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

  • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. If a decision is made to prescribe ONFI concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use. Advise both patients and caregivers about the risks of respiratory depression and sedation when ONFI is used with opioids1
  • ONFI causes somnolence and sedation. Monitor patients for somnolence and sedation, particularly with concomitant use of other central nervous system (CNS) depressants. Caution patients against engaging in hazardous activities that require mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known1
  • ONFI 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. Only the CONTAIN trial included a placebo group, allowing comparison of adverse reaction rates on ONFI at several doses to placebo1
  • Since ONFI has a CNS depressant effect, caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol and that the effects of other CNS depressant drugs or alcohol may be potentiated1
  • Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with ONFI in both children and adults during the post-marketing period. Discontinue ONFI at the first sign of rash, unless the rash is clearly not drug-related1
  • Antiepileptic drugs (AEDs), including ONFI, increase the risk of suicidal thoughts or behavior in patients. Inform patients, their caregivers, and families of the risk and advise them to monitor and report any emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. If these symptoms occur, consider whether it may be related to the AED or illness, because epilepsy itself can increase these risks1
  • Based on animal data, ONFI may cause fetal harm and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus1
  • ONFI is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ONFI, discontinue nursing or discontinue the drug1

ONFI safety results

ADVERSE REACTIONS REPORTED FOR ≥5% OF PATIENTS AND MORE FREQUENTLY THAN PLACEBO IN ANY TREATMENT GROUP1

ONFI® (clobazam) CIV safety results chart. See Indication and full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
  • The adverse reactions associated with ONFI treatment discontinuation in ≥1% of patients in decreasing order of frequency included lethargy, somnolence, ataxia, aggression, fatigue, and insomnia1

Tolerance

  • There was no evidence that tolerance to the therapeutic effect of ONFI developed during the 3-month maintenance period of CONTAIN1

Withdrawal and dependence

  • Withdrawal symptoms were not observed when ONFI was tapered in the CONTAIN Trial2
  • Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses1
  • As with all AEDs, withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus1
  • Withdrawal symptoms (eg, 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 (eg, dysphoria, anxiety, and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic doses for several months1
  • In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence is present even with the use of ONFI at the recommended dose range over periods of only a few weeks. The risk of dependence increases with increasing dose and duration of treatment. The risk of dependence is increased in patients with a history of alcohol or drug abuse1

DISCOVER PROVEN RESULTS1,2

Results from the CONTAIN Trial, the largest LGS clinical trial conducted to date

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IMPORTANT SAFETY INFORMATION

Indications and Usage

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

Important Safety Information

WARNING:  RISKS FROM CONCOMITANT USE WITH OPIOIDS;

ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS

See full Prescribing Information for complete boxed warning.

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.

The use of benzodiazepines, including ONFI, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death.

  • Before prescribing ONFI and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

Abrupt discontinuation or rapid dosage reduction of ONFI after continued use may precipitate acute withdrawal reactions, which can be life-threatening.

  • To reduce the risk of withdrawal reactions, use a gradual taper to discontinue or reduce the dosage of ONFI.  
IMPORTANT SAFETY INFORMATION

Indications and Usage

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

Important Safety Information

WARNING:  RISKS FROM CONCOMITANT USE WITH OPIOIDS;

ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS

See full Prescribing Information for complete boxed warning.

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.

The use of benzodiazepines, including ONFI, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death.

  • Before prescribing ONFI and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

Abrupt discontinuation or rapid dosage reduction of ONFI after continued use may precipitate acute withdrawal reactions, which can be life-threatening.

  • To reduce the risk of withdrawal reactions, use a gradual taper to discontinue or reduce the dosage of ONFI.  

Contraindication: Hypersensitivity
ONFI is contraindicated in patients with a history of hypersensitivity to the drug or its ingredients. Hypersensitivity reactions have included serious dermatological reactions.

WARNING: Risks from Concomitant Use with Opioids
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 ONFI concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use. Advise both patients and caregivers about the risks of respiratory depression and sedation when ONFI is used with opioids.

WARNING: Abuse, Misuse, and Addiction
Abuse and misuse of benzodiazepines often (but not always) involves the use of doses greater than the maximum recommended dosage and commonly involves concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death.

Use of ONFI, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of ONFI along with monitoring for signs and symptoms of abuse, misuse, and addiction. Prescribe the lowest effective dosage; avoid or minimize concomitant use of Central Nervous System (CNS) depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

WARNING: Dependence and Withdrawal Reactions
Patients at an increased risk of withdrawal reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages and those who have had longer durations of use.

The continued use of benzodiazepines, including ONFI, may lead to clinically significant physical dependence. Abrupt discontinuation or rapid dosage reduction of ONFI after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures).

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

Potentiation of Sedation from Concomitant Use with CNS Depressants
ONFI has a CNS depressant effect. Caution patients or their caregivers against simultaneous use with other CNS depressant drugs or alcohol, and that the effects of other CNS depressant drugs or alcohol may be potentiated.

Somnolence or Sedation
ONFI 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. Monitor patients for somnolence and sedation, particularly with concomitant use of other CNS depressants. Caution patients against engaging in hazardous activities that require mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known.

Serious Dermatological Reactions
Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with ONFI in both children and adults during the post-marketing period. Discontinue ONFI at the first sign of rash, unless the rash is clearly not drug-related.

Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including ONFI, increase the risk of suicidal thoughts or behavior in patients. Inform patients, their caregivers, and families of the risk and advise them to monitor and report any emergence or worsening of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. If these symptoms occur, consider whether it may be related to the AED or illness, because epilepsy itself can increase these risks.

Pregnancy, Registry and Nursing Mothers

  • Based on animal data, ONFI may cause fetal harm and should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
    • Talk to your patients about enrolling in the North American Antiepileptic Drug Pregnancy Registry; encourage them to call 1-888-233-2334 or visit http://www.aedpregnancyregistry.org/.
  • ONFI is excreted in human milk. Because of the potential for serious adverse reactions from ONFI in nursing infants, discontinue nursing or discontinue the drug.

Adverse Reactions
The most commonly observed adverse reactions reported in an LGS randomized, double-blind, placebo-controlled, parallel group clinical trial of patients who received clobazam as adjunctive therapy (≥10% in any treatment group and at least 5% greater than placebo, respectively) were somnolence or sedation (32% vs. 15%), somnolence (25% vs. 12%), pyrexia (17% vs. 3%), lethargy (15% vs. 5%), aggression (14% vs. 5%), drooling (14% vs. 3%), irritability (11% vs. 5%), ataxia (10% vs. 3%), and constipation (10% vs. 0%).

For more information, please see the full Prescribing Information, including Boxed WarningMedication Guide, and Instructions for Use, or visit ONFIHCP.com.

References
  • ONFI [package insert]. Deerfield, IL: Lundbeck.
  • Ng YT, Conry JA, Drummond R, et al. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011;77(15):1473-1481.