Transcript Carbamazepine (Tegretol) Carbamazepine is one of the older drugs

Carbamazepine (Tegretol)
Carbamazepine is one of the older drugs used for
the treatment of epilepsy . It has a long history of
effectiveness & safety . It is structurally similar to
the tricyclic anti depressant agents . It has been the
drug of choice for the treatment of trigeminal
neuralgia & is used in treatment of generalised as
well as complex partial seizures .
It is most frequently prescribed for those patients
who have failed to respond to other anti convulsant
therapy or for those who have developed significant
side effects from other anti convulsant agents .
Preparation, Dosage & Drug levels:
Tegretol is prepaired as 200mg oral tablets
,100mg chewable tablets & 100mg/5ml
suspension . The usual dose of tegretol is
200mg given 3times daily . Like many
drugs that to be taken continuously, It
takes from 7 to 14 days to build up the
blood level . The range of therapeutic
serum concentration for carbamazepine is
4 to to 12 mg/L .
Toxic Side Effects:
Many patients will develop symptoms of toxicity
when plasma concentration exceed 9mg/L.
Therefore , many clinicians prefer to use a
therapeutic range of 4 to 8 mg/L. These side effects
are :
- Dizziness: a feeling that the room is spinning
around .
- Drunken sensation : a feeling of clumsiness,a
staggering gait or feeling of slowest movement .
- Light headedness :feeling like you might faint.
- Double vision : inability to focus well .
Slurred speech: feeling of thick or swollen tongue
,inability to control it while speaking .
-
Confusion : inability to think clearly.
- Memory lapses : difficulty remembering the
sorts of things you usually remember.
Common side effects:
Tegretol can damage your liver . If this occurs
the whites of your eyes may turn yellow (jaundice),
you may have diarrhea . Tegretol can damage your
bone marrow where white blood cells are produced
Metabolism:
Tegretol is metabolised by the liver .
Therefore, the amount of tegretol that you
need to take depends on how fast your liver
metabolizes it .Anything that adversely
affects liver function such as hepatitis or
alcohol abuse will affect its ability to
metabolise.
Key parameters :
Therapeutic plasma conc.
4 - 12 mg/L
Bioavailability
80 %
Salt form (S)
1
Volume of distribution
1.4 L/kg
Clearance (CL)
Conc. Dependent
Half Life (t ½)
Conc. Dependent
Uses:
Tegretol is most effective when used to treat
generalised tonic-clonic seizures.These are
the type of seizures during which you lose
consciousness & your arms or legs may
stiffen or jerk . During complex partial
seizures you will lose consciousness aware ness of your surroundings,but you may
appear awake to those around you .people
who witness a partial complex seizures
often describe the afflicted person as
confused or staring.Tegretol is not very
effective in treating other types of seizures.
Bioavailability(F):
Carbamazepine is a lipid soluble compound which
is slowly absorbed from the G.I.T. Peak plasma
conc. Occur approximately 6hrs(range :2 to 24 hrs)
after oral ingestion . Although the bioavailability of
carbamazepine has not been directly determined ,it
is estimated to be greater than 70% & may approch
100% . Since carbamazepine is so slowly absorbed ,
changes in gastrointestinal function, especially those
associated with rapid transit, could decrease its
bioavailability & result in variable plasma conc. Of
carbamazepine .
Volume of distribution (vd):
The volume of distribution of carbamazepine
is approximately 1.4 L/Kg . Carbamazepine,
a neutral compound that is primarily bound
to albumin & α1-acid glycoprotein, has a free
fraction (alpha) of approximately 0.2 to 0.3 .
Clearance (Cl):
Carbamazepine is eliminated almost by the
metabolic route,with less than 2% of an oral
dose being excreted unchanged in the urine .
Clearance values are difficult to estimate
because bioavailability is uncertain.
Nevertheless ,the average clearance value
appears to be approximately 0.064 L/Kg
in patients who have received the drug
chronically . In patients who are taking other
enzyme inducing antiepileptic drugs ,the
clearance is increased to approximately
Half life (t1/2):
Single dose studies predict a carbamazepine
half life of approximately 30 to 35 hrs ,steady
state data suggest a half life of approximately
15 hrs in patients receiving carbamazepine
monotherapy & approximately 10hrs in
patients receiving other enzyme inducing anti
epileptic drugs .
Time of sampling:
Obtaining carbamazepine plasma samples
within the first few weeks of therapy may be
useful to establish a relationship between
carbamazepine concentration & a patients
clinical response . Once steady state has been
achieved , the time of sampling within a
dosing interval is arbitrary given the long half
life & relatively short dosing interval for
carbamazepine .Nevertheless ,it is reasonable
to obtain carbamazepine plasma samples at
a consistent time within the dosing interval.
Question#1: N.S.,a 36 year old,
60 Kg female is to be given carbamazepine as an anticonvulsant agent.
alculate a daily dose that will produce
n avearage steady state plasma conc.
f approximately 6 mg/L.
=0.8 , cl=3.84l/hr (0.064l/kg x 60kg) ,S=1
Maintenance dose = (cl)(cpss ave)(t)
(s) (f)
= (3.84l/hr)(6mg/l)(24hr/1day)
(1) (0.8)
Cl= 3.84L/hr , the anticipated
carbamazepine level in N.S.for a dose
of 600mg/day would be approximately
5mg/L .
Cpss ave= (s)(f)(dose/t)
Cl
= (1)(0.8)(300mg/12hr)
3.84L/hr
= 5.2 mg/L
the observed level of 4 mg/L is within the
predicted range, considering the fact that
both bioavailability & clearance values
derived from average literature values may
not be applicable to N.S. At this point,it would
= (1)(0.8)(600 mg/24hr)
4 mg/l
= 5 L/hr
this clearance value could then be used to
calculate the maintenance dose as illustrated
in question 1.However this time the clearance
value which has been derived from the
patient’s specific data would be used rather
than an average value from the literature .
Maintenance dose = (cl)(cpss ave)(t)
(s)(f)
= (5L/hr)(6mg/L)(24hr/day)
(1)(0.8)