Cardiac disease

Uncontrolled generalized tonic-clonic seizures are likely to be hazardous in patients with severe heart disease. The antiepileptic drugs that act on membrane ion channels can induce cardiac arrhythmias in predisposed patients. Studies have concentrated on carbamazepine, which should generally be avoided in patients with pre-existing disturbances in the cardiac conduction system or cardiomyopathies. There may also be a risk also with phenytoin, lamotrigine, oxcarbazepine and topiramate. Routine electro-cardiography ECG should be obtained to exclude cardiac disease before starting treatment with these drugs, especially in elderly patients and in those with a history suggestive of heart disease. Intravenous administration of phenytoin should be made only with caution in patients with cardiac disturbances.

Table 2.1 Pharmacokinetic parameters of antiepileptic drugs.

Oral bioavailability (%)

Time to peak level (h)

Metabolism

Half-lifet (h)

Protein binding (%)

Active metabolite

Drug interactions

Carbamazepine

75-85

4-8

Hepatic

5-261

75

CBZ-epoxide

A A

Clobazam

90

1-4

Hepatic

10-77 (502)

83

W-desmethyl clobazam

A

Clonazepam

80

1-4

Hepatic

20-80

86

None

A

Ethosuximide

< 100

< 4

Hepatic

30-601

< 10

None

A A

Gabapentin

< 653

2-3

None

5 -7

None

None

None

Lamotrigine

< 100

1-3

Hepatic

12-601

55

None

A A

Levetiracetam

< 100

1-2

Non-hepatic

6-8

None

None

None

Oxcarbazepine

< 100

4-6

Hepatic

8-101'2

382

MHD

A A

Phenobarbital

80-100

1-3

Hepatic

75-1201

45 -60

None

A A

Phenytoin

95

4-12

Hepatic

7-421,4

85-95

None

A A

Pregabalin

90

1

None

6

None

None

None

Primidone

< 100

3

Hepatic

5-181 (75-1202)

25

Phenobarbital

A A

Tiagabine

< 96

1-25

Hepatic

5-91

96

None

A A

Topiramate

< 100

2-4

Hepatic

19 —251

15

None

A A

Valproate

< 100

0.5-86

Hepatic

12—171

85-95

None

A A

Vigabatrin

< 100

0.5-2

None

4—7

None

None

None

Zonisamide

< 100

2-4

Hepatic

49-691

30-60

None

A A

t, Half-life in healthy adult.

1, Half-life varies with co-medication; 2, value for active metabolite; 3, absorption of gabapentin is by a saturable active transport system, and rate will depend on capacity of the system;4, phenytoin has non-linear kinetics, and so half-life can increase at higher doses; 5, absorption of tiagabine is markedly slowed by food, and it is recommended that the drug is taken at the end of meals; 6, the time to peak concentration varies according to formulation (0.5-2 h for normal formulation, 3-8 h for enteric coated).

**, Many interactions, frequently of clinical relevance and many require dose modification; *, minor interactions common, but not usually of much clinical relevance; MHD, the monohydroxy metabolite of oxcarbazepine.

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