{ "query": "clobazam", "ingredient": "clobazam", "slug": "clobazam", "rxcui": "21241", "brands": [ "Onfi", "Sympazan" ], "names": [ "clobazam" ], "classes": [ { "id": "N05BA", "name": "Benzodiazepine derivatives" } ], "alternatives": [ "alprazolam", "bromazepam", "chlordiazepoxide", "clorazepate dipotassium", "clotiazepam", "cloxazolam", "diazepam", "ethyl loflazepate", "halazepam", "ketazolam", "lorazepam", "medazepam", "nordazepam", "oxazepam", "prazepam", "tofisopam" ], "label": { "route_mode": "ORAL", "route_counts": { "ORAL": 22 }, "boxed_warning": "WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ]. The use of benzodiazepines, including clobazam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing clobazam and throughout treatment, assess each patient's risk for abuse, misuse, and addiction [see Warnings and Precautions (5.2) ]. The continued use of benzodiazepines, including clobazam, may lead to clinically significant physical dependence. The risks of dependence and withdraw...", "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 tablets are a benzodiazepine indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older ( 1 )", "contraindications": "Clobazam is 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 (5.6, 5.7) ]. History of hypersensitivity to the drug or its ingredients ( 4 )", "warnings_and_cautions": "Somnolence or Sedation: Monitor for central nervous system (CNS) depression. Risk may be increased with concomitant use of other CNS depressants. ( 5.4 , 5.5 ) 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. ( 5.6 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: Discontinue if no alternative etiology (5.7) Suicidal Behavior and Ideation: Monitor for suicidal thoughts or behaviors ( 5.8 ) Neonatal Sedation and Withdrawal Syndrome: Clobazam use during pregnancy can result in neonatal sedation and/or neonatal withdrawal ( 5.9 , 8.1 ) 5.1 Risks 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 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...", "warnings": "", "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) ] 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 Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda...", "drug_abuse_and_dependence": "9.1 Controlled Substance Clobazam is a Schedule IV controlled substance. 9.2 Abuse Clobazam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or i...", "controlled_substance": "9.1 Controlled Substance Clobazam is a Schedule IV controlled substance.", "recent_major_changes": "Warnings and Precautions ( 5. 7) 3/2024", "information_for_patients": "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) ]. Abuse, Misuse, and Addiction Inform patients that the use of clobazam, even at recommended dosages, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform patients about the signs and symptoms of benzodiazepine abuse, misuse, and addiction; to seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug [see Warnings and Precautions (5.2) and Drug Abuse and Dependence (9.2) ]. Withdrawal Reactions Advise patients or caregivers that abrupt withdrawal of AEDs may increase their risk of seizure. Inform patients that the continued use of clobazam may lead to clinically significant physical dependence and...", "spl_medguide": "MEDICATION GUIDE Clobazam (kloe-ba-zam) Tablets, CIV This Medication Guide has been approved by the U.S. Food and Drug Administration. What is the most important information I should know about clobazam tablets? Clobazam is 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: shallow or slowed breathing breathing stops (which may lead to the heart stopping) 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. Serious 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 ...", "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 \u226430 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 \u226430 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 ...", "brand_name": "Clobazam", "manufacturer": "Upsher-Smith Laboratories, LLC", "application_number": "ANDA209687", "pharm_class_epc": [ "Benzodiazepine [EPC]" ], "route": [ "ORAL" ], "effective_time": "20240724", "set_id": "6da2c381-057b-456a-b57b-464f8b383371", "has_boxed_warning": true, "controlled": true, "mentions_rems": false }, "faers": { "total": 24742, "serious": 19980, "death": 1612, "hospitalization": 8942, "primary_suspect": 24522, "top_reactions": [ [ "Seizure", 5332 ], [ "Drug Ineffective", 3183 ], [ "Off Label Use", 2508 ], [ "Somnolence", 1980 ], [ "Drug Interaction", 1182 ], [ "Fatigue", 1115 ], [ "Epilepsy", 1078 ], [ "Condition Aggravated", 837 ], [ "Generalised Tonic-Clonic Seizure", 744 ], [ "Product Use In Unapproved Indication", 743 ], [ "Fall", 740 ], [ "Status Epilepticus", 739 ], [ "Decreased Appetite", 737 ], [ "Pneumonia", 711 ], [ "Vomiting", 673 ] ], "by_year": { "2019": 2510, "2020": 2299, "2021": 2879, "2022": 2036, "2023": 2223, "2024": 2453, "2025": 2295, "2026": 1092 }, "by_year_primary": { "2019": 2507, "2020": 2293, "2021": 2869, "2022": 2004, "2023": 2174, "2024": 2412, "2025": 2237, "2026": 1071 } }, "faers_base": { "total": 20692304, "serious_share": 0.5742697381596559, "death_share": 0.09102355155810585 }, "recalls": [ { "class": "Class II", "date": "20250107", "reason": "Presence of Foreign Tablets/Capsules", "firm": "Amerisource Health Services LLC", "status": "Ongoing" }, { "class": "Class II", "date": "20241213", "reason": "Presence of Foreign Tablets/Capsules", "firm": "Amerisource Health Services LLC", "status": "Ongoing" }, { "class": "Class II", "date": "20240212", "reason": "CGMP Deviations: Out of specification for residual solvents.", "firm": "Micro Labs Limited", "status": "Ongoing" }, { "class": "Class II", "date": "20190716", "reason": "Microbial Contamination of Non-Sterile Products: Out-of-specification results for Microbial Enumeration Tests USP <61> was observed.", "firm": "Bionpharma Inc.", "status": "Terminated" } ], "recall_total": 4, "drugsfda": { "applications": 34, "nda": 3, "anda": 31, "first_approval": "20111021", "rems": false, "rems_last": "", "labeling_supplements": 19, "labeling_recent": 10, "sponsors": [ "ACCORD HLTHCARE", "ALKEM LABS LTD", "AMNEAL", "AMNEAL PHARMS CO", "APOTEX", "AUROBINDO PHARMA LTD", "BIONPHARMA", "CHARTWELL MOLECULAR" ], "unapproved": false, "first_approval_fmt": "10/21/2011" }, "trials": { "total": 27, "completed": 15, "terminated": 6, "with_results": 9, "industry": 15, "phase3": 9, "results_share": 0.6, "terminated_share": 0.2222222222222222 }, "pubmed": { "rct": 56, "meta": 8, "recent_rct": 3, "cochrane": [ { "pmid": "31638272", "title": "Clobazam add-on therapy for drug-resistant epilepsy", "year": "2019" }, { "pmid": "29995989", "title": "Clobazam monotherapy for focal or generalized seizures", "year": "2018" }, { "pmid": "25280512", "title": "Clobazam monotherapy for partial-onset or generalized-onset seizures", "year": "2014" }, { "pmid": "18425899", "title": "Clobazam as an add-on in the management of refractory epilepsy", "year": "2008" } ] }, "payments": { "year": "2024", "usd": 86191.27, "records": 230, "by_name": [ [ "Sympazan", 86166.36 ], [ "Onfi", 24.91 ] ], "names_checked": [ "clobazam", "Onfi", "Sympazan" ], "source": "bulk-index" }, "partd": { "year": "2024", "claims": 183581, "beneficiaries": 22167, "spend": 56179198.83, "by_brand": [ { "brand": "Clobazam", "claims": 172413, "per_claim": 128.73595889, "is_generic": true }, { "brand": "Onfi", "claims": 9712, "per_claim": 3236.4796736, "is_generic": false }, { "brand": "Sympazan", "claims": 1456, "per_claim": 1751.8924176, "is_generic": false } ], "per_claim": 306.0185903225279 }, "mdl": [], "dsc": [ { "date": "20231128", "title": "FDA warns of rare but serious drug reaction to the antiseizure medicines levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam) and clobazam (Onfi, Sympazan)", "url": "https://www.fda.gov/drugs/drug-safety-communications/fda-warns-rare-serious-drug-reaction-antiseizure-medicines-levetiracetam-keppra-keppra-xr-elepsia-xr", "kind": "drug", "matched": "onfi" }, { "date": "20131203", "title": "FDA warns of serious skin reactions with the anti-seizure drug Onfi (clobazam) and has approved label changes", "url": "https://www.fda.gov/Drugs/DrugSafety/ucm377204.htm", "kind": "drug", "matched": "onfi" } ], "settlements": [], "prescrire": null, "eml": { "listed": false, "status": "", "name": "", "matched": null, "stewardship": [] }, "exposure": { "years": [ "2024", "2025", "2026" ], "reports_recent": 5720, "fills": 183581, "per_million": 31157.90849815613, "ratio": 11.252608847633939, "median": 2768.949753790441 }, "scores": { "safety": { "score": 24, "letter": "F", "why": [ "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)", "FDA issued 2 Drug Safety Communication(s) naming this drug since 2010, most recently 2023 (-16)", "31,158 FDA reports naming it as the suspect drug per million Medicare fills, 11.3x the median drug on this site (-15)", "Federally controlled substance: dependence and misuse risk (-10)", "Death share in reports is near or below the FAERS average (0.7x)", "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)" ], "weight": 0.35 }, "evidence": { "score": 47, "letter": "F", "why": [ "56 randomized trials and 8 systematic reviews/meta-analyses indexed in PubMed", "4 independent Cochrane review(s) exist", "22% of registered trials were terminated, withdrawn, or suspended (-8)" ], "weight": 0.25 }, "regulatory": { "score": 81, "letter": "B", "why": [ "Recalls since 2016: 0 Class I, 4 Class II, 0 Class III across 31 generic makers (-6)", "10 label changes approved since 2021: the safety story is still moving (-8)", "Label lists recent major changes to warnings or indications (-5)" ], "weight": 0.15 }, "conflict": { "score": 100, "letter": "A", "why": [ "Pharma paid doctors $86,191 tied to this drug last year: negligible", "Not named in any pending federal MDL" ], "weight": 0.15 }, "options": { "score": 100, "letter": "A", "why": [ "Generic versions approved (31 applications)", "16 same-class alternatives exist" ], "weight": 0.1 } }, "total": 57, "grade": "D", "questions": [ "In 2023 the FDA issued a safety communication about this drug (FDA warns of rare but serious drug reaction to the antiseizure medicines levetiracetam (Keppra, Keppra XR, Ele). Does that risk apply to me?", "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?", "This is a controlled substance. What is the plan for how long I take it and how I stop?", "The most-reported problems in FDA's adverse event data are seizure, somnolence. How would we recognize and handle those?", "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?", "Why this one over alprazolam, bromazepam, chlordiazepoxide? What would make you pick one of those instead?", "What result are we expecting, by when, and what is the plan if it does not happen?", "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)" ] }