Indicated for 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. 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.

The use of benzodiazepines, including ONFI, 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 ONFI and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

The continued use of benzodiazepines, including ONFI, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. 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 ONFI or reduce the dosage.

Abrupt discontinuation of ONFI should be avoided. ONFI should be tapered by decreasing the dose every week by 5-10 mg/day until discontinuation.

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

Plasma concentrations at any given dose are generally higher in the elderly: proceed slowly with dose escalation. The starting dose should be 5 mg/day for all elderly patients.

Prescribers should caution patients against engaging in hazardous activities requiring mental alertness, such as operating dangerous machinery or motor vehicles, until the effect of ONFI is known.

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.

There is no experience with ONFI in patients with severe renal impairment or end stage renal disease (ESRD). It is not known if clobazam or its active metabolite, N-desmethylclobazam, is dialyzable.

ONFI is hepatically metabolized; however, there are limited data to characterize the effect of hepatic impairment on the pharmacokinetics of ONFI. For this reason, proceed slowly with dosing escalations.

Patients with a history of substance abuse should be under careful surveillance when receiving ONFI or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Antiepileptic drugs (AEDs), including ONFI, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

In CYP2C19 poor metabolizers, levels of N-desmethylclobazam, clobazam’s active metabolite, will be increased.

As some hormonal contraceptives are metabolized by CYP3A4, their effectiveness may be diminished when given with ONFI. Additional non-hormonal forms of contraception are recommended when using ONFI.

ONFI inhibits CYP2D6. Dose adjustment of drugs metabolized by CYP2D6 may be necessary.

Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam, the active metabolite of clobazam. This may increase the risk of dose-related adverse reactions. Dosage adjustment of ONFI may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g., omeprazole). 

There are no adequate and well-controlled studies of ONFI in pregnant women. Animal studies: developmental toxicity including increased incidences of fetal malformations.

There are clinical considerations regarding exposure to benzodiazepines during the second and third trimester of pregnancy or immediately prior to or during childbirth. These risks include decreased fetal movement and/or fetal heart rate variability, “floppy infant syndrome,” dependence, and withdrawal.

ONFI is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from ONFI, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

GoToSource

• Use in patients under the age of 2. GoToSource

• Alcohol withdrawal. GoToSource

• Anxiety. GoToSource

• Restless legs syndrome. GoToSource

• Seizures not associated with lennox-gastaut syndrome. GoToSource

• Epileptic encephalopathy, prophylaxis of febrile seizures and as an adjunctive therapy for the management of refractory epilepsy. GoToSource

⚠️  In patients with CYP2C19 gene variation standard doses of clobazam lead to higher levels of norclobazam and increased risk of adverse effects.

Somnolence (sleepiness), pyrexia (fever), upper respiratory infections and lethargy. GoToSource

Urinary tract infection, aggression, dysarthria (speech disorder) and insomnia. GoToSource

Hypothermia (abnormally low body temperature). GoToSource

Hyperactivity and behavioral problems, salivation, ataxia (lack of muscle control), weight gain. GoToSource

Constipation, hypomania (mild form of mania), pneumonia, falls, otitis media (ear infections), convulsions, sinusitis, and nasopharyngitis. GoToSource

Increased risk of suicidal thoughts and behavior. GoToSource

Increased risk of dementia. GoToSource

Stevens-johnson syndrome and toxic epidermal necrolysis (life-threatening skin condition). GoToSource

Withdrawal syndrome. GoToSource

Lawsuits filed for stevens-johnson syndrome.