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

What to know when prescribing ONFI

RxPad_dosing

Physicians who decide that ONFI is clinically appropriate for their LGS patients should write “DISPENSE AS WRITTEN (DAW)” on the prescription or follow their state’s instructions for indicating branded versus generic products to ensure that patients receive ONFI as intended

ONFI provides flexible dosing formulations, including an oral suspension

ONFI Oral Suspension 2.5 mg/mL provides dosing in a liquid formulation1

ONFI® (clobazam) CIV oral suspension bottle and dosing instructions icons. See Indication and full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
  • Shake well before each use
  • ONFI oral suspension contains potential carbohydrates in the form of sucralose, propylene glycol, and maltitol. The potential carbohydrate content is 0.19 g/mL2
  • The relative bioavailability of ONFI tablets compared to ONFI oral suspension is approximately 100%

ONFI Scored Tablets can be broken in half or administered whole

ONFI® (clobazam) CIV tablets and dosing instructions icons. See Indication and full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
  • Can be administered whole, halved along the score, or crushed and mixed with applesauce

RECOMMENDED TOTAL DAILY DOSING BY WEIGHT GROUP1

Chart of ONFI® (clobazam) CIV dosing recommendations by weight group - see Indication and full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
  • Do not proceed with dose escalation more rapidly than weekly1
  • Titration schedule and final dose should be based on response to therapy and tolerability1
  • As with all antiepileptic drugs (AEDs) and benzodiazepines, withdraw ONFI gradually. Taper by decreasing the total daily dose by 5 - 10 mg/day on a weekly basis until discontinued1
  • ONFI causes somnolence and sedation. In clinical trials, somnolence or sedation was reported at all effective doses and was dose-related1
  • Instruct patients to read the “Instructions for Use” carefully

RECOMMENDED DOSING IN SPECIFIC POPULATIONS1

Chart of ONFI® (clobazam) CIV dosing recommendations for specific populations - see Indication and full Prescribing Information, including Boxed Warning for risks from concomitant use with opioids.
  • No dose adjustment is required for patients with mild and moderate renal impairment1
  • No definitive data available in patients with severe hepatic impairment, severe renal impairment, or end-stage renal disease1

Drug interactions

Opioids

  • 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 and may result in profound sedation, respiratory depression, coma, and death1
  • When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists1
  • Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate1
  • Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation1

CNS depressants and alcohol

  • Concomitant use with other CNS depressants may increase the risk of sedation and somnolence1
  • Alcohol, as a CNS depressant, will interact with ONFI in a similar way and also increases the maximum plasma exposure of clobazam by approximately 50%1
  • 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 potentiated1

Effect of ONFI on other drugs

  • ONFI is a weak CYP3A4 inducer. As some hormonal contraceptives are metabolized by CYP3A4, their effectiveness may be diminished when given with ONFI. Additional nonhormonal forms of contraception are recommended when using ONFI1
  • ONFI is a CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 may be necessary1

Effect of other drugs on ONFI

  • Dosage adjustment of ONFI may be necessary when coadministered with strong CYP2C19 inhibitors (eg, fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (eg, omeprazole) due to increased risk of dose-related adverse events1

Combining ONFI with other AEDs

The following AEDs did not significantly alter the pharmacokinetics of ONFI or its active metabolite1:

  • Valproic acid
  • Phenobarbital
  • Phenytoin
  • Carbamazepine
  • Felbamate
  • Oxcarbazepine

Pregnancy and nursing

  • 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

MEET DR. ABDELMOITY, AN LGS THOUGHT LEADER

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

VIEW SAFETY PROFILE

Learn about the safety profile and results from our clinical data

EXPLORE DOWNLOADABLE RESOURCES

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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
  • ONFI [package insert]. Deerfield, IL: Lundbeck.
  • Data on file. Lundbeck, Deerfield, IL.