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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 ftus. 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 AEDs

                        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

 

   

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