Patient Encounter 3 Discontinuing AED Therapy

The consultant pharmacist is reviewing the care of AN, who is a 79-year-old male resident of a long-term care facility. According to his records, he has received phenytoin and phenobarbital ever since suffering a stroke 12 years ago. There is no record of a seizure in his chart, and the nursing staff has not observed a seizure since he arrived at the facility 2 years ago. His family recalls that he had one seizure around the time of his stroke, but has not had any more seizures.

Can his antiepileptic medications be discontinued?

What additional information would be helpful to determine the possibility of discontinuing his AEDs?

If the AEDs are stopped, how should they be discontinued?

Table 30-4 Cytochrome P450 and AED Interactions

Enzyme

lufatmta

Common Inducer?

Common Inhibitor*

CVP IAZ

timer iiine

Phefiytoiri

Ciprofloxacin

Phniütuibilíl

trylhrtxnyiin

Hifanrpin

OMNn^Cln

CrP ÍC9

PhenohsibiiaP

Caitoamajepire

Ami ada none

Phenyl oin^

Ph¥*iy«jin

C¡metfc)¡ne

Carba iras? pine

PhMVJüafbiial

fluconazole

Valproate

Rifampin

Valproate

CW Ztl?

PIH?iK)l>iit>Wl

tíllHírtití

Phenymln

"Tit to |Hdlne

Vaifraaa*

Tbti»itmatc"

UK«¿rn¡(Je

Z<jri¡semkk?

drP 2D6

¿oniumida-

Caifaamazepkie

CY1> 3M

CjrbamiZtpirM'

CjiLviirVkit'pipie

T¡agjtnneJ

Phetiywin

Eryihrorriítin

ionisainkJe-

Phenobaihlal

Piropo ¡typhene

Rifampin

ReilXÍMvíZotí

Uridine diptoophati?

Lanroti igine"

Lamoiiigin?

Vulpwste

gltJOLiionyl-transieraEe

Carta rrwepire

Pheoobaibial

VoUjioate

Phi-Yvyi^iin

Hormonal cgii|r^plh«

"Primary route of meiabaliirn

"Primary route of meiabaliirn

Special Populations

Children and women present special challenges in the management of epilepsy and use of AEDs. In children, developmental changes occur rapidly, and metabolic rates are greater than those seen in adults. When treating a child it is imperative to control seizures as quickly as possible to avoid interference with development of the brain and cognition. AED doses are increased rapidly, and frequent changes in the regimen are made to maximize control of seizures. Due to the rapid metabolic rates seen in children, doses of AEDs are typically higher on a milligram per kilogram basis compared to adults, and serum concentrations are used more extensively to help ensure an adequate trial of a drug has been given.

For women, the treatment of epilepsy poses challenges, including teratogenicity interactions between AEDs and hormonal contraceptives, and reduced fertility.40, Recommendations for managing women of child-bearing potential and who are pregnant have been developed (Table 30-5). Several AEDs have been implicated in caus-

ing both minor and serious birth defects. Of special concern are neural tube defects (e.g., spina bifida, microcephaly, anencephaly) associated most commonly with val-proate and possibly carbamazepine. Additionally, valproate has been associated with impaired cognitive development in children born to women taking valproate during pregnancy. Use of valproate is not absolutely contraindicated in women who may be come pregnant, but it is appropriate to use alternative AEDs, if possible, in women of child-bearing potential. All women of child-bearing potential who have epilepsy should take 1 to 4 mg daily of supplemental folic acid to reduce the risk of these defects. Many AEDs are excreted in breast milk. However, infants were exposed to higher concentrations of AED in utero, so it is unclear if drugs in breast milk are harmful to the child. Decisions about breast-feeding should be made on an individual basis.

Table 30-5 Management of AEDs During Pregnancy

Give supplemental folic acid 1-4 mg daily to all women of child-bearing potential Use monotherapy whenever possible Use lowest doses that control seizures

Continue pharmacotherapy that best controls seizures prior to pregnancy Monitor AED serum concentrations at start of pregnancy and monthly thereafter Adjust AED doses to maintain baseline serum concentrations

Administer supplemental vitamin K during eighth month of pregnancy to women receiving enzyme-inducing AEDs

Monitor postpartum AED serum concentrations to guide adjustments of drug doses

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