"The U.S. Food and Drug Administration today approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat seizures associated with epilepsy.
Epilepsy is a brain disorder caused by abnormal or excessive activity in the brain"...
Clinically significant adverse reactions that appear in other sections of the labeling include the following:
- Somnolence or Sedation [see WARNINGS AND PRECAUTIONS]
- Potentiation of Sedation from Concomitant Use with Central Nervous System Depressants [see WARNINGS AND PRECAUTIONS]
- Withdrawal Symptoms [see WARNINGS AND PRECAUTIONS]
- Serious Dermatological Reactions [see WARNINGS AND PRECAUTIONS]
- Physical and Psychological Dependence [see WARNINGS AND PRECAUTIONS]
- Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
During its development for the adjunctive treatment of seizures associated with LGS, 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. The conditions and duration of exposure varied greatly and included single- and multiple-dose clinical pharmacology studies in healthy volunteers and two double-blind studies in patients with LGS (Study 1 and 2) [see Clinical Studies ]. Only Study 1 included a placebo group, allowing comparison of adverse reaction rates on ONFI at several doses to placebo.
Adverse Reactions Leading To Discontinuation In An LGS Placebo Controlled Clinical Trial (Study 1)
The adverse reactions associated with ONFI treatment discontinuation in ≥ 1% patients in decreasing order of frequency included lethargy, somnolence, ataxia, aggression, fatigue, and insomnia.
Most Common Adverse Reactions In An LGS Placebo Controlled Clinical Trial (Study 1)
Table 3 lists the adverse reactions that occurred in ≥ 5% of ONFI treated patients (at any dose), and at a rate greater than placebo treated patients, in the randomized, double-blind, placebo-controlled, parallel group clinical study of adjunctive AED therapy for 15 weeks (Study 1).
Table 3: Adverse Reactions Reported for ≥ 5% of
Patients and More Frequently than Placebo in Any Treatment Group
|ONFI Dose Level||All ONFI
|Highc N=59 %|
|General Disorders and Administration Site Conditions|
|Infections and Infestations|
|Upper respiratory tract infection||10||10||13||14||12|
|Urinary tract infection||0||2||5||5||4|
|Metabolism and Nutrition Disorders|
|Nervous System Disorders|
|Somnolence or Sedation||15||17||27||32||26|
|a Maximum daily dose of 5 mg for ≤ 30 kg
body weight; 10 mg for > 30 kg body weight
b Maximum daily dose of 10 mg for ≤ 30 kg body weight; 20 mg for > 30 kg body weight
c Maximum daily dose of 20 mg for ≤ 30 kg body weight; 40 mg for > 30 kg body weight
Post Marketing Experience
These reactions are reported voluntarily from a population of uncertain size; therefore, it is not possible to estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions are categorized by system organ class.
Eye Disorders: Diplopia, vision blurred
Gastrointestinal Disorders: Abdominal distention
Investigations: Hepatic enzyme increased
Musculoskeletal: Muscle spasms
Psychiatric Disorders: Agitation, anxiety, apathy, confusional state, depression, delirium, delusion, hallucination
Respiratory Disorders: Aspiration, respiratory depression
Skin and Subcutaneous Tissue Disorders: Rash, urticaria
Read the Onfi (clobazam tablets and oral suspension) Side Effects Center for a complete guide to possible side effects
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 non-hormonal forms of contraception are recommended when using ONFI [see CLINICAL PHARMACOLOGY, PATIENT INFORMATION].
Drugs Metabolized By CYP2D6
ONFI inhibits CYP2D6. Dose adjustment of drugs metabolized by CYP2D6 may be necessary [see CLINICAL PHARMACOLOGY].
Effect Of Other Drugs On ONFI
Strong And Moderate Inhibitors Of CYP2C19
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) [see CLINICAL PHARMACOLOGY].
CNS Depressants And Alcohol
Concomitant use of ONFI with other CNS depressants may increase the risk of sedation and somnolence [see WARNINGS AND PRECAUTIONS].
Alcohol, as a CNS depressant, will interact with ONFI in a similar way and also increases clobazam's maximum plasma exposure by approximately 50%. Therefore, 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 potentiated [see WARNINGS AND PRECAUTIONS].
Drug Abuse And Dependence
ONFI contains clobazam which is a Schedule IV controlled substance.
ONFI can be abused in a similar manner as other benzodiazepines, such as diazepam.
The pharmacological profile of ONFI is similar to that of other benzodiazepines listed in Schedule IV of the Controlled Substance Act, particularly in its potentiation of GABAergic transmission through its action on GABAa receptors, which leads to sedation and somnolence.
The World Health Organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam.
Drug abuse is the intentional non-therapeutic use of a drug, repeatedly or even sporadically, for its rewarding psychological or physiological effects.
Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels of the drug, and/or administration of an antagonist. In clinical trials, cases of dependency were reported following abrupt discontinuation of ONFI.
The risk of dependence is present even with 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 abuse.
In ONFI clinical pharmacology trials in healthy volunteers, the most common withdrawal symptoms after abrupt discontinuation were headache, tremor, insomnia, anxiety, irritability, drug withdrawal syndrome, palpitations, and diarrhea [see WARNINGS AND PRECAUTIONS].
Other withdrawal reactions to clobazam reported in the literature include restlessness, panic attacks, profuse sweating, difficulty in concentrating, nausea and dry retching, weight loss, blurred vision, photophobia, and muscle pain and stiffness. In general, benzodiazepine withdrawal may cause seizures, psychosis, and hallucinations [see WARNINGS AND PRECAUTIONS].
Read the Onfi Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 12/4/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Onfi Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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