EPILEPSY: PHENYTOIN

Question 1

Category

Answer 1

Category 1

High risk drug

Maintain on a specific manufacturers product (same brand or generic drug manufacturer)

Different oral formulations vary in bioavailability

Question 2

Phenytoin sodium vs Phenytoin base

Answer 2

Phenytoin sodium is NOT bioequivalent to Phenytoin base

100 mg of Phenytoin sodium = 92 mg of Phenytoin base

Question 3

What type of seizures is it used for?

Answer 3

Focal
Generalised tonic-clonic

Question 4

What type of seizures should it NOT be used for?

Answer 4

Absence
Myoclonic
Exacerbates seizures

Question 5

What are the other uses of phenytoin?

Answer 5

• Status epilepticus
• Prevention and treatment of seizures during or following neurosurgery or severe head injury

Question 6

Contraindications

Answer 6

• Acute porphyrias
• Sino-atrial and heat block if given IV

Question 7

Therapeutic range (ADULTS)

Answer 7

10-20 mg/L OR
40-80 micromol/L

Question 8

Therapeutic range (NEONATES)

Answer 8

6-15 mg/L OR
25-60 micromoles/L

Question 9

Is phenytoin a CYP450 inducer or inhibitor

Answer 9

inducer

Question 10

Relationship between dose + plasma concentration (Cp)

Answer 10

Non-linear
Small changes in dose/missed dose/changes in drug absorption = large changes in Cp

Question 11

Phenytoin + protein binding

Answer 11

Phenytoin is a highly protein-bound drug

Reduced protein binding = monitor plasma free-drug concentration.

The patient groups show early signs of toxicity

Question 12

What groups of people have reduced protein-binding?

Answer 12

Pregnancy
Children (neonates)
Elderly
Liver failure

Question 13

Signs + symptoms of toxicity

Answer 13

A
SNAtCHeD
* Slurred speech
* Nystagmus (uncontrolled repetitive eye movements e.g. eye rolling)
* Ataxia (involuntary co-ordination of muscle movement)
* Confusion
* Hyperglycaemia
* Diplopia (double vision), blurred vision

Question 14

Side effects

Answer 14

• Skin disorder/acne
• Coarsening of facial appearnace/ hirsuitism
• Constipation
• Drowsiness
• Gingival hypertrophy
• Hepatotoxicity
• Blood disorders
• Suicidal thoughts
• Low vitamin D levels
• Paraesthesia

Question 15

Hypersensitivity reactions (AHS)

Answer 15

Fever
Rash
Swollen lymph nodes

Question 16

Blood disorders

Answer 16

Occurs as phenytoin is also an antifolate
Report signs of infection
* Fever
* Sore throat
* Mouth ulcers
* Unexplained bruising or bleeding

Leucopoenia that is severe, progressive or associated with clinical symptoms requires withdrawal.
Monitor FBC

Question 17

Skin disorders

Answer 17

Rash
* Reintroduce if mild
* Discontinue if recurrence
* Han chinese and Thai patients with HLA-B*1502 Allele = increased risk of Steven-Johnson syndrome

Question 18

Low vitamin D

Answer 18

Vit D def
Leads to osteomalacia and rickets
Vit D supplements:
- Immobilised patients
- Inadequate vit D exposure
- Inadequate dietary intake of calcium

Question 19

Hepatotoxicity

Answer 19

Discontinue immediately
Monitor LFTs
Do not restart
* Dark urine
* N + V
* Abdominal pain
* Jaundice
* Itching

Question 20

Suicidal ideation

Answer 20

Small increased risk
Can occur within 1 week of starting treatment
Seek help

Question 21

IV phenytoin - Most common SE

Answer 21

Bradycardia
Hypotension
If these SE occur, reduce administration rate.

Question 22

IV phenytoin - Other common SE

Answer 22

Arrhythmias
Cardiovascular collapse
Respiratory arrest
Rapid administration = CVS/CNS depression
Monitor = ECG/BP

Question 23

IV fosphenytoin - SE

Answer 23

Severe cardiovascular reactions.
* Asystole
* Ventricular fibrillation
* Cardiac arrest
* Heart block
* Hypotension
* Bradycardia

Question 24

IV fosphenytoin - monitoring

Answer 24

Observe patient for 30 minutes after infusion
* HR
* BP
* Respiratory function during infusion

Question 25

Fosphenytoin vs Phenytoin sodium

Answer 25

1.5 mg of Fosphenytoin = 1 mg of Phenytoin sodium

Question 26

Administration of Fosphenytoin

Answer 26

Prodrug of Phenytoin
IV or IM only.
IV = less injection site reactions and can be given more rapidly

Question 27

Drugs that increase phenytoin concentration

Answer 27

Increased concentrat
Enzyme inhibitors
* Amiodarone
* Chloramphenicol
* Cimetidine
* Clarithromycin
* Diltiazem
* Fluconazole
* Fluoxetine
* Metronidazole
* Miconazole
* Sertraline
* Trimethoprim
* Valproate

Question 28

Drugs that reduce phenytoin concentration

Answer 28

Reduced concentration = therapeutic failure
* Rifampicin
* St. Johns wort

Question 29

Increased antifolate effect

Answer 29

Increased antifolate effect = increased risk of blood dyscrasias
* Methotrexate
* Trimethoprim

Question 30

Drugs that antagonise the anticonvulsant effect of phenytoin

Answer 30

Lower the seizure threshold
* Quinolones
* Tramadol
* Mefloquine
* SSRIs
* Antipsychotics
* TCA/related antidepressants

Question 31

Phenytoin reduces the concentration of which drugs?

Answer 31

Phenytoin is an enzyme inducer = reduces drug concentrations
* Contraceptives/HRT
* Warfarin
*Corticosteroids/Levothyroxine/Liothyronine (increases risk of hypothyroidism)

Question 32

Phenytoin and enteral feeding?

Answer 32

• Phenytoin can interact with the enteral tube itself as well as the proteins in the enteral feed
• overall reducing drug concentration

Question 33

How long should you wait between enteral feeding and dose of phenytoin

Answer 33

Recommended to withhold enteral feeding 2 hours before and after the dose of phenytoin

Question 34

Pregnancy

Answer 34

• Yes
• Dose should be adjusted based on plasma drug concentration
• Note: changes in plasma-protein binding make interpretations of plasma-phenytoin concentrations difficult

Question 36

Bf

Answer 36

• Yes
• But monitor infant for any
  ADRS