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.
Blood Disorders: Anemia, eosinophilia, leukopenia, thrombocytopenia
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