|
|
|
ANTIEPILEPTIC DRUG INTERACTIONS CHART
Up =
Increase
concentration of current drug
Down = Decrease concentration of current drug
Both = increase or decrease [ ] of current drug
|
ADDED
DRUG
|
C U R R E N
T T H
E R A P Y
|
|
|
GPT
|
LTG
|
CBZ
|
DPH
|
VPA
|
PHB
|
VGB
|
|
CBZ
|
no
Δ
|
down
|
|
down
|
down
|
?
|
no
Δ
|
|
DPH
|
no
Δ
|
down
|
down
|
|
both
|
both
|
no
Δ
|
|
VPA
|
no
Δ
|
up
|
up
|
up*
|
|
up
|
no
Δ
|
|
PHB
|
no
Δ
|
down
|
down
|
both
|
?
|
|
no
Δ
|
|
LTG
|
?
|
|
no
Δ
|
no
Δ
|
down
|
?
|
no Δ+
|
|
GPT
|
|
?
|
no
Δ
|
no
Δ
|
no
Δ
|
no
Δ
|
no
Δ
|
|
VGB
|
no
Δ
|
no
Δ
|
no
Δ
|
no
Δ
|
no
Δ
|
no
Δ
|
|
*: can both increase and decrease
total DPH [], increases free fraction of DPH
+: good association potentiation of both drugs.
CBZ: Carbamazepine Tegretol
DPH: Diphenyl Hydantoin Dilantin
VPA: Valproic Acid Depakene, Epilval
PHB: Phenobarbital
LTG: Lamotrigen Lamictal
GPT: Gabapentin
VGB: Vigabatrin Sabril
Carbamazepine (Tegretol)
Dosages:
· Adults: Between 600 and 2,000 mg per day.
· Children: 10 to 30 mg/kg per day. It is usually less than 24 mg/Kg/day. They are chewable tablets available.
· Comment: Dosages should be modified according by clinical response; initial doses are usually lower; CBZ has several pharmacokinetic interactions with other medications (in particular one group of antibiotics frequently used in children: the Macrolides e.g. erythromycin) that may affect dosage requirements.
· Presentation: 100 chewable, 200 and 400 mg tablets, 200 and 400 CR, liquid suspension 20 mg/ml.
· Usually CBZ must be taken three to four times per day; two times per day for sustained release preparation, (Tegretol CR)
Pharmocokinetics:
The elimination of the drug is through liver metabolism. This clearing of the drug uses a pathway used by several other medications named the cytochrome P450 pathway. It is therefore recommended to always ask your pharmacist if a second medication can be used in association with Carbamazepine.
Some clinically relevant pharmacokinetic drug interactions:
Carbamazepine increase the metabolism of cyclosporine , tricyclic antidepressants, and warfarin (Coumadin), oral contraceptive agents, including ethinyl estradiol and levonorgestrel, with the potential problem of breakthrough bleeding or even contraceptive failure.
Carbamazepine levels can be increased by verapamil and diltiazem (2 frequently used heart medications), erythromycin and other macrolide antibiotics (except Azythromycin), isoniazid (an anti tuberculous agent), cimetidine (use in the management of gastric ulcers), and propoxyphene (Darvon).
Carbamazepine can increases phenytoin metabolism, primidone biotransformation to phenobarbital is also enhanced. Carbamazepine increases metabolism of valproate, ethosuximide, and lamotrigine. On the other hand carbamazepine metabolism is increased by phenytoin, phenobarbital, primadone, and felbamate.
It may take up to a month for the body to adapt to the medication and levels can be quite variable during the initial titration period.
Adverse effects
Dose related: Lethargy, Somnolence, Ataxia, Double vision, Dizziness, Nausea, Headache
Not dose related: Rash, Leucopenia , EKG conduction anomalies, weight gain.
Like almost all antiepileptic drugs, CBZ can affect the unborn fœtus. There are some evidences for increased incidence of neural tube defects.
Indications:
· Partial seizures, simple complex with or without secondary generalization. CBZ can increase some types of seizures such as Myoclonic seizures, or seizures seen in the rare syndrome of continuous spikes waves of slow sleep.
clonazepam
(Rivotril)
Dosages :
Adults: 2-4 mg per day.
Children: 0.1-0.3 mg/kg per day .
As usual, individual maintenance doses will be determined by clinical response.
The medication is usually taken two to three times per day.
· Pharmacokinetics
Elimination after metabolism through the liver.
Pharmacokinetic drug interactions are uncommon, but administration of hepatic enzyme inducing agents such as carbamazepine, phenobarbital and phenytoin may fasten clonazepam elimination and lower levels.
· Adverse effects
Dose related: Drowsiness, Ataxia, Irritability can be a problem particularly in children. Hypersalivation in children with special needs can be enough of a problem to have to discontinue the drug.
Not dose related: Rash, Leucopenia are rare.
· Indications:
Myoclonic seizures
Absence seizures, Partial seizures, and Secondarily generalized seizures when first line treatment has failed.
|
PRINCIPALS of THERAPY.
1. Diagnostic:
It is primordial to have a precise diagnosis for the type of SEIZURES and the type of EPILEPSY.
There is usually no urgency to start an AED. It is preferable to take the time for a good history, a good physical and a good set of investigations including EEG, preferably with sleep EEG.
For example it is easy to diagnose a West syndrome, but it is much better to distinguish a cryptogenic one from a symptomatic one. Treatment and prognosis may well be different.
Similarly, a child may well present with what appears to be absences. But if the EEG does not show any generalized, regular 3 c/s SW, it may be complexe partial seizures and they will respond better to Tegretol.
2. Monotherapy:
We will always look for the best adapted AED, with the least side effects.
|
Generalized
Epilepsies
|
AED
of choice
|
2nd
choice
|
|
West
Syndrome
|
Corticosteroid
ACTH
VGB VPA
|
CZP
NZP
|
|
Lennox-Gastaut
Syndrome
|
VPA
|
CZP
CBZ
|
|
Absence without GTCS
with GTCS
|
VPA
VPA
|
ESM
PHB or PRM
|
|
Myoclonic
Absences c/s GTCS
|
VPA
|
PHB
or PRM
|
|
Idiopathic
GTCS
|
VPA
|
PHB
or PRM
|
|
GTCS
without certainty if onset was Generalized or Partial
|
See:
partial epilepsies
|
|
|
Partial
Epilepsies
|
|
|
|
Complex
or simple Sz
|
CBZ
VGB
DPH
|
PHB or PRM
VPA
|
|
Febrile
Seizures
|
VPA
|
PHB
Valium
|
|
Usual AED's Dosages
|
Drug
|
Abrev
|
mg/Kg/Day
|
Plasm.
[]
|
#/day
|
|
Carbamazepine
(Tegretol)
|
CBZ
|
20
to 25
|
4 to 12
20 to 50
|
2
to 3
|
|
Ethosuximide
Zarontin
|
ESM
|
20
to 25
|
40 to 80
|
1
to 2
|
|
Phenitoine
Dilantin
|
DPH
|
5
to 7
|
15 to
30
60 to
120
|
1
to 2
|
|
Phenobarbital
|
PHB
|
2
to 5
|
15 to
40
80 to
180
|
1
to 2
|
|
Primidone
|
PRM
|
15
to 20
|
????????
|
1
to 2
|
|
Valproic Acid
Depakene
|
VPA
|
20
to 60
|
40 to
100
300 to
700
|
1
to 2
|
|
Clonazepam
Rivotril |
CZP
|
0.1
to
0.2
|
20
to 70
|
2
to 3
|
|
|
|
STATUS EPILEPTICUS
|
TIME
|
PROCEDURE
|
|
0
min.
|
1. ABC
2.
Veinous access
3. EEG if possible
|
|
5
min.
|
4.
N/S + 2 cc/kg D50W
|
|
10
min.
|
5.
DZP iv .3mg/Kg Repeat *3 at 5 minutes. DPH iv 18mg/Kg
(2*9mg/kg at 30 min).
|
|
30-40
min.
|
6. If still Sz:
-PHB 20mg/kg
-DZP
infusion 3-4 mg/Kg/day ICU
|
|
50-60
min
|
7. If still Sz:
-Thiopental
10 30mg/kg
|
|
|
THERAPEUTIC RESPONSES
|
|
%
control
|
%
relapse
|
|
Typical
& myoclonic absences
|
84
|
25
|
|
Typical
Absences & GTCS
|
60
|
65
|
|
Myoclonic
Absences & GTCS
|
75
|
91
|
|
GTCS
|
84
|
58
|
|
Simple
Partial Seizures
|
50
|
25
|
|
Complexe
Partial Seizures
|
42
|
87
|
|
SPS
& GTCS
|
40
|
25
|
|
CPS
& GTCS
|
48
|
58
|
|
Mixed
focal GTCS
|
74
|
73
|
|
|
SIDE EFFECTS of
AED’s
|
SIDE
EFFECTS
|
|
|
Allergies
|
Dose-related
|
Non
Dose related
|
|
CBZ
|
++
Pruritus,
exantheme, bullous dermatitis, aggranulocytosis,
Lymphadenopathies, Autoimmune pblms
|
Vertigo,
Ataxia, diplopia headache, lethargy
|
Leucopenia,
weight gain
EKG
conduction anomalies
|
|
CZP
|
+
|
Lethargy,
ataxia, behavior changes
|
Hypersalivation,
bronchial hypersecretions
|
|
ESM
|
+
|
Nausea,
vomiting, lethargy, Psychiatric dist, headache
|
Leucopenia,
gastralgia
|
|
DPH
|
++
|
Nystagmus,
tremor, Ataxia, dipopia
|
Gingival
hyperplasia, Hirsutism, anemia, polyneuropathy, insomnia
|
|
PHB
|
+
|
lethargy,
hyperactivity, Ataxia, nystagmus
|
Anemia,
periarthritis, Dupuytren, loss libido
|
|
PRM
|
+
|
Lethargy,
nystagmus, ataxia, nausea vertigo
|
Megaloblastic
anemia, idem PHB
|
|
VPA
|
?
|
tremor,
lethargy
|
alopecia,thrombocytopenia,
gastralgia, weight gain, liver failure
|
|
|
|
|
