What is the mechanism of action of Frisium?

Clobazam, like other benzodiazepines acts through the GABA A receptor

complex in the brain. However, unlike the , ! benzodiazepines", #t binds
with the omega $ Benzodiazepine binding sites on the alpha sub%unit o&
the GABA A receptor complex to exert its anti%convulsant and anxiol'tic
e&&ects. (hus it &acilitates increased Cl% ion conductance thereb' leading to
neuronal inhibition. Clobazam tends to inhibit the spread o& seizure activit'
and increase the seizure threshold. #t has less sedative ) behavioral e&&ects
than the other benzodiazepines and also has less neuro%toxic ) m'orelaxant
e&&ects
*1, 4 benzodiazepines bind non specifically to both omega 1, 2 & 3
benzodiazepine binding sites. Thus they exert sedatie hypnotic !omega 1",
anticonulsant !omega 2", anxiolytic !omega 2" and muscle relaxant effects
!omega 3"
What is the half life of Frisium?
Clobazam has a hal& li&e o& * hours while the active metabolite +
desmeth'l Clobazam ,+ -.C/ has a hal& li&e o& 01 !1 hours.
In what doses should Frisium be prescribed?
Dosage in adults and adolescents above 15 years of age:
2mall doses such as 3%3mg4da' as initial dose graduall' increasing to a
maximum dail' dose o& about *5mg4da'.
Constant doses ,e.g. $5mg4da'/ or even intermittent therap' ,stopping
6risium in between and restarting it later have proved e&&ective.
Dosage in children from 3-15 years of age7
+ormall' the treatment in this age group is started with 3mg and a
maintenance dose o& 5.0%mg4kg bod' weight4da' is usuall' enough
How long can Frisium can be prescribed for?
(here are two wa's o& prescribing Clobazam &or epileps'
Short term therapy7 Clobazam could be used onl' once or during a
short period o& &ew da's as add%on therap' &or acute treatment o&
serial seizures ) status or to prevent seizures in a particular risk'
situation e.g. 8ust be&ore an important social event or during the period
when usual therap' has to be changed. #n such situation the dosage o&
Clobazam could var' &rom a minimum o& 5mg4da' &or a short period
to a maximum o& mg4kg bod' weight administered on a one%time
basis. (his intermittent therap' with Clobazam usuall' has good
tolerabilit' and does not involve tolerance.
Long term therapy7 Clobazam could be used as monotherap' or
more o&ten as pol'therap' as an ad8unctive treatment along with a &irst
line A9- &or management o& re&ractor' seizures.
What is the efficacy of Frisium In long term therapy?
(he e&&icac' o& Clobazam varies &rom !5 55: with an average o& ;:.
9&&icac' is rapidl' obtained within the &irst $ or 0 da's o& therap' in most
patients. (he percentage o& total &ailure at the beginning o& treatment is low
) ranges &rom 5 to 0$: with an average o& ;:.
What is the extent of tolerance to Frisiums anticonvulsant effects?
(olerance to Clobazam therap' is highl' variable ranging &rom 5 to *<: in
various studies with an average o& 0<:. (he tolerance reported in long%term
therap' o& at least one 'ear varies &rom $0 to *<: with an average o& !3:.
(olerance appears within to 1 months. =e%introduction o& Clobazam a&ter
another $%0 months will again produce a signi&icant but transient response.
>atest $55 trial b' ?ena @arla published in #AB shows that the incidence o&
tolerance in #ndian population is 3:.
Why is Frisium the ideal add-on?
Why is Frisium superior to other add-on drugs?
Epilepsy patients with ncontrolled Sei!ures can e"pect a Sei!ure #ree
Life with #risium because
6risium7 An ideal add%on A9-
Efficacious & Broad spectrum
Efficacious & Broad spectrum
Efficacious in wide spectrum
of seizure types
including GTC, myoclonic, partial,
uncontrolled & refractory
Efficacious in wide spectrum
of seizure types
including GTC, myoclonic, partial,
uncontrolled & refractory
Fast Acting
Fast Acting
Long term seizure control
Long term seizure control
Compatible wit !rimary AE" &
well tolerated
Compatible wit !rimary AE" &
well tolerated
Lac# of clinically
$ignificant "rug interactions,
e%cellent safety record
Lac# of clinically
$ignificant "rug interactions,
e%cellent safety record
&ig 'etention rate ()*+ at ,
years-
&ig 'etention rate ()*+ at ,
years-
'apid onset of action,
antiepileptic acti.ity seen witin
few ours
'apid onset of action,
antiepileptic acti.ity seen witin
few ours
E%tensi.e clinical e%perience
E%tensi.e clinical e%perience
/0 years of strong 1ndian clinical
e%perience
/0 years of strong 1ndian clinical
e%perience
1"EAL A""234 AE"
F'1$156
#n Cncontrolled 2eizures, &irst add 6risium &or
o 6ast Action
$enefits: #n patients with uncontrolled seizure the treating
Bh'sicians and the patients looks &or an A9- which controls the &reDuenc'
o& seizure &aster. 6risium due to its &aster onset o& action controls seizure
&aster and o&&er better Eo> to the epileps' patients.
o Higher 2eizure 6ree =ate
$enefits: #n comparison to newer A9-Fs like >amotrigine,
(opiramate or >evitracetam 6risium o&&ers higher seizure &ree rate.
.oreover 6risium is economical in comparison to newer A9-Fs.
o High =etention =ate
$enefits: =etention is marker o& e&&icac' and tolerabilit' o& an'
drug especiall' in chronic diseases like 9pileps'.
2tudies conducted with 6risium shows that at the end o& 'ear the retention
rate with 6risium is ;5: and at the end o& ! 'ears the retention rate with
6risium is !5:%35: which clearl' shows that the statements regarding
development o& tolerance with 6risium has been exaggerated.
Hence >ow incidence o& tolerance with 6risium ensures higher
2eizure 6ree rates.
=ecent evidences shows that tolerance with 6risium was 3.1:
which is lesser than the incidence seen in Aapanese or western
population.
%ew evidence of #risium :
Study protocol:
&b'ective7 (o determine long%term sa&et' and e&&icac' o& ad8unctive
clobazam &or patients with >ennox%Gastaut s'ndrome ,>G2/.
Study type: &pen-label e"tension
(atient population7 (rial pts &rom =C(s o& Clobazam in >G2
%umber of (articipants7 G& $1; patients who enrolled in the G>9,
** ,;5:/ completed the trial. !!: completed 3 'ears
Study duration7 >argest and longest%running trial in >G2, 1'rs G>9
trial
)esult:
Sustained Sei!ure freedom: longest *5 yrs+ follow up in L,S
High median percentage decrease drop seizures ,*3<:/ was
maintained through Hear 3
.edian percentage decrease in total seizures was also maintained,
with an *3: reduction in those patients who had reached Hear 3
2ustained seizure &reedom and substantial seizure improvements at
stable dosages
6risium is e&&icacious over the long term and can be used sa&el' to
treat this chronic disorder
E##-./.0
(/)/1E2E)
H= $ H= 0H= ! H= 3 H=
Decrease in
drop sei!ures
*3: *; <$ <; <
Decrease in
total sei!ures
;<: ;< *$ ;3 *3
2tud' conclusion7
>argest and longest trial o& Clobazam as an ad8uvant A9- in >G2
with a 1 'r. &ollow up
<: decrease in drop seizures and *3: decrease in total seizures at
Hear 3.
2ustained seizure &reedom and 2ubstantial seizure improvements at
stable dosages through 0 'ears o& therap' in this di&&icult% to%treat
patient population
2table and predictable sa&et' pro&ile provide evidence that clobazam
is a valuable long%term treatment option &or >G2.