PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 42571-315-01
Clobazam Tablets CIV
10 mg
DISPENSE THE ENCLOSED MEDICATION GUIDE
WITH EACH PRESCRIPTION
Rx Only
100 Tablets
Micro Labs Limited

NDC 42571-316-01
Clobazam Tablets CIV
20 mg
DISPENSE THE ENCLOSED MEDICATION GUIDE
WITH EACH PRESCRIPTION
Rx Only
100 Tablets
Micro Labs Limited

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Warnings and Precautions ( 5.7) 3/2024

DESCRIPTION SECTION

11 DESCRIPTION

Clobazam tablet is a benzodiazepine derivative. The chemical name of clobazam is 7-Chloro-1-methyl-5-phenyl-1H-1,5 benzodiazepine-2,4(3H,5H)-dione with the following structure:

Structure
Clobazam is a white or almost white, crystalline powder with a slightly bitter taste; is slightly soluble in water, sparingly soluble in ethanol, and freely soluble in methylenechloride. The melting range of clobazam is from 182ºC to 185ºC. The molecular formula is C 16H 13O 2N 2Cl and the molecular weight is 300.7.

Each clobazam tablet contains 10 mg or 20 mg of clobazam. Tablets also contain as inactive ingredients: colloidal silicon dioxide, lactose monohydrate, lactose anhydrous, magnesium stearate, maize starch 5%, pregelatinized starch, and talc.

INDICATIONS & USAGE SECTION

Highlight: Clobazam tablet is a benzodiazepine indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older ( 1)

1 INDICATIONS AND USAGE

Clobazam tablet is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: * Tablet: 10 mg and 20 mg with a functional score ( 3)

3 DOSAGE FORMS AND STRENGTHS

10 mg- White to off**-**white, oval shaped tablets with a functional score line on one face and "1" and "0" debossed on the other face.

20 mg- White to off**-**white, oval shaped tablets with a functional score line on one face and "2" and "0" debossed on the other face.

BOXED WARNING SECTION

**WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND

ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS****See full prescribing information for complete boxed warning.**

ADVERSE REACTIONS SECTION

Highlight: Adverse reactions that occurred at least 10% more frequently than placebo in any clobazam tablet dose included constipation, somnolence or sedation, pyrexia, lethargy, and drooling ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA, Inc. at 1-855-839-8195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6 ADVERSE REACTIONS

Clinically significant adverse reactions that appear in other sections of the labeling include the following:

• Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1)]
• Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2)]
• Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3)]
• Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants [see Warnings and Precautions (5.4)]
• Somnolence or Sedation [see Warnings and Precautions (5.5)]
• Serious Dermatological Reactions [see Contraindications (4), Warnings and Precautions (5.6)]
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.7)]
• Suicidal Behavior and Ideation [see Warnings and Precautions (5.8)]
• Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

During its development for the adjunctive treatment of seizures associated with LGS, clobazam was administered to 333 healthy volunteers and 300 patients with a current or prior diagnosis of LGS, including 197 patients treated for 12 months or more. The conditions and duration of exposure varied greatly and included single- and multiple- dose clinical pharmacology studies in healthy volunteers and two double-blind studies in patients with LGS (Study 1 and 2) [seeClinical Studies (14)] . Only Study 1 included a placebo group, allowing comparison of adverse reaction rates on clobazam at several doses to placebo.

Adverse Reactions Leading to Discontinuation in an LGS Placebo Controlled Clinical Trial (Study 1)

The adverse reactions associated with clobazam treatment discontinuation in ≥1% of patients in decreasing order of frequency included lethargy, somnolence, ataxia, aggression, fatigue, and insomnia.

Most Common Adverse Reactions in an LGS Placebo Controlled Clinical Trial (Study 1)

Table 3 lists the adverse reactions that occurred in ≥5% of clobazam-treated patients (at any dose), and at a rate greater than placebo-treated patients, in the randomized, double-blind, placebo-controlled, parallel group clinical study of adjunctive AED therapy for 15 weeks (Study 1).

Table 3. Adverse Reactions Reported for ≥5% of Patients and More Frequently than Placebo in Any Treatment Group

	Placebo N=59%	Clobazam Dose Level	All Clobazam N=179%
Lowa N=58%	MediumbN=62%	Highc N=59%
Gastrointestinal Disorders
Vomiting	5	9	5	7	7
Constipation	0	2	2	10	5
Dysphagia	0	0	0	5	2
General Disorders and Administration Site Conditions
Pyrexia	3	17	10	12	13
Irritability	5	3	11	5	7
Fatigue	2	5	5	3	5
Infections and Infestations
Upper respiratory tract infection	10	10	13	14	12
Pneumonia	2	3	3	7	4
Urinary tract infection	0	2	5	5	4
Bronchitis	0	2	0	5	2
Metabolism and Nutrition Disorders
Decreased appetite	3	3	0	7	3
Increased appetite	0	2	3	5	3
Nervous System Disorders
Somnolence or Sedation	15	17	27	32	26
Somnolence	12	16	24	25	22
Sedation	3	2	3	9	5
Lethargy	5	10	5	15	10
Drooling	3	0	13	14	9
Ataxia	3	3	2	10	5
Psychomotor hyperactivity	3	3	3	5	4
Dysarthria	0	2	2	5	3
Psychiatric Disorders
Aggression	5	3	8	14	8
Insomnia	2	2	5	7	5
Respiratory Disorders
Cough	0	3	5	7	5

aMaximum daily dose of 5 mg for ≤30 kg body weight; 10 mg for >30 kg body weight

bMaximum daily dose of 10 mg for ≤30 kg body weight; 20 mg for >30 kg body weight

cMaximum daily dose of 20 mg for ≤30 kg body weight; 40 mg for >30 kg body weight

6.2 Postmarketing Experience

These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions are categorized by system organ class.

Blood Disorders:Anemia, eosinophilia, leukopenia, thrombocytopenia

Eye Disorders:Diplopia, vision blurred

Gastrointestinal Disorders:Abdominal distention

General Disorders and Administration Site Conditions:Hypothermia

Investigations:Hepatic enzyme increased

Musculoskeletal:Muscle spasms

Psychiatric Disorders:Agitation, anxiety, apathy, confusional state, depression, delirium, delusion, hallucination

Renal and Urinary Disorders:Urinary retention

Respiratory Disorders:Aspiration, respiratory depression

Skin and Subcutaneous Tissue Disorders:Rash, urticaria, angioedema, and facial and lip edema

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

The effectiveness of clobazam for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome was established in two multicenter controlled studies (Study 1 and Study 2). Both studies were similar in terms of disease characteristics and concomitant AED treatments. The most common concomitant AED treatments at baseline included: valproate, lamotrigine, levetiracetam, and topiramate.

Study 1

Study 1 (N=238) was a randomized, double-blind, placebo-controlled study consisting of a 4-week baseline period followed by a 3-week titration period and 12-week maintenance period. Patients age 2 to 54 years with a current or prior diagnosis of LGS were stratified into 2 weight groups (12.5 kg to ≤30 kg or >30 kg) and then randomized to placebo or one of three target maintenance doses of clobazam according to Table 5.

Table 5. Study 1 Total Daily Dose

	≤30 kg Body Weight	>30 kg Body Weight
Low Dose	5 mg daily	10 mg daily
Medium Dose	10 mg daily	20 mg daily
High Dose	20 mg daily	40 mg daily

Doses above 5 mg/day were administered in two divided doses.

The primary efficacy measure was the percent reduction in the weekly frequency of drop seizures (atonic, tonic, or myoclonic), also known as drop attacks, from the 4-week baseline period to 12-week maintenance period.

The pre-dosing baseline mean weekly drop seizure frequency was 98, 100, 61, and 105 for the placebo, low-, medium-, and high-dose groups, respectively. Figure 1 presents the mean percent reduction in weekly drop seizures from this baseline. All dose groups of clobazam were statistically superior (p≤0.05) to the placebo group. This effect appeared to be dose dependent.

Figure 1. Mean Percent Reduction from Baseline in Weekly Drop Seizure Frequency (Study 1)

Figure 2 shows changes from baseline in weekly drop seizure frequency by category for patients treated with clobazam and placebo in Study 1. Patients in whom the seizure frequency increased are shown at left as “worse.” Patients in whom the seizure frequency decreased are shown in five categories.

Figure 2. Drop Seizure Response by Category for Clobazam and Placebo (Study 1)

There was no evidence that tolerance to the therapeutic effect of clobazam developed during the 3-month maintenance period.

Study 2

Study 2 (N=68) was a randomized, double-blind comparison study of high- and low-dose clobazam, consisting of a 4-week baseline period followed by a 3-week titration period and 4-week maintenance period. Patients age 2 to 25 years with a current or prior diagnosis of LGS were stratified by weight, then randomized to either a low or high dose of clobazam, and then entered a 3-week titration period.

A statistically significantly greater reduction in seizure frequency was observed in the high-dose group compared to the low-dose group (median percent reduction of 93% vs 29%; p<0.05).

SPL MEDGUIDE SECTION

MEDICATION GUIDE

Clobazam (KLOE-ba-zam) Tablets, CIV

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

**• Clobazam tablets are a benzodiazepine medicine. Taking benzodiazepines with opioid medicines, alcohol, or other central nervous system (CNS) depressants (including street drugs) can cause severe drowsiness, breathing problems (respiratory depression), coma, and death.**Get emergency help right away if any of the following happens:

o shallow or slowed breathing
o breathing stops (which may lead to the heart stopping)
o excessive sleepiness (sedation)
Do not drive or operate heavy machinery until you know how taking clobazam tablets with opioids affects you.

• Risk of abuse, misuse, and addiction. There is a risk of abuse, misuse, and addiction with benzodiazepines, including clobazam tablets, which can lead to overdose and serious side effects including coma and death.

oSerious side effects including coma and death have happened in people who have abused or misused benzodiazepines, including clobazam tablets.These serious side effects may also include delirium, paranoia, suicidal thoughts or actions, seizures, and difficulty breathing.Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these serious side effects.
o You can develop an addiction even if you take clobazam tablets as prescribed by your healthcare provider.
o Take clobazam tablets exactly as your healthcare provider prescribed.
****o Do not share your clobazam tablets with other people.
o Keep clobazam tablets in a safe place and away from children.

•**Physical dependence and withdrawal reactions.Clobazam tablets can cause physical dependence and withdrawal reactions.
oDo not suddenly stop taking clobazam tablets.Stopping clobazam tablets suddenly can cause serious and life-threatening side effects, including, unusual movements, responses, or expressions, seizures, sudden and severe mental or nervous system changes, depression, seeing or hearing things that others do not see or hear, an extreme increase in activity or talking, losing touch with reality, and suicidal thoughts or actions.Call your healthcare provider or go to the nearest hospital emergency room right away if you get any of these symptoms.
oSome people who suddenly stop benzodiazepines have symptoms that can last for several weeks to more than 12 months,**including, anxiety, trouble remembering, learning, or concentrating, depression, problems sleeping, feeling like insects are crawling under your skin, weakness, shaking, muscle twitching, burning or prickling feeling in your hands, arms, legs or feet, and ringing in your ears.
o 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.
o Do not take more clobazam tablets than prescribed or take clobazam tablets for longer than prescribed.

• Clobazam tablets can make you sleepy or dizzy and can slow your thinking and motor skills.
****o Do not drive, operate heavy machinery, or do other dangerous activities until you know how clobazam tablets affects you.
o Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking clobazam tablets without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, clobazam tablets may make your sleepiness or dizziness much worse.

•**Serious skin reactions have been seen when clobazam tablets are taken with other medicines and may require stopping its use.**Do not stop taking clobazam tablets without first talking to your healthcare provider.
o A serious skin reaction can happen at any time during your treatment with clobazam tablets, but is more likely to happen within the first 8 weeks of treatment. These skin reactions may need to be treated right away.
o Call your healthcare provider immediately if you have skin blisters, rash, sores in the mouth, hives or any other allergic reaction.
•**A serious allergic reaction that may affect your skin or other parts of your body such as your liver, kidneys, heart, or blood cells.**This allergic reaction can be life-threatening and can cause death, particularly if it is not treated as early as possible. Call your healthcare provider right away if you have:
o a skin rash o fever or swollen glands that do not go away
o swelling of your face o shortness of breath
o dark urine o yellowing of the skin or whites of the eyes
• Like other antiepileptic medicines, clobazam 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:

o thoughts about suicide or dying o attempts to commit suicide
o new or worse depression o new or worse anxiety or irritability
o feeling agitated or restless o an extreme increase in activity and talking (mania)
o trouble sleeping (insomnia) o new or worse panic attacks
o acting aggressive, being angry or violent o acting on dangerous impulses
o other unusual changes in behavior or mood
How can I watch for early symptoms of suicidal thoughts and actions?
o Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
o 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.

Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).

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.

** What are clobazam tablets?**

• Clobazam tablets are a prescription medicine used along with other medicines to treat seizures associated with Lennox-Gastaut syndrome in people 2 years of age or older.

•**Clobazam tablet is a federally controlled substance (C-IV) because it contains clobazam that can be abused or lead to dependence.**Keep clobazam tablets in a safe place to prevent misuse and abuse. Selling or giving away clobazam 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.

It is not known if clobazam tablets are safe and effective in children less than 2 years old.

** Do not take clobazam tablet if you:**

• are allergic to clobazam or any of the ingredients in clobazam tablets. See the end of this Medication Guide for a complete list of ingredients in clobazam tablets.

** Before you take clobazam tablets, tell your healthcare provider about all your medical conditions, including if you:**
• have liver or kidney problems
• have lung problems (respiratory disease)
• have or have had depression, mood problems, or suicidal thoughts or behavior
• use birth control medicine. Clobazam tablets may cause your birth control medicine to be less effective. Talk to your healthcare provider about the best birth control method to use.
• are pregnant or plan to become pregnant.
o Taking clobazam tablets late in pregnancy may cause your baby to have symptoms of sedation (breathing problems, sluggishness, low muscle tone), and/or withdrawal symptoms (jitteriness, irritability, restlessness, shaking, excessive crying, feeding problems).
o Tell your healthcare provider right away if you become pregnant or think you are pregnant while taking clobazam tablets.
o If you become pregnant while taking clobazam 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. For more information about the registry go to http://www.aedpregnancyregistry.org. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.
• are breastfeeding or plan to breastfeed. Clobazam can pass into breast milk.
o Breastfeeding during treatment with clobazam tablets may cause your baby to have sleepiness, feeding problems, and decreased weight gain.
o Talk to your healthcare provider about the best way to feed your baby if you take clobazam tablets.
**Tell your healthcare provider about all the medicines you take,**including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking clobazam tablets with certain other medicines can cause side effects or affect how well clobazam tablets or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider.

** How should I take clobazam tablets?**
****• Take clobazam tablets exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much clobazam tablets to take and when to take it.
• Clobazam tablets can be taken whole, broken in half along the score, or crushed and mixed in applesauce.
• Clobazam tablets can be taken with or without food.
• Your healthcare provider may change your dose if needed. Do not change your dose of clobazam tablets without talking to your healthcare provider.
• Do not stop taking clobazam tablets without first talking to your healthcare provider.
• Stopping clobazam tablets suddenly can cause serious problems.
• If you take too much clobazam tablets, call your healthcare provider or go to the nearest hospital emergency room right away.

** What should I avoid while taking clobazam tablets?**

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

** What are the possible side effects of clobazam tablets?**

Clobazam tablets may cause serious side effects, including: See “What is the most important information I should know about clobazam tablets?”

** The most common side effects of clobazam tablets include:**
• sleepiness • drooling • constipation
• cough • pain with urination • fever
• acting aggressive, being angry or violent • difficulty sleeping • slurred speech
• tiredness • problems with breathing

These are not all the possible side effects of clobazam 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 clobazam tablets?**
• Store clobazam tablets between 68°F to 77°F (20°C to 25°C).
Tablets

• Keep clobazam tablets in a dry place.
• Keep clobazam tablets and all medicines out of the reach of children.

** General information about the safe and effective use of clobazam tablets. **

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use clobazam tablets for a condition for which it was not prescribed. Do not give clobazam 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 clobazam tablets that is written for health professionals.

What are the ingredients in clobazam tablets?

**Active ingredient:**clobazam
**Inactive ingredients:**colloidal silicon dioxide, lactose monohydrate, lactose anhydrous, magnesium stearate, maize starch 5%, pregelatinized starch, and talc.

For more information call1-855-839-8195.

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

Manufactured by:
Micro Labs Limited
****Goa- 403 722, INDIA.

Manufactured for:
Micro Labs USA, Inc.
****Somerset, NJ 08873

Rev. 03/2024

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Drug Labeling Information

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

DESCRIPTION SECTION

11 DESCRIPTION

INDICATIONS & USAGE SECTION

1 INDICATIONS AND USAGE

DOSAGE FORMS & STRENGTHS SECTION

3 DOSAGE FORMS AND STRENGTHS

BOXED WARNING SECTION

**WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND

ADVERSE REACTIONS SECTION

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

SPL MEDGUIDE SECTION

MEDICATION GUIDE