Carbamazepine

Question 1

HIGH RISK

Answer 1

Narrow TI

Inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability

Question 2

Use

Answer 2

1st line focal seizures, generalized tonic-clonic seizures

Question 3

Therapeutic range

Answer 3

4-12mg/L or 20-50umol/L

Question 4

Toxicity symptoms

Answer 4

“i HANDBAG”
incoordination
Hyponatremia
Ataxia (lack of voluntary co-ordination of muscle movement)
Nystagmus (eye rolling)
Drowsiness
Blurred vision and diploma (double vision)
Arrhythmias
GI disturbance (nausea, vomiting, diarrhoea)

Question 5

Side effects

Answer 5

1. Blood dyscrasias e.g. leucopenia, thrombocytopenia - report signs of infection i.e. sore throat, mouth ulcers, unexplained bruising/bleeding
   * MONITOR FBC
2. Hepatotoxicity - report dark urine, vomiting, nausea, abdo pain, itching, jaundice
   * MONITOR LFTS
3. Hypersensitivity - anti-antiepileptic syndrome - report fever, rash, lymphadenopathy
4. Rashes (skin disorders) - report rashes - Han Chinese and Thai patients with HLAB*1502 allele are increased risk of Steven-Johnson syndrome
5. Hyponatremia - in rare cases can lead to water intoxication

Question 6

Interactions - increases conc = toxicity

Answer 6

ENZYME INHIBITORS

1. Cimetidine
2. Macrolides
3. Fluoxetine
4. Miconazole

Question 7

Avoid use

Answer 7

Exacerbated atonic, clonic and myoclonic seizures

Question 8

Monitoring

Answer 8

1. Plasma conc after 1-2 weeks
2. FBC
3. LFTs
4. Na+ - hyponatremia
5. HLAB*1502 allele

Question 9

Dose related and dose limiting side effects

Answer 9

Headaches, ataxia, drowsiness, nausea, vomiting, blurred vision, unsteadiness, allergic skin reactions
More common at start of treatment and in elderly

Question 10

How to reduce side effects?

Answer 10

MR preparations

Question 11

Interactions - decrease conc = failure

Answer 11

ENZYME INDUCERS

1. St John’s Wort
2. Phenytoin

Question 12

Interactions - anticonvulsant effect antagonized

Answer 12

LOWER SEIZURE THRESHOLD 1. Quinolones

2. Mefloquine
3. SSRIs
4. Antipsychotics
5. TCA / anti-depressants

Question 13

Interactions - increased risk of hyponatremia

Answer 13

1. Aldosterone antagonists e.g. spironolactone / eplerenone
2. SSRIs
3. TCAs
4. Diuretics
5. NSAIDs e.g. naproxen

Question 14

Interactions - increased risk of hepatotoxicity

Answer 14

1. Tetracyclines
2. Sulfasalazine
3. Sodium Valproate
4. Methotrexate
5. Isoniazid
6. Statins
7. Fluconazole
8. Alcohol