CLONAZEPAM- clonazepam tablet

United States - English - NLM (National Library of Medicine)

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Active ingredient:
CLONAZEPAM (UNII: 5PE9FDE8GB) (CLONAZEPAM - UNII:5PE9FDE8GB)
Available from:
REMEDYREPACK INC.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
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. Some loss of effect may occur during the course of clonazepam treatment (see PRECAUTIONS : Loss of Effect ). Clonazepam 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 was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the DSM-IIIR category of panic disorder (see CLINICAL PHARMACOLOGY: Clinical Trials). Panic disorder (DSM-V) is characterized by recurrent unexpected pa
Product summary:
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: Bottles of 100       NDC 16729-136-00 Bottles of 500       NDC 16729-136-16 Clonazepam tablets USP 1 mg are blue, round, flat faced, beveled edge, debossed with “C 1” on one side and plain on the other. They are supplied as follows: Bottles of 100       NDC 16729-137-00 Bottles of 500       NDC 16729-137-16 Clonazepam tablets USP 2 mg are white to off white, round, flat faced, beveled edge tablets debossed with “C 2” on one side and plain on the other. They are supplied as follows: Bottles of 100       NDC 16729-138-00 Bottles of 500       NDC 16729-138-16 Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature]. Manufactured For: Accord Healthcare, Inc., 1009, Slater Road, Suite 210-B, Durham, NC 27703, USA. Manufactured By: Intas Pharmaceuticals Limited, Ahmedabad -380 009, India. 10 0533 2 682353 Issued April 2018
Authorization status:
Abbreviated New Drug Application
Authorization number:
70518-2232-0, 70518-2232-1

REMEDYREPACK INC.

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Medication Guide

Medication Guide

Clonazepam Tablets, USP

(kloe-NA-za-pam)

What is the most important information I should know about clonazepam tablets?

Clonazepam tablets is a benzodiazepine medicine. Benzodiazepines can cause severe drowsiness, breathing

problems (respiratory depression), coma, and death when taken with opioid medicines.

Clonazepam tablets can make you sleepy or dizzy and can slow your thinking and motor skills. This may get

better over time.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

clonazepam tablets affects you.

Clonazepam tablets may cause problems with your coordination, especially when you are walking or

picking things up.

Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking clonazepam tablets

until you talk to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or

dizziness, clonazepam may make your sleepiness or dizziness worse.

Like other antiepileptic drugs, clonazepam tablets may cause suicidal thoughts or actions in a very

small number of people, about 1 in 500.

Call your healthcare provider right away if you have any of these symptoms, especially if they are new,

worse, or worry you:

thoughts about suicide or dying

attempt to commit suicide

new or worse depression

new or worse anxiety

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or

actions, your healthcare provider may check for other causes.

Do not stop clonazepam tablets without first talking to a healthcare provider.

Stopping clonazepam tablets suddenly can cause serious problems. Stopping clonazepam tablets suddenly

can cause seizures that will not stop (status epilepticus).

Clonazepam tablets can cause abuse and dependence.

Do not stop taking clonazepam all of a sudden. Stopping clonazepam tablets suddenly can cause

seizures that do not stop, hearing or seeing things that are not there (hallucinations), shaking, and

stomach and muscle cramps.

Talk to your healthcare provider about slowly stopping clonazepam tablets to avoid withdrawal

symptoms.

Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more

about the differences between physical dependence and drug addiction.

Clonazepam tablets is a federal controlled substance (C-IV) because it can be abused or lead to dependence.

Keep clonazepam tablets in a safe place to prevent misuse and abuse. Selling or giving away clonazepam

tablets may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been

dependent on alcohol, prescription medicines or street drugs.

What is Clonazepam tablets?

Clonazepam tablets is a prescription medicine used alone or with other medicines to treat:

certain types of seizure disorders (epilepsy) in adults and children

panic disorder with or without fear of open spaces (agoraphobia) in adults

It is not known if clonazepam tablets is safe or effective in treating panic disorder in children younger

than 18 years old.

Who should not take Clonazepam tablets?

Do not take clonazepam tablets if you:

are allergic to benzodiazepines

have significant liver disease

have an eye disease called acute narrow angle glaucoma

Ask your healthcare provider if you are not sure if you have any of the problems listed above.

Before you take clonazepam tablets, tell your healthcare provider if you:

have liver or kidney problems

have lung problems (respiratory disease)

have or have had depression, mood problems, or suicidal thoughts or behavior

have any other medical problems

are pregnant or plan to become pregnant. It is not known if clonazepam tablets can harm your unborn

baby. Tell your healthcare provider right away if you become pregnant while taking clonazepam

tablets. You and your healthcare provider will decide if you should take clonazepam tablets while you

are pregnant.

Studies in pregnant animals have shown harmful effects of benzodiazepine medications (including the

active ingredient in clonazepam tablets on the developing fetus.

Children born to mothers receiving benzodiazepine medications including clonazepam tablets late in

pregnancy may be at some risk of experiencing breathing problems, feeding problems, hypothermia,

and withdrawal symptoms.

If you become pregnant while taking clonazepam tablets, talk to your healthcare provider about

registering with the North American Antiepileptic Drug Pregnancy Registry. You can register by

calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of

antiepileptic drugs during pregnancy.

are breastfeeding or plan to breastfeed. Clonazepam can pass into breast milk. You and your healthcare

provider should decide how you will feed your baby while you take clonazepam.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter

medicines, vitamins, and herbal supplements.

Taking clonazepam tablets with certain other medicines can cause side effects or affect how well clonazepam

tablets or the other medicines work. Do not start or stop other medicines without talking to your healthcare

provider.

How should I take clonazepam tablets?

Take clonazepam tablets exactly as your healthcare provider tells you. If you take clonazepam tablets

for seizures, your healthcare provider may change the dose until you are taking the right amount of

medicine to control your symptoms.

Clonazepam is available as a tablet.

Do not stop taking clonazepam tablets without first talking to your healthcare provider.

Stopping clonazepam tablets suddenly can cause serious problems.

Clonazepam tablets should be taken with water and swallowed whole.

If you take too much clonazepam tablets, call your healthcare provider or local Poison Control Center

right away.

What should I avoid while taking clonazepam tablets?

Clonazepam tablets can slow your thinking and motor skills. Do not drive, operate heavy machinery,

or do other dangerous activities until you know how clonazepam tablets affect you.

Do not drink alcohol or take other medicines that may make you sleepy or dizzy while taking

clonazepam tablets until you talk to your healthcare provider. When taken with alcohol or medicines

that cause sleepiness or dizziness, clonazepam tablets may make your sleepiness or dizziness much

worse.

What are the possible side effects of clonazepam tablets?

See “What is the most important information I should know about clonazepam tablets?”

Clonazepam tablets can also make your seizures happen more often or make them worse. Call your

healthcare provider right away if your seizures get worse while taking clonazepam tablets.

The most common side effects of clonazepam tablets include:

Drowsiness

Problems with walking and coordination

Dizziness

Depression

Fatigue

Problems with memory

These are not all the possible side effects of clonazepam tablets. Call your doctor for medical advice about

side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store clonazepam tablets?

Store clonazepam tablets between 59ºF to 86ºF (15ºC to 30ºC).

Keep clonazepam tablets and all medicines out of the reach of children.

General Information about clonazepam tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use

clonazepam tablets for a condition for which it was not prescribed. Do not give clonazepam tablets to other

people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist

or healthcare provider for information about clonazepam tablets that is written for health professionals.

For more information, go to www.accordhealthcare.us or call Accord Healthcare Inc. at 1-866-941-7875.

What are the ingredients in clonazepam tablets?

Active Ingredient: clonazepam

Inactive Ingredients:

Tablets:

0.5 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose, starch (corn) and FD&C Yellow No. 6 Lake.

1 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose, starch (corn) and FD&C Blue No. 2 Lake.

2 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose and starch (corn)

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Medication guide available at https://www.accordhealthcare.us/medication-guides

Manufactured For:

Accord Healthcare, Inc.,

1009, Slater Road,

Suite 210-B,

Durham, NC 27703,

USA.

Manufactured By:

Intas Pharmaceuticals Limited,

Ahmedabad -380 009, India.

10 0533 2 682353

Issued April 2018

Revised: 7/2019

Document Id: 8e63bd6c-81e0-1f56-e053-2995a90af71f

34391-3

Set id: 095a80b0-09f9-4bd1-b377-5212d7c966ba

Version: 1

Effective Time: 20190723

REMEDYREPACK INC.

CLONAZEPAM- clonazepam tablet

REMEDYREPACK INC.

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Clonazepam Tablets, USP

CIV

Rx only

WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS

Concomitant use of benzodiazepines and opioids may result in profound sedation,

respiratory depression, coma, and death (see WARNINGS and PRECAUTIONS).

Reserve concomitant prescribing of these drugs for use 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.

DESCRIPTION

Clonazepam, 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. 6 Lake and 1 mg- FD&C Blue No.2 Lake.

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:

CLINICAL PHARMACOLOGY

Pharmacodynamics :

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.

Pharmacokinetics :

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 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.

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

derivative can be acetylated, hydroxylated and glucuronidated. Cytochrome P-450 including CYP3A,

may play an important role in clonazepam reduction and oxidation. The elimination half-life of

clonazepam is typically 30 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 2 – 18 years) and 0.88 ± 0.4 mL/min/kg

(ages 7 – 12 years) were reported; these values decreased with increasing body weight. Ketogenic diet

in children does not affect clonazepam concentrations.

Clinical Trials:

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 1 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 2 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.

INDICATIONS AND USAGE

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.

Some loss of effect may occur during the course of clonazepam treatment (see PRECAUTIONS : Loss

of Effect).

Panic Disorder:

Clonazepam 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 was established in two 6- to 9-week trials in panic disorder patients whose

diagnoses corresponded to the DSM-IIIR 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 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 for

extended periods should periodically reevaluate the long-term usefulness of the drug for the individual

patient (see DOSAGE AND ADMINISTRATION).

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

Risks from Concomitant Use with Opioids: Concomitant use of benzodiazepines, including clonazepam,

and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these

risks, reserve concomitant prescribing of benzodiazepines and opioids for use 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 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 is used with opioids (see PRECAUTIONS : Information for Patients and

PRECAUTIONS : Drug Interactions).

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 a motor vehicle. They should also be warned

about the concomitant use of alcohol or other CNS-depressant drugs during clonazepam therapy (see

PRECAUTIONS: Drug Interactions and Information for Patients).

Suicidal Behavior and Ideation:

Antiepileptic 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.

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

Psychiatric

Other

Total

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 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.

Withdrawal Symptoms:

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines

(see DRUG ABUSE AND DEPENDENCE).

PRECAUTIONS

General:

Worsening of Seizures:

When used in patients in whom several different types of seizure disorders coexist, clonazepam may

increase 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.

Loss of Effect:

In some studies, up to 30% of patients who initially responded have shown a loss of anticonvulsant

activity, often within 3 months of administration. In some cases, dosage adjustment may reestablish

efficacy.

Laboratory Testing During Long-Term Therapy:

Periodic blood counts and liver function tests are advisable during long-term therapy with clonazepam.

Psychiatric and Paradoxical Reactions:

Paradoxical reactions, such as agitation, irritability, aggression, anxiety, anger, nightmares,

hallucinations, and psychoses are known to occur when using benzodiazepines (see ADVERSE

REACTIONS: Psychiatric). Should this occur, the use of the drug should be discontinued gradually

(see PRECAUTIONS: Risks of Abrupt Withdrawal and DRUG ABUSE AND DEPENDENCE:

Physical and Psychological Dependence). Paradoxical reactions are more likely to occur in children

and in the elderly.

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.

Caution 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.

Hypersalivation:

Clonazepam may produce an increase in salivation. This should be considered before giving the drug to

patients who have difficulty handling secretions.

Respiratory Depression:

Clonazepam may cause respiratory depression and should be used with caution in patients with

compromised respiratory function (e.g., chronic obstructive pulmonary disease, sleep apnea).

Porphyria:

Clonazepam may have a porphyrogenic effect and should be used with care in patients with porphyria.

Information for Patients:

A Clonazepam Medication Guide must be given to the patient each time clonazepam is dispensed, as

required by law. 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:

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).

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.

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 therapy does not affect them adversely.

Suicidal Thinking and Behavior:

Patients, their caregivers, and families should be counseled that AEDs, including clonazepam, 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:

Patients should be advised to notify their physician if they become pregnant or intend to become

pregnant during therapy with clonazepam (see PRECAUTIONS: Pregnancy). Patients should be

encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they

become pregnant. This registry is collecting information about the safety of antiepileptic drugs during

pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS:

Pregnancy).

Nursing:

Patients should be advised to notify their physician if they are breastfeeding or intend to breastfeed

during therapy.

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.

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 GABAA 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 carbamazepine or phenobarbital.

Clonazepam has the potential to influence concentrations of phenytoin. Monitoring of phenytoin

concentration is recommended when clonazepam is co-administrated with phenytoin. 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

of clonazepam was 20% lower when the orally

disintegrating tablet was given with propantheline compared to when it was given alone.

The selective serotonin reuptake inhibitors sertraline (weak CYP3A4 inducer) and fluoxetine (CYP2D6

inhibitor), and the anti-epileptic drug felbamate (CYP2C19 inhibitor and CYP3A4 inducer) do not affect

the pharmacokinetics of clonazepam. Cytochrome P450 inducers, such as phenytoin, carbamazepine,

lamotrigine, and phenobarbital induce clonazepam metabolism, causing an approximately 38% 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 (e.g., fluconazole), should be used cautiously in patients

receiving clonazepam because they may impair the metabolism of clonazepam leading to exaggerated

concentrations and effects.

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis

Carcinogenicity studies have not been conducted with clonazepam.

Mutagenesis

The data currently available are not sufficient to determine the genotoxic potential of clonazepam.

Impairment of Fertility

In a two-generation fertility study in which clonazepam was given orally to rats at 10 and 100 mg/kg/day,

there was a decrease in the number of pregnancies and in the number of offspring surviving until

weaning. The lowest dose tested is approximately 5 and 24 times the maximum recommended human

dose (MRHD) of 20 mg/day for seizure disorders and 4 mg/day for panic disorder, respectively, on a

body surface area (mg/m

) basis.

Pregnancy:

There are no adequate and well-controlled studies of clonazepam in pregnant women. Available human

data on the risk of teratogenicity are inconclusive. There is insufficient evidence in humans to assess

the effect of benzodiazepine exposure during pregnancy on neurodevelopment. Administration of

benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia,

hypotonia, respiratory depression, and difficulty feeding. In addition, infants born to mothers who have

taken benzodiazepines during the later stages of pregnancy can develop dependence, and subsequently

withdrawal, during the postnatal period.

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

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 20 and 100 times the MRHD of 4 mg/day for panic

disorder, respectively, on a mg/m

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

To provide information regarding the effects of in utero exposure to clonazepam, physicians are

advised to recommend that pregnant patients taking clonazepam enroll in the NAAED Pregnancy

Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by

patients themselves. Information on this registry can also be found at the website

http://www.aedpregnancyregistry.org/

Labor and Delivery:

The effect of clonazepam on labor and delivery in humans has not been specifically studied; however,

perinatal complications have been reported in children born to mothers who have been receiving

benzodiazepines late in pregnancy, including findings suggestive of either excess benzodiazepine

exposure or of withdrawal phenomena (see PRECAUTIONS: Pregnancy).

Nursing Mothers:

The effects of clonazepam on the breastfed infant and on milk production are unknown. The

developmental and health benefits of breastfeeding should be considered along with the mother's

clinical need for clonazepam and any potential adverse effects on the breastfed infant from clonazepam

or from the underlying maternal condition.

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 (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.

Geriatric Use:

Clinical studies of clonazepam 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 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. 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 and observed closely.

ADVERSE REACTIONS

The adverse experiences for clonazepam are provided separately for patients with seizure disorders

and with panic disorder.

Seizure Disorders:

The most frequently occurring side effects of clonazepam are referable to CNS depression.

Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of

patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior

problems have been noted in approximately 25% of patients. Others, listed by system, including those

identified during postapproval use of clonazepam are:

Cardiovascular: Palpitations

Dermatologic: Hair loss, hirsutism, skin rash, ankle and facial edema

Gastrointestinal: Anorexia, coated tongue, constipation, diarrhea, dry mouth, encopresis, gastritis,

increased appetite, nausea, sore gums

Genitourinary: Dysuria, enuresis, nocturia, urinary retention

Hematopoietic: Anemia, leukopenia, thrombocytopenia, eosinophilia

Hepatic: Hepatomegaly, transient elevations of serum transaminases and alkaline phosphatase

Musculoskeletal: Muscle weakness, pains

Miscellaneous: Dehydration, general deterioration, fever, lymphadenopathy, weight loss or gain

Neurologic: Abnormal eye movements, aphonia, choreiform movements, coma, diplopia, dysarthria,

dysdiadochokinesis, “glassy-eyed” appearance, headache, hemiparesis, hypotonia, nystagmus,

respiratory depression, slurred speech, tremor, vertigo

Psychiatric: 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: irritability, aggression,

agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares, abnormal dreams,

hallucinations.

Respiratory: Chest congestion, rhinorrhea, shortness of breath, hypersecretion in upper respiratory

passages

Panic Disorder:

Adverse events during exposure to clonazepam were obtained by spontaneous report and recorded by

clinical investigators using terminology of their own choosing. Consequently, it is not possible to

provide a meaningful estimate of the proportion of individuals experiencing adverse events without first

grouping similar types of events into a smaller number of standardized event categories. In the tables

and tabulations that follow, CIGY dictionary terminology has been used to classify reported adverse

events, except in certain cases in which redundant terms were collapsed into more meaningful terms, as

noted below.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at

least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-

emergent if it occurred for the first time or worsened while receiving therapy following baseline

evaluation.

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials:

Adverse Events Associated with Discontinuation of Treatment:

Overall, the incidence of discontinuation due to adverse events was 17% in clonazepam compared to 9%

for placebo in the combined data of two 6- to 9-week trials. The most common events (≥ 1%) associated

with discontinuation and a dropout rate twice or greater for clonazepam than that of placebo included the

following:

Table 2 Most Common Adverse Events (≥ 1%) Associated with Discontinuation of

Treatment

Adverse

Event

Clonazepam

(N = 574)

Placebo

(N = 294)

Somnolence

Depression

Dizziness

< 1%

Nervousness

Ataxia

Intellectual Ability Reduced

Adverse Events Occurring at an Incidence of 1% or More among Clonazepam-Treated Patients:

Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events

that occurred during acute therapy of panic disorder from a pool of two 6- to 9-week trials. Events

reported in 1% or more of patients treated with clonazepam (doses ranging from 0.5 to 4 mg/day) and

for which the incidence was greater than that in placebo-treated patients are included.

The prescriber should be aware that the figures in Table 3 cannot be used to predict the incidence of

side effects in the course of usual medical practice where patient characteristics and other factors

differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be

compared with figures obtained from other clinical investigations involving different treatments, uses

and investigators. The cited figures, however, do provide the prescribing physician with some basis

for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the

population studied.

Table 3. Treatment-Emergent Adverse Event Incidence in 6- to 9- Week Placebo-Controlled

Clinical Trials

Clonazepam Maximum Daily Dose

Adverse Event

by Body System

< 1 mg

n = 96

1- < 2 mg

n = 129

2- < 3 mg

n = 113

≥ 3 mg

n = 235

All Clonazepam

Groups

N = 574

Placebo

N = 294

Central & Peripheral Nervous System

Somnolence

Dizziness

Coordination Abnormal

*

Coordination Abnormal

Ataxia

Dysarthria

Psychiatric

Depression

Memory Disturbance

Nervousness

Intellectual Ability Reduced

Emotional Lability

Libido Decreased

Confusion

Respiratory System

Upper Respiratory

Tract Infection

Sinusitis

Rhinitis

Coughing

Pharyngitis

Bronchitis

Gastrointestinal System

Constipation

Appetite Decreased

Abdominal Pain

Body as a Whole

Fatigue

Allergic Reaction

Musculoskeletal

Myalgia

Resistance Mechanism Disorders

Influenza

Urinary System

Micturition Frequency

Urinary Tract Infection

Vision Disorders

Blurred Vision

Reproductive Disorders

Female

Dysmenorrhea

Colpitis

Male

Ejaculation Delayed

Impotence

Commonly Observed Adverse Events:

Table 4. Incidence of Most Commonly Observed Adverse Events

in Acute Therapy in Pool

of 6- to 9- Week Trials

Adverse Event

Clonazepam

(N = 574)

Placebo

(n = 294)

Somnolence

Depression

Coordination Abnormal

Ataxia

Treatment-Emergent Depressive Symptoms:

Events reported by at least 1% of patients treated with clonazepam and for which the incidence was greater than

that for placebo.

Indicates that the p-value for the dose-trend test (Cochran-Mantel-Haenszel) for adverse event incidence was ≤

0.10.

Denominators for events in gender-specific systems are: n = 24 0 (clonazepam), 102 (placebo) for male, and 334

(clonazepam), 192 (placebo) for female.

*

Treatment-emergent events for which the incidence in the clonazepam patients was ≥ 5% and at least twice

that in the placebo patients.

Treatment-Emergent Depressive Symptoms:

In the pool of two short-term placebo-controlled trials, adverse events classified under the preferred

term “depression” were reported in 7% of clonazepam-treated patients compared to 1% of placebo-

treated patients, without any clear pattern of dose relatedness. In these same trials, adverse events

classified under the preferred term “depression” were reported as leading to discontinuation in 4% of

clonazepam-treated patients compared to 1% of placebo-treated patients. While these findings are

noteworthy, Hamilton Depression Rating Scale (HAM-D) data collected in these trials revealed a larger

decline in HAM-D scores in the clonazepam group than the placebo group suggesting that clonazepam-

treated patients were not experiencing a worsening or emergence of clinical depression.

Other Adverse Events Observed During the Premarketing Evaluation of Clonazepam in Panic Disorder:

Following is a list of modified CIGY terms that reflect treatment-emergent adverse events reported by

patients treated with clonazepam at multiple doses during clinical trials. All reported events are included

except those already listed in Table 3 or elsewhere in labeling, those events for which a drug cause

was remote, those event terms which were so general as to be uninformative, and events reported only

once and which did not have a substantial probability of being acutely life-threatening. It is important to

emphasize that, although the events occurred during treatment with clonazepam, they were not

necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency. These

adverse events were reported infrequently, which is defined as occurring in 1/100 to 1/1000 patients.

Body as a Whole: weight increase, accident, weight decrease, wound, edema, fever, shivering,

abrasions, ankle edema, edema foot, edema periorbital, injury, malaise, pain, cellulitis, inflammation

localized

Cardiovascular Disorders: chest pain, hypotension postural

Central and Peripheral Nervous System Disorders: migraine, paresthesia, drunkenness, feeling of

enuresis, paresis, tremor, burning skin, falling, head fullness, hoarseness, hyperactivity, hypoesthesia,

tongue thick, twitching

Gastrointestinal System Disorders: abdominal discomfort, gastrointestinal inflammation, stomach upset,

toothache, flatulence, pyrosis, saliva increased, tooth disorder, bowel movements frequent, pain pelvic,

dyspepsia, hemorrhoids

Hearing and Vestibular Disorders: vertigo, otitis, earache, motion sickness

Heart Rate and Rhythm Disorders: palpitation

Metabolic and Nutritional Disorders: thirst, gout

Musculoskeletal System Disorders: back pain, fracture traumatic, sprains and strains, pain leg, pain nape,

cramps muscle, cramps leg, pain ankle, pain shoulder, tendinitis, arthralgia, hypertonia, lumbago, pain

feet, pain jaw, pain knee, swelling knee

Platelet, Bleeding and Clotting Disorders: bleeding dermal

Psychiatric Disorders: insomnia, organic disinhibition, anxiety, depersonalization, dreaming excessive,

libido loss, appetite increased, libido increased, reactions decreased, aggression, apathy, disturbance in

attention, excitement, anger, hunger abnormal, illusion, nightmares, sleep disorder, suicide ideation,

yawning

Reproductive Disorders, Female: breast pain, menstrual irregularity

Reproductive Disorders, Male: ejaculation decreased

Resistance Mechanism Disorders: infection mycotic, infection viral, infection streptococcal, herpes

simplex infection, infectious mononucleosis, moniliasis

Respiratory System Disorders: sneezing excessive, asthmatic attack, dyspnea, nosebleed, pneumonia,

pleurisy

Skin and Appendages Disorders: acne flare, alopecia, xeroderma, dermatitis contact, flushing, pruritus,

pustular reaction, skin burns, skin disorder

Special Senses Other, Disorders: taste loss

Urinary System Disorders: dysuria, cystitis, polyuria, urinary incontinence, bladder dysfunction, urinary

retention, urinary tract bleeding, urine discoloration

Vascular (Extracardiac) Disorders: thrombophlebitis leg

Vision Disorders: eye irritation, visual disturbance, diplopia, eye twitching, styes, visual field defect,

xerophthalmia

DRUG ABUSE AND DEPENDENCE

Controlled Substance Class:

Clonazepam is a Schedule IV controlled substance.

Physical and Psychological Dependence:

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (e.g.,

convulsions, psychosis, hallucinations, behavioral disorder, mood changes, tremor, abdominal and

muscle cramps) have occurred following abrupt discontinuance of clonazepam. The more severe

withdrawal symptoms have usually been limited to those patients who received excessive doses over an

extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have

been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic

levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally

be avoided and a gradual dosage tapering schedule followed (see DOSAGE AND

ADMINISTRATION). 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.

Following the short-term treatment of patients with panic disorder in Studies 1 and 2 (see CLINICAL

PHARMACOLOGY: Clinical Trials), patients were gradually withdrawn during a 7-week downward-

titration (discontinuance) period. Overall, the discontinuance period was associated with good

tolerability and a very modest clinical deterioration, without evidence of a significant rebound

phenomenon. However, there are not sufficient data from adequate and well-controlled long-term

clonazepam studies in patients with panic disorder to accurately estimate the risks of withdrawal

symptoms and dependence that may be associated with such use.

OVERDOSAGE

Human Experience:

Symptoms of clonazepam overdosage, like those produced by other CNS depressants, include

somnolence, confusion, coma, and diminished reflexes.

Overdose Management:

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. Prior to the administration of flumazenil, necessary measures

should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an

adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with

flumazenil should be monitored for resedation, respiratory depression and other residual

benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a

risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine

users and in cyclic antidepressant overdose. The complete flumazenil package insert, including

CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, should be consulted prior to use.

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.

Serious sequelae are rare unless other drugs or alcohol have been taken concomitantly.

DOSAGE AND ADMINISTRATION

Clonazepam is available as a tablet. The tablets should be administered with water by swallowing the

tablet whole.

Seizure Disorders:

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

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

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.

Pediatric Patients:

Clonazepam is 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.

Geriatric Patients:

There is no clinical trial experience with clonazepam in seizure 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).

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. 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

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.

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.

Pediatric Patients:

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

Geriatric Patients:

There is no clinical trial experience with clonazepam 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).

HOW SUPPLIED

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:

Bottles of 100 NDC 16729-136-00

Bottles of 500 NDC 16729-136-16

Clonazepam tablets USP 1 mg are blue, round, flat faced, beveled edge, debossed with “C 1” on one

side and plain on the other. They are supplied as follows:

Bottles of 100 NDC 16729-137-00

Bottles of 500 NDC 16729-137-16

Clonazepam tablets USP 2 mg are white to off white, round, flat faced, beveled edge tablets debossed

with “C 2” on one side and plain on the other. They are supplied as follows:

Bottles of 100 NDC 16729-138-00

Bottles of 500 NDC 16729-138-16

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room

Temperature].

Manufactured For:

Accord Healthcare, Inc.,

1009, Slater Road,

Suite 210-B,

Durham, NC 27703,

USA.

Manufactured By:

Intas Pharmaceuticals Limited,

Ahmedabad -380 009, India.

10 0533 2 682353

Issued April 2018

Medication Guide

Medication Guide

Clonazepam Tablets, USP

(kloe-NA-za-pam)

What is the most important information I should know about clonazepam tablets?

Clonazepam tablets is a benzodiazepine medicine. Benzodiazepines can cause severe

drowsiness, breathing problems (respiratory depression), coma, and death when taken with

opioid medicines.

Clonazepam tablets can make you sleepy or dizzy and can slow your thinking and motor skills.

This may get better over time.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

clonazepam tablets affects you.

Clonazepam tablets may cause problems with your coordination, especially when you are walking or

picking things up.

Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking

clonazepam tablets until you talk to your healthcare provider. When taken with alcohol or drugs that

cause sleepiness or dizziness, clonazepam may make your sleepiness or dizziness worse.

Like other antiepileptic drugs, clonazepam tablets may cause suicidal thoughts or actions in a

very small number of people, about 1 in 500.

Call your healthcare provider right away if you have any of these symptoms, especially if they are

new, worse, or worry you:

thoughts about suicide or dying

attempt to commit suicide

new or worse depression

new or worse anxiety

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania)

other unusual changes in behavior or mood

How can I watch for early symptoms of suicidal thoughts and actions?

Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.

Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts

or actions, your healthcare provider may check for other causes.

Do not stop clonazepam tablets without first talking to a healthcare provider.

Stopping clonazepam tablets suddenly can cause serious problems. Stopping clonazepam tablets

suddenly can cause seizures that will not stop (status epilepticus).

Clonazepam tablets can cause abuse and dependence.

Do not stop taking clonazepam all of a sudden. Stopping clonazepam tablets suddenly can cause

seizures that do not stop, hearing or seeing things that are not there (hallucinations), shaking, and

stomach and muscle cramps.

Talk to your healthcare provider about slowly stopping clonazepam tablets to avoid withdrawal

symptoms.

Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more

about the differences between physical dependence and drug addiction.

Clonazepam tablets is a federal controlled substance (C-IV) because it can be abused or lead to

dependence. Keep clonazepam tablets in a safe place to prevent misuse and abuse. Selling or

giving away clonazepam tablets may harm others, and is against the law. Tell your healthcare

provider if you have ever abused or been dependent on alcohol, prescription medicines or street

drugs .

What is Clonazepam tablets?

Clonazepam tablets is a prescription medicine used alone or with other medicines to treat:

certain types of seizure disorders (epilepsy) in adults and children

panic disorder with or without fear of open spaces (agoraphobia) in adults

It is not known if clonazepam tablets is safe or effective in treating panic disorder in children

younger than 18 years old.

Who should not take Clonazepam tablets?

Do not take clonazepam tablets if you:

are allergic to benzodiazepines

have significant liver disease

have an eye disease called acute narrow angle glaucoma

Ask your healthcare provider if you are not sure if you have any of the problems listed above.

Before you take clonazepam tablets, tell your healthcare provider if you:

have liver or kidney problems

have lung problems (respiratory disease)

have or have had depression, mood problems, or suicidal thoughts or behavior

have any other medical problems

are pregnant or plan to become pregnant. It is not known if clonazepam tablets can harm your unborn

baby. Tell your healthcare provider right away if you become pregnant while taking clonazepam

tablets. You and your healthcare provider will decide if you should take clonazepam tablets while

you are pregnant.

Studies in pregnant animals have shown harmful effects of benzodiazepine medications (including

the active ingredient in clonazepam tablets on the developing fetus.

Children born to mothers receiving benzodiazepine medications including clonazepam tablets late in

pregnancy may be at some risk of experiencing breathing problems, feeding problems, hypothermia,

and withdrawal symptoms.

If you become pregnant while taking clonazepam tablets, talk to your healthcare provider about

registering with the North American Antiepileptic Drug Pregnancy Registry. You can register by

calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of

antiepileptic drugs during pregnancy.

are breastfeeding or plan to breastfeed. Clonazepam can pass into breast milk. You and your healthcare

provider should decide how you will feed your baby while you take clonazepam.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements.

Taking clonazepam tablets with certain other medicines can cause side effects or affect how well

clonazepam tablets or the other medicines work. Do not start or stop other medicines without talking to

your healthcare provider.

How should I take clonazepam tablets?

Take clonazepam tablets exactly as your healthcare provider tells you. If you take clonazepam

tablets for seizures, your healthcare provider may change the dose until you are taking the right

amount of medicine to control your symptoms.

Clonazepam is available as a tablet.

Do not stop taking clonazepam tablets without first talking to your healthcare provider.

Stopping clonazepam tablets suddenly can cause serious problems.

Clonazepam tablets should be taken with water and swallowed whole.

If you take too much clonazepam tablets, call your healthcare provider or local Poison Control

Center right away.

What should I avoid while taking clonazepam tablets?

Clonazepam tablets can slow your thinking and motor skills. Do not drive, operate heavy machinery,

or do other dangerous activities until you know how clonazepam tablets affect you.

Do not drink alcohol or take other medicines that may make you sleepy or dizzy while taking

clonazepam tablets until you talk to your healthcare provider. When taken with alcohol or medicines

that cause sleepiness or dizziness, clonazepam tablets may make your sleepiness or dizziness much

worse.

What are the possible side effects of clonazepam tablets?

See “What is the most important information I should know about clonazepam tablets?”

Clonazepam tablets can also make your seizures happen more often or make them worse. Call your

healthcare provider right away if your seizures get worse while taking clonazepam tablets.

The most common side effects of clonazepam tablets include:

Drowsiness

Problems with walking and coordination

Dizziness

Depression

Fatigue

Problems with memory

These are not all the possible side effects of clonazepam tablets. Call your doctor for medical advice

about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store clonazepam tablets?

Store clonazepam tablets between 59ºF to 86ºF (15ºC to 30ºC).

Keep clonazepam tablets and all medicines out of the reach of children.

General Information about clonazepam tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use clonazepam tablets for a condition for which it was not prescribed. Do not give clonazepam tablets

to other people, even if they have the same symptoms that you have. It may harm them. You can ask your

pharmacist or healthcare provider for information about clonazepam tablets that is written for health

professionals.

For more information, go to www.accordhealthcare.us or call Accord Healthcare Inc. at 1-866-941-

7875.

What are the ingredients in clonazepam tablets?

Active Ingredient: clonazepam

Inactive Ingredients:

T ablets:

0.5 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose, starch (corn) and FD&C Yellow No. 6 Lake.

1 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose, starch (corn) and FD&C Blue No. 2 Lake.

2 mg tablets contain anhydrous lactose, lactose monohydrate, magnesium stearate, microcrystalline

cellulose and starch (corn)

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Medication guide available at https://www.accordhealthcare.us/medication-guides

Manufactured For:

Accord Healthcare, Inc.,

1009, Slater Road,

Suite 210-B,

Durham, NC 27703,

USA.

Manufactured By:

Intas Pharmaceuticals Limited,

Ahmedabad -380 009, India.

10 0533 2 682353

Issued April 2018

PRINCIPAL DISPLAY PANEL

DRUG: Clonazepam

GENERIC: clonazepam

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 70518-2232-0

NDC: 70518-2232-1

COLOR: white

SHAPE: ROUND

SCORE: No score

SIZE: 8 mm

IMPRINT: C;2

OUTER PACKAGING: 100 in 1 BOX

INNER PACKAGING: 1 in 1 POUCH

ACTIVE INGREDIENT(S):

CLONAZEPAM 2mg in 1

INACTIVE INGREDIENT(S):

ANHYDROUS LACTOSE

CELLULOSE, MICROCRYSTALLINE

MAGNESIUM STEARATE

LACTOSE MONOHYDRATE

STARCH, CORN

CLONAZEPAM

clonazepam tablet

Product Information

Product T ype

HUMAN

PRESCRIPTION DRUG

Ite m Code (Source )

NDC:70 518 -

2232(NDC:16 729 -138 )

Route of Administration

ORAL

DEA Sche dule

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CLO NAZEPAM (UNII: 5PE9 FDE8 GB) (CLONAZEPAM - UNII:5PE9 FDE8 GB)

CLONAZEPAM

2 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

STARCH, CO RN (UNII: O8 232NY3SJ)

Product Characteristics

Color

white (white to o ff white)

S core

no sco re

S hap e

ROUND

S iz e

8 mm

Flavor

Imprint Code

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:70 518 -2232-0

10 0 in 1 BOX

0 7/23/20 19

1

NDC:70 518 -2232-1

1 in 1 POUCH; Type 0 : No t a Co mbinatio n Pro duct

REMEDYREPACK INC.

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 77147

0 7/23/20 19

Labeler -

REMEDYREPACK INC. (829572556)

Revised: 7/2019

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