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

Increased responder rates with increased dosage

Greater response rates of 50% or more with ONFI vs placebo1

SECONDARY EFFICACY RESULTS BY DOSE: RESPONDER RATES1

P<0.05,   P<0.01. The logistic regression model was unable to provide valid estimates of statistical significance for the 100% response threshold.

Study Design: CONTAIN (ClObazam in PatieNTs with Lennox-GAstaut SyNdrome) was a randomized, double-blind, placebo-controlled study consisting of a 4-week baseline period followed by a 3-week titration period and a 12-week maintenance period (N=238, randomized). 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 1 of 3 target maintenance doses of ONFI. The dosage groups were: placebo (n=59); low-dose (5 mg/10 mg, n=58); medium-dose (10 mg/20 mg, n=62); and high-dose (20 mg/40 mg, n=59). Doses above 5 mg/day were administered in 2 divided doses. The primary endpoint was the percentage reduction in mean weekly rate of drop seizures (atonic, tonic, or myoclonic) from the 4-week baseline period to the 12-week maintenance period.

  • 43%, 59%, and 78% of patients achieved a ≥50% reduction in weekly rate of drop seizures at low, medium, and high doses of ONFI, respectively1
  • In addition, 25% of patients on a high dose of ONFI achieved a 100% reduction in weekly rate of drop seizures1
  • Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death2
  • 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 potentiated2
  • As with all antiepileptic drugs (AEDs), withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses2
  • 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-harm2

READ MORE CLINICAL TRIAL RESULTS

Download the CONTAIN Trial abstract to see an overview of results with ONFI.

DOWNLOAD TRIAL RESULTS

MEET DR. ABDELMOITY, AN LGS THOUGHT LEADER

He discusses the increased efficacy with increased dosage demonstrated in the CONTAIN Trial

LEARN ABOUT FLEXIBLE DOSING FORMULATIONS

Two dosing formulations, including an oral suspension

EXPLORE ONFI SAVINGS & SUPPORT

Cost-savings information, education, and resources to help your patients

IMPORTANT SAFETY INFORMATION

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.
  • 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.

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.

Risks from Concomitant Use with Opioids (see Boxed Warning)

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.

Potentiation of Sedation from Concomitant Use with Central Nervous System (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.

Withdrawal Symptoms

As with all antiepileptic drugs (AEDs), withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses.

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.

Physical and Psychological Dependence

Carefully monitor patients with a history of substance abuse when receiving ONFI or other psychotropic agents because of the predisposition of such patients to habituation and dependence. In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence increases with increasing dose and duration of treatment.

Suicidal Behavior and Ideation

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

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 Warning for risks from concomitant use with opioids; Medication Guide; and Instructions for Use.

IMPORTANT SAFETY INFORMATION

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.
  • 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.

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.

Risks from Concomitant Use with Opioids (see Boxed Warning)

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.

Potentiation of Sedation from Concomitant Use with Central Nervous System (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.

Withdrawal Symptoms

As with all antiepileptic drugs (AEDs), withdraw ONFI gradually to minimize the risk of precipitating seizures, seizure exacerbation, or status epilepticus. Withdrawal symptoms occurred following abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater with higher doses.

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.

Physical and Psychological Dependence

Carefully monitor patients with a history of substance abuse when receiving ONFI or other psychotropic agents because of the predisposition of such patients to habituation and dependence. In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI. The risk of dependence increases with increasing dose and duration of treatment.

Suicidal Behavior and Ideation

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

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 Warning for risks from concomitant use with opioids; Medication Guide; and Instructions for Use.

References
  • 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.
  • ONFI [package insert]. Deerfield, IL: Lundbeck.
  • Conry JA, Ng YT, Paolicchi JM, et al. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009;50(5):1158-1166.