Clonazepam 0.25 MG Disintegrating Oral Tablet
Generic Name: CLONAZEPAM
Brand Name: Clonazepam
- Substance Name(s):
- CLONAZEPAM
WARNINGS
Risks from Concomitant Use With Opioids: Concomitant use of benzodiazepines, including clonazepam orally disintegrating tablets, and opioids may result in profound sedation, respiratory depression, coma, and death.
Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone.
If a decision is made to prescribe clonazepam orally disintegrating tablets 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.
Advise both patients and caregivers about the risks of respiratory depression and sedation when clonazepam orally disintegrating tablet is used with opioids (see PRECAUTIONS; Information for Patients and PRECAUTIONS: Drug Interactions ).
Abuse, Misuse, and Addiction: The use of benzodiazepines, including clonazepam orally disintegrating tablets, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death.
Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see DRUG ABUSE AND DEPENDENCE: Abuse ) .
Before prescribing clonazepam orally disintegrating tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).
Use of clonazepam orally disintegrating tablets, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clonazepam orally disintegrating tablets along with monitoring for signs and symptoms of abuse, misuse, and addiction.
Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.
If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.
Dependence and Withdrawal Reactions: To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clonazepam orally disintegrating tablets or reduce the dosage (a patient-specific plan should be used to taper the dose) (see DOSAGE AND ADMINISTRATION : Discontinuation or Dosage Reduction of CLONAZEPAM ORALLY DISINTEGRATING TABLETS ) .
Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.
Acute Withdrawal Reactions The continued use of benzodiazepines, including clonazepam orally disintegrating tablets, may lead to clinically significant physical dependence.
Abrupt discontinuation or rapid dosage reduction of clonazepam orally disintegrating tablets after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see DRUG ABUSE AND DEPENDENCE: Dependence ) .
Protracted Withdrawal Syndrome In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see DRUG ABUSE AND DEPENDENCE : Dependence ).
Interference With Cognitive and Motor Performance: Since clonazepam orally disintegrating tablets produces CNS depression, patients receiving this drug should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating machinery or driving a motor vehicle.
They should also be warned about the concomitant use of alcohol or other CNS-depressant drugs during clonazepam orally disintegrating tablets therapy [see PRECAUTIONS, Drug Interactions and Information for Patients ].
Suicidal Behavior and Ideation : Antiepileptic drugs (AEDs),including clonazepam orally disintegrating tablets, 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.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo.
In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43% compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated.
There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
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 assessed.
Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.
The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication.
The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.
Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
Table 1: Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1000 Patients Drug Patients with Events Per 1000 Patients Relative Risk: Incidence of Events in Drug Patients/ Incidence In Placebo Patients Risk Difference: Additional Drug Patients with Events per 1000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing clonazepam orally disintegrating tablets or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness.
Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior.
Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers.
Neonatal Sedation and Withdrawal Syndrome: Use of clonazepam orally disintegrating tablets late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (see PRECAUTIONS: Pregnancy ).
Monitor neonates exposed to clonazepam orally disintegrating tablets during pregnancy or labor for signs of sedation and monitor neonates exposed to clonazepam orally disintegrating tablets during pregnancy for signs of withdrawal; manage these neonates accordingly.
DRUG INTERACTIONS
Drug Interactions: Effect of Concomitant Use of Benzodiazepines and Opioids: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
Benzodiazepines interact at GABA A sites, and opioids interact primarily at mu receptors.
When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation.
Effect of Clonazepam on the Pharmacokinetics of Other Drugs: Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital.
The effect of clonazepam on the metabolism of other drugs has not been investigated.
Effect of Other Drugs on the Pharmacokinetics of Clonazepam: Literature reports suggest that ranitidine, an agent that decreases stomach acidity, does not greatly alter clonazepam pharmacokinetics.
In a study in which the 2 mg clonazepam orally disintegrating tablet was administered with and without propantheline (an anticholinergic agent with multiple effects on the GI tract) to healthy volunteers, the AUC of clonazepam was 10% lower and the C max of clonazepam was 20% lower when the orally disintegrating tablet was given with propantheline compared to when it was given alone.
Fluoxetine does not affect the pharmacokinetics of clonazepam.
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 system, notably oral antifungal agents, should be used cautiously in patients receiving clonazepam.
Pharmacodynamic Interactions: The CNS-depressant action of the benzodiazepine class of 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.
OVERDOSAGE
Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma.
In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia.
Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur.
In severe overdosage cases, patients may develop respiratory depression and coma.
Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see WARNINGS: Abuse, Misuse, and Addiction ).
Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage.
In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance.
Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency.
The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy.
Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus).
If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage.
See the flumazenil injection Prescribing Information.
Consider contacting a poison center (1-800-222-1222) poisoncontrol.org, or a medical toxicologist for additional overdosage management recommendations.
DESCRIPTION
Clonazepam Orally Disintegrating Tablets, USP, a benzodiazepine, is available as an orally disintegrating tablet containing 0.125 mg, 0.25 mg, 0.5 mg, 1 mg or 2 mg clonazepam.
Each orally disintegrating tablet contains aspartame, crospovidone, magnesium stearate, mannitol, silicon dioxide, sorbitol, sodium lauryl sulfate, and talc.
Chemically, clonazepam is 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2 H -1,4-benzodiazepin-2-one.
It is a light yellow crystalline powder.
It has a molecular weight of 315.72 and the following structural formula: This is the structural formula.
HOW SUPPLIED
Clonazepam Orally Disintegrating Tablets USP, 0.125 mg are white, round, flat-faced, beveled edge tablets, debossed with “K5” and is available in a blister package of 60 (6 tablets/blister card, 10 blister cards/carton), NDC 49884-306-02.
Clonazepam Orally Disintegrating Tablets USP, 0.25 mg are white, round, flat-faced, beveled edge tablets, debossed with “K6” and is available in a blister package of 60 (6 tablets/blister card, 10 blister cards/carton), NDC 49884-307-02.
Clonazepam Orally Disintegrating Tablets USP, 0.5 mg are white, round, flat-faced, beveled edge tablets, debossed with “K7” and is available in a blister package of 60 (6 tablets/blister card, 10 blister cards/carton), NDC 49884-308-02.
Clonazepam Orally Disintegrating Tablets USP, 1 mg are white, round, flat-faced, beveled edge tablets, debossed with “K8” and is available in a blister package of 60 (6 tablets/blister card, 10 blister cards/carton), NDC 49884-309-02.
Clonazepam Orally Disintegrating Tablets USP, 2 mg are white, round, flat-faced, beveled edge tablets, debossed with “K9” and is available in a blister package of 60 (6 tablets/blister card, 10 blister cards/carton), NDC 49884-310-02.
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Rx only Dist by: Par Pharmaceutical Cranbury, NJ 08512 U.S.A.
Revised:11/2022 This is 0.125 mg picture of pills.
This is 0.25 mg picture of pills.
This is 0.5 mg picture of pills.
This is 1 mg picture of pills.
This is 2 mg picture of pills.
GERIATRIC USE
Geriatric Use: Clinical studies of clonazepam orally disintegrating tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
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 orally disintegrating tablets elimination.
Metabolites of clonazepam orally disintegrating tablets 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.
Because elderly patients are more likely to have decreased hepatic and/or renal function, care should be taken in dose selection, and it may be useful to assess hepatic and/or renal function at the time of dose selection.
Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of clonazepam orally disintegrating tablets and observed closely.
INDICATIONS AND USAGE
Seizure Disorders: Clonazepam orally disintegrating tablet 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 orally disintegrating tablets 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 orally disintegrating tablet is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-V.
Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks.
The efficacy of clonazepam orally disintegrating tablets was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the DSM-lIlR category of panic disorder (see CLINICAL PHARMACOLOGY : Clinical Trials ).
Panic disorder (DSM-V) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes.
The effectiveness of clonazepam orally disintegrating tablets in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials.
The physician who elects to use clonazepam orally disintegrating tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see DOSAGE AND ADMINISTRATION ).
PEDIATRIC USE
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 orally disintegrating tablet is important in pediatric patients being treated for seizure disorder [see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION ].
Safety and effectiveness in pediatric patients with panic disorder below the age of 18 have not been established.
PREGNANCY
Pregnancy: Pregnancy Exposure Registry: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AED’s, such as clonazepam orally disintegrating tablets, during pregnancy.
Healthcare providers are encouraged to recommend that pregnant patients taking clonazepam orally disintegrating tablets enroll in the NAAED Pregnancy Registry by calling 1-888-233-2334, or online at http://www.aedpregnancyregistry.org/.
Risk Summary Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome , PRECATIONS: Clinical Considerations ).
Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data).
Administration of clonazepam to pregnant rabbits during the period of organogenesis resulted in developmental toxicity, including increased incidences of fetal malformations, at doses similar to or below therapeutic doses in patients (see Animal Data) .
Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses.
The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.
In the U.S.
general population, the estimated risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates.
Monitor neonates exposed to clonazepam orally disintegrating tablets during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems.
Monitor neonates exposed to clonazepam orally disintegrating tablets during pregnancy for signs of withdrawal.
Manage these neonates accordingly (see WARNINGS: Neonatal Sedation and Withdrawal Syndrome ) .
Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects.
Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted.
In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings.
Animal Data In three studies in which clonazepam orally disintegrating tablets was administered orally to pregnant rabbits at doses of 0.2, 1, 5 or 10 mg/kg/day (low dose approximately 0.2 times the maximum recommended human dose of 20 mg/day for seizure disorders and equivalent to the maximum dose of 4 mg/day for panic disorder, on a mg/m 2 basis) during the period of organogenesis, a similar pattern of malformations (cleft palate, open eyelid, fused sternebrae and limb defects) was observed in a low, non-dose-related incidence in exposed litters from all dosage groups.
Reductions in maternal weight gain occurred at dosages of 5 mg/kg/day or greater and reduction in embryo-fetal growth occurred in one study at a dosage of 10 mg/kg/day.
No adverse maternal or embryo-fetal effects were observed in mice and rats following administration during organogenesis of oral doses up to 15 mg/kg/day or 40 mg/kg/day, respectively (4 and 20 times the maximum recommended human dose of 20 mg/day for seizure disorders and 20 and 100 times the maximum dose of 4 mg/day for panic disorder, respectively, on a mg/m 2 basis).
NUSRING MOTHERS
Nursing Mothers: Risk Summary Clonazepam is excreted in human milk.
There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk.
There are no data on the effects of clonazepam on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for clonazepam orally disintegrating tablets and any potential adverse effects on the breastfed infant from clonazepam orally disintegrating tablets or from the underlying maternal condition.
Clinical Considerations Infants exposed to clonazepam through breast milk should be monitored for sedation, poor feeding and poor weight gain.
BOXED WARNING
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation (see WARNINGS and PRECAUTIONS).
The use of benzodiazepines, including clonazepam orally disintegrating tablets, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death.
Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes.
Before prescribing clonazepam orally disintegrating tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see WARNINGS) .
The continued use of benzodiazepines, including clonazepam orally disintegrating tablets, may lead to clinically significant physical dependence.
The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose .
Abrupt discontinuation or rapid dosage reduction of clonazepam orally disintegrating tablets after continued use may precipitate acute withdrawal reactions, which can be life-threatening.
To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clonazepam orally disintegrating tablets or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS) .
INFORMATION FOR PATIENTS
Information for Patients: A clonazepam orally disintegrating tablets Medication Guide must be given to the patient each time clonazepam orally disintegrating tablets is dispensed, as required by law.
Patients should be instructed to take clonazepam orally disintegrating tablets only as prescribed.
Physicians are advised to discuss the following issues with patients for whom they prescribe clonazepam orally disintegrating tablets: Risks from Concomitant Use With Opioids Inform patients and caregivers that potentially fatal additive effects may occur if clonazepam is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider (see WARNINGS: Risks from Concomitant Use With Opioids and PRECAUTIONS: Drug Interactions ).
Abuse, Misuse, and Addiction: Inform patients that the use of clonazepam orally disintegrating tablets, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances .
Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see WARNINGS: Abuse, Misuse, and Addiction and DRUG ABUSE AND DEPENDENCE ) .
Withdrawal Reactions: Inform patients that the continued use of clonazepam orally disintegrating tablets may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of clonazepam orally disintegrating tablets may precipitate acute withdrawal reactions, which can be life-threatening.
Inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.
Instruct patients that discontinuation or dosage reduction of clonazepam orally disintegrating tablets may require a slow taper (see WARNINGS: Dependence and Withdrawal Reaction s and DRUG ABUSE AND DEPENDENCE ) .
Interference With Cognitive and Motor Performance : Because benzodiazepines have the potential to impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that clonazepam orally disintegrating tablets therapy does not affect them adversely.
Suicidal Thinking and Behavior: Patients, their caregivers, and families should be counseled that AEDs, including clonazepam orally disintegrating tablet, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers.
Pregnancy: Advise pregnant females that use of clonazepam orally disintegrating tablets late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see WARNINGS : Neonatal Sedation and Withdrawal Syndrome and PRECAUTIONS: Pregnancy ).
Instruct patients to inform their healthcare provider if they are pregnant or intend to become pregnant.
Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant while taking clonazepam orally disintegrating tablets.
This registry is collecting information about the safety of antiepileptic drugs during pregnancy.
(see PRECAUTIONS: Pregnancy ).
Nursing: Instruct patients to inform their healthcare provider if they are breastfeeding or intend to breastfeed.
Instruct breastfeeding patients who take clonazepam orally disintegrating tablets to monitor their infants for excessive sedation, poor feeding and poor weight gain, and to seek medical attention if they notice these signs (see PRECAUTIONS: Nursing Mothers ).
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.
Alcohol: Patients should be advised to avoid alcohol while taking clonazepam orally disintegrating tablets.
Phenylketonurics: Patients should be informed that clonazepam orally disintegrating tablets contain phenylalanine (a component of aspartame).
Each orally disintegrating tablet contains 0.56 mg phenylalanine.
DOSAGE AND ADMINISTRATION
Clonazepam is available as an orally disintegrating tablet.
The orally disintegrating tablet should be administered as follows: After opening the carton, peel back the foil on the blister.
Do not push tablet through foil.
Immediately upon opening the blister, using dry hands, remove the tablet and place it in the mouth.
Tablet disintegration occurs rapidly in saliva so it can be easily swallowed with or without water.
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 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 orally disintegrating tablets to an existing anticonvulsant regimen.
Pediatric Patients: Clonazepam orally disintegrating tablets are administered orally.
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 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 to 0.5 mg every third day until a daily maintenance dose of 0.1 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.
Geriatric Patients: There is no clinical trial experience with clonazepam orally disintegrating tablets in seizure disorder patients 65 years of age and older.
In general, elderly patients should be started on low doses of clonazepam orally disintegrating tablets and observed closely [see PRECAUTIONS, Geriatric Us e ].
Panic Disorder: Adults: The initial dose for adults with panic disorder is 0.25 mg twice daily.
An increase to the target dose for most patients of 1 mg/day may be made after 3 days.
The recommended dose of 1 mg/day is based on the results from a fixed dose study in which the optimal effect was seen at 1 mg/day.
Higher doses of 2, 3 and 4 mg/day in that study 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 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.
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 orally disintegrating tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.
Pediatric Patients: There is no clinical trial experience with clonazepam orally disintegrating tablets in panic disorder patients under 18 years of age.
Geriatric Patients: There is no clinical trial experience with clonazepam orally disintegrating tablets in panic disorder patients 65 years of age and older.
In general, elderly patients should be started on low doses of clonazepam and observed closely [see PRECAUTIONS, Geriatric Use ].
Discontinuation or Dosage Reduction of clonazepam orally disintegrating tablets To reduce the risk of withdrawal reactions, increased seizure frequency, and status epilepticus, use a gradual taper to discontinue clonazepam orally disintegrating tablets or reduce the dosage.
If a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level.
Subsequently decrease the dosage more slowly (see WARNINGS: Dependence and Withdrawal Reactions and DRUG ABUSE AND DEPENDENCE : Dependence ).