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

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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.
  • Data on file. Lundbeck, Deerfield, IL.