The role of a pharmacist in the management of seizures presented at Wesley Guild Hospital, Ilesha, Osun State, Nigeria.

1. MANAGING SEIZURES:
THE ROLE OF A PHARMACIST
Presented by:
DAMILOLA DANIEL TIJANI

2. Introduction
A study carried out by Yifat Roth on an evaluation of pharmacist knowledge
on treatment with antiepileptic drugs without consulting reference books
indicate the need for improving pharmacists’ education regarding epilepsy.
Excerpts from the study shows
Only 12% identified correctly all situations requiring urgent physician
consultation.
27% could not identify any of them.
Patients generally know more about epilepsy in general than about their
own condition.
Another study revealed that an estimated 30-60% of patients with epilepsy
are not adherent with their treatment regimen.
• Control of seizure & quality of life are of utmost importance…

3. Definitions
• Seizures is simply the clinical manifestation of disturbed electrical
activity where the excitatory transmission supersedes the inhibitory
transmission.
• Epilepsy refers to a disorder comprising a collection of recurrent
seizures that differ in cause, symptoms, severity, treatment and do
occur unprovoked.
• A person is considered to have epilepsy after having two or more
unprovoked seizures.
• Hence, people with isolated seizures or seizures that are due to
secondary causes such as hypoglycaemia, alcohol withdrawal, high
fever are not categorised to be suffering from epilepsy.

4. Epidemiology
• Approximately 50 million people worldwide live with epilepsy and about 40
million in developing countries
• Most common non-infectious neurologic disease in developing African
countries including Nigeria
• 5.3-37 persons per 1000 in Nigeria
• Febrile seizure in children is the most commonly treated form in WGH
mostly due to cerebral malaria(prevalence: 18%(WGH), comparative to
Enugu(21.5%) although lower in other places such as Jos(8.1%)
• The reason for most visits to the neurology clinic at OAUTHC
• About 1000 people die each year from epilepsy related causes
• Increased risk of mental health problem in persons with uncontrolled
epilepsy, especially depression

5. Types of seizures
Based on cause of seizure
Idiopathic (6/10): the cause is unknown
Secondary/symptomatic epilepsy: causes of such include
 Brain damage from prenatal/perinatal causes
 Congenital abnormalities
 Severe head injury
 Stroke
 Brain infection
 Genetic syndromes
 Brain tumour

6. Types of seizures(cont’d)
Based on Origin and further broken down based on description
• Focal (formerly called partial) seizures
Focal aware
Focal impaired awareness
Focal may spread to both sides eventually (secondary generalised seizures)
• Generalised seizures
Tonic-clonic
Tonic
Atonic
Myoclonic jerks
Absence

7. Management
Pharmacologic (70-80%): about 25 AEDs in the following categories
oValproic acid
oGABA analogues such as pregabalin and the likes
oEthosuximide
oPhenytoin
oCarbamazepine
Up to half experience adverse effects
Based on National Institute for Health and Care Excellence(NICE) guidelines,
monotherapy is recommended although more than one may be needed
sometimes. Co-morbidity is also a significant factor that could lead to drug-
drug interactions
Special consideration: women of child bearing age and patients of Asian
origin( Chinese& Thai)( carbamazepine is contraindicated in them)

8. Seizure
type
First line drugs Second line/
adjunct
therapy
Warning Note
Focal *Carbamazepine/lamotrigine/*Lev
etiracetam/Oxcarbamazepine/
*sodium valproate
vigabatrin-irreversible effects on
visual fields
Generalised
tonic-clonic
*Sodium
valproate/Lamotrigine/*carbamaze
pine/oxcarbamazepine
Lamotrigine aggravates myoclonic
seizures.
Carbamazepine/oxcarbamazepine
worsens myoclonic/absence
seizures
Absence Ethosuximide/sodium
valproate/Lamotrigine
Do not consider
gabapentin/phenytoin/pregabalin/ti
agabine/vigabatrin/carbamazepine/
oxcarbamazepine
Tonic/atonic Sodium valproate lamotrigine Do not consider
gabapentin/pregabalin/tiagabine/vi
gabatrin/carbamazepine/oxcarbama
zepine

9. Seizure type First line drugs Second line/ adjunct
therapy
Warning Note
Myoclonic *Sodium
valproate/*levetirace
tam/topiramate
Do not consider
gabapentin/phenytoi
n/pregabalin/tiagabi
ne/vigabatrin/carba
mazepine/oxcarbama
zepine/lamotrigine
Topiramate has a less
favourable side-
effect profile
Infantile spasms due to
tuberous sclerosis
Steroid(prednisolone
/tetracosactide)/
vigabatrin
Assess risk-benefit
ratio
Status epilepticus Lorazepam/*diazepa
m/*midazolam
*Phenobarbital/*phe
nytoin/*propofol
* The asterisk shows the drugs that are commonly used in OAUTHC
Non-pharmacologic management including surgery, vagus nerve stimulation therapy
and ketogenic diet(20-30%)

10. Roles of pharmacists
The roles are the drug-related obligations to both the physician, the patient and relatives,
namely:
Identifying potential and actual adverse effects
Lamotrigine-induced rash, levetiracetam-induced suicidal thoughts and seizure
aggravation, valproate-teratogenicity, memory impairment,
Dose verification/proposal of changes in prescription
If an AED has failed because of adverse effects or continued seizures, a second
drug should be started (which may be an alternative first-line or second-line
drug) and built up to an adequate or maximum tolerated dose and then the first
drug should be tapered off slowly
Brand substitution: risk/benefits
If using carbamazepine, offer controlled-release carbamazepine preparations

11. BROAD SPECTRUM CLASSIFICATION OF AEDs
DRUG(BRAND) INITIAL ADULT
DOSING
MAX DAILY
DOSE
COMMENTS
Clonazepam(Klonopin) 0.5 mg qd 20 mg Toxic serum conc greater than 80 ng/mL
Felbamate(Felbatol) 400 mg tid 3600 mg Need informed consent from patient and physician. Renal dose
adjustment
Lamotrigine(Lamictal) 100 mg bid 500 mg Hepatic and drug interaction dose adjustment. Black box warning:
severe and potentially life-threatening skin rashes: risk increases
with coadministration of valproic acid, high starting doses, and
rapid dose titration
Levetiracetam(Keppra) 500 mg bid 3000 mg Renal dose adjustment
Rufinamide(Banzel) 200 mg bid 3200 mg Not recommended in severe hapatic impairment
Topiramate(Topamax) 25 mg bid 400 mg Renal dose adjustment. Caution: risk for metabolic acidosis,
nephrolithiasis, weight loss
Valproic acid(Depakote) 15 mg/kg/day 60 mg/kg Hepatic and renal dose adjustment: serum concentration 50-150
mcg/mL. Black box warning: life-threatening pancreatitis
Zonisamide(Zonegran) 100 mg qd 600 mg Hepatic and renal dose adjustment. Caution: risk for
nephrolithiasis

12. NARROW SPECTRUM CLASSIFICATION OF AEDs
DRUG(BRAND) INITIAL ADULT
DOSING
MAX DAILY
DOSE
COMMENTS
Carbamazepine(Tegretol) 220 mg bid 2400 mg Serum concentration 4-12 mcg/mL. Black box warning:
potentially fatal blood cell abnormalities: do not use for patients
with HLA-B 1502 genotype. Caution: risk for hyponatremia
Ethosuximide(Zarontin) 500 mg qd 1500 mg Serum Conc 40-100 mcg/mL. Caution: renal/hepatic dysfunction
Gabapentin(Neurontin) 300 mg tid 3600 mg Renal dose adjustment
Lacosamide(Vimpat) 50 mg bid 400 mg Hepatic and renal dose adjustment
Oxcarbamazepine(Trileptal) 300 mg bid 2400 mg Renal dose adjustment. Caution: risk for hyponatremia
Phenobarbital(luminal) 50 mg bid 300 mg Serum concentration 20-40 mcg/mL. Syncope, bradycardia and
hypotension risk
Phenytoin(Dilantin) 300 mg qd ER
or 100 mg tid
900 mg Serum concentration 10-20 mcg/mL. Syncope, arrhythmias, and
hypotension risk with Iv use. Dose-related: drowsiness, lethargy,
cognitive impairment, nystagmus, ataxia. Non-dose related:
gingival hyperplasia, coarsening of facial features, hirsutism,
acne, rash
Pregabalin(Lyrica) 50 mg tid or
75 mg bid
600 mg Renal dose adjustment. Life-threatening angioedema risk:
rhabdomyolysis risk
Vigabatrin(Sabril) 500 mg bid 3000 mg Renal dose adjustment.

13. Roles of pharmacists(cont’d)
Drug interaction (particularly enzyme induction and inhibition)
Lamotrigine-valproic acid
Phenytoin-tacrolimus
AEDs and contraceptives, pregnancies, menopause such as
• Lamotrigine-contraceptives= possible treatment failure
• Enzyme-inducing AEDs needs higher dose progestogen implant(levonorgestrel
is preferred) else, pregnancy may occur

14. Roles of pharmacists(cont’d)
Patient education and counselling( IUD, pregnancy, consistency of
time of administration,
 Depo-provera® is preferred.
 However for patients on valproate, IUD is preferred
Consultation by patient
Adherence monitoring
Pharmacotherapeutic follow-up/therapeutic drug monitoring(esp
valproic acid, phenytoin adjustments, pregnancy)
Referral to physician (poor seizure control, adverse drug reaction,
pregnancy)

15. Recent discoveries/progress
• In march 2018, MHRA issued a warning that sodium valproate must
no longer be used in any woman or girl able to have children unless
she has a pregnancy prevention plan in place. 4 in 10 babies are at
risk of developmental disorders and approximately 1 in 10 are at risk
of birth defects
• Perampanel(FYCOMPA®) is the first AMPA receptor antagonist
designed to block glutamate pathway and is particulaurly indicated
for focal seizures as well as primarily generalised and secondarily
generalised toni-clonic seizures. The starting dose is 2mg for those
that are not other enzyme-inducing AEDs while it is 4mg for those
taking those inducers such as carbamazepine, phenytoin and the likes

16. Conclusion
The mainstay in managing seizures is pharmacotherapy and
pharmacists have important roles to play. Hence, pharmacist should be
actively involved in the care of people living with seizures concerning
their drug-related needs.

17. References
• Stephen C. Schachter (2013) Pharmacists: What role do pharmacists play in the care of patients with epilepsy?
www.epilepsy.com/learn/diagnosis/you-and-your-healthcare-team/pharmacists
• Yifat Roth et al. (2016) An evaluation of pharmacist knowledge on treatment with antiepileptic drugs
www.sciencedirect.com/science/article/pii/S10591311115002794 retrieved on 05/03/2019
• Epilepsy society(2018) Epilepsy For Pharmacists www.epilepsysociety.org.uk/epilepsy-pharmacists#.XH2o1KA080M retrieved on
05/03/2019
• Pharmacy times(2017) www.pharmacytimes.com/publications/issue/2017/september2017/r867_september2017
• Hien Ha (2013) Epilepsy: Treatment and Management www.uspharmacist.com/article/epilepsy-treatment-and-management
retrieved on 05/03/2019
• National Institute for Health and Care Excellence(2018) Epilepsies: diagnosis and management www.nice.org.uk/guidance/cg137
retrieved on 08/03/2019
• Akinsulore Adesanmi and Abiodun Adewuya(2010), Psychosocial aspects of epilepsy in Nigeria: A review, African Journal of
Psychiatry, Vol 13, page 351-356
• Olubosede A. o. et al(2015) Prevalence, etiology and Outcome of Febrile Convulsions at the Wesley Guild Hospital, Ilesa, South-
West Nigeria, BJMMR, Vol 8, issue 5, page 470-476
• Ngugi, A.K.,Kariuki, S.M., Sander, J.W.(2014), Prevalence and potential causes of epilepsy in Nigeria, Epilepsy Research,
http://dx.doi.org/10.1016/j.eplepsyres.2014.04.015

18. •THANK YOU