CLONA

Clonazepam tablets

USP, a benzodiazepine, is available as scored tablets debossed with “1” and “2” containing 0.5 mg of clonazepam and unscored tablets debossed with “C 1” on 1 mg tablets and “C 2” on 2 mg tablets containing 1 mg or 2 mg of clonazepam.

Each tablet contains anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and starch (corn), with the following colorants: 0.5 mg-FD&C Yellow No.

Lake and 1 mg.

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: Clonazepam Structural Formula.

Disorders: Clonazepam tablets are 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 tablets may be useful.

Some loss of effect may occur during the course of clonazepam treatment.

Clonazepam tablets are 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 tablets was established in two 6.

• to 9-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder.

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: palpitations, pounding heart or accelerated heart rate; sweating; trembling or shaking; sensations of shortness of breath or smothering; feeling of choking; chest pain or discomfort; nausea or abdominal distress; feeling dizzy, unsteady, lightheaded or faint; derealization (feelings of unreality) or depersonalization (being detached from oneself); fear of losing control; fear of dying; paresthesias (numbness or tingling sensations); chills or hot flushes.

The effectiveness of clonazepam 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 tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient See DOSAGE AND ADMINISTRATION.

Alcoholism Lactation History of depression Ataxia Severe depression Cumulative doses Child under 15 years of age Epilepsy State of dependency, history Female likely to be pregnant Pregnancy Suicidal ideation, history (of) Mild to moderate hepatic impairment Renal impairment Respiratory impairment Nephropathy Newborn exposed in utero to the medicine Polymedic patient High dose treated patient Porphyry Psychosis Elderly Extended treatment.

The precise mechanism by which clonazepam exerts its antiseizure and antipanic effects is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system.

Clonazepam is rapidly and completely absorbed after oral administration.

The absolute bioavailability of clonazepam is about 90%.

Maximum plasma concentrations of clonazepam are reached within 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.

Biotransformation occurs mainly by reduction of the 7-nitro group to the 4-amino derivative.

This derivative can be acetylated, hydroxylated and glucuronidated.

P-450 including CYP3A, may play an important role in clonazepam reduction and oxidation.

The elimination half-life of clonazepam is typically to 40 hours.

Clonazepam pharmacokinetics are dose-independent throughout the dosing range.

There is no evidence that clonazepam induces its own metabolism or that of other drugs in humans.

Pharmacokinetics in Demographic Subpopulations and in Disease States: Controlled studies examining the influence of gender and age on clonazepam pharmacokinetics have not been conducted, nor have the effects of renal or liver disease on clonazepam pharmacokinetics been studied.

Because clonazepam undergoes hepatic metabolism, it is possible that liver disease will impair clonazepam elimination.

Thus, caution should be exercised when administering clonazepam to these patients See CONTRAINDICATIONS.

In children, clearance values of 0.42 ± 0.32 mL/min/kg (ages to 18 years) and 0.88 ± 0.4 mL/min/kg (ages to 12 years) were reported; these values decreased with increasing body weight.

Ketogenic diet in children does not affect clonazepam concentrations.

Panic Disorder: The effectiveness of clonazepam in the treatment of panic disorder was demonstrated in two double-blind, placebo-controlled studies of adult outpatients who had a primary diagnosis of panic disorder (DSM-IIIR) with or without agoraphobia.

In these studies, clonazepam was shown to be significantly more effective than placebo in treating panic disorder on change from baseline in panic attack frequency, the Clinician’s Global Impression Severity of Illness Score and the Clinician’s Global Impression Improvement Score.

Study was a 9-week, fixed-dose study involving clonazepam doses of 0.5, 1, 2, 3 or 4 mg/day or placebo.

This study was conducted in four phases: a 1-week placebo lead-in, a 3-week upward titration, a 6-week fixed dose, and a 7-week discontinuance phase.

A significant difference from placebo was observed consistently only for the 1 mg/day group.

The difference between the 1 mg dose group and placebo in reduction from baseline in the number of full panic attacks was approximately 1 panic attack per week.

At endpoint, 74% of patients receiving clonazepam 1 mg/day were free of full panic attacks, compared to 56% of placebo-treated patients.

Study was a 6-week, flexible-dose study involving clonazepam in a dose range of 0.5 to 4 mg/day or placebo.

This study was conducted in three phases: a 1-week placebo lead-in, a 6-week optimal-dose, and a 6-week discontinuance phase.

The mean clonazepam dose during the optimal dosing period was 2.3 mg/day. The difference between clonazepam and placebo in reduction from baseline in the number of full panic attacks was approximately 1 panic attack per week.

At endpoint, 62% of patients receiving clonazepam were free of full panic attacks, compared to 37% of placebo-treated patients.

Subgroup analyses did not indicate that there were any differences in treatment outcomes as a function of race or gender.

Mechanism of action

Clonazepam belongs to the class 1-4 benzodiazepines and has a pharmacodynamic activity qualitatively similar to that of other compounds in this class: myorelaxant, anxiolytic, sedative, hypnotic, anticonvulsant, amnesian.

These effects are related to a specific agonistic action on a central receptor forming part of the complex "GABA-OMEGA macromolecular receptors", also known as BZ1 and BZ2 and modulating the opening of the chlorine channel.

• Liver enzymes (increase)
• Urticaria (Rare)
• Skin colour impairment (Rare)
• Rash (Rare)
• Pruritus (Rare)
• Alopecia (Rare)
• Fatigue Wearing Early puberty Thrombocytopenia (Rare)
• Leucopenia (Rare)
• Anemia (Exceptional)
• Oedema of Quincke (Rare)
• Anaphylactic reaction (Very rare)
• Hypersensitivity Nystagmus (Common)
• Blurty vision Diplopia Sialorrhoea (Common)
• Feeling dizzy
• Libido disorder (Rare)
• Aggressiveness Hallucination Depression Agitation Nightmare
• Bounce phenomenon Abnormal dreams Concentration (decrease)
• Behavioural disorder Mood disorder
• Irritability Mental confusion Emotional disorder Sleep disorder Pharmacodependence
• Psychosis Delicious Temporospatial disorientation Anxiety Hostility Nervousness Cardiac arrest
• Heart failure Nausea (Rare)
• Epigastric fungus Muscle hypotonia Muscle weakness Fracture
• Convulsions (Very rare)
• Headache (Rare)
• Paradoxic reaction Somnolence Psychomotor slowing down
• Dysarthria Amnesia Alteration of consciousness Balance disorder Ataxia Epilepsy (crisis)
• Hyperactivity Anterograde amnesia Respiratory depression Bronchial hypersecretion
• Weaning syndrome Erection disorder (Rare)
• Urinary retention Urinary incontinence.

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

Consider contacting the Poison

Help line or a medical toxicologist for additional overdosage management recommendations.

Concomitant use of benzodiazepines, including clonazepam tablets, and opioids may result in profound sedation, respiratory depression, coma, and death.

Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for 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 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 tablets are used with opioids.

Abuse, Misuse, and Addiction: The use of benzodiazepines, including clonazepam 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.

Before prescribing clonazepam tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool).

Use of clonazepam tablets, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of clonazepam 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.

To reduce the risk of withdrawal reactions, use a gradual taper to discontinue clonazepam 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 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.

The continued use of benzodiazepines, including clonazepam tablets, may lead to clinically significant physical dependence.

Abrupt discontinuation or rapid dosage reduction of clonazepam tablets after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) .

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.

Interference with Cognitive and Motor Performance

Since clonazepam 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 therapy.

Antiepileptic drugs (AEDs), including clonazepam 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 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 with 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.

Use of clonazepam 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.

Monitor neonates exposed to clonazepam tablets during pregnancy or labor for signs of sedation and monitor neonates exposed to clonazepam tablets during pregnancy for signs of withdrawal; manage these neonates accordingly.

Clonazepam tablets are 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).

Clonazepam is available as a tablet.

The tablets should be administered with water by swallowing the tablet whole.

Disorders: The use of multiple anticonvulsants may result in an increase of CNS depressant adverse effects.

This should be considered before adding clonazepam tablets to an existing anticonvulsant regimen.

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. Pediatric Patients: Clonazepam 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 mg 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.

There is no clinical trial experience with clonazepam tablets in seizure disorder patients 65 years of age and older.

In general, elderly patients should be started on low doses of clonazepam tablets and observed closely.

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 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 mg to 0.25 mg twice daily 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 twice daily 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 tablets for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient.

There is no clinical trial experience with clonazepam tablets in panic disorder patients under 18 years of age.

There is no clinical trial experience with clonazepam tablets in panic disorder patients 65 years of age and older.

Discontinuation or Dosage Reduction of Clonazepam Tablets: To reduce the risk of withdrawal reactions, increased seizure frequency, and status epilepticus, use a gradual taper to discontinue clonazepam 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.

Clonazepam tablets

USP 0.5 mg are orange, round, flat faced, beveled edge, scored, debossed with “1” and “2” on one side and plain on other.

They are supplied as follows

NDC: 70518-1801-00 NDC: 70518-1801-01 OUTER PACKAGING: 100 in 1 BOX INNER PACKAGING: 1 in 1 POUCH Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). .

Suite #4 Indiana, PA 1-724-465-8762.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as clonazepam tablets, during pregnancy.

Healthcare providers are encouraged to recommend that pregnant women taking clonazepam tablets enroll in the NAAED Pregnancy Registry by calling 1-888-233-2334 or online at 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, and 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.

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.

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 defect, 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.

Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates.

Monitor neonates exposed to clonazepam tablets during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems.

Monitor neonates exposed to clonazepam tablets during pregnancy for signs of withdrawal.

Manage these neonates accordingly See WARNINGS: Neonatal Sedation and Withdrawal Syndrome.

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.

In three studies in which clonazepam was administered orally to pregnant rabbits at doses of 0.2, 1, 5, or 10 mg/kg/day during the period of organogenesis, a similar pattern of malformations (cleft palate, open eyelid, fused sternebrae and limb defects) was observed at all doses, in a low, non-dose-related incidence.

The lowest dose tested is less than the maximum recommended human dose (MRHD) of 20 mg/day for seizure disorders and similar to the MRHD of 4 mg/day for panic disorder, on a mg/m 2 basis.

Reductions in maternal weight gain occurred at doses of 5 mg/kg/day or greater and reduction in embryofetal growth occurred in one study at a dose of 10 mg/kg/day. No adverse maternal or embryofetal effects were observed in mice or rats following oral administration of clonazepam during organogenesis of doses up to 15 or 40 mg/kg/day, respectively (4 and 20 times the MRHD of 20 mg/day for seizure disorders and and 100 times the MRHD of 4 mg/day for panic disorder, respectively, on a mg/m 2 basis).

Data for other benzodiazepines suggest the possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines.

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 tablets and any potential adverse effects on the breastfed infant from clonazepam tablets or from the underlying maternal condition.

Infants exposed to clonazepam through breast milk should be monitored for sedation, poor feeding and poor weight gain.

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 tablets 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.

Clinical studies of clonazepam tablets did not include sufficient numbers of subjects aged 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 elimination.

Metabolites of clonazepam 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 tablets and observed closely.