logo

Anticonvulsants (Adult dosing)

brivaracetam- BRIVIACT® --®
carbamazepine - Tegretol ® clonazepam Klonopin ®
clobazam - ONFI diazepam - Valium®
eslicarbazepine acet- APTIOM® ethosuximide - Zarontin®
ezogabine - POTIGA™ felbamate - Felbatol®
fosphenytoin - Cerebyx ® gabapentin (Neurontin ®)
lacosamide -VIMPAT® levetiracetam - Keppra®
lamotrigine - Lamictal® lorazepam - Ativan®
oxcarbazepine - Trileptal® perampanel - FYCOMPA®new icon
phenobarbital phenytoin - Dilantin®
pregabalin  -Lyrica® primidone - Mysoline®
rufinamide -BANZEL® tiagabine - Gabitril ®
topiramate - Topamax ®, TROKENDI XR, QUDEXY ® XR valproic acid: Depacon ® Depakene ® Depakote ®
vigabatrin -Sabril® zonisamide - Zonegran ®
Please see package insert for additional information and possible updates. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.    [  Read the disclaimer    |   <<Back    |    New drug index   ]

oxcarbazepine - Trileptal®: top of page

INDICATIONS AND USAGE
Oxcarbazepine Tablets are an antiepileptic drug indicated for:
Adults:
Monotherapy or adjunctive therapy in the treatment of partial seizures
Children:
Monotherapy in the treatment of partial seizures in children 4 to 16 years
Adjunctive therapy in the treatment of partial seizures in children 2 to 16 years.

DOSAGE AND ADMINISTRATION

ADULTS: initiated with a dose of 600 mg/day, given in twice-a-day regimen.
Adjunctive Therapy:
Maximum increment of 600 mg/day at approximately weekly intervals. The recommended daily dose is 1200 mg/day.
Conversion to Monotherapy: Concomitant AEDs should be completely withdrawn over 3-6 weeks, while maximum dose of oxcarbazepine should be reached in about 2 to 4 weeks. Maximum increment of 600 mg/day at approximately weekly intervals to a recommended daily dose of 2400 mg/day.

Initiation of Monotherapy: Increments of 300 mg/day every third day to a dose of 1200 mg/day.


CHILDREN: initiation with 8 to 10 mg/kg/day, given in twice-a-day regimen. For patients aged 2 to <4 years and under 20 kg, a starting dose of 16 to 20 mg/kg/day may be considered. Recommended daily dose is dependent upon patient weight.

Adjunctive Patients (Aged 2 to 16 Years): For patients aged 4 to 16 years, target maintenance dose should be achieved over 2 weeks.. For patients aged 2 to <4 years, maximum maintenance dose should be achieved over 2 to 4 weeks and should not to exceed 60mg/kg/day.

Conversion to Monotherapy for Patients (Aged 4 to 16 Years) Maximum increment of 10 mg/kg/day at weekly intervals, concomitant antiepileptic drugs can be completely withdrawn over 3 to 6 weeks.
Initiation of Monotherapy for Patients (Aged 4 to 16 Years) Increments of 5 mg/kg/day every third day.


DOSAGE FORMS AND STRENGTHS
Tablets:  150, 300, 600mg tablets

Oral suspension:  Oxcarbazepine Oral Suspension is supplied as 300 mg/5 mL (60 mg/mL) of oral suspension. The suspension is off-white and is available in bottles of 250 mL with a 10 mL dosing syringe and press-in bottle adapter.  0054-0199-59 300 mg/5 mL, off-white suspension, bottle of 250 mL

perampanel - FYCOMPA®: top of page

WARNINGS: WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
See full prescribing information for complete boxed warning.

Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA.
Monitor patients for these reactions as well as for changes in mood, behavior, or personality that are not typical for the patient, particularly during the titration period and at higher doses.
FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening
 

Drug UPDATES
FYCOMPA ® (perampanel) tablets , for oral use , CIII

[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)
ABBREVIATED MONOGRAPH - SEE PACKAGE INSERT.

Initial U.S. Approval:  2012

Mechanism of Action: Perampanel is a non-competitive antagonist of the ionotropic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal over excitation.

The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans is unknown.

INDICATIONS AND USAGE
FYCOMPA, a non-competitive AMPA glutamate receptor antagonist, is indicated as adjunctive therapy for the treatment of:

Partial-Onset Seizures with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older (1.1)
Primary Generalized Tonic-Clonic Seizures in patients with epilepsy 12 years of age and older (1.2)

DOSAGE AND ADMINISTRATION
Dosing in the absence of enzyme-inducing antiepileptic drugs (AEDs)

Starting dose: 2 mg once daily at bedtime (2.1, 2.2)

May increase dose based on clinical response and tolerability by increments of 2 mg once daily no more frequently than at weekly intervals (2.1, 2.2)

Recommended maintenance dose: Partial-Onset Seizures – 8 to 12 mg once daily at bedtime;

Primary Generalized Tonic-Clonic Seizures – 8 mg once daily at bedtime (2.1, 2.2)

Individual dosing should be adjusted based on clinical response and tolerability

Dosing in the presence of concomitant enzyme-inducing AEDs: see section 2.3

Specific Populations
Mild and Moderate Hepatic Impairment: Maximum recommended daily dose is 6 mg (mild) and 4 mg (moderate) once daily at bedtime (2.4)
Severe Hepatic Impairment: Not recommended (2.4)
Severe Renal Impairment or on Hemodialysis: Not recommended (2.5)
Elderly: Increase dose no more frequently than every 2 weeks (2.6)


HOW SUPPLIED:  Tablets: 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg


phenobarbital: top of page

DOSAGE AND ADMINISTRATION
Dosing (Adults): 
Sedation: Oral, IM: 30-120 mg/day in 2-3 divided doses. 

Hypnotic
: Oral, IM, IV, SQ: 100-320 mg at bedtime. 

Preoperative sedation
: IM: 100-200 mg 1-1.5 hours before procedure.   

Status epilepticus:
Adults: 300-800 mg initially followed by 120-240 mg/dose at 20-minute intervals until seizures are controlled or a total dose of 20mg/kg. 
(Maintenance):  1 to 3 mg/kg/day in divided doses or 50-100 mg 2 to 3 times/day.

DOSAGE FORMS AND STRENGTHS
Supplied:
Tablet: 15 mg, 30 mg, 32 mg, 60 mg, 65 mg, 100 mg.
Elixir: 20 mg/5 ml (473 ml).    Injection:  65 mg/ml (1 ml); 130 mg/ml (1 ml).

phenytoin - Dilantin®: top of page

DOSAGE AND ADMINISTRATION
Loading Dose
(IV)
:  10 - 20 mg/kg. Maximum  rate: 50 mg/min. Recommended infusion rate for adults: 40-50 mg/min. Elderly (>65): Recommended infusion rate: 20-25 mg/min.  

Oral loading: Give in 3 to 4 divided doses at q2h intervals. (Divided doses increase bioavailability as well as decrease potential for GI side effects such as N&V). The maximum single oral dose should not exceed 400 mg in order to minimize GI side effects and also increase absorption (decrease likelihood of concretions). 

Maintenance:
4-6 mg/kg/day given in  2 to 3 divided doses. Equation used to estimate the dose required to increase current level to normal range if sub-therapeutic: [ 0.7 x IBW x (15 - current level)].
Oral suspension administration: Shake well prior to use. Divide the daily dose of phenytoin and withhold the administration of nutritional supplements for 1-2 hours before and after each phenytoin dose.

Sampling: 18 to 24 hours after the loading dose, and then every 5 to 7 days to assess trend. 
Average time to steady state: 10-14 days. 
Half-life
: 7 to 42 hours (average = 24 hours).

Conversion to once daily dosing: Consider only after a divided dose regimen on extended phenytoin capsules is established. (Only extended release Dilantin caps are recommended for once daily administration.)  A patient should never receive a once daily dose of elixir or injection as maintenance.
When do you start the maintenance dose? The maintenance dose is started 18-24 hours after the loading dose.

Capsules/injection= 92% phenytoin (sodium salt).    Elixir/tabs=100% phenytoin.  

Equation used to estimate the dose required to increase current level to normal range if subtherapeutic: = [0.7 x IBW x (15 - current level) ] / 0.92* * (if capsules/injection used) 

Adjusted phenytoin concentration if low serum albumin 
= measured total concentration / [ (0.2 x albumin) + 0.1].

Renal failure: Cadjusted = Cmeasured / [ (0.1 x albumin) + 0.1) ]

DOSAGE FORMS AND STRENGTHS
Capsule:  30 mg, 100mg extended phenytoin sodium capsule.
Tablet: Dilantin Infatabs are supplied as: 50 mg phenytoin in a yellow triangular scored chewable tablet.
Suspension: Dilantin-125® Suspension (phenytoin oral suspension, USP), 125 mg phenytoin/5 mL with a maximum alcohol content not greater than 0.6 percent, an orange suspension with an orange-vanilla flavor; available in 8-oz bottles.

Injection:  Phenytoin Sodium Injection, USP, 50 mg/mL is supplied in single-dose containers as follows: 2 ml , 5 ml]

pregabalin  -Lyrica®: top of page

INDICATIONS AND USAGE
---LYRICA is indicated for:
Neuropathic pain associated with diabetic peripheral neuropathy (DPN).
Postherpetic neuralgia (PHN).
Adjunctive therapy for adult patients with partial onset seizures.
Fibromyalgia.
Neuropathic pain associated with spinal cord injury.

DOSAGE AND ADMINISTRATION
For all indications, begin dosing at 150 mg/day.
Dosing recommendations:
INDICATION Dosing Regimen Maximum Dose
Diabetic peripheral neuropathy -DPN Pain 3 divided doses per day 300 mg/day within 1 week
Postherpetic neuralgia (PHN) 2 or 3 divided doses per day 300 mg/day within 1 week. Maximum dose of 600 mg/day.
Adjunctive Therapy for Adult Patients with Partial Onset Seizures 2 or 3 divided doses per day Maximum dose of 600 mg/day.
Fibromyalgia 2 divided doses per day 300 mg/day within 1 week.
Maximum dose of 450 mg/day.
Neuropathic Pain Associated with Spinal Cord Injury 2 divided doses per day 300 mg/day within 1 week. Maximum dose of 600 mg/day.
Dose should be adjusted in patients with reduced renal function.
Pregabalin Dosage Adjustment Based on Renal Function
Creatinine Clearance (CLcr)
(mL/min)
Total Pregabalin Daily Dose
(mg/day)*
Dose Regimen
TID= Three divided doses; BID = Two divided doses; QD = Single daily dose.
geq60 150 300 450 600 BID or TID
30-60 75 150 225 300 BID or TID
15-30 25-50 75 100-150 150 QD or BID
<15 25 25-50 50-75 75 QD
Supplementary dosage following hemodialysis (mg)†
Patients on the 25 mg QD regimen: take one supplemental dose of 25 mg or 50 mg
Patients on the 25-50 mg QD regimen: take one supplemental dose of 50 mg or 75 mg
Patients on the 50-75 mg QD regimen: take one supplemental dose of 75 mg or 100 mg
Patients on the 75 mg QD regimen: take one supplemental dose of 100 mg or 150 mg
*Total daily dose (mg/day) should be divided as indicated by dose regimen to provide mg/dose.
†Supplementary dose is a single additional dose.


DOSAGE FORMS AND STRENGTHS
Capsules: 25mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg.
Oral Solution: 20 mg/ mL.

primidone - Mysoline®: top of page

INDICATIONS AND USAGE
Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.

DOSAGE AND ADMINISTRATION
Adult Dosage
Patients 8 years of age and older who have received no previous treatment may be started on Mysoline according to the following regimen using either 50 mg or scored 250 mg Mysoline tablets:

Days 1 to 3: 100 to 125 mg at bedtime.
Days 4 to 6: 100 to 125 mg b.i.d.
Days 7 to 9: 100 to 125 mg t.i.d.
Day 10 to maintenance: 250 mg t.i.d.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg Mysoline tablets in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 µg/mL.

In Patients Already Receiving Other Anticonvulsants
Mysoline should be started at 100 to 125 mg at bedtime and gradually increased to maintenance level as the other drug is gradually decreased. This regimen should be continued until satisfactory dosage level is achieved for the combination, or the other medication is completely withdrawn. When therapy with Mysoline alone is the objective, the transition from concomitant therapy should not be completed in less than two weeks.

Pediatric Dosage
For children under 8 years of age, the following regimen may be used:

Days 1 to 3: 50 mg at bedtime.
Days 4 to 6: 50 mg b.i.d.
Days 7 to 9: 100 mg b.i.d.
Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.

For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.


DOSAGE FORMS AND STRENGTHS
Tablet:  50mg, 250 mg.

rufinamide -BANZEL®: top of page

INDICATIONS AND USAGE
BANZEL (rufinamide) is an anti-epileptic drug indicated for:

Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in children 4 years and older and adults.

USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. To enroll in the North American Antiepileptic Drug Pregnancy Registry call 1-888-233-2334, toll free.
Renal impairment: Renally impaired patients (creatinine clearance less than 30 mL/min) do not require any specific dosage change. Adjusting the BANZEL dose for the loss of drug upon dialysis should be considered.
Hepatic impairment: Use in patients with severe hepatic impairment is not recommended. Caution should be exercised in treating patients with mild to moderate hepatic impairment.


DOSAGE AND ADMINISTRATION
Local monograph

tiagabine - Gabitril ®: top of page

INDICATIONS AND USAGE
GABITRIL (tiagabine hydrochloride) is indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures.

DOSAGE AND ADMINISTRATION
General:
The blood level of tiagabine obtained after a given dose depends on whether the patient also is receiving a drug that induces the metabolism of tiagabine. The presence of an inducer means that the attained blood level will be substantially reduced. Dosing should take the presence of concomitant medications into account.

GABITRIL (tiagabine HCl) is recommended as adjunctive therapy for the treatment of partial seizures in patients 12 years and older.

The following dosing recommendations apply to all patients taking GABITRIL:

--GABITRIL is given orally and should be taken with food.
--Do not use a loading dose of GABITRIL.
--Dose titration: Rapid escalation and/or large dose increments of GABITRIL should not be used.
--Missed dose(s): If the patient forgets to take the prescribed dose of GABITRIL at the scheduled time, the patient should not attempt to make up for the missed dose by increasing the next dose. If a patient has missed multiple doses, patient should refer back to his or her physician for possible re-titration as clinically indicated.
--Dosage adjustment of GABITRIL should be considered whenever a change in patient’s enzyme-inducing status occurs as a result of the addition, discontinuation, or dose change of the enzyme-inducing agent.

Induced Adults and Adolescents 12 Years or Older:
The following dosing recommendations apply to patients who are already taking enzyme-inducing antiepilepsy drugs (AEDs) (e.g., carbamazepine, phenytoin, primidone, and phenobarbital). Such patients are considered induced patients when administering GABITRIL.

In adolescents 12 to 18 years old, GABITRIL should be initiated at 4 mg once daily. Modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated. The total daily dose of GABITRIL may be increased by 4 mg at the beginning of Week 2. Thereafter, the total daily dose may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or up to 32 mg/day. The total daily dose should be given in divided doses two to four times daily. Doses above 32 mg/day have been tolerated in a small number of adolescent patients for a relatively short duration.

In adults, GABITRIL should be initiated at 4 mg once daily. Modification of concomitant antiepilepsy drugs is not necessary, unless clinically indicated. The total daily dose of GABITRIL may be increased by 4 to 8 mg at weekly intervals until clinical response is achieved or, up to 56 mg/day. The total daily dose should be given in divided doses two to four times daily. Doses above 56 mg/day have not been systematically evaluated in adequate and well-controlled clinical trials.

Experience is limited in patients taking total daily doses above 32 mg/day using twice daily dosing. A typical dosing titration regimen for patients taking enzyme-inducing AEDs (induced patients) is provided in Table 1.
Table 1: Typical Dosing Titration Regimen for Patients Already Taking Enzyme-Inducing AEDs

Initiation and Titration Schedule Total Daily Dose
Week 1 Initiate at 4 mg once daily 4 mg/day
Week 2 Increase total daily dose by 4 mg 8 mg/day
(in two divided doses)
Week 3 Increase total daily dose by 4 mg 12 mg/day
(in three divided doses)
Week 4 Increase total daily dose by 4 mg 16 mg/day
(in two to four divided doses)
Week 5 Increase total daily dose by 4 to 8 mg 20 to 24 mg/day
(in two to four divided doses)
Week 6 Increase total daily dose by 4 to 8 mg 24 to 32 mg/day
(in two to four divided doses)
 Usual Adult Maintenance Dose in Induced Patients: 32 to 56 mg/day in two to four divided doses

Non-Induced Adults and Adolescents 12 Years or Olde
r:

The following dosing recommendations apply to patients who are taking only non-enzyme-inducing AEDs. Such patients are considered non-induced patients:

Following a given dose of GABITRIL, the estimated plasma concentration in the non-induced patients is more than twice that in patients receiving enzyme-inducing agents. Use in non-induced patients requires lower doses of GABITRIL. These patients may also require a slower titration of GABITRIL compared to that of induced patients.


DOSAGE FORMS AND STRENGTHS
[Supplied: 2, 4, 12, 16, 20mg tablets]

topiramate - Topamax ®, QUDEXY ® XR ,TROKENDI XR : top of page

INDICATIONS AND USAGE
TOPAMAX® is an antiepileptic (AED) agent indicated for:
Monotherapy epilepsy: Initial monotherapy in patients geq 2 years of age with partial onset or primary generalized tonic-clonic seizures.

Adjunctive therapy epilepsy: Adjunctive therapy for adults and pediatric patients (2 to 16 years of age) with partial onset seizures or primary generalized tonic-clonic seizures, and in patients geq2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS).

Migraine: Treatment for adults for prophylaxis of migraine headache.



DOSAGE AND ADMINISTRATION
  Initial Dose Titration Recommended Dose
Epilepsy monotherapy: children 2 to <10 years 25 mg/day administered nightly for the first week The dosage should be titrated over 5-7 weeks Daily doses in two divided doses based on weight (Table 2)
Epilepsy monotherapy: adults and pediatric patients geq10 years 50 mg/day in two divided doses The dosage should be increased weekly by increments of 50 mg for the first 4 weeks then 100 mg for weeks 5 to 6. 400 mg/day in two divided doses
Epilepsy adjunctive therapy: adults with partial onset seizures or LGS 25 to 50 mg/day The dosage should be increased weekly to an effective dose by increments of 25 to 50 mg. 200-400 mg/day in two divided doses
Epilepsy adjunctive therapy: adults with primary generalized tonic-clonic seizures 25 to 50 mg/day The dosage should be increased weekly to an effective dose by increments of 25 to 50 mg. 400 mg/day in two divided doses
Epilepsy adjunctive therapy: pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures or LGS 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week The dosage should be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses). Dose titration should be guided by clinical outcome. 5 to 9 mg/kg/day in two divided doses
Migraine 25 mg/day administered nightly for the first week The dosage should be increased weekly by increments of 25 mg. Dose and titration should be guided by clinical outcome. 100 mg/day administered in two divided doses


Patients with Renal Impairment
In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

Geriatric Patients (Ages 65 Years and Over)
Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate <70 mL/min/1.73 m2) is evident.

Patients Undergoing Hemodialysis
Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.


DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 50 mg, 100 mg, and 200 mg
Sprinkle Capsules: 15 mg and 25 mg

Drug UPDATESTROKENDI XR (topiramate) extended-release capsules, for oral use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2013

Mechanism of Action:  The precise mechanisms by which topiramate exerts its anticonvulsant effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.

INDICATIONS AND USAGE:  TROKENDI XR® is indicated for:
Partial Onset Seizure and Primary Generalized Tonic-Clonic Seizures - initial monotherapy in patients 10 years of age and older with partial onset or primary generalized tonic-clonic seizures and adjunctive therapy in patients 6 years of age and older with partial onset or primary generalized tonic-clonic seizures (1.1)
Lennox-Gastaut Syndrome (LGS) - adjunctive therapy in patients 6 years of age and older with seizures associated with Lennox-Gastaut syndrome

HOW SUPPLIED: Extended-release capsules: 25 mg, 50 mg, 100 mg, and 200 mg

Drug UPDATESQUDEXY ® XR (topiramate) extended-release capsules, for oral use
Initial U.S. Approval: 1996
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2014

Mechanism of Action: The precise mechanisms by which topiramate exerts its anticonvulsant effects are unknown; however, preclinical studies have revealed four properties that may contribute to topiramate's efficacy for epilepsy. Electrophysiological and biochemical evidence suggests that topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/kainate subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.

INDICATIONS AND USAGE
QUDEXY XR is indicated for:

Partial Onset Seizures and Primary Generalized Tonic-Clonic Seizures - initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures and adjunctive therapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures (1.1)
Lennox-Gastaut Syndrome (LGS) - adjunctive therapy in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome (1.2)

HOW SUPPLIED: Extended-release capsules: 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg

valproic acid: Depacon ® Depakene ® Depakote ®: top of page

DOSAGE AND ADMINISTRATION
PO: Administer with or immediately after meals to minimize GI irritation.
Delayed-release divalproex sodium may cause less GI irritation than valproic acid capsules.

Dosing (Adults) 
Seizures
ORAL: Initially 10-15 mg/kg/day (orally) in 1-3 divided doses. Increase by 5-10 mg/kg/day q7 days until therapeutic levels are achieved. Maintenance: 30-60 mg/kg/day. Adult usual dose: 1000-2500 mg/day. 
IV: Administer as a 60-minute infusion (leq 20 mg/minute) with the same frequency as oral products; switch patient to oral products as soon as possible.
Alternatively, rapid infusions have been given: leq 15 mg/kg over 5-10 minutes (1.5  to 3 mg/kg/minute).  Rectal (unlabeled): Dilute syrup 1:1 with water for use as a retention enema; loading dose: 17-20 mg/kg one time; maintenance: 10-15 mg/kg/dose every 8 hours.

Status epilepticus (unlabeled use): Loading dose: 15-25 mg/kg IV administered at 3 mg/kg/minute.  Maintenance dose: I.V. infusion: 1-4 mg/kg/hour; titrate dose as needed based upon patient response and evaluation of drug-drug interactions.

Mania: Oral: 750-1500 mg/day in divided doses; dose should be adjusted as rapidly as possible to desired clinical effect; a loading dose of 20 mg/kg may be used; maximum recommended dosage: 60 mg/kg/day.

Migraine prophylaxis: Oral:  Extended release tablets: 500 mg once daily for 7 days, then increase to 1000 mg once daily; adjust dose based on patient response; usual dosage range 500-1000 mg/day.  Delayed release tablets: 250 mg twice daily; adjust dose based on patient response, up to 1000 mg/day.


Administered orally. The recommended initial dose is 15 mg/kg/day orally, increasing at 1-week intervals by 5 to 10 mg/kg/day until seizures are controlled or side effects preclude further increases. Maximum recommended dose is 60 mg/kg/day. When the total daily dose exceeds 250 mg, it should be given in a divided regimen. A 500 mg enteric-coated capsule may be substituted for two 250 mg capsules. The frequency of adverse effects (particularly elevated liver enzymes) may increase with increasing dose. Therefore, the benefit gained by improved seizure control must be weighed against the increased incidence of adverse effects.

Note: Regular release and delayed release formulations are usually given in 2-4 divided doses/day, extended release formulation (Depakote® ER) is usually given once daily.

Conversion to Depakote® ER from a stable dose of Depakote® may require an increase in the total daily dose between 8% and 20% to maintain similar serum concentrations (ER form has reduced bioavailability)


Therapeutic Range:
Epilepsy: 50-100 mcg/mL (SI: 350-690 µmol/L).
Mania: 50-125 mcg/mL (SI: 350-860 µmol/L).

Conversion from DEPAKOTE to DEPAKOTE ER :
In adult patients and pediatric patients 10 years of age or older with epilepsy previously receiving DEPAKOTE, DEPAKOTE ER should be administered once-daily using a dose 8 to 20% higher than the total daily dose of DEPAKOTE (see table below). For patients whose DEPAKOTE total daily dose can not be directly converted to DEPAKOTE ER, consideration may be given at the clinician's discretion to increase the patient's DEPAKOTE total daily dose to the next higher dosage before converting to the appropriate total daily dose of DEPAKOTE ER.

 
Dose Conversion
DEPAKOTE
Total Daily Dose (mg)
DEPAKOTE ER
(mg)
500 -625* 750
750-875* 1000
1000 -1125* 1250
1250-1375 1500
1500-1625 1750
1750 2000
1875-2000 2250
2125-2250 2500
2375 2750
2500-2750 3000
2875 3250
3000-3125 3500
*These total daily doses of DEPAKOTE cannot be directly converted to an 8 to 20% higher total daily dose of DEPAKOTE ER because the required dosing strengths of DEPAKOTE ER are not available. Consideration may be given at the clinician's discretion to increase the patient's DEPAKOTE total daily dose to the next higher dosage before converting to the appropriate total daily dose of DEPAKOTE ER.


DOSAGE FORMS AND STRENGTHS
Note: Strength expressed as valproic acid
Valproic acid (Depakene®): 250 mg cap.
Capsule (sprinkles) as divalproex sodium (Depakote® Sprinkle®): 125 mg
Injection soln - valproate sodium (Depacon®): 100 mg/mL (5 mL) 
Syrup ( valproic acid) Depakene®: 250 mg/5 mL (480 mL)
Delayed release tablet - divalproex sodium (Depakote®): 125, 250, 500 mg
Extended release tab - divalproex sodium (Depakote® ER): 250, 500 mg

vigabatrin -Sabril®: top of page


Local monograph

zonisamide - Zonegran®: top of page

INDICATIONS AND USAGE
(Chemical class: sulfonamide).  
Zonisamide capsules are indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.

DOSAGE AND ADMINISTRATION
Zonisamide capsules are recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Zonisamide capsules should be administered once or twice daily, using 25 mg, 50 mg or 100 mg capsules. Zonisamide capsules are given orally and can be taken with or without food. Capsules should be swallowed whole.

Adults over Age 16
The prescriber should be aware that, because of the long half-life of zonisamide, up to two weeks may be required to achieve steady state levels upon reaching a stable dose or following dosage adjustment. Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of zonisamide at steady state, noting that many of the side effects of zonisamide are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100 to 200 mg/day, the increase appears small and formal dose-response studies have not been conducted.

The initial dose of zonisamide capsules should be 100 mg daily. After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that zonisamide capsules doses of 100 to 600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day. There is little experience with doses greater than 600 mg/day.

Patients with Renal or Hepatic Disease
Because zonisamide is metabolized in the liver and excreted by the kidneys, patients with renal or hepatic disease should be treated with caution, and might require slower titration and more frequent monitoring

DOSAGE FORMS AND STRENGTHS
[Supplied:25, 50, 100 mg capsule]

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.
Medical Calculators - A thru Z
Lab Values - A thru Z