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University of the Western Cape

School of Pharmacy
Clinical Pharmacy Unit

Pharmacotherapeutic Work-Up Notes


EPILEPSY Student Name: Lucinda Conradie
Student Number: 3345101
Definition:
Epilepsy is defined as recurrent unprovoked seizures. Epilepsy is associated with many psychological, social
and legal problems, and cultural misperceptions.

Status Epilepticus:
A seizure lasting > 5 minutes or recurrent seizures without recovery to baseline between episodes.
A. PATIENT ASSESSMENT
CURRENT MEDICAL CONDITIONS AND MEDICATIONS
Date:
INFORMATION

Name:
CONTACT

Address:
Tel. (w): Tel. (h): Cell:

Age: 65 years Birth Date: 14.06.201 Gender Male


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DEMOGRAPHICS

Weight: Height: BMI:


Pregnancy: Breast Feeding: IBW:
Occupation: CrCl:
Living
arrangements:
REASON FOR ENCOUNTER

Dosage Regimen
Medication dose, route, frequency, Start Date Stop Date Indication
Past Medication Therapy

duration

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MEDICAL HISTORY

Medication Allergies (drug, timing, reaction—rash, shock, asthma, nausea, anemia)


ALLERGIES & ALLERTS

Adverse reactions to drugs in the past

Other Alerts/Health Aids/Special Needs (sight, hearing, mobility, literacy, disability)

Substance History of Use Substance History of Use


SOCIAL DRUG
USE

Tobacco Alcohol

Caffeine Other

Laboratory investigations Diagnostic investigations

1. Take an adequate history to define the type of epilepsy. Is usually made clinically.
2. Although rare, juvenile myoclonic epilepsy and absence - Requires an accurate witness description of the seizure.
seizures should be specifically considered and identified, as Some different types of seizures:
some standard medications may be less efficacious in these Partial Simple partial Seizure on one
side of the body
conditions or may even worsen seizure frequency or severity. with no loss of
3. All patients with new onset epilepsy should have a CT scan consciousness
Complex partial Partial seizure
and other investigations as clinically indicated.
associated with
4. A single unprovoked seizure is usually not an indication for
loss of
treatment although 40% of patients may have a subsequent
consciousness.
seizure within 2 years. Generalised Generalised tonic - Loss of
5. Anticonvulsants should be commenced after a single Clonic consciousnes
s preceded
INVESTIGATIONS

unprovoked seizure in patients at high risk of subsequent


by:
seizures (e.g. abnormal neurological examination, strong - a brief stiff
phase,
family history, abnormal brain imaging)
followed by
- jerking of all
of the limbs
Tonic One or more limbs
become stiff
without any
jerking.
Myoclonic Brief, usually
generalised jerks,
with retained
awareness.
Absence - Occurs in
childhood.
- Sudden
cessation of
activity
followed by a
blank
stare.

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- Usually no
muscle
twitching.
- Some
children will
smack their
lips.

General Systems Poor appetite GU/Reproductive Dysmenorrhea/ menstrual


bleeding
Weight change Incontinence

Pain Impotence

Headache Decreased sexual drive

Dizziness (Vertigo) Vaginal discharge or itching

EENT Change in vision Hot flashes


Hearing loss Kidney/Urinary Urinary frequency

Ringing in ears (Tennitus) Bloody urine (hematuria)

Bloody Nose (epistaxis) Renal dysfunction

Allergic rhinitis Excessive bruising

Glaucoma Hematopoietic Excessive bruising

Bloody sputum (hemoptysis) Symptoms Bleeding


Cardiovascular Chest pain Anemia
REVIEW OF SYSTEMS

Hyperlipidemia Musculoskeletal Back pain

Hypertension Arthritis pain


(osteo/rheumatoid)

Myocardial Infarction Tendonitis

Orthostatic hypotension Painful muscles

Pulmonary Asthma Neuropsychiatric Numb, tingling sensation in


extremities (parasthesia)
Shortness of Breath Tremor

Wheezing Loss of balance

Gastrointestinal Heartburn Depression

Abdominal Pain Suicidal


Nausea Anxiety, nervousness

Vomiting Inability to concentrate

Constipation Seizure

Dirrhoea Stroke/TIA

Skin Eczema/Psoriasis Memory loss


Itching (pruritis) Infectious Disease HIV/AIDS
Rash Malaria

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Endocrine Systems Diabetes Syphilis

Hypothyroidism Gonorrhea
Menopausal Symptoms Herpes

Hepatic Cirrhosis Chlamydia

Hepatitis Tuberculosis

Nutrition/Fluid/ Dehydration
Electrolytes Edema

Potassium deficiency
VITAL SIGNS

Blood Pressure: Hear Rate: Respiratory Rate: Temperature:


DIAGNOSIS

Medication Dosage Start Date Stop Date Reason for DC*

STG: (2014)
General rule: a single medicine is best.
- Combination therapy should only be initiated by a specialist.
 Recommended doses are general guides and will be effective in most patients.
 Some patients may need much higher or lower doses. Doses should only be increased at 2-weekly intervals.
 Therapeutic monitoring will assist with dosage adjustments, or in suspected non-adherence. However, it is only
mandatory in the case of higher than usual doses of phenytoin.
CURRENT MEDICATION (POST DIAGNOSIS)

Generalised tonic clonic seizures


Adults: The aim is to use
monotherapy, i.e. a single
anticonvulsant,
progressively
increasing the dose until the
seizures are controlled or
clinically important side
effects occur
Lamotrigine, oral (Doctor 25 mg daily for 2 weeks.
o Then 50 mg daily for 2
initiated).
weeks.
o Thereafter, increase by
50 mg every 2 weeks
according to response.
o Usual maintenance dose:
100–200 mg daily as a
single dose.
OR:
Carbamazepine, oral o 100 mg 12 hourly for one
(Doctor initiated). week then, 200 mg 12
hourly.
o Titrate upwards every 2
weeks according to
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response to a maximum
dose of
600 mg 12 hourly.
If the initial medicine fails to achieve satisfactory control with optimal dosages, or causes unacceptable adverse
effects, then a 2nd medicine may be started. The 1st medicine should be continued for 2 weeks and then gradually reduced
over 6–8 weeks until stopped.
Only if already well controlled
on phenytoin, continue with:
Phenytoin, oral, 4.5–5 mg/kg daily on lean
body mass, at night (Doctor
initiated).
o Phenytoin is a useful and
effective agent. However, doses
> 300 mg/day are
potentially toxic, and increased
dosages should be monitored
carefully, both
clinically and by medicine
concentrations.
Children: The decision to initiate long-term therapy is generally made if the child has experienced ≥ 2 unprovoked
convulsions (except febrile convulsions).
Phenobarbital and oral, 3.5–5 mg/kg at night (< Monitor the behaviour profile
carbamazepine are both 6 months of age) (Doctor and academic performance of
effective in generalised tonic prescribed). children on
clonic seizures. phenobarbital. Change
Phenobarbital, treatment if any problems are
identified.

OR: oral, 5 mg/kg 12 hourly for 2


weeks, then 7.5–
Carbamazepine,
10 mg/kg 12 hourly (Doctor
prescribed).
- Maximum dose: 10
mg/kg 12 hourly.
HIV-infected individuals on ART
Children For HIV-infected children on ART, valproate is preferred because of fewer medicine
interactions. When switching to valproate, commence treatment with maintenance dose of
the medicine as below and discontinue the other anticonvulsant after 7
days.
Valproate oral, 5 mg/kg 12 hourly
(Doctor prescribed).
- Titrate according to
response over 4 weeks
up to 15 mg/kg 12
hourly.
- If poorly tolerated divide
total daily dose into 3
equal doses.
- Maximum daily dose 40
mg/kg/day.
Adults For HIV-infected adults on ART, lamotrigine is preferred because of fewer medicine
interactions. When switching to lamotrigine, commence treatment as below and
discontinue the other anticonvulsant after 28 days.
Lamotrigine, oral (Doctor initiated) Note: The dose of lamotrigine
- 25 mg daily for 2 weeks.
will need to be doubled when
- Then 50 mg daily for 2
weeks. patients are

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- Thereafter, increase by switched from efavirenz- or
50 mg every 2 weeks nevirapine-based ART to
according to response.
lopinavir/ritonavir-based
- Usual maintenance
dose: 100–200 mg/day ART because the metabolism of
as a single dose. lamotrigine is induced by
lopinavir/ritonavir.
Poorly controlled epilepsy
Ask about the following, as these factors can influence decisions regarding
medicine therapy:
- Has the patient been adherent in taking the medication regularly for at least 2 weeks or more before the seizure? Ask about
medicine dosage and frequency.
- Has the patient recently used some other medicine? (i.e. look for drug interactions).
- Is there a chance that alcohol is involved?
If ≥ 1 of the above are present, address the problem/s but leave anticonvulsant therapy unchanged (unless dose adjustment is
necessary because of a drug interaction). Reassess the patient within 2 weeks.
STG HOSPITAL GUIDELINES (2015)
MEDICINE TREATMENT
- The aim is to use monotherapy, i.e. a single anticonvulsant, progressively increasing the dose until the seizures are
controlled or clinically important side effects occur.
- If the initial medication fails to achieve satisfactory control with optimal dosages, or causes unacceptable adverse
effects, then a second medicine may be started.
- The first drug should be continued for 2 weeks and then gradually reduced over 6– 8 weeks until stopped. If the
second drug fails, and alcohol and poor adherence are excluded, then combination therapy may be required.
- Refer patients for specialist investigation.
- Patients with a history of myoclonic seizures or typical absence seizures should preferably be treated with valproate,
as those seizures may be aggravated by the use of either phenytoin or carbamazepine.

Partial seizures or generalised tonic clonic seizures


The choice between therapeutic agents must be made on the acceptability of side effects and how the number of doses
influences lifestyle.
Carbamazepine, oral.
o Start with 100 mg 12
hourly.
o Increase by 100–200
mg/day at weekly intervals
according to
seizure control and adverse
events.
o Usual maximal dose: 600
mg 12 hourly.

OR oral.
Lamotrigine, o 25 mg daily for 2 weeks,
then 50 mg daily for 2
weeks.
o Thereafter, increase by
50 mg every 2 weeks
according to
response.
o Usual maintenance dose:
100–200 mg daily as a
single dose.

OR oral, 4.5–5 mg/kg (lean body


Phenytoin, mass) daily.
o Usual starting dose in an
adult male: 300mg once
daily.
o Dose changes above 300
mg should be done only in
no more than

6
50 mg increments at
intervals no shorter than 2
weeks.
For patients not stabilised on or who do not tolerate the above medications:
Valproate, oral. Usual starting dose: 200–
o 300 mg 12 hourly.
o Increase, as required,
every 2 weeks to a
maximum daily dose of
1.2 g 12 hourly.
Other epilepsy types
Manage in consultation with a specialist.
Specifically, juvenile myoclonic epilepsy is best controlled with valproate
initially, and absence seizures with valproate or lamotrigine.
HIV-infected individuals on ARVs: Phenytoin, phenobarbital and carbamazepine are enzyme inducing antiepileptic
medicines. Due to potential drug interactions with antiretroviral
drugs, switch patients on these anti-epileptics to lamotrigine or valproate.
Lamotrigine, oral. Note: The metabolism of
o 25 mg daily for 2 weeks, lamotrigine is induced by
then 50 mg daily for 2 lopinavir/ritonavir and
weeks. atazanavir/ritonavir. The
o Thereafter, increase by dose of lamotrigine may
50 mg every 2 weeks need to be increased when
according to patients are switched to a
response. lopinavir/ritonavir- or
o Usual maintenance dose: atazanavir/ritonavir -
100–200 mg daily, as a containing regimen.
single dose or 12
hourly.
OR
Valproate, oral.
o Usual starting dose: 200–
300 mg 12 hourly.
o Increase, as required,
every 2 weeks to a
maximum dose of 1200
mg 12 hourly.
Add on therapy to valproate:

Lamotrigine , oral.
o Start with 25 mg daily on
alternate days for 2 weeks,
increasing to
25 mg daily for 2 weeks.
o Thereafter increase by
25–50 mg every 2 weeks
according to
response.

Pregnancy: Optimal control of epilepsy on a single agent is the best management. ( Do not initiate valproate during
pregnancy, as it is associated with a higher teratogenic potential than the other first line agents)
Before pregnancy is
considered, folate
supplementation:
Folic acid, oral, 5 mg daily.
o Pregnancy alters drug
levels, adjust dose according
to levels.
Prophylaxis in head trauma: Phenytoin may be of benefit during initial period following significant head trauma.

Phenytoin , IV, 20 mg/kg diluted in


sodium chloride 0.9% (not
dextrose)

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administered not faster than
50 mg/minute preferably with
cardiac
monitoring.
o If arrhythmias occur,
interrupt the infusion
temporarily and
reintroduce slowly.
o Continue with, IV, 5
mg/kg/day (300 mg daily for
most adults).
STATUS EPILEPTICUS: Seizures should be stopped promptly as prolonged seizures can cause
permanent brain damage. Aim for definitive control within 60 minutes of onset.
INITIAL TREATMENT

Lorazepam, IV/IM, 4 mg, repeat after 5–


10 minutes if necessary.
OR IV, 10 mg, not faster than 2
Diazepam, mg/minute,
repeat after 5–10 minutes if
necessary.
OR IV, 2 mg, repeat after 5–10
Clonazepam, minutes if
necessary.
OR IM/IV 10 mg, repeat after 5–
Midazolam, 10 minutes if
necessary.
OR buccal, 10 mg using the
Midazolam parenteral
formulation.
AND IV, 20 mg/kg diluted in
Phenytoin, sodium chloride 0.9% (not
dextrose)
administered not faster than
50 mg/minute preferably with
cardiac
monitoring.
o If arrhythmias occur,
interrupt the infusion
temporarily and reintroduce
slowly.
Seizures continuing after Intubate and ventilate
30 minutes patient.
Thiopental , IV, 4 mg/kg, followed by 50 Higher initial maintenance
mg bolus every 2–3 minutes doses of phenytoin may be
to needed in patients
control seizures. who have had thiopental.
o Maintenance dose: 1–5 Doses should be guided by
mg/kg/hour. daily therapeutic drug
o Beware of hypotension. monitoring until phenytoin
o Once seizures controlled levels have stabilised after
for 24 hours, wean off thiopental has been
thiopental by weaned off.
decreasing the dose by 1
mg/kg every 12 hours.
OR
Propofol, IV, 3mg/kg/dose
as a bolus
o Maintenance dose: 30–
100 mcg/kg/minute.
MAINTENANCE THERAPY Higher initial maintenance
doses of phenytoin may be
needed in patients
who have had thiopental.
Doses should be guided by
daily therapeutic drug
monitoring until phenytoin
levels have stabilised after
thiopental has been
weaned off.

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If seizures are controlled: IV/oral, 300 mg daily.
Phenytoin, o First maintenance dose
should be no more than 12
hours after the
loading dose.

B. THERAPEUTIC PLAN
INDICATION EFFECTIVENESS SAFETY COMPLIANCE
DRP-1: Unnecessary Drug DRP-3: Alternative Drug DRP-5: Adverse Drug Reaction DRP-7: Non-adherence
Therapy Therapy  Undesirable effect  Directions not
 No medical indication  More effective drug  Unsafe drug for patient understood
 Duplicate therapy available  Drug interaction  Patient prefers not to
 Nondrug therapy  Condition refractory to  Dosage administered or take
indicated drug changed too rapidly  Patient forgets to take
 Treating avoidable ADR  Dosage form  Allergic reaction  Patient cannot afford
 Addictive/recreational inappropriate  Contraindications present  Cannot
DRP-2: Needs Additional Drug  Not effective for DRP-6: Dosage too High swallow/administer
Therapy condition  Wrong Dose  Drug product not
 Untreated condition DRP-4: Dosage too Low  Frequency inappropriate available
 Preventive/prophylactic  Wrong dose  Duration inappropriate DRP-8: Other
 Synergistic/potentiating  Frequency inappropriate  Drug interaction
 Drug interaction  Incorrect administration
 Duration inappropriate
Description of Drug Related Problem Therapeutic Alternatives (medicine, dose, duration)

Goal of Therapy Measurable Endpoint

1.
GOALS OF THERAPY

2.
3.
4.
5.
6.

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- Extensive health education.
- Record keeping in a seizure diary recording dates and, if possible, the times of the seizures.
- Present seizure diary at each consultation for assessment of therapy.
- Carry a disease identification bracelet, necklace or card.
- Counselling and advice on:
 the adverse effect of alcohol on seizures,
 the effect of missing a dose of medication,
NON-PHARMACOLOGICAL THERAPY & PAITENT EDUCATION

 the risks of discontinuingmedicine treatment without advice of the doctor.


- Patient should be counseled about driving, working at heights, swimming and operating machinery - the patient should sign in the
notes that they have received this advice.

- Record dates and, if possible, times of seizures in a seizure diary. Present seizure diary at each consultation for
assessment of therapy.

- Disease identification bracelet, necklace or card.

- Counselling and advice on:


 the adverse effect of alcohol on seizures
 sleep hygeine,
 the effect of missing a dose of medication,
 discontinuing the medication without advice of a doctor, and
 family planning is important in women of child-bearing potential as anticonvulsants, especially valproate, can be
teratogenic. Note that there are important drug-drug interactions between hormonal contraceptive (except
DMPA) and several anticonvulsant medicines (carbamazepine, phenobarbital, phenytoin).
Patients with uncontrolled seizures should avoid driving and operating machinery until they have been seizure
free. Physician to provide guidance.

- Start treatment immediately. Do not wait for results of special investigations.


- Secure the airway.
- Check serum glucose, and treat if hypoglycaemic.
- Check for hyponatraemia or uraemia and measure anticonvulsant levels if the patient is on therapy.
- Consider poisoning, e.g. isoniazid, theophylline, tricyclic antidepressants, cocaine.

C. FOLLOW-UP AND MONITORING

Medicine Therapy Effectiveness Monitoring Safety Monitoring

Routine therapeutic drug monitoring is not


useful except:
» To confirm toxicity in a symptomatic
patient.
» To confirm poor adherence.
FOLLOW-UP EVALUATION

» With poor control despite good self


reported adherence.
Phenytoin, phenobarbitone and
carbamazepine are potent enzyme
inducing agents and should be used with
caution with other medicines
metabolised by the liver, especially warfarin,
ARVs, progestin subdermal
implants and oral contraceptives.
Clinical signs that seizures are controlled
are autonomic
stability and the absence of abnormal
movement.

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Date: Notes/Remarks
PROGRESS NOTES

D. LABORATORY RESULTS
HAEMATOLOGY
WCC 4 – 11 /L
RBC 3.8 – 4.8 /L
Haemoglobin (HB) 14 – 18 gm/L
Hematocrit 0.368 – 0.473 L/L
MCV 77.1 – 91.5 fl

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MCH 25.8 – 31.7 pg
Platelets 140 – 440 /L
CRP 0 – 10
INR 1.0 – 1.2
PTT 35 – 45 sec
Fibrinogen 1.8 – 3 g/L
PT 10 –12 sec
D-Dimer < 250
Iron Serum 10 – 30 umol/L
Ferritin 10 – 120 ug/L
Vit B12 200 – 1100
Folic Acid 2 – 15
ARTERIAL BLOOD GAS
PH 7.35 – 7.45
PO2 75 – 90 mm Hg
PCO2 35 – 45 mm Hg
Base Excess -2 to +2
HCO3 20 – 25 mmol/L
Oxygen sats 95 – 98 %
CEREBROSPINAL FLUID
Protein 0.1 - 0.45g/L
Glucose 2.5 – 5.5 mmol/L
Chloride 120 – 130 mmol/l
CSF - ADA < 6 u/L
CHEMISTRY
Na 135 – 147 mmol/L
K 3.5 – 5.3 mmol/L
Cl 95 – 105 mmol/L
Urea 2.6 – 7.0
Creatinine Mmol/L
Phosphates 0.80 – 1.60 mmol/L
Calcium 2.20 – 2.56 mmol/L
LIVER FUNCTION TEST
Total Protein 60 – 85 g/L
Albumien 40 – 60 g/L
Total Billirubin 3.42 – 25.7 umol/L
ALP 40 – 120 u/L
AST 5 – 40 u/L
ALT 5 – 40 u/L
GGT 0 – 60 u/L
Total Cholesterol 3.87 – 5.17 mmol/L
LDL <4.1 mmol/L
HDL >1.04 mmol/L

Carbamazepine, phenytoin and phenobarbital are associated with many medicine


interactions.
» Always check for possible interactions before prescribing concomitant medicines.
Oral contraceptives and subdermal implants may be less effective. Progestin-only
injectable contraceptives or IUDs are preferred. See Chapter 7: Family planning.

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