Phenytoin

Question 1

Use

Answer 1

Focal seizures and generalised tonic-clonic seizures

Question 2

Avoid use

Answer 2

Exacerbates absence and myoclonic seizures

Question 3

Therapeutic range (NARROW TI)

Answer 3

Adult: 10-20mg/L or 40-80umol/L

Neonate (<3months): 6-16mg/L or 25-60umol/L

Question 4

Monitoring

Answer 4

1. Plasma concentration
   - non-linear relationship with dose
   - small changes in dose/missed/change in drug absorption = large change in plasma conc
2. Plasma free-drug conc
   - highly protein bound drug
   - protein binding reduced in elderly, neonates <3months, liver failure, pregnancy
3. FBC - antifolate and infection
4. Vit D
5. LFTs
6. Blood Glucose - Hyperglycemia
7. ECG / BP - bradycardia, hypotension, arrhythmias
8. HLAB*1502 allele

Question 5

Toxicity Symptoms

Answer 5

“SNAtCHeD”
Slurred speech
Nystagmus (eye rolling)
Ataxia (lack of voluntary co-ordination of muscle movement)
Confusion
Hyperglycaemia
Diplopia (double vision) and blurred vision

Question 6

Rx Rules

Answer 6

1. Category 1 = prescribe by brand / same manufacturer. Different oral formulations vary in Bio.A i.e. Phenytoin Sodium is not equiv to Phenytoin Base
2. When switching between phenytoin products dose conversion 100mg phenytoin sodium = 92mg phenytoin base

Question 7

Side effects

Answer 7

1. Change in appearance - coarsen ing of facial features, acne, hirsutism, gingival hypertrophy (maintain good oral hygeine)
2. Blood dyscrasias (ANTIFOLATE) - patient counselling: report signs of infection e.g. fever, sore throat, mouth ulders, unexplained bruising
   Leucopoenia severe, progressive or associated with clinical symptoms requires withdrawal
   MONITOR FBC
3. Hypersensitivity reaction - ANTIEPILEPTIC HYPERSENSITIVITY SYNDROME - report fever, rash, swollen lymph nodes
4. Rash (skin disorders) - discontinue. If mild, reintroduce cautiously but stop if recurrent
   Pre-treatment screening: Han Chinese and Thai patients with HLA-B* 1502 allele have increased risk of Steven-Johnson Syndrome
5. Low Vit D - osteomalacia and riskets
   induces vit d metabolism. consider supplements in immobilized pt’s, inadequate sun / dietary intake of calcium
   MONITOR VIT D
6. Hepatotoxicity - stop immediately and do NOT re-start. Report signs of dark urine, nausea, vomitting, abdo pain, itching, jaundice
   MONITOR LFTS
7. SUICIDAL IDEATION

Question 8

IV phenytoin side effects

Answer 8

1. Bradycardia
2. Hypotension
   - if occur reduce infusion rate. STAFF AWARENESS!
3. Arrythmias
4. CV collapse
5. Respiratory arrest
6. If too rapid = CVS/CNS depression
   * MONITOR ECG/BP

Question 9

IV Fosphenytoin

Answer 9

Severe CV reactions

1. Asystole
2. Ventricular Fibrillation
3. Cardiac arrest
4. Heart block
5. Hypotension
6. Bradycardia
   * monitor HR, BP, resp fx during infusion and observe pt for 30mins after infusion

Question 10

Fosphenytoin

Answer 10

Pro-drug of phenytoin
IV/IM only
1.5mg fosphenytoin : 1mg phenytoin sodium
Has less injection site reactions
Given more rapidly with IV

Question 11

Interactions - increase phenytoin conc = toxicity

Answer 11

ENZYME INHIBITORS

1. Amiodarone
2. Cimetidine
3. Miconazole
4. Fluconazole
5. Chloramphenicol
6. Metronidazole
7. Clarithromycin
8. Fluoxetine
9. Sertraline
10. Diltiazem
11. Valproate
12. Trimethorpim (increase antifolate effect!)

Question 12

Interactions - reduce phenytoin conc = therapeutic failure

Answer 12

ENZYME INDUCERS

1. St John’s Wort
2. Rifampicin

Question 13

INTERACTIONS Anticonvulsant effect antagonisted

Answer 13

1. Quinolones
2. Tramadol
3. Mefloquine
4. SSRIs
5. Antipsychotics
6. TCA / anti-depressants
   * LOWER SEIZURE THRESHOLD

Question 14

Interaction - increase antifolate effect

Answer 14

increase risk of blood dyscrasias

1. Methotrexate
2. Trimethoprim

Question 15

Interaction - acting as enzyme inducer so reduces conc of ….

Answer 15

1. Hormonal contraceptives/HRT (reduced efficacy)
2. Warfarin (reduced anticoag effect)
3. Corticosteroids
4. Levothyroxine and Liothyronine (increased risk of hypothyroidsm)