Treatment of Chronic Epilepsy in Uganda

AED Prescribing Rubrics

 Key References
Guiding Documents
World Health Organization (WHO) mhGAP 2.0 Epilepsy Module
Uganda National Clinical Guidelines

Epilepsy Experts
Makerere University School of Medicine/Mulago National Referral Hospital
Dr. Angelina Kakooza-Mwesige
Dr. Martin Kaddumukasa
Dr. Mark Kaddumukasa

Duke University School of Medicine/Duke Health

Dr. Aatif Husain
Dr. Dmitry Tchapyjnikov
Dr. Bradley Kolls
Typical AED availability in Uganda Public Health Settings
 Uganda AED Drug Usage Patterns

Fuller AT, Almojuela A, Kaddumukasa MN, Chakraborty P, Smith PJ, Kolls BJ, Van Belleghem F, Muhumuza C, Nshemerirwe S, Kaddumukasa M, Nakasujja N, Nakku J,
Kakooza-Mwesige A, Haglund MM, Koltai DC. Hospital-based epilepsy care in Uganda: A prospective study of three major public referral hospitals. Epilepsy Behav. 2021
 AED Treatment Framework
An Introduction
● Monotherapy is the gold standard to begin treatment of focal and generalized seizures, with the goal of
obtaining 100% control; however, it is important to realize that about 20-30% do not achieve this goal.

● To begin treatment with AEDs, one must start administering the drug gradually to arrive at the recommended
therapeutic dose. In children, one should always calculate the milligrams per kilogram of weight, however in
adults, you do not always do so and may need to consider the aspects related to the particular AED, the
characteristics of the patient, as well as cost and bioavailability of the drug.

● In general, the first choice of AED will primarily depend on the clinical confirmation of epilepsy through:

● (i)  The identification of the type of epileptic seizure-(i.e. focal/generalized)

● (ii) The diagnosis of the epileptic syndrome presented by the patient, where applicable

● (iii) The ability to be able to determine the etiology of the epilepsy, if possible.
 AED Treatment Framework
An Introduction (cont.)
● The goal of administering AEDs is the complete control of epileptic seizures, and they are effective if
prescribed correctly for the syndrome or type of seizure. The recommendation is to begin treatment with a
single AED.

● The dose of the AED must be reached slowly and progressively until arriving at the recommended therapeutic
dose.

● Consistency in taking the treatment is very important, and the patient must be informed of the gravity of
suspending medication abruptly. It is essential to jointly develop an understandable, agreeable treatment plan,
so the patient appreciates the need for ongoing and consistent use of medication even in the absence of
seizures, and that it may take several adjustments to achieve maximum control with minimal side effects.

● When despite taking a first-line AED at adequate doses and you are assured of good therapeutic adherence by
the patient, and the patient continues to get repeated seizures, we must reconsider the correct diagnosis of the
type of seizure and the differential diagnosis by conducting a new clinical evaluation and clinical tests.
 AED Treatment Framework
An Introduction (cont.)
Initiating a 2nd AED when monotherapy has failed:

● If the first AED is not well tolerated at low doses, another AED from among those recommended for
first‑line therapy must be used.

● When an average therapeutic dose of the chosen AED is reached, without achieving 100% control
in a maximum period of 6 months, another AED with a different pharmacological profile must be
used.

● The second AED must be introduced gradually at the recommended dose.

● Once seizure control is achieved, decisions about subsequent gradual suspension of the first AED
must be evaluated carefully. Once seizure control is achieved, consideration should be given to
slowly taper or maintain each medicine by reviewing drug and drug combination efficacy, the side
effect profile, and the clinical syndrome. Realistic consideration of drug availability and cost as it
relates to the patient’s circumstances are also warranted.
 AED Treatment Framework
An Introduction (cont.)
Referral and Consultation

● Some seizures are hard to control and may indicate atypical or rare conditions. Refer to regional
and national referral hospitals as needed.

Other AEDs

● This module includes information about those drugs available in the Uganda public sector, which
are first generation AEDs. Information about alternative medications can be found:

● epilelpsy.com (Epilepsy Foundation)

● ILAE.org (International League Against Epilepsy)

 Epilepsy AED Treatment Framework

● If high doses with side effects

Start with monotherapy.
are required and seizures are
● Effective dose must be reached progressively
Step 1 infrequent, less than complete
● Aim at the lowest dose able to control (prevent) the seizures.
control can be the goal
● Monitor patient for tolerance and side effects
● Follow-up monthly until stable,
then every 3 months
*Proceed to Step 2 if treatment is ineffective (<50% reduction in seizures)
● Warn patients that treatment
Add a second AED agent to achieve seizure control. Once control is achieved,
interruptions can trigger
consideration can be given to slowly taper the first agent to see if control can be
seizures or even status
Step 2 maintained. Decisions about tapering or maintaining each medication will be made
epilepticus
by reviewing drug and drug combination efficacy, the side effect profile, and the
clinical syndrome.

*Proceed to Step 3 if Step 2 combination trial fails

Step 3 Refer to a specialist (Regional or National Referral Hospital).

Simplified rules of thumb in Prescribing
 Absence (petit-mal) seizures are characterized by blank stares and typically occur in
children. For absence seizures, try ethosuximide first.

 For suspected generalized seizures, for children <2 begin with Phenobarbital.

 For suspected generalized seizures in adults or children >2, begin with sodium valproate (1)
or carbamazepine (2) as first line.

 For suspected focal seizures carbamazepine should be tried first (1).

 Carbamazepine should also be used first in women of childbearing age, due to

teratogenicity of valproate,

 If seizure control is not achieved, try to other agent of the front-line agents not used yet. If
this combination therapy does not work, refer to regional or national referral center.
Treatment of Child Chronic
Epilepsy
 Pediatric AED Treatment by Epilepsy Type
Generalized Epilepsy Focal

Tonic Clonic Absence Atonic or tonic Myoclonus

Carbamazepine 3: children <2 years old 1

2: children >2 years old

Phenobarbital 1: children <2 years old 3 (atypical) 2 2 3

3 : children >2 years old

Phenytoin 3: children <2 years old 3 3 2

3: children >2 years old

Sodium Valproate 2: children <2 years old 2 (atypical) 1 1 2

1: children >2 years old

Ethosuximide 1
 Pediatric Master AED dosing chart
Lowest Health Drug Regional Dosage Pharmacokinetics Used in Side Effects Notes
Center Level Referral Children
Administration Needed <2yo

HC2 Phenobarbital No Starting: 2-3 mg/kg/day for 2 weeks
If not controlled, increase to 3
mg/kg/day for 2 months.
If not controlled, increase weekly by 1-2
mg/kg/day depending on tolerance until
maximum of 6mg/kg/day.
Given once a day in the evening to
reduce drowsiness
Maximum: 6 mg/kg/day
It takes 2-3 weeks for the drug to
achieve steady blood levels so
assess its effects only after this
period
Yes Dose determined effects:
Drowsiness, lethargy,
hyperactivity, irritability, and
depression
Idiosyncratic effects: rash, bone-
marrow depression, and hepatic
failure
Avoid phenobarbital in children with
intellectual disability and/or behavioural
problems
Phenobarbital can cause behavioral
disturbances and hyperkinesia
May be sedating

Phenytoin No Starting: 3-4 mg/kg/day Increase 5 No Common: sedation, confusion, Avoid phenytoin in children with
mg/kg/day every 3-4 weeks. dizziness, tremor, motor twitching, intellectual disability and/or behavioural
Given daily in 2 divided doses ataxia, double vision, nystagmus,
problems
Maximum: 300 mg/day slurred speech, nausea, vomiting,
and constipation

Serious: hematologic abnormalities,

hepatitis, polyneuropathy, gum
hypertrophy, acne.
lymphadenopathy, increase in
suicidal ideation

HC3 Carbamazepine No Starting: 5 mg/kg/day Yes Skin rash, diplopia, blurred vision, General warning: can exacerbate
Increase by 5mg/kg/day weekly. ataxia (staggering gait), and nausea generalized seizures
Given daily in 2-3 divided doses
Maximum: 40 mg/kg/day or 1400 mg Serious: hepatoxicity, cardiac
daily conduction delay, and low sodium
levels

HC4 Sodium Valproate No Starting: 15-20 mg/kg/day Yes Liver toxicity, blood disorders, GI Monitor liver function and full blood count
Increase by ¼ to ½ of initial dose every 3 disorders, weight gain, transient hair
Be cautious of toxicity with children <2 years old
days until control achieved loss
when using sodium valproate
Given 2 times daily
Maintenance: 15-40 mg/kg/day Avoid use in females of child bearing age, due to
Maximum dose: 60 mg/kg/day its teratogenic potential
 Treatment of Pediatric Tonic-Clonic Seizures
● In children, look for presence of
associated intellectual disability
Start with phenobarbital for children<2 and sodium valproate for children>2. or behavioral problems. If
● Effective dose must be reached progressively present, consider
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. carbamazepine or valproate
● Monitor patient for tolerance and side effects (avoid phenobarbital and
phenytoin) and manage
associated intellectual disability
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) or behavioral problem.

Add sodium valproate for children<2; add carbamazepine for children>2.

Subsequent decisions about tapering or maintaining each medication will be made ● If high doses with side effects
Step 2 by reviewing drug and drug combination efficacy, the side effect profile, and the are required and seizures are
clinical syndrome. For absence, move to step 3 for further studies for seizure infrequent, less than complete
characterization. control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if 2 monotherapy trials fail then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Pediatric Tonic-Clonic Seizures
Lowest Health Drug Regional Dosage Pharmacokinetics Used in Side Effects Notes
Center Level Referral Children
Administration Needed <2yo

HC2 Phenobarbital No Starting: 2-3 mg/kg/day for 2 weeks
If not controlled, increase to 3
mg/kg/day for 2 months.
If not controlled, increase weekly by 1-2
mg/kg/day depending on tolerance until
maximum of 6mg/kg/day.
Given once a day in the evening to
reduce drowsiness
Maximum: 6 mg/kg/day
It takes 2-3 weeks for the drug to
achieve steady blood levels so
assess its effects only after this
period
Yes Dose determined effects:
Drowsiness, lethargy,
hyperactivity, irritability, and
depression
Idiosyncratic effects: rash, bone-
marrow depression, and hepatic
failure
Avoid phenobarbital in children with
intellectual disability and/or behavioural
problems
Phenobarbital can cause behavioral
disturbances and hyperkinesia
May be sedating

Phenytoin No Starting: 3-4 mg/kg/day Increase 5 No Common: sedation, confusion, Avoid phenytoin in children with
mg/kg/day every 3-4 weeks. dizziness, tremor, motor twitching, intellectual disability and/or behavioural
Given daily in 2 divided doses ataxia, double vision, nystagmus,
problems
Maximum: 300 mg/day slurred speech, nausea, vomiting,
and constipation

Serious: hematologic abnormalities,

hepatitis, polyneuropathy, gum
hypertrophy, acne.
lymphadenopathy, increase in
suicidal ideation

HC3 Carbamazepine No Starting: 5 mg/kg/day Yes Skin rash, diplopia, blurred vision, General warning: can exacerbate
Increase by 5mg/kg/day weekly. ataxia (staggering gait), and nausea generalized seizures
Given daily in 2-3 divided doses
Maximum: 40 mg/kg/day or 1400 mg Serious: hepatoxicity, cardiac
daily conduction delay, and low sodium
levels

HC4 Sodium Valproate No Starting: 15-20 mg/kg/day Yes Liver toxicity, blood disorders, GI Monitor liver function and full blood count
Increase by ¼ to ½ of initial dose every 3 disorders, weight gain, transient hair
Be cautious of toxicity with children <2 years old
days until control achieved loss
when using sodium valproate
Given 2 times daily
Maintenance: 15-40 mg/kg/day Avoid use in females of child bearing age, due to
Maximum dose: 60 mg/kg/day its teratogenic potential
 Treatment of Pediatric Absence Seizures

● In children, look for presence of

Start with ethosuximide. associated intellectual disability
● Effective dose must be reached progressively or behavioral problems. If
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. present, consider
● Monitor patient for tolerance and side effects carbamazepine or valproate
(avoid phenobarbital and
phenytoin) and manage
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) associated intellectual disability
or behavioral problem.
Add sodium valproate or phenobarbital for atypical absence seizures. Subsequent
Step 2 decisions about tapering or maintaining each medication will be made by
reviewing drug and drug combination efficacy, the side effect profile, and the
● If high doses with side effects
clinical syndrome.
are required and seizures are
infrequent, less than complete
*Proceed to Step 3 if Step 2 combination trial fails control can be the goal
● Follow up monthly until stable,
then every 3 months
Step 3 Refer to a specialist (Regional or National Referral Hospital). ● Warn patients that treatment
interruptions can trigger
seizures or even status
epilepticus
 Pediatric Absence Seizures: Atypical and Typical
Lowest Health Drug Regional Referral Dosage Pharmacokinetics Used in Side Effects Notes
Center Level Needed? Children
Administration <2yo
Typical Atypical
Absence Absence
Seizures Seizures

HC2 Phenobarbital No Yes Starting: 2-3 mg/kg/day for 2 It takes 2-3 weeks for the Yes Dose determined Avoid phenobarbital in children with
weeks drug to achieve steady effects: Drowsiness, intellectual disability and/or
If not controlled, increase to 3 blood levels so assess its lethargy, hyperactivity, behavioural problems
mg/kg/day for 2 months. effects only after this irritability, and
If not controlled, increase weekly by period depression Phenobarbital can cause behavioral
disturbances and hyperkinesia
1-2 mg/kg/day depending on
tolerance until maximum of Idiosyncratic effects:
May be sedating
6mg/kg/day. rash, bone-marrow
Given once a day in the evening to depression, and hepatic
reduce drowsiness failure
Maximum: 6 mg/kg/day

HC4 Sodium Valproate Yes Yes Starting: 15-20 mg/kg/day Yes Liver toxicity, blood Monitor liver function and full blood
count
Increase by ¼ to ½ of initial dose disorders, GI disorders,
every 3 days until control achieved weight gain, transient Be cautious of toxicity with children <2
Given 2 times daily hair loss years old when using sodium valproate
Maintenance: 15-40 mg/kg/day
Maximum dose: 60 mg/kg/day Avoid use in females of child bearing
age, due to its teratogenic potential

RR Ethosuximide Yes Yes Child 1 mo - 6yo: 250 mg single dose Yes GI disorders, blood
at night increased gradually every 5-7 disorders, gum
days as required to usual dose of 20- hyperplasia, drowsiness
40 mg/kg daily in 2 divided doses.
Child > 6yo: Initially 250 mg in 2
divided doses, increase if necessary by
250 mg every 5-7 days up to a usual
daily dose of 1-1.5 g in 2 divided doses
 Treatment of Pediatric Atonic or Tonic Seizures
● In children, look for presence of
associated intellectual disability
Start with sodium valproate. or behavioral problems. If
● Effective dose must be reached progressively present, consider
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. carbamazepine or valproate
● Monitor patient for tolerance and side effects (avoid phenobarbital and
phenytoin) and manage
associated intellectual disability
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) or behavioral problem.

Add phenobarbital or phenytoin. Subsequent decisions about tapering or

Step 2 maintaining each medication will be made by reviewing drug and drug combination ● If high doses with side effects
efficacy, the side effect profile, and the clinical syndrome. are required and seizures are
infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Treatment of Pediatric Atonic and Tonic Seizures
Lowest Health Drug Regional Dosage
Center Level Referral
Administration Needed
HC2 Phenobarbital No Starting: 2-3 mg/kg/day for 2
weeks
If not controlled, increase to 3
mg/kg/day for 2 months.
If not controlled, increase
weekly by 1-2 mg/kg/day
depending on tolerance until
maximum of 6mg/kg/day.
Given once a day in the evening
to reduce drowsiness
Maximum: 6 mg/kg/day
Phenytoin No Starting: 3-4 mg/kg/day
Increase 5 mg/kg/day every 3-4
weeks.
Given daily in 2 divided doses
Maximum: 300 mg/day
HC4 Sodium Valproate No Starting: 15-20 mg/kg/day
Increase by ¼ to ½ of initial dose
every 3 days until control
achieved
Given 2 times daily
Maintenance: 15-40 mg/kg/day
Maximum dose: 60 mg/kg/day
Pharmacokinetics
It takes 2-3 weeks for the drug
to achieve steady blood levels
so assess its effects only after
this period
Used in Side Effects Notes
Children
<2yo
Yes Dose determined effects: Avoid phenobarbital in children with
Drowsiness, lethargy, intellectual disability and/or
hyperactivity, irritability, and behavioural problems
depression
Phenobarbital can cause behavioral
disturbances and hyperkinesia
Idiosyncratic effects: rash,
bone-marrow depression, and
May be sedating
hepatic failure
No Common: sedation, confusion, Avoid phenytoin in children with
dizziness, tremor, motor twitching, intellectual disability and/or
ataxia, double vision, nystagmus,
behavioural problems
slurred speech, nausea, vomiting,
and constipation
Serious: hematologic abnormalities,
hepatitis, polyneuropathy, gum
hypertrophy, acne.
lymphadenopathy, increase in
suicidal ideation
Yes Liver toxicity, blood disorders, Monitor liver function and full blood
GI disorders, weight gain, count
transient hair loss
Be cautious of toxicity with children <2
years old when using sodium valproate
Avoid use in females of child bearing
age, due to its teratogenic potential
 Treatment of Pediatric Myoclonic Seizures
● In children, look for presence of
associated intellectual disability
Start with sodium valproate (if available). or behavioral problems. If
● Effective dose must be reached progressively present, consider
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. carbamazepine or valproate
● Monitor patient for tolerance and side effects (avoid phenobarbital and
phenytoin) and manage
associated intellectual disability
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) or behavioral problem.

Add phenobarbital or phenytoin. Subsequent decisions about tapering or ● If high doses with side effects
Step 2 maintaining each medication will be made by reviewing drug and drug combination are required and seizures are
efficacy, the side effect profile, and the clinical syndrome. infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Treatment of Pediatric Myoclonic Seizures
Lowest Health Drug Regional Dosage Pharmacokinetics Used in Side Effects Notes
Center Level Referral Children
Administration Needed <2yo

HC2 Phenytoin No Starting: 3-4 mg/kg/day No Common: sedation, confusion, Avoid phenytoin in children with
Increase 5 mg/kg/day every 3-4 dizziness, tremor, motor intellectual disability and/or behavioural
weeks. twitching, ataxia, double vision, problems
Given daily in 2 divided doses nystagmus, slurred speech,
Maximum: 300 mg/day nausea, vomiting, and
constipation

Serious: hematologic
abnormalities, hepatitis,
polyneuropathy, gum hypertrophy,
acne. lymphadenopathy, increase
in suicidal ideation

Phenobarbital No Starting: 2-3 mg/kg/day for 2
weeks
If not controlled, increase to 3
mg/kg/day for 2 months.
If not controlled, increase
weekly by 1-2 mg/kg/day
depending on tolerance until
maximum of 6mg/kg/day.
Given once a day in the evening
to reduce drowsiness
Maximum: 6 mg/kg/day
It takes 2-3 weeks for the drug
to achieve steady blood levels
so assess its effects only after
this period
Yes Dose determined effects:
Drowsiness, lethargy,
hyperactivity, irritability, and
depression
Idiosyncratic effects: rash,
bone-marrow depression, and
hepatic failure
Avoid phenobarbital in children with
intellectual disability and/or
behavioural problems
Phenobarbital can cause behavioral
disturbances and hyperkinesia
May be sedating

HC4 Sodium Valproate No Starting: 15-20 mg/kg/day Yes Liver toxicity, blood disorders, Monitor liver function and full blood
Increase by ¼ to ½ of initial dose GI disorders, weight gain, count
every 3 days until control transient hair loss
Be cautious of toxicity with children <2
achieved
years old when using sodium valproate
Given 2 times daily
Maintenance: 15-40 mg/kg/day Avoid use in females of child bearing
 Treatment of Pediatric Focal Seizures
● In children, look for presence of
associated intellectual disability
Start with carbamazepine. or behavioral problems. If
● Effective dose must be reached progressively present, consider
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. carbamazepine or valproate
● Monitor patient for tolerance and side effects (avoid phenobarbital and
phenytoin) and manage
associated intellectual disability
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) or behavioral problem.

Add phenytoin or sodium valproate. Subsequent decisions about tapering or ● If high doses with side effects
Step 2 maintaining each medication will be made by reviewing drug and drug combination are required and seizures are
efficacy, the side effect profile, and the clinical syndrome. infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Treatment of Pediatric Focal Seizures
Lowest Health Drug Regional Dosage Pharmacokinetics Used in Side Effects Notes
Center Level Referral Children
Administration Needed <2yo

HC2 Phenobarbital No Starting: 2-3 mg/kg/day for 2
weeks
If not controlled, increase to 3
mg/kg/day for 2 months.
If not controlled, increase weekly by
1-2 mg/kg/day depending on
tolerance until maximum of
6mg/kg/day.
Given once a day in the evening to
reduce drowsiness
Maximum: 6 mg/kg/day
It takes 2-3 weeks for the drug to
achieve steady blood levels so
assess its effects only after this
period
Yes Dose determined effects:
Drowsiness, lethargy, hyperactivity,
irritability, and depression
Idiosyncratic effects: rash, bone-
marrow depression, and hepatic
failure
Avoid phenobarbital in children with
intellectual disability and/or behavioural
problems
Phenobarbital can cause behavioral
disturbances and hyperkinesia
May be sedating

Phenytoin No Starting: 3-4 mg/kg/day Increase 5 No Common: sedation, confusion, Avoid phenytoin in children with
mg/kg/day every 3-4 weeks dizziness, tremor, motor twitching, intellectual disability and/or
Given daily in 2 divided doses ataxia, double vision, nystagmus,
behavioural problems
Maximum: 300 mg/day slurred speech, nausea, vomiting,
and constipation

Serious: hematologic abnormalities,

hepatitis, polyneuropathy, gum
hypertrophy, acne.
lymphadenopathy, increase in
suicidal ideation

HC3 Carbamazepine*** No Starting: 5 mg/kg/day Yes Skin rash, diplopia, blurred vision, General warning: can exacerbate
Increase by 5mg/kg/day weekly. ataxia (staggering gait), and nausea generalized seizures
Given daily in 2-3 divided doses
Maximum: 40 mg/kg/day or 1400 Serious: hepatoxicity, cardiac
mg daily conduction delay, and low sodium
levels

HC4 Sodium Valproate No Starting: 15-20 mg/kg/day Yes Liver toxicity, blood disorders, GI Monitor liver function and full blood count
Increase by ¼ to ½ of initial dose disorders, weight gain, transient hair
Be cautious of toxicity with children <2
every 3 days until control achieved loss
years old when using sodium valproate
Given 2 times daily
Maintenance: 15-40 mg/kg/day Avoid use in females of child bearing age,
Treatment of Adult Chronic
Epilepsy
 Adult AED Treatment by Epilepsy Type
Generalized Epilepsy Focal

Tonic Clonic Absence* Atonic or tonic Myoclonus

Carbamazepine Male: 2 Male: 1

Female: 1 Female: 1

Phenobarbital 2 2 Male: 3
Female: 3

Phenytoin Male: 2 Male: 2

Female: 1 Female: 2

Sodium Valproate Male: 1 Male: 1 1 1 Male: 2

Female: 2 Female: 3

Ethosuximide Male: 1
Female: 1

Valproic acid should be used cautiously in women of child bearing age.

Whenever AEDs are used in women of childbearing age, use folic acid 1 mg per day as well.
Absence seizures rare in adults; staring spells are more often focal unaware seizures (complex partial seizures).
 Adult Master AED dosing chart
Lowest Health Drug Regional Dosage Pharmacokinetics Side Effects Notes
Center Level Referral
Administration Needed

HC2 Phenobarbital No Starting: 60mg daily in two divided doses It takes 2-3 weeks for the drug to Drowsiness, lethargy, hyperactivity Sedative in adults
Increase by adding 30 mg weekly until control achieve steady blood levels so and irritability in children, skin rash,
assess after this period
achieved depression
Maintenance: 60-180mg/day

Phenytoin No Starting: 200 mg/day as single dose or 2 Drowsiness, ataxia, slurred speech,
divided doses. blurred vision, twitching, confusion,
Increase by 200mg weekly until control gum hyperplasia, blood abnormalities,
achieved rash, hepatitis
Maintenance: 200-1400 mg/day
*Note: Regular TID; Long-acting BID

HC3 Carbamazepine No Starting: 200 mg/day Skin rash, diplopia, blurred vision,
Increase in 100 mg increments every 1-2 ataxia (staggering gait), nausea
weeks
Maintenance: 400 -1400 mg/day

RR Sodium Yes Starting: 200 mg/day Liver toxicity, blood disorders, GI Monitor liver function and full
Valproate Increase by 200 mg weekly until control achieved blood count
disorders, weight gain, transient hair
Maintenance: 400-3000 mg/day loss

*Note: Sodium valproate BID; Valproic acid BID

or TID dosing
 Treatment of Adult Tonic-Clonic Seizures
● All pregnant women with
epilepsy should be referred to
Start with: males: sodium valproate specialist for appropriate
females: carbamazepine or phenytoin management (most AEDs have
Step 1 ● Effective dose must be reached progressively increased risk of congenital
● Aim at the lowest dose able to control (prevent) the seizures. malformations)
● Monitor patient for tolerance and side effects

*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis)

Add carbamazepine or phenytoin for males, carbamazepine or phenytoin

● If high doses with side effects
Step 2 (whichever not tried as first line) for females. Subsequent decisions about tapering
or maintaining each medication will be made by reviewing drug and drug are required and seizures are
combination efficacy, the side effect profile, and the clinical syndrome. infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Adult Tonic-clonic Seizures
Lowest Health Drug Regional Dosage Pharmacokinetics Side Effects Notes
Center Level Referral
Administration Needed

Phenytoin No Starting: 200 mg/day as single dose or 2 Drowsiness, ataxia, slurred speech,
divided doses. blurred vision, twitching, confusion,
Increase by 200mg weekly until control gum hyperplasia, blood abnormalities,
achieved rash, hepatitis
Maintenance: 200-1400 mg/day
*Note: Regular TID; Long-acting BID

HC3 Carbamazepine No Starting: 200 mg/day Skin rash, diplopia, blurred vision,
Increase in 100 mg increments every 1-2 ataxia (staggering gait), nausea
weeks
Maintenance: 400 -1400 mg/day

RR Sodium Yes Starting: 200 mg/day Liver toxicity, blood disorders, GI Monitor liver function and full
Valproate Increase by 200 mg weekly until control achieved blood count
disorders, weight gain, transient hair
Maintenance: 400-3000 mg/day loss

*Note: Sodium valproate BID; Valproic acid BID

or TID dosing
 Treatment of Adult Absence Seizures
● All pregnant women with
epilepsy should be referred to
Start with ethosuximide. specialist for appropriate
● Effective dose must be reached progressively management (most AEDs have
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. increased risk of congenital
● Monitor patient for tolerance and side effects malformations)

*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis)

Add sodium valproate. Subsequent decisions about tapering or maintaining each ● If high doses with side effects
Step 2 medication will be made by reviewing drug and drug combination efficacy, the side are required and seizures are
effect profile, and the clinical syndrome. infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Adult Absence Seizures: Atypical and Typical
Lowest Health Drug Regional Referral Dosage Pharmacokinetics Side Effects Notes
Center Level Needed?
Administration
Typical Atypical
Absence Absence
Seizures Seizures

HC4 Sodium Valproate Yes Yes Starting: 200 mg/day Liver toxicity, blood Monitor liver function and
full blood count
Increase by 200 mg weekly until control disorders, GI disorders,
achieved weight gain, transient hair
Maintenance: 400-3000 mg/day loss

*Note: Sodium valproate BID; Valproic

acid BID or TID dosing

RR Ethosuximide Yes Yes Initially 250 mg in 2 divided doses GI disorders, blood

Increase by 250 mg every 5-7 days disorders, gum hyperplasia,
Maintenance: Up to a daily dose of 1-1.5 g in drowsiness
2 divided doses
 Treatment of Adult Atonic or tonic Seizures

● If high doses with side effects

Start with sodium valproate. are required and seizures are
● Effective dose must be reached progressively infrequent, less than complete
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. control can be the goal
● Monitor patient for tolerance and side effects ● Follow up monthly until stable,
then every 3 months
● Warn patients that treatment
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) can cause liver toxicity, so liver
function must be monitored.

Add phenobarbital. Subsequent decisions about tapering or maintaining each

Step 2 medication will be made by reviewing drug and drug combination efficacy, the side
effect profile, and the clinical syndrome.

*Proceed to Step 3 if Step 2 combination trial fails

Step 3 Refer to a specialist (Regional or National Referral Hospital).

 Treatment of Adult Atonic or Tonic Seizures

Lowest Health Drug Regional Dosage Pharmacokinetics Side Effects Notes

Center Level Referral
Administration Needed

HC2 Phenytoin No Starting: 200 mg/day as single dose or Drowsiness, ataxia, slurred
2 divided doses. speech, blurred vision,
Increase by 200mg weekly until control twitching, confusion, gum
achieved hyperplasia, blood
Maintenance: 200-1400 mg/day abnormalities, rash, hepatitis
*Note: Regular TID; Long-acting BID

RR Sodium Valproate Yes Starting: 200 mg/day Liver toxicity, blood disorders, Monitor liver function and full blood
Increase by 200 mg weekly until control count
GI disorders, weight gain,
achieved
transient hair loss
Maintenance: 400-3000 mg/day

*Note: Sodium valproate BID; Valproic

acid BID or TID dosing
 Treatment of Adult Myoclonic Seizures

● If high doses with side effects

Start with sodium valproate. are required and seizures are
● Effective dose must be reached progressively infrequent, less than complete
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. control can be the goal
● Monitor patient for tolerance and side effects ● Follow up monthly until stable,
then every 3 months
● Warn patients that treatment
*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis) can cause liver toxicity, so liver
function must be monitored.

Add phenobarbital. Subsequent decisions about tapering or maintaining each

Step 2 medication will be made by reviewing drug and drug combination efficacy, the side
effect profile, and the clinical syndrome.

*Proceed to Step 3 if Step 2 combination trial fails

Step 3 Refer to a specialist (Regional or National Referral Hospital).

 Adult Myoclonic Seizures

Lowest Health Drug Regional Dosage Pharmacokinetics Side Effects Notes

Center Level Referral
Administration Needed

HC2 Phenytoin No Starting: 200 mg/day as single dose or Drowsiness, ataxia, slurred
2 divided doses. speech, blurred vision,
Increase by 200mg weekly until control twitching, confusion, gum
achieved hyperplasia, blood
Maintenance: 200-1400 mg/day abnormalities, rash, hepatitis
*Note: Regular TID; Long-acting BID

RR Sodium Valproate Yes Starting: 200 mg/day Liver toxicity, blood disorders, Monitor liver function and full blood
Increase by 200 mg weekly until control count
GI disorders, weight gain,
achieved
transient hair loss
Maintenance: 400-3000 mg/day

*Note: Sodium valproate BID; Valproic

acid BID or TID dosing
 Treatment of Adults Focal Seizures
● All pregnant women with
epilepsy should be referred to
Start with carbamazepine. specialist for appropriate
● Effective dose must be reached progressively management (most AEDs have
Step 1 ● Aim at the lowest dose able to control (prevent) the seizures. increased risk of congenital
● Monitor patient for tolerance and side effects malformations)

*Proceed to Step 2 if treatment is ineffective (<50% reduction in crisis)

Add phenytoin or sodium valproate for males, phenytoin for females. Subsequent
● If high doses with side effects
Step 2 decisions about tapering or maintaining each medication will be made by
reviewing drug and drug combination efficacy, the side effect profile, and the are required and seizures are
clinical syndrome. infrequent, less than complete
control can be the goal
● Follow up monthly until stable,
*Proceed to Step 3 if if Step 2 combination trial fails then every 3 months
● Warn patients that treatment
interruptions can trigger
Step 3 Refer to a specialist (Regional or National Referral Hospital). seizures or even status
epilepticus
 Adult Focal Seizures
Lowest Health Drug Regional Dosage Pharmacokinetics Side Effects Notes
Center Level Referral
Administration Needed

HC2 Phenobarbital No Starting: 60mg daily in two divided doses It takes 2-3 weeks for the drug to Drowsiness, lethargy, hyperactivity Sedative in adults
Increase by adding 30 mg weekly until control achieve steady blood levels so and irritability in children, skin rash,
assess after this period
achieved depression
Maintenance: 60-180mg/day

Phenytoin No Starting: 200 mg/day as single dose or 2 Drowsiness, ataxia, slurred speech,
divided doses. blurred vision, twitching, confusion,
Increase by 200mg weekly until control gum hyperplasia, blood abnormalities,
achieved rash, hepatitis
Maintenance: 200-1400 mg/day
*Note: Regular TID; Long-acting BID

HC3 Carbamazepine No Starting: 200 mg/day Skin rash, diplopia, blurred vision,
Increase in 100 mg increments every 1-2 ataxia (staggering gait), nausea
weeks
Maintenance: 400 -1400 mg/day

RR Sodium Yes Starting: 200 mg/day Liver toxicity, blood disorders, GI Monitor liver function and full
Valproate Increase by 200 mg weekly until control achieved blood count
disorders, weight gain, transient hair
Maintenance: 400-3000 mg/day loss

*Note: Sodium valproate BID; Valproic acid BID

or TID dosing