Phenytoin

Question 1

Therapeutic Range:

Answer 1

Therapeutic Range: 10 to 20mg/L (or 40 to 80 micromol/litre)
Non-linear relationship between dose and plasma drug concentration: small changes in dose/ missed
dose / change in drug absorption can result in marked change in plasma drug concentration

Question 2

Monitoring

Answer 2

Serum concentration, ECG and blood pressure with intravenous use, liver function, full blood count,
serum folate, vitamin D. Phenytoin is highly protein bound; patients with impaired liver function, elderly
or those who are gravely ill may show early signs of toxicity

Question 3

Major Route of Elimination

Answer 3

Hepatic metabolism

Question 4

Warning Signs

Answer 4

• Toxicity e.g. nystagmus, ataxia, slurred speech, hyperglycaemia, diplopia or blurred vision,
confusion
• Skin disorders e.g. rash, toxic epidermal necrolysis
• Blood disorders (fever, sore throat, mouth ulcers, unexplained bruising or bleeding) e.g.
leucopenia, aplastic anaemia, megaloblastic anaemia
• Suicidal thoughts
• Low vitamin D levels e.g. rickets, osteomalacia

Question 5

Actions Required

Answer 5

• Advise patient to report immediately to a doctor if any warning signs occur
• Use caution when dispensing: Brand-specifc prescribing recommended as preparations
containing phenytoin sodium (100mg) are equivalent to those containing phenytoin base
(92mg). The dose is the same for all phenytoin products when initiating therapy, but if switching
between formulations, the difference in phenytoin content may be clinically signifcant

Question 6

Interactions

Answer 6

• Increased plasma concentrations with amiodarone, chloramphenicol, cimetidine, disulfram,
diltiazem, fuconazole, fuoxetine, miconazole, topiramate, trimethoprim (also increased
antifolate effect), metronidazole, clarithromycin, telithromycin (avoid during and 2 weeks after
phenytoin)
• Reduced plasma concentrations with rifamycins, St John’s Wort, theophylline, itraconazole,
ciclosporin
• Phenytoin accelerates metabolism of coumarins (possibility of reduced anticoagulant effect
but enhancement also reported), corticosteroids, oestrogens, protestogens
• Anticonvulsant effect possibly antagonised by antipsychotics, mefoquine, SSRIs, tricyclics
and tricyclic-related antidepressants
• Phenytoin possibly reduces plasma concentration of aripiprazole, itraconazole, oestrogens
and progestogens (reduced contraceptive effect), theophylline and tricyclics