Clobazam 10 mg Tablet, 100-count
Other active recalls for Clobazam (different manufacturers) — 3 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Benzodiazepine class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Clobazam is used with other medication(s) to control seizures in adults and children 2 years of age and older who have Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). Clobazam is in a class of medications called benzodiazepines. It works by decreasing abnormal electrical activity in the brain.
Read the full MedlinePlus article ↗- Clobazam is prescribed as an add-on seizure medication for people with Lennox-Gastaut Syndrome (LGS), a severe form of epilepsy. It works alongside other seizure medicines — it's n...
- It's best to avoid alcohol completely while you're taking clobazam. Alcohol is itself a sedative, and when combined with clobazam it can boost clobazam levels in your blood by abou...
- Is it okay to have a drink of alcohol while I'm on clobazam?
- The most common things people notice are drowsiness, low energy, drooling, constipation, and sometimes fever or irritability. Drowsiness is most common early on and often improves...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Clobazam — tap one for details:
Clobazam may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.359 | $35.90 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.8088 | $80.88 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.6481 | $64.81 / 100 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Clobazam 10 mg 00832-0580-11 | Upsher-Smith | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 16714-0887-01 | NorthStar | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 42571-0315-01 | Micro | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 60687-0423-21 | American | 30 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 67877-0665-01 | Ascend | 100 tablets | $0.247 | — | Availability likely | save 31% |
| Clobazam 10 mg 68180-0157-01 | Lupin | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 69238-1305-01 | Amneal | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mg 72205-0047-91 | Novadoz | 100 tablets | $0.247 | AB | Availability likely | save 31% |
| Clobazam 10 mgthis 51672-4202-01 | Taro | 100 tablets | $0.359 | — | Discontinued | — |
| Clobazam 10 mg 31722-0639-01 | Camber | 100 tablets | $0.427 | AB | FDA listed | +19% |
| Onfi 10 mg 67386-0314-01 | Lundbeck | 100 tablets | $29.914 | AB | Availability likely | +8233% |
| Clobazam 10 mg 51407-0585-01 | Golden | 100 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 51672-4202-01 You're viewing this | 100 TABLET in 1 BOTTLE (51672-4202-1) | 2018-10-22 | Discontinued by firm |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
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 (5.1) , Drug Interactions (7.1) ]. 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. WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS See full prescribing information for complete boxed warning. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death ( 5.1 , 7.1 ) .
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.
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Clobazam tablets are indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older. Clobazam is a benzodiazepine indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For doses above 5 mg/day administer in two divided doses ( 2.1 ) Patients ≤30 kg body weight: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily ( 2.1 ) Patients >30 kg body weight: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily ( 2.1 ) Dosage adjustment needed in following groups: Geriatric patients ( 2.4 , 8.5 ) Known CYP2C19 poor metabolizers ( 2.5 ) Mild or moderate hepatic impairment; no information for severe hepatic impairment ( 2.7 , 8.8 ) Reduce dose, or discontinue drug gradually ( 2.2 ) Administer whole, broken in half along the score, or crush and mix in applesauce ( 2.3 ) Can be taken with or without food ( 2.3 )
2.1Dosing Information A daily dose of clobazam tablets greater than 5 mg should be administered in divided doses twice daily; a 5 mg daily dose can be administered as a single dose. Dose patients according to body weight. Individualize dosing within each body weight group, based on clinical efficacy and tolerability.
Each dose in Table 1 (e.g., 5 mg to 20 mg in ≤30 kg weight group) has been shown to be effective, although effectiveness increases with increasing dose [see Clinical Studies (14) ]. Do not proceed with dose escalation more rapidly than weekly, because serum concentrations of clobazam and its active metabolite require 5 and 9 days, respectively, to reach steady-state. Table 1.
Recommended Total Daily Dosing by Weight Group ≤30 kg Body Weight >30 kg Body Weight Starting Dose 5 mg 10 mg Starting Day 7 10 mg 20 mg Starting Day 14 20 mg 40 mg
2.2Gradual Withdrawal As with all antiepileptic drugs and benzodiazepines, withdraw clobazam tablets gradually. Taper by decreasing the total daily dose by 5 mg/day to 10 mg/day on a weekly basis until discontinued [see Warnings and Precautions (5.4) ] .
2.3Important Administration Instructions Clobazam Tablet Oral Administration Clobazam tablets can be taken with or without food. Clobazam tablets can be administered whole, broken in half along the score, or crushed and mixed in applesauce.
2.4Dosage Adjustments in Geriatric Patients Plasma concentrations at any given dose are generally higher in the elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients. Then titrate elderly patients according to weight, but to half the dose presented in Table 1, as tolerated.
If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on weight) may be started on day 21 [see Use in Specific Populations (8.5) ] .
2.5Dosage Adjustments in CYP2C19 Poor Metabolizers In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam's active metabolite, will be increased. Therefore, in patients known to be CYP2C19 poor metabolizers, the starting dose should be 5 mg/day and dose titration should proceed slowly according to weight, but to half the dose presented in Table 1, as tolerated. If necessary and based upon clinical response, an additional titration to the maximum dose (20 mg/day or 40 mg/day, depending on the weight group) may be started on day 21 [see Use in Specific Populations (8.6) , Clinical Pharmacology (12.5) ] .
2.6Patients with Renal Impairment No dose adjustment is required for patients with mild and moderate renal impairment. There is no experience with clobazam tablets in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if clobazam or its active metabolite, N-desmethylclobazam, is dialyzable [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3) ] .
2.7Dosage Adjustments in Patients with Hepatic Impairment Clobazam is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of clobazam. For this reason, proceed slowly with dosing escalations. For patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9), the starting dose should…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: 10 mg and 20 mg with a functional score for oral administration. Each clobazam tablet is a white to off-white, caplet shape tablet functionally-scored on both sides debossed with "T" over the score and "10" under the score or a "T" over the score and "20" under the score on one side and plain on the other side. 10 mg and 20 mg functionally-scored on both sides ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Clobazam tablets are contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions [see Warnings and Precautions (5.5) ] . History of hypersensitivity to the drug or its ingredients ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Somnolence or Sedation: Monitor for central nervous system (CNS) depression. Risk may be increased with concomitant use of other CNS depressants ( 5.2 , 5.3 ) Withdrawal: Symptoms may occur with rapid dose reduction or discontinuation. Discontinue clobazam gradually ( 5.4 ) Serious Dermatological Reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis): Discontinue clobazam at first sign of rash unless the rash is clearly not drug-related ( 5.5 ) Physical and Psychological Dependence: Monitor patients with a history of substance abuse for signs of habituation and dependence ( 5.6 , 9 ) Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behaviors ( 5.7 )
5.1Risks from Concomitant Use with Opioids Concomitant use of benzodiazepines, including clobazam, 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 clobazam 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 clobazam is used with opioids [see Drug Interactions (7.1) ] .
5.2Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants Since clobazam has a central nervous system (CNS) depressant effect, patients or their caregivers should be cautioned against simultaneous use with other CNS depressant drugs or alcohol, and cautioned that the effects of other CNS depressant drugs or alcohol may be potentiated [see Drug Interactions (7.2) ] .
5.3Somnolence or Sedation Clobazam causes somnolence and sedation. In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related. In general, somnolence and sedation begin within the first month of treatment and may diminish with continued treatment.
Prescribers should monitor patients for somnolence and sedation, particularly with concomitant use of other central nervous system depressants. Prescribers should caution patients against engaging in hazardous activities requiring mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of clobazam is known.
5.4Withdrawal Symptoms Abrupt discontinuation of clobazam should be avoided. Clobazam should be tapered by decreasing the dose every week by 5 mg/day to 10 mg/day until discontinuation [see Dosage and Administration (2.2) ] . Withdrawal symptoms occurred following abrupt discontinuation of clobazam; the risk of withdrawal symptoms is greater with higher doses.
As with all antiepileptic drugs, clobazam should be withdrawn gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms (e.g., convulsions, psychosis, hallucinations, behavioral disorder, tremor, and anxiety) have been reported following abrupt discontinuance of benzodiazepines. The more severe withdrawal symptoms have usually been limited to patients who received excessive doses over an extended period of time, followed by an abrupt discontinuation.
Generally milder withdrawal symptoms (e.g., dysphoria, anxiety, and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic doses for several months.
5.5Serious Dermatological Reactions Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with clobazam in both children and adults during the post…
🤒 Adverse Reactions ▾
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) ] Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants [see Warnings and Precautions (5.2) ] Somnolence or Sedation [see Warnings and Precautions (5.3) ] Withdrawal Symptoms [see Warnings and Precautions (5.4) ] Serious Dermatological Reactions [see Contraindications (4) , Warnings and Precautions (5.5) ] Physical and Psychological Dependence [see Warnings and Precautions (5.6) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.7) ] Adverse reactions that occurred at least 10% more frequently than placebo in any clobazam dose included constipation, somnolence or sedation, pyrexia, lethargy, and drooling ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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) [see Clinical 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 % Low Maximum daily dose of 5 mg for ≤30 kg body weight; 10 mg for >30 kg body weight N=58 % Medium Maximum daily dose of 10 mg for ≤30 kg body weight; 20 mg for >30 kg body weight N=62 % High Maximum daily dose of 20 mg for ≤30 kg body weight; 40 mg for >30 kg body weight 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
6.2Postmarketing Experience These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Alcohol: Increases blood levels of clobazam by about 50% ( 7.2 ) Drugs metabolized by CYP2D6: Lower doses of these drugs may be required when used concomitantly with clobazam ( 7.3 ) Strong or Moderate CYP2C19 Inhibitors: Dosage adjustment of clobazam may be necessary ( 7.4 )
7.1Opioids The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites, and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation [see Warnings and Precautions (5.1) ] .
7.2CNS Depressants and Alcohol Concomitant use of clobazam with other CNS depressants may increase the risk of sedation and somnolence [see Warnings and Precautions (5.2) ] . Alcohol, as a CNS depressant, will interact with clobazam in a similar way and also increases clobazam's maximum plasma exposure by approximately 50%. Therefore, caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol, and caution that the effects of other CNS depressant drugs or alcohol may be potentiated [see Warnings and Precautions (5.2) ] .
7.3Effect of Clobazam on Other Drugs Hormonal Contraceptives Clobazam is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their effectiveness may be diminished when given with clobazam. Additional non-hormonal forms of contraception are recommended when using clobazam [see Clinical Pharmacology (12.3) , Patient Counseling Information (17) ] .
Drugs Metabolized by CYP2D6 Clobazam inhibits CYP2D6. Dose adjustment of drugs metabolized by CYP2D6 may be necessary [see Clinical Pharmacology (12.3) ] .
7.4Effect of Other Drugs on Clobazam Strong and moderate inhibitors of CYP2C19 Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the active metabolite of clobazam. This may increase the risk of dose-related adverse reactions. Dosage adjustment of clobazam may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g., omeprazole) [see Clinical Pharmacology (12.3) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 )
8.1Pregnancy Pregnancy Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as clobazam, during pregnancy. Physicians are advised to recommend that pregnant patients taking clobazam tablets enroll in the North American Antiepileptic Drug (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 the registry can also be found at the website http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate and well-controlled studies of clobazam in pregnant women. Available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies.
Although some early epidemiological studies suggested a relationship between benzodiazepine drug use in pregnancy and congenital anomalies such as cleft lip and/or palate, these studies had considerable limitations. More recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies. There is insufficient evidence to assess the effect of benzodiazepine pregnancy exposure on neurodevelopment.
There are clinical considerations regarding exposure to benzodiazepines during the second and third trimester of pregnancy or immediately prior to or during childbirth. These risks include decreased fetal movement and/or fetal heart rate variability, "floppy infant syndrome," dependence, and withdrawal [see Clinical Considerations and Human Data ]. Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients [see Animal Data ].
Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. Clobazam should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Advise a pregnant woman and women of childbearing age of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Fetal/Neonatal Adverse Reactions Infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period.
Clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting. These complications can appear shortly after delivery to 3 weeks after birth and persist from hours to several months depending on the degree of dependence and the pharmacokinetic profile of the benzodiazepine. Symptoms may be mild and transient or severe.
Standard management for neonatal withdrawal syndrome has not yet been defined. Observe newborns who are exposed to clobazam in utero during the later stages of pregnancy for symptoms of withdrawal and manage accordingly. Labor and Delivery Administration of benzodiazepines immediately prior to or during childbirth can result in a floppy infant syndrome, which is characterized by lethargy, hypothermia, hypotonia, respiratory depression, and difficulty feeding.
Floppy infant syndrome occurs mainly within the first hours after birth and may last up to 14…
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as clobazam, during pregnancy. Physicians are advised to recommend that pregnant patients taking clobazam tablets enroll in the North American Antiepileptic Drug (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 the registry can also be found at the website http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate and well-controlled studies of clobazam in pregnant women. Available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies.
Although some early epidemiological studies suggested a relationship between benzodiazepine drug use in pregnancy and congenital anomalies such as cleft lip and/or palate, these studies had considerable limitations. More recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies. There is insufficient evidence to assess the effect of benzodiazepine pregnancy exposure on neurodevelopment.
There are clinical considerations regarding exposure to benzodiazepines during the second and third trimester of pregnancy or immediately prior to or during childbirth. These risks include decreased fetal movement and/or fetal heart rate variability, "floppy infant syndrome," dependence, and withdrawal [see Clinical Considerations and Human Data ]. Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients [see Animal Data ].
Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. Clobazam should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Advise a pregnant woman and women of childbearing age of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Fetal/Neonatal Adverse Reactions Infants born to mothers who have taken benzodiazepines during the later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period.
Clinical manifestations of withdrawal or neonatal abstinence syndrome may include hypertonia, hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting. These complications can appear shortly after delivery to 3 weeks after birth and persist from hours to several months depending on the degree of dependence and the pharmacokinetic profile of the benzodiazepine. Symptoms may be mild and transient or severe.
Standard management for neonatal withdrawal syndrome has not yet been defined. Observe newborns who are exposed to clobazam in utero during the later stages of pregnancy for symptoms of withdrawal and manage accordingly. Labor and Delivery Administration of benzodiazepines immediately prior to or during childbirth can result in a floppy infant syndrome, which is characterized by lethargy, hypothermia, hypotonia, respiratory depression, and difficulty feeding.
Floppy infant syndrome occurs mainly within the first hours after birth and may last up to 14 days. Observe exposed newborns for these symptoms and manage accordingly. Data Human Data C…
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in patients less than 2 years of age have not been established. In a study in which clobazam (0 mg/kg/day, 4 mg/kg/day, 36 mg/kg/day, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. The effect on bone density, but not on behavior, was reversible when drug was discontinued.
The no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (AUC) to clobazam and its major active metabolite, N-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of clobazam did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, elderly subjects appear to eliminate clobazam more slowly than younger subjects based on population pharmacokinetic analysis. For these reasons, the initial dose in elderly patients should be 5 mg/day.
Patients should be titrated initially to 10 mg/day to 20 mg/day. Patients may be titrated further to a maximum daily dose of 40 mg if tolerated [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ] .
🆘 Overdosage ▾
10 OVERDOSAGE
10.1Signs and Symptoms of Overdosage Overdose and intoxication with benzodiazepines, including clobazam, may lead to CNS depression, associated with drowsiness, confusion and lethargy, possibly progressing to ataxia, respiratory depression, hypotension, and, rarely, coma or death. The risk of a fatal outcome is increased in cases of combined poisoning with other CNS depressants, including opioids and alcohol.
10.2Management of Overdosage The management of clobazam overdose may include gastric lavage and/or administration of activated charcoal, intravenous fluid replenishment, early control of airway and general supportive measures, in addition to monitoring level of consciousness and vital signs. Hypotension can be treated by replenishment with plasma substitutes and, if necessary, with sympathomimetic agents. The efficacy of supplementary administration of physostigmine (a cholinergic agent) or of flumazenil (a benzodiazepine antagonist) in clobazam overdose has not been assessed.
The administration of flumazenil in cases of benzodiazepine overdose can lead to withdrawal and adverse reactions. Its use in patients with epilepsy is typically not recommended.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor.
12.2Pharmacodynamics Effects on Electrocardiogram The effect of clobazam 20 mg and 80 mg administered twice daily on QTc interval was evaluated in a randomized, evaluator-blinded, placebo-, and active-controlled (moxifloxacin 400 mg) parallel thorough QT study in 280 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on the Fridericia correction method was below 10 ms, the threshold for regulatory concern.
Thus, at a dose two times the maximum recommended dose, clobazam did not prolong the QTc interval to any clinically relevant extent.
12.3Pharmacokinetics The peak plasma levels (C max ) and the area under the curve (AUC) of clobazam are dose-proportional over the dose range of 10 mg to 80 mg following single- or multiple-dose administration of clobazam. Based on a population pharmacokinetic analysis, the pharmacokinetics of clobazam are linear from 5 mg/day to 160 mg/day. Clobazam is converted to N-desmethylclobazam which has about 1/5 the activity of clobazam.
The estimated mean elimination half-lives (t ½ ) of clobazam and N-desmethylclobazam were 36 hours to 42 hours and 71 hours to 82 hours, respectively. Absorption Clobazam is rapidly and extensively absorbed following oral administration. The time to peak concentrations (T max ) of clobazam tablets under fasted conditions ranged from 0.5 hours to 4 hours after single- or multiple-dose administrations.
The relative bioavailability of clobazam tablets compared to an oral solution is approximately 100%. After single dose administration of the oral suspension under fasted conditions, the T max ranged from 0.5 hours to 2 hours. Based on exposure (C max and AUC) of clobazam, clobazam tablets and suspension were shown to have similar bioavailability under fasted conditions.
The administration of clobazam tablets with food or when crushed in applesauce does not affect absorption. Although not studied, the oral bioavailability of the oral suspension is unlikely to be affected under fed conditions. Distribution Clobazam is lipophilic and distributes rapidly throughout the body.
The apparent volume of distribution at steady state was approximately 100 L. The in vitro plasma protein binding of clobazam and N-desmethylclobazam is approximately 80% to 90% and 70%, respectively. Metabolism and Excretion Clobazam is extensively metabolized in the liver, with approximately 2% of the dose recovered in urine and 1% in feces as unchanged drug.
The major metabolic pathway of clobazam involves N-demethylation, primarily by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. N-desmethylclobazam, an active metabolite, is the major circulating metabolite in humans, and at therapeutic doses, plasma concentrations are 3 times to 5 times higher than those of the parent compound. Based on animal and in vitro receptor binding data, estimates of the relative potency of N-desmethylclobazam compared to parent compound range from 1/5 to equal potency.
N-desmethylclobazam is extensively metabolized, mainly by CYP2C19. N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine. Following a single oral dose of radiolabeled drug, approximately 11% of the dose was excreted in the feces and approximately 82% was excreted in the urine.
The polymorphic CYP2C19 is the major contributor to the metabolism of the pharmacologically active N - desmethylclobazam [see Clinical Pharmacology (12.5) ] . In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2- to 3-fold higher in the urine than in CYP2C19 extensive…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Each clobazam tablet contains 10 mg or 20 mg of clobazam and is a white to off-white, caplet shape tablet functionally-scored on both the sides debossed with "T" over the score and "10" under the score or a "T" over the score and "20" under the score on one side and plain on the other side. NDC 51672-4202-1: 10 mg scored tablet, Bottles of 100 NDC 51672-4203-1: 20 mg scored tablet, Bottles of 100 Store tablets at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].
📦 Storage and Handling ▾
Store tablets at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Table 4. Description Established Name: Clobazam Tablets Dosage Form: Tablet Route of Administration: Oral Established Pharmacologic Class of Drug: Benzodiazepine Chemical Name: 7-Chloro-1-methyl-5-phenyl-1H-1,5 benzodiazepine-2,4( 3H,5H) -dione Structural Formula: 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 methylene chloride. The melting range of clobazam is from 182°C to 185°C.
The molecular formula is C 16 H 13 O 2 N 2 Cl 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 silicone dioxide, lactose monohydrate, magnesium stearate, pregelatinized maize starch, and talc.
Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Risks from Concomitant Use with Opioids Inform patients and caregivers that potentially fatal additive effects may occur if clobazam is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . Somnolence or Sedation Advise patients or caregivers to check with their healthcare provider before clobazam is taken with other CNS depressants such as other benzodiazepines, opioids, tricyclic antidepressants, sedating antihistamines, or alcohol [see Warnings and Precautions (5.2 , 5.3) ].
If applicable, caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that clobazam does not affect them adversely (e.g., impair judgment, thinking or motor skills). Increasing or Decreasing the Clobazam Dose Inform patients or caregivers to consult their healthcare provider before increasing the clobazam dose or abruptly discontinuing clobazam. Advise patients or caregivers that abrupt withdrawal of AEDs may increase their risk of seizure [see Dosage and Administration (2.2) , Warnings and Precautions (5.4) ].
Hypersensitivity Inform patients or caregivers that clobazam is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients [see Warnings and Precautions (5.5) ] . Interactions with Hormonal Contraceptives Counsel women to also use non-hormonal methods of contraception when clobazam is used with hormonal contraceptives and to continue these alternative methods for 28 days after discontinuing clobazam to ensure contraceptive reliability [see Drug Interactions (7.3) , Clinical Pharmacology (12.3) ].
Serious Dermatological Reactions Advise patients or caregivers that serious skin reactions have been reported in patients taking clobazam. Serious skin reactions, including SJS/TEN, may need to be treated in a hospital and may be life-threatening. If a skin reaction occurs while taking clobazam, patients or caregivers should consult with healthcare providers immediately [see Warnings and Precautions (5.5) ].
Suicidal Thinking and Behavior Counsel patients, their caregivers, and their families that AEDs, including clobazam, may increase the risk of suicidal thoughts and behavior and advise them 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 of self-harm. Patients should report behaviors of concern immediately to healthcare providers [see Warnings and Precautions (5.7) ]. Pregnancy Advise pregnant women and women of childbearing potential that the use of clobazam during pregnancy can cause fetal harm which may occur early in pregnancy before many women know they are pregnant.
Instruct patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy. When appropriate, prescribers should counsel pregnant women and women of childbearing potential about alternative therapeutic options. Advise patients that there is a pregnancy exposure registry that collects information about the safety of antiepileptic drugs during pregnancy [see Use in Specific Populations (8.1) ].
Nursing Counsel patients that clobazam is excreted in breast milk. Instruct patients to notify their physician if they are breast feeding or intend to breast feed during therapy and counsel nursing mothers to observe their infants for poor sucking and somnolence [see Use in Specific Populations (8.2) ].
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: June 2018 20999-0618-1 MEDICATION GUIDE CIV Clobazam (KLOE ba zam) Tablets What is the most important information I should know about clobazam tablets?
Do not stop taking clobazam tablets without first talking to your healthcare provider. Stopping clobazam tablets suddenly can cause serious side effects. Clobazam is a benzodiazepine medicine.
Benzodiazepines can cause severe drowsiness, breathing problems (respiratory depression), coma, and death when taken with opioid medicines. Clobazam 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 clobazam tablets affect you. Clobazam 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 clobazam tablets until you talk 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. Clobazam tablets can cause withdrawal symptoms. Do not stop taking clobazam tablets all of a sudden without first talking to a healthcare provider.
Stopping clobazam tablets suddenly can cause seizures that will not stop (status epilepticus), hearing or seeing things that are not there (hallucinations), shaking, nervousness, and stomach and muscle cramps. Talk to your healthcare provider about slowly stopping clobazam tablets to avoid withdrawal symptoms. Clobazam tablets can be abused and cause dependence.
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. Clobazam is a federally controlled substance (CIV) because it 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.
Serious skin reactions have been seen when clobazam is taken with other medications and may require stopping its use. Do not stop taking clobazam tablets without first talking to your healthcare provider. 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 need to be treated right away. Call your healthcare provider immediately if you have skin blisters, rash, sores in the mouth, hives or any other allergic reaction. Like other antiepileptic drugs, 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: thoughts about suicide or dying new or worse depression feeling agitated or restless trouble sleeping (insomnia) acting aggressive, being angry, or violent an extreme increase in activity and talking (mania) attempts to commit suicide new or worse anxiety panic attacks new or worse irritability acting on dangerous impulses 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. What are clobazam tablets?
Clobazam tabl…