Mechanism of Action

Onfi (clobazam) is an antiepileptic drug of the benzodiazepine class. The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.

Side Effects

Adverse events associated with the use of Onfi may include, but are not limited to, the following:

Somnolence

Sedation

Drooling

Constipation

Cough

Urinary tract infection

Aggression

Insomnia

Dysarthria

Fatigue

Dosing/Administration

Onfi is supplied as a a tablet for oral administration. The tablets can be administered whole, or crushed and mixed in applesauce. Onfi tablets should be administered in divided doses twice daily. Patients should be dosed according to body weight:

30kg Body Weight and Under:
Starting dose: 5mg
Starting Day 7: 10mg
Starting Day 14: 20mg

30kg Body Weight and Above:
Starting dose: 10mg
Starting Day 7: 20mg
Starting Day 14: 40mg

Clinical Trial Results

FDA Approval
The FDA approval of Onfi was based on two multicenter controlled studies (Study 1 and Study 2).

Study 1
This randomized, double-blind, placebo-controlled study enrolled 238 subjects who were divided into two weight groups and administered the doses as outlined above. The primary efficacy measure was the percent reduction in the weekly frequency of drop seizures (atonic, tonic, or myoclonic) from the four-week baseline period to 12-week maintenance period. The pre-dosing baseline mean weekly drop seizure frequency was 98, 100, 61 and 105 for the placebo, low-, medium- and high-dose groups, respectively. All dose groups of Onfi were statistically superior (p=0.05) to the placebo group. This effect appeared to be dose dependent.

Study 2
This randomized, double-blind comparison study enrolled 68 subjects and evaluated high- and low-dose Onfi. A statistically significantly greater reduction in seizure frequency was observed in the high-dose group compared to the low-dose group (median percent reduction of 93 percent vs 29 percent; p<0.05).