1 mg ‐ FD&C blue No. 1 aluminum lake.
Usage
Indications:
Seizure Disorders: Clonazepam is useful alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic and myoclonic seizures. In patients with absence seizures (petit mal) who have failed to respond to succinimides, Clonazepam may be useful. In some studies, up to 30% of patients have shown a loss of anticonvulsant activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish efficacy.
Panic Disorder:
Clonazepam is indicated for the treatment of panic disorder, with or without agoraphobia. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the consequences of the attacks, and/or a significant change in behavior related to the attacks. The effectiveness of Clonazepam in long-term use for more than 9 weeks has not been studied in controlled clinical trials. The physician who elects to use Clonazepam, for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Contraindications:
Clonazepam is contraindicated in patients with the following conditions:
• History of sensitivity to benzodiazepines
• Clinical or biochemical evidence of significant liver disease
• Acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy).
Pregnancy:
Category D, Teratogenic Effects
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Clonazepam.
Pregnancy Risks: Data from several sources raise concerns about the use of Clonazepam during pregnancy.
General Concerns about Anticonvulsants: Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life.
General Concerns about Benzodiazepines: An increased risk of congenital malformations associated with the use of benzodiazepine drugs has been suggested in several studies. There have been reports of neonatal flaccidity, respiratory and feeding difficulties, and hypothermia in children born to mothers who have been receiving benzodiazepines late in pregnancy.
In general, the use of Clonazepam in women of childbearing potential, and more specifically during known pregnancy, should be considered only when the clinical situation warrants the risk to the fetus.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Lactation:
Patients should be advised not to breastfeed an infant if they are taking Clonazepam.
Pediatric Use:
Because of the possibility that adverse effects on physical or mental development could become apparent only after many years, a benefit-risk consideration of the long-term use of Clonazepam is important in pediatric patients being treated for seizure disorder
Geriatric Use:
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Because Clonazepam undergoes hepatic metabolism, it is possible that liver disease will impair Clonazepam elimination. Metabolites of Clonazepam are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function.
Side Effects
Adverse Reactions:
The most frequently occurring side effects of Clonazepam are referable to CNS depression.
Others side effects are: drowsiness, ataxia, behavior problems, Palpitations, Hair loss, hirsutism, skin rash, ankle and facial edema, Anorexia, coated tongue, constipation, diarrhea, dry mouth, encopresis, gastritis, increased appetite, nausea, sore gums, Dysuria, enuresis, nocturia, urinary retention, Anemia, leukopenia, thrombocytopenia, eosinophilia, Hepatomegaly, transient elevations of serum transaminases and alkaline phosphatase, Muscle weakness, pains, Dehydration, general deterioration, fever, lymphadenopathy, weight loss or gain, Abnormal eye movements, aphonia, choreiform movements, coma, diplopia, dysarthria, dysdiadochokinesis, “glassy-eyed” appearance, headache, hemiparesis, hypotonia, nystagmus, respiratory depression, slurred speech, tremor, vertigo, Confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis (the behavior effects are more likely to occur in patients with a history of psychiatric disturbances). The following paradoxical reactions have been observed: (excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams), Chest congestion, rhinorrhea, shortness of breath, hypersecretion in upper respiratory passages, Somnolence, Intellectual Ability Reduced, Emotional Lability, Libido Decreased, Sinusitis, Rhinitis, Upper Respiratory Tract Infection, Coughing, Pharyngitis, Bronchitis, Myalgia, Influenza, Urinary Tract Infection, Blurred Vision, Dysmenorrhea, Colpitis, Ejaculation Delayed, Impotence.
| Properties | Mechanism of action: The precise mechanism by which Clonazepam exerts its anti-seizure and anti-panic effects is unknown, although it is believed to be related to its ability to enhance the activity of gamma amino butyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Clonazepam is capable of decreasing the frequency, amplitude, duration and spread of discharge in minor motor seizures. PharmacokineticsClonazepam is rapidly and completely absorbed after oral administration. The absolute bioavailability of Clonazepam is about 90%. Maximum plasma concentrations of Clonazepam are reached within 1 to 4 hours after oral administration. Clonazepam is approximately 85% bound to plasma proteins. Clonazepam is highly metabolized, with less than 2% unchanged Clonazepam being excreted in the urine. The elimination half-life of Clonazepam is typically 30 to 40 hours. |
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| Dosage |
Dosage and Administration:
1. Seizure Disorders:
Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 mg to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg. The use of multiple anticonvulsants may result in an increase of depressant adverse effects. This should be considered before adding Clonazepam to an existing anticonvulsant regimen.
Pediatric Patients: In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 mg/kg/day and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses. Dosage should be increased by no more than 0.25 mg to 0.5 mg every three days until a daily maintenance dose of 0.1 mg/kg to 0.2 mg/kg of body weight has been reached, unless seizures are controlled or side effects preclude further increase. Whenever possible, the daily dose should be divided into three equal doses. If doses are not equally divided, the largest dose should be given before retiring.
2. Panic Disorder:
Adults: The initial dose for adults with panic disorder is 0.25 mg bid. An increase to the target dose for most patients of 1 mg/day may be made after 3 days. Higher doses of 2 mg/day, 3 mg/day and 4 mg/day were less effective than the 1 mg/day dose and were associated with more adverse effects. Nevertheless, it is possible that some individual patients may benefit from doses of up to a maximum dose of 4 mg/day, and in those instances, the dose may be increased in increments of 0.125 mg to 0.25 mg bid every 3 days until panic disorder is controlled or until side effects make further increases undesired. To reduce the inconvenience of somnolence, administration of one dose at bedtime may be desirable. Treatment should be discontinued gradually, with a decrease of 0.125 mg bid every 3 days, until the drug is completely withdrawn.
Pediatric Patients: There is no clinical trial experience with Clonazepam in panic disorder patients under 18 years of age.
3. Geriatric Patients: There is no clinical trial experience with Clonazepam in seizure
disorder and panic disorder patients 65 years of age and older. In general, elderly patients should be started on low doses of Clonazepam and observed closely.
Overdosage:
Symptoms of Clonazepam overdosage, like those produced by other CNS depressants, include somnolence, confusion, coma and diminished reflexes.
Treatment includes monitoring of respiration, pulse and blood pressure, general supportive measures and immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of levarterenol or metaraminol. Dialysis is of no known value.
Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected.
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| Drug interactions |
Drug Interactions:
Effect of Concomitant use of Benzodiazepines and Opioids: Concomitant use of benzodiazepines, including Clonazepam, and opioids may result in profound sedation, respiratory depression, coma, and death, because of actions at different receptor sites in the CNS that control respiration. Because of these risks, concomitant prescribing of benzodiazepines and opioids should be reserved for use in patients for whom alternative treatment options are inadequate. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.. If a decision is made to prescribe Clonazepam concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation.
Effect of Other Drugs on the Pharmacokinetics of Clonazepam:
Reports suggest that ranitidine does not greatly alter Clonazepam pharmacokinetics.
Cytochrome P-450 inducers, such as phenytoin, carbamazepine and phenobarbital, induce Clonazepam metabolism, causing an approximately 30% decrease in plasma Clonazepam levels.
Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in Clonazepam metabolism, inhibitors of this enzyme notably oral antifungal agent should be used cautiously in patients receiving Clonazepam.
Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants, and by other anticonvulsant drugs.
Alcohol: Patients should be advised to avoid alcohol while taking Clonazepam.
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| precautions and precautions |
Contraindications:
Clonazepam is contraindicated in patients with the following conditions:
• History of sensitivity to benzodiazepines
• Clinical or biochemical evidence of significant liver disease
• Acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy).
Warnings:
Interference with Cognitive and Motor Performance: Since Clonazepam produces CNS depression, patients receiving this drug should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating machinery or driving.
Suicidal Behavior and Ideation: Anti-epileptic drugs (AEDs); including Clonazepam, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment.
Withdrawal Symptoms: Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines.
Precautions:
Worsening of Seizures: When used in patients in whom several different types of seizure disorders coexist, Clonazepam may increases the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Clonazepam may produce absence status.
Laboratory Testing During Long-Term Therapy: Periodic blood counts and liver function tests are advisable during long-term therapy with Clonazepam
Risks of Abrupt Withdrawal: The abrupt withdrawal of Clonazepam, particularly in those patients on long-term, high-dose therapy, may precipitate status epilepticus. Therefore, when discontinuing Clonazepam, gradual withdrawal is essential. While Clonazepam is being gradually withdrawn, the simultaneous substitution of another anticonvulsant may be indicated.
aution in renally Impaired Patients: Metabolites of Clonazepam are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function.
Chypersalivation: Clonazepam may produce an increase in salivation. This should be considered before giving the drug to patients who have difficulty handling secretions.
Respiratory Compromise: Clonazepam should be used with caution in patients with compromised respiratory function.
Porphyria: Clonazepam may have a porphyrogenic effect and should be used with care in patients with porphyria.
Information for Patients:
Patients should be instructed to take Clonazepam only as prescribed.
Physicians are advised to discuss the following issues with patients for whom they prescribe Clonazepam
Dose Changes: To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.
Concomitant Medication: Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.
Drug Abuse and Dependence:
Clonazepam is a Schedule IV controlled substance.
Withdrawal symptoms, similar to those noted with barbiturates and alcohol (e.g., convulsions, psychosis, hallucinations, behavioral disorder, tremor, abdominal and muscle cramps) have occurred following abrupt discontinuance of Clonazepam. The more severe withdrawal symptoms have usually been limited to patients who received excessive doses over an extended period of time. Consequently, after extended therapy, abrupt discontinuation should be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving Clonazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.
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| Package |
Storage conditions: Keep below 25 °C, protect from light and moisture.
How supplied: a carton box contains 20 tablets .
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