Anti-Convulsants

brivaracetam- BRIVIACT® 

Initial U.S. Approval:  2016

Mechanism of Action:
The precise mechanism by which BRIVIACT exerts its anticonvulsant activity is not known. Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which may contribute to the anticonvulsant effect.

INDICATIONS AND USAGE:
BRIVIACT is indicated as adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy.

DOSAGE AND ADMINISTRATION
Dosage Information
When initiating treatment, gradual dose escalation is not required. The recommended starting dosage is 50 mg twice daily (100 mg per day). Based on individual patient tolerability and therapeutic response, the dosage may be adjusted down to 25 mg twice daily (50 mg per day) or up to 100 mg twice daily (200 mg per day) [see Clinical Studies (14)].

BRIVIACT injection may be used when oral administration is temporarily not feasible. BRIVIACT injection should be administered at the same dosage and same frequency as BRIVIACT tablets and oral solution.

The clinical study experience with BRIVIACT injection is limited to 4 consecutive days of treatment.

2.2 Administration Instructions for BRIVIACT Tablets and BRIVIACT Oral Solution

BRIVIACT can be initiated with either intravenous or oral administration.
BRIVIACT tablets and oral solution may be taken with or without food.

BRIVIACT Tablets
BRIVIACT tablets should be swallowed whole with liquid. BRIVIACT tablets should not be chewed or crushed.

BRIVIACT Oral Solution
A calibrated measuring device is recommended to measure and deliver the prescribed dose accurately. A household teaspoon or tablespoon is not an adequate measuring device.

When using BRIVIACT oral solution, no dilution is necessary. BRIVIACT oral solution may also be administered using a nasogastric tube or gastrostomy tube.

Discard any unused BRIVIACT oral solution remaining after 5 months of first opening the bottle.

2.3 Preparation and Administration Instructions for BRIVIACT Injection
BRIVIACT injection is for intravenous use only.

Preparation
BRIVIACT injection can be administered intravenously without further dilution or may be mixed with diluents listed below.

Diluents
0.9% Sodium Chloride injection, USP
Lactated Ringer's injection
5% Dextrose injection, USP

Administration
BRIVIACT injection should be administered intravenously over 2 to 15 minutes.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Product with particulate matter or discoloration should not be used. BRIVIACT injection is for single dose only.

Storage and Stability
The diluted solution should not be stored for more than 4 hours at room temperature and may be stored in polyvinyl chloride (PVC) bags. Discard any unused portion of the BRIVIACT injection vial contents.

HOW SUPPLIED:
Tablets
10 mg: white to off white, round, film-coated, and debossed with "u10" on one side.
25 mg: grey, oval, film-coated, and debossed with "u25" on one side.
50 mg: yellow, oval, film-coated, and debossed with "u50" on one side.
75 mg: purple, oval, film-coated, and debossed with "u75" on one side.
100 mg: green-grey, oval, film-coated, and debossed with "u100" on one side.

Oral Solution
10 mg/mL: slightly viscous, clear, colorless to yellowish, raspberry-flavored liquid.

Injection
50 mg in 5 mL in one single-dose vial. It is a clear, colorless, sterile solution.

carbamazepine - Tegretol ®:

INDICATIONS AND USAGE
 Epilepsy: Carbamazepine tablets are indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types:

1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types.

2. Generalized tonic-clonic seizures (grand mal).

3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General).

Trigeminal Neuralgia: Carbamazepine tablets are indicated in the treatment of the pain associated with true trigeminal neuralgia.  Beneficial results have also been reported in glossopharyngeal neuralgia.   This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

DOSAGE AND ADMINISTRATION
Monitoring of blood levels has increased the efficacy and safety of anticonvulsants. Dosage should be adjusted to the needs of the individual patient. A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level. Tablets should be taken with meals.

Conversion of patients from oral carbamazepine tablets to carbamazepine suspension: Patients should be converted by administering the same number of mg per day in smaller, more frequent doses (i.e., b.i.d. tablets to t.i.d. suspension).

Epilepsy:

Adults And Children Over 12 Years Of Age - Initial: 200 mg b.i.d. Increase at weekly intervals by adding up to 200 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily in children 12 to 15 years of age, and 1200 mg daily in patients above 15 years of age. Doses up to 1600 mg daily have been used in adults in rare instances.
Maintenance: Adjust dosage to the minimum effective level, usually 800 to 1200 mg daily.
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Children 6 to 12 years of age - Initial: 100 mg b.i.d. Increase at weekly intervals by adding up to 100 mg/day using a t.i.d. or q.i.d. regimen until the optimal response is obtained. Dosage generally should not exceed 1000 mg daily.   Maintenance: Adjust dosage to the minimum effective level, usually 400 to 800 mg daily.
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Children Under 6 Years Of Age - Initial: 10 to 20 mg/kg/day b.i.d. or t.i.d. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d.      Maintenance: Ordinarily, optimal clinical response is achieved at daily doses below 35 mg/kg. If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the therapeutic range. No recommendation regarding the safety of carbamazepine for use at doses above 35 mg/kg/24 hours can be made.
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Combination Therapy: Carbamazepine may be used alone or with other anticonvulsants. When added to existing anticonvulsant therapy, the drug should be added gradually while the other anticonvulsants are maintained or gradually decreased, except phenytoin, which may have to be increased.

Trigeminal Neuralgia:
Initial: On the first day, 100 mg b.i.d., for a total daily dose of 200 mg. This daily dose may be increased by up to 200 mg/day using increments of 100 mg every 12 hours for tablets, only as needed to achieve freedom from pain. Do not exceed 1200 mg daily.

Maintenance: Control of pain can be maintained in most patients with 400 to 800 mg daily. However, some patients may be maintained on as little as 200 mg daily, while others may require as much as 1200 mg daily. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or even to discontinue the drug.

DOSAGE FORMS AND STRENGTHS
Extended release cap: 100 mg, 200 mg, 300 mg.
Oral suspension: 100 mg/5 ml (10 ml, 450 ml).
Tablet: 200 mg.  Chewable tab: 100 mg.  ER Tab: 100 mg, 200 mg, 400 mg.

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Drug UPDATES:  CARNEXIV™ (carbamazepine) injection, for intravenous use
[Drug information  /  PDF]     REVIEW PACKAGE INSERT FOR POSSIBLE UPDATES
PACKAGE INSERT -Dosing:  Click (+) next to Dosage and Administration section (drug info link)

BOXED WARNING:   [Review package insert]
WARNING: SERIOUS DERMATOLOGIC REACTIONS and APLASTIC ANEMIA AND AGRANULOCYTOSIS
Serious Dermatologic Reactions and HLA-B*1502 Allele
Serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have occurred in patients treated with carbamazepine. There is a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA-B gene that is found almost exclusively in patients with Asian ancestry. Avoid use of CARNEXIV in patients testing positive for the allele unless the benefit clearly outweighs the risk. Discontinue CARNEXIV if you suspect that the patient is having a serious dermatologic reaction [see Warnings and Precautions (5.1)].

Aplastic Anemia and Agranulocytosis
Aplastic anemia and agranulocytosis can occur during treatment with CARNEXIV. Obtain a complete blood count (CBC) before beginning treatment with CARNEXIV, and monitor CBC periodically. Consider discontinuing CARNEXIV if significant bone marrow depression develops

Initial U.S. Approval:  2016   [Revised: 10/2016]

Mechanism of Action: The mechanism by which carbamazepine exerts its anticonvulsant activity is unknown. The principal metabolite of carbamazepine, carbamazepine-10,11-epoxide, has demonstrated anticonvulsant activity in in vivo animal models of seizures. However, its contribution to the therapeutic effect of carbamazepine is unknown.

INDICATIONS AND USAGE:
CARNEXIV is indicated as replacement therapy for oral carbamazepine formulations, when oral administration is temporarily not feasible, in adults with the following seizure types (1):

Partial seizures with complex symptomatology
Generalized tonic-clonic seizures
Mixed seizure patterns which include the above, or other partial or generalized seizures

DOSAGE AND ADMINISTRATION:
CARNEXIV is a replacement therapy for oral carbamazepine. Carbamazepine treatment should generally be initiated with an oral carbamazepine formulation.

The total daily dose of CARNEXIV is 70% of the total daily oral carbamazepine dose from which patients are being switched (see Table 1). The total daily dose of CARNEXIV should be equally divided in four 30-minute infusions, separated by 6 hours. Patients should be switched back to oral carbamazepine administration at their previous total daily oral dose and frequency of administration as soon as clinically appropriate. The use of CARNEXIV for periods of more than 7 days has not been studied.

Table 1. Determination of Total Daily Dose for CARNEXIV Infusion

Administration Information

CARNEXIV is for intravenous use only and must be diluted in a compatible diluent prior to infusion.
Using Table 2 as a guide, prepare the solution for each infusion by transferring the single dose volume of CARNEXIV to 100 mL of diluent solution (0.9% sodium chloride, lactated Ringer's solution, or 5% dextrose) and mixing gently.
Before administration, the prepared solution for infusion may be stored for a maximum of 4 hours at 20°C to 25°C (68°F to 77°F) or a maximum of 24 hours if refrigerated at 2°C to 8°C (36°F to 46°F).

Parenteral drug products should be inspected visually for particulate matter, cloudiness, or discoloration prior to administration, whenever solution and container permit. If any of these are present, discard the solution.

Administer each infusion intravenously over 30 minutes.

CARNEXIV injection vials are for single-dose only. Discard any unused portion.
Table 2. CARNEXIV Dose to Volume and Infusion

Renal Function Monitoring
Patients with renal impairment may be at greater risk for an adverse effect of CARNEXIV on renal function, and should have close monitoring of renal function during treatment with CARNEXIV. CARNEXIV should generally not be used in patients with moderate or severe renal impairment.

Serum Level Monitoring

Monitor serum carbamazepine concentrations in conditions in which alterations in carbamazepine metabolism can occur. This includes patients who have hepatic impairment and patients on drugs that either induce or inhibit carbamazepine metabolism.

Laboratory Testing Prior to Carbamazepine Initiation
Prior to initial treatment with carbamazepine, test patients with ancestry in genetically at-risk populations for the presence of the HLA-B*1502 allele. The high resolution genotype test is positive if one or two HLA-B*1502 alleles are present. Avoid use of CARNEXIV in patients testing positive for the allele, unless the benefit clearly outweighs the risk [see PACKAGE INSERT Boxed Warning and Warnings and Precautions (5.1)].

Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of CARNEXIV should be considered if any evidence of significant bone marrow depression develops [see PACKAGE INSERT Warnings and Precautions (5.2)].

Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with carbamazepine because liver damage may occur. Discontinue CARNEXIV in cases of aggravated liver dysfunction or active liver disease [see PACKAGE INSERT Warnings and Precautions (5.10)].

HOW SUPPLIED:
CARNEXIV injection contains 200 mg/20 mL (10 mg/mL) carbamazepine as a clear, colorless, sterile solution in a single dose vial.

clonazepam  - Klonopin®:

Panic Disorder: Clonazepam is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in DSM-IV. Panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks.
 

DOSAGE AND ADMINISTRATION
Start 0.5 mg orally three times daily.  Maximum: 20 mg/day. 

DOSAGE FORMS AND STRENGTHS
 [Supplied: 0.5,1, 2mg tabs]

diazepam - Valium®:

Oral:

Parenteral:
Dosage should be individualized for maximum beneficial effect. The usual recommended dose in older children and adults ranges from 2 mg to 20 mg I.M. or I.V., depending on the indication and its severity. In some conditions, e.g., tetanus, larger doses may be required. (See dosage for specific indications.) In acute conditions the injection may be repeated within one hour although an interval of 3 to 4 hours is usually satisfactory. Lower doses (usually 2 mg to 5 mg) and slow increase in dosage should be used for elderly or debilitated patients and when other sedative drugs are administered.

For dosage in infants above the age of 30 days and children, see the specific indications below. When intravenous use is indicated, facilities for respiratory assistance should be readily available.

Intramuscular: Diazepam Injection, USP should be injected deeply into the muscle.

Intravenous use: (See package insert for WARNINGS, particularly for use in children.) The solution should be injected slowly, taking at least one minute for each 5 mg (1 mL) given. Do not use small veins, such as those on the dorsum of the hand or wrist. Extreme care should be taken to avoid intra-arterial administration or extravasation.

Do not mix or dilute diazepam with other solutions or drugs in syringe or infusion flask. If it is not feasible to administer diazepam directly I.V., it may be injected slowly through the infusion tubing as close as possible to the vein insertion.

Once the acute symptomatology has been properly controlled with diazepam injection, the patient may be placed on oral therapy with diazepam if further treatment is required.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. NOTE: Solution may appear colorless to light yellow.

DOSAGE FORMS AND STRENGTHS
Tablets: 2mg , 5 mg, 10 mg
Diazepam Injection, 5 mg/mL [2ml, 10 ml]
Diazepam Oral Solution, 5 mg per 5 mL (Orange-colored, wintergreen-spice flavored solution)

Diazepam Intensol^TM Oral Solution (Concentrate), 5 mg per mL
NDC 0054-3185-44: Bottle of 30 mL with calibrated dropper [graduations of 0.2 mL (1 mg), 0.4 mL (2 mg), 0.6 mL (3 mg), 0.8 mL (4 mg), and 1 mL (5 mg) on the dropper].

ethosuximide - Zarontin®:

DOSAGE AND ADMINISTRATION
Zarontin is administered by the oral route.

The initial dose for patients 3 to 6 years of age is one capsule (250 mg) per day;
for patients 6 years of age and older, 2 capsules (500 mg) per day. The dose thereafter must be individualized according to the patient's response. Dosage should be increased by small increments. One useful method is to increase the daily dose by 250 mg every four to seven days until control is achieved with minimal side effects.

Dosages exceeding 1.5 g daily, in divided doses, should be administered only under the strictest supervision of the physician.

The optimal dose for most pediatric patients is 20 mg/kg/day. This dose has given average plasma levels within the accepted therapeutic range of 40 to 100 mcg/mL. Subsequent dose schedules can be based on effectiveness and plasma level determinations.

Zarontin may be administered in combination with other anticonvulsants when other forms of epilepsy coexist with absence (petit mal). The optimal dose for most pediatric patients is 20 mg/kg/day.

DOSAGE FORMS AND STRENGTHS
Capsule: 250 mg.

Ethosuximide Syrup, USP 250 mg/5 mL is supplied as: NDC 46672-641-16 - 16 fl oz bottles. Each 5 mL of Syrup contains 250 mg ethosuximide in a raspberry flavored base.

Solution: NDC 0071-2418-23-1 pint bottles. Each 5 mL of oral solution contains 250 mg ethosuximide in a raspberry flavored base.

ezogabine - POTIGA™:

Local monograph

felbamate - Felbatol®:

Felbatol® is not indicated as a first line antiepileptic treatment. Felbatol® is recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.

If these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgement, Felbatol® can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children.

DOSAGE AND ADMINISTRATION
Felbatol® (felbamate) has been studied as monotherapy and adjunctive therapy in adults and as adjunctive therapy in children with seizures associated with Lennox-Gastaut syndrome. As Felbatol® is added to or substituted for existing AEDs, it is strongly recommended to reduce the dosage of those AEDs in the range of 20-33% to minimize side effects.

Dosage Adjustment in the Renally Impaired: Felbamate should be used with caution in patients with renal dysfunction. In the renally impaired, starting and maintenance doses should be reduced by one-half. Adjunctive therapy with medications which affect felbamate plasma concentrations, especially AEDs, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.

Adults (14 years of age and over)
The majority of patients received 3600 mg/day in clinical trials evaluating its use as both monotherapy and adjunctive therapy.

Monotherapy: (Initial therapy) Felbatol® (felbamate) has not been systematically evaluated as initial monotherapy. Initiate Felbatol® at 1200 mg/day in divided doses three or four times daily. The prescriber is advised to titrate previously untreated patients under close clinical supervision, increasing the dosage in 600-mg increments every 2 weeks to 2400 mg/day based on clinical response and thereafter to 3600 mg/day if clinically indicated.

Conversion to Monotherapy: Initiate Felbatol® at 1200 mg/day in divided doses three or four times daily. Reduce the dosage of concomitant AEDs by one-third at initiation of Felbatol® therapy. At week 2, increase the Felbatol® dosage to 2400 mg/day while reducing the dosage of other AEDs up to an additional one-third of their original dosage. At week 3, increase the Felbatol® dosage up to 3600 mg/day and continue to reduce the dosage of other AEDs as clinically indicated.

Adjunctive Therapy: Felbatol® should be added at 1200 mg/day in divided doses three or four times daily while reducing present AEDs by 20% in order to control plasma concentrations of concurrent phenytoin, valproic acid, phenobarbital, and carbamazepine and its metabolites. Further reductions of the concomitant AEDs dosage may be necessary to minimize side effects due to drug interactions. Increase the dosage of Felbatol® by 1200 mg/day increments at weekly intervals to 3600 mg/day. Most side effects seen during Felbatol® adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.

While the above Felbatol® conversion guidelines may result in a Felbatol® 3600 mg/day dose within 3 weeks, in some patients titration to a 3600 mg/day Felbatol® dose has been achieved in as little as 3 days with appropriate adjustment of other AEDs.

Children with Lennox-Gastaut Syndrome (Ages 2-14 years)
Adjunctive Therapy: Felbatol® should be added at 15 mg/kg/day in divided doses three or four times daily while reducing present AEDs by 20% in order to control plasma levels of concurrent phenytoin, valproic acid, phenobarbital, and carbamazepine and its metabolites. Further reductions of the concomitant AEDs dosage may be necessary to minimize side effects due to drug interactions. Increase the dosage of Felbatol® by 15 mg/kg/day increments at weekly intervals to 45 mg/kg/day. Most side effects seen during Felbatol® adjunctive therapy resolve as the dosage of concomitant AEDs is decreased.

DOSAGE FORMS AND STRENGTHS
Supplied: [400 , 600 mg  tablets]

fosphenytoin - Cerebyx ®:

Fosphenytoin sodium injection can be used for the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.

DOSAGE AND ADMINISTRATION
The dose, concentration in dosing solutions, and infusion rate of IV fosphenytoin sodium injection is expressed as phenytoin sodium equivalents (PE) to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Fosphenytoin sodium injection should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). Fosphenytoin sodium injection has important differences in administration from those for parenteral phenytoin sodium (see below).

Products with particulate matter or discoloration should not be used. Prior to IV infusion, dilute fosphenytoin sodium injection in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL.

Status Epilepticus
>The loading dose of fosphenytoin sodium injection is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min.
>Because of the risk of hypotension, fosphenytoin should be administered no faster than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of fosphenytoin sodium injection infusions.
>Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin sodium injection or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an IV benzodiazepine, will usually be necessary for the control of status epilepticus.
>The loading dose should be followed by maintenance doses of fosphenytoin sodium injection or phenytoin either orally or parenterally.

If administration of fosphenytoin sodium injection does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered.

IM fosphenytoin sodium injection should not be used in the treatment of status epilepticus because therapeutic phenytoin concentrations may not be reached as quickly as with IV administration. If IV access is impossible, loading doses of fosphenytoin sodium injection have been given by the IM route for other indications.

No Emergent Loading and Maintenance Dosing
The loading dose of fosphenytoin sodium injection is 10 to 20 mg PE/kg given IV or IM. The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of fosphenytoin sodium injection infusions.

The initial daily maintenance dose of fosphenytoin sodium injection is 4 to 6 mg PE/kg/day.

IM or IV Substitution for Oral Phenytoin Therapy
Fosphenytoin sodium injection can be substituted for oral phenytoin sodium therapy at the same total daily dose.

Phenytoin sodium capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as fosphenytoin sodium injection, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV fosphenytoin sodium injection is substituted for oral phenytoin sodium therapy.

The rate of administration for IV fosphenytoin sodium injection should be no greater than 150 mg PE/min.

In controlled trials, IM fosphenytoin sodium injection was administered as a single daily dose utilizing either 1 or 2 injection sites. Some patients may require more frequent dosing.

Dosing in Special Populations
Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution. Unbound phenytoin concentrations may be more useful in these patient populations. After IV fosphenytoin sodium injection administration to patients with renal and/or hepatic disease, or in those with hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance. This has the potential to increase the frequency and severity of adverse events.

Elderly Patients: Age does not have a significant impact on the pharmacokinetics of fosphenytoin following fosphenytoin sodium injection administration. Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric: The safety of fosphenytoin sodium injection in pediatric patients has not been established.

DOSAGE FORMS AND STRENGTHS
Fosphenytoin Sodium Injection 50 mg/ml [2 ml , 10 ml vials]

gabapentin (Neurontin ®):

Dosing (Adults): 
Anticonvulsant:
Oral:  Initial: 300 mg 3 times/day, if necessary the dose may be increased up to 1800 mg/day.    Maintenance: 900-1800 mg/day administered in 3 divided doses; doses of up to 2400 mg/day have been tolerated in long-term clinical studies; up to 3600 mg/day has been tolerated in short-term studies. 

Postherpetic neuralgia:
Day 1: 300 mg, Day 2: 300 mg twice daily, Day 3: 300 mg 3 times/day; dose may be titrated as needed for pain relief (range: 1800-3600 mg/day, daily doses >1800 mg do not generally show greater benefit)

Renal dosing:   
Crcl > 60 ml/minute: 300-1200 mg 3 times/day.
Crcl >30-59 ml/minute:200-700 mg twice/day.
Crcl >15-29 ml/minute: 200-700 mg/day.  
Crcl 15 ml/minute: 100-300mg/day.
Crcl <15 ml/minute: Reduce daily dose in proportion to creatinine clearance.

DOSAGE FORMS AND STRENGTHS
Supplied: Capsule: 100 mg, 300 mg, 400 mg.  Oral Solution: 250 mg/5 ml (480 ml).  Tablet: 100 mg, 300 mg, 400 mg.

lacosamide -VIMPAT®:

levetiracetam - Keppra®:

-Partial onset seizures in patients one month of age and older with epilepsy.
-Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy.
-Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy.

KEPPRA XR is an antiepileptic drug indicated for adjunctive therapy in the treatment of partial onset seizures in patients ≥16 years of age with epilepsy

DOSAGE AND ADMINISTRATION
Oral Solution:
Use the oral solution for pediatric patients with body weight ≤ 20 kg.
For pediatric patients, use weight-based dosing for the oral solution with a calibrated measuring device (not a household teaspoon or tablespoon).

Partial Onset Seizures
1 Month To < 6 Months: 7 mg/kg twice daily, increase in increments of 7 mg/kg twice daily every 2 weeks to recommended dose of 21 mg/kg twice daily.
6 Months To < 4 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 25 mg/kg twice daily.
4 Years To < 16 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily.
Adults 16 Years And Older: 500 mg twice daily, increase as needed and tolerated in increments of 500 mg twice daily every 2 weeks to a maximum recommended dose of 1500 mg twice daily.

Myoclonic Seizures In Adults and Pediatric Patients 12 Years And Older
500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily.

Primary Generalized Tonic-Clonic Seizures:
6 Years To < 16 Years: 10 mg/kg twice daily, increase in increments of 10 mg/kg twice daily every 2 weeks to recommended dose of 30 mg/kg twice daily.
Adults 16 Years And Older: 500 mg twice daily, increase by 500 mg twice daily every 2 weeks to recommended dose of 1500 mg twice daily.

Adult patients with impaired renal function
Dose adjustment is recommended, based on the patient's estimated creatinine clearance.

XR Tablets:  KEPPRA XR is an antiepileptic drug indicated for adjunctive therapy in the treatment of partial onset seizures in patients ≥16 years of age with epilepsy:
Treatment should be initiated with a dose of 1000 mg once daily. The daily dosage may be adjusted in increments of 1000 mg every 2 weeks to a maximum recommended daily dose of 3000 mg.
See full prescribing information for use in patients with impaired renal function.

Injection - Single-use 100 mL bags for injection and 500 mg/5 mL single-use vial
Levetiracetam in Sodium Chloride Injection is an antiepileptic drug indicated for adults (16 years and older) with the following seizure types when oral administration is temporarily not feasible.

Partial onset seizures
Myoclonic seizures in patients with juvenile myoclonic epilepsy
Primary generalized tonic-clonic seizures

For intravenous use only. Do not dilute prior to its use.
Administer dose-specific 100 mL bag intravenously over 15-minutes.
Levetiracetam can be initiated with either intravenous or oral administration.

Single use vials (500mg/5ml):
Levetiracetam injection should be diluted in 100 mL of a compatible diluent and administered intravenously as a 15-minute infusion

Initial Exposure to Levetiracetam
Partial Onset Seizures: Initial dose is 1000 mg/day, divided as 500 mg twice daily. Increase dose as needed and tolerated in increments of 1000 mg/day, every 2 weeks to a maximum recommended daily dose of 3000 mg.
Myoclonic Seizures in Patients with Juvenile Myoclonic Epilepsy: Initial dose is 1000 mg/day, divided as 500 mg twice daily. Increase dose by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been studied.

Primary Generalized Tonic-Clonic Seizures: Initial dose is 1000 mg/day, divided as 500 mg twice daily. Increase dose by 1000 mg/day every 2 weeks to the recommended daily dose of 3000 mg. The effectiveness of doses lower than 3000 mg/day has not been adequately studied (2.2).

Switching to Intravenous Dosing: Initial total daily intravenous levetiracetam dose regimen should be equivalent to total daily dose and frequency of oral levetiracetam.

Switching to Oral Dosing: Give equivalent daily dose and frequency of oral as intravenous levetiracetam.

Renal Impairment: Dose adjustment necessary based on creatinine clearance

DOSAGE FORMS AND STRENGTHS
Tablets: 250 mg, 500 mg, 750 mg, and 1000 mg film-coated, scored tablets
Solution: 100 mg/mL solution
XR tablets:   500 mg, 750 mg film-coated extended-release tablet.

Single-use 100 mL bags for injection:
Levetiracetam in 0.82 % sodium chloride (500 mg/100 mL)
Levetiracetam in 0.75 % sodium chloride (1000 mg/100 mL)
Levetiracetam in 0.54% sodium chloride (1500 mg/100 mL)

500 mg/5 mL single-use vial

lamotrigine - Lamictal®:

Maintenance dose: 100-400 mg/day in 1-2 divided doses (usual range 100-200 mg/day).   

Patients receiving enzyme-inducing AED regimens without valproic acid: Initial dose: 50 mg/day x 2 weeks, then 100 mg in 2 doses x 2 weeks; thereafter, daily dose can be increased by 100 mg every 1-2 weeks to be given in 2 divided doses. Usual maintenance dose: 300-500 mg/day in 2 divided doses.

Bipolar disorder: 25 mg/day x 2 weeks, followed by 50 mg/day x 2 weeks, followed by 100 mg/day x 1 week. Thereafter, daily dosage may be increased to 200 mg/day.

Patients receiving valproic acid: Initial: 25 mg every other day x 2 weeks, followed by 25 mg/day x 2 weeks, followed by 50 mg/day x 1 week, followed by 100 mg/day (target dose) thereafter. Note: If valproate is discontinued, increase daily lamotrigine dose in 50 mg increments at weekly intervals until daily dosage of 200 mg is attained.

Patients receiving enzyme-inducing drugs: Initial: 50 mg/day x 2 weeks, followed by 100 mg/day (in divided doses) x 2 weeks, followed by 200 mg/day (in divided doses) x 1 week, followed by 300 mg/day (in divided doses) x 1 week. May increase to 400 mg/day (in divided doses) during week 7 and thereafter.
 Note: If carbamazepine (or other enzyme-inducing drug) is discontinued, decrease daily lamotrigine dose in 100 mg increments at weekly intervals until daily dosage of 200 mg is attained.

Possible life-threatening rash. 

DOSAGE FORMS AND STRENGTHS
[Supplied: 25, 100, 150, 200mg tablets]

lorazepam - Ativan®:

Anxiety and sedation: Oral: 1-10 mg/day in 2-3 divided doses; usual dose: 2-6 mg/day in divided doses; initial dose should not exceed 2 mg in debilitated patients. 

Insomnia: Oral: 2-4 mg at bedtime.    

Preoperative:  IM: 0.05 mg/kg administered 2 hours before surgery; maximum: 4 mg/dose.  IV: 0.044 mg/kg 15-20 minutes before surgery; usual maximum: 2 mg/dose.  

Status epilepticus: IV: 4 mg/dose given slowly over 2-5 minutes; may repeat in 10-15 minutes; usual maximum dose: 8 mg.    

Rapid tranquilization of agitated patient (administer every 30-60 minutes):   
Oral: 1-2 mg. IM: 0.5-1 mg.  

Agitation in the ICU patient (unlabeled):  
IV: 0.02-0.06 mg/kg every 2-6 hours. Alternatively - IV infusion: 0.01-0.1 mg/kg/hour.

Onset:   
Hypnosis: IM: 20-30 minutes.
Sedation: IV: 5-20 minutes.
Anticonvulsant: IV: 5 minutes, oral: 30-60 minutes.

Duration:
6-8 hours.

DOSAGE FORMS AND STRENGTHS
Supplied:  Injection: 2 mg/ml (1 ml, 10 ml); 4 mg/ml (1 ml, 10 ml). Oral concentrate: 2 mg/ml (30 ml). Tablet: 0.5 mg, 1 mg, 2 mg.

oxcarbazepine - Trileptal®:

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®:

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:

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®:

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: C_adjusted = C_measured / [ (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®:

DOSAGE AND ADMINISTRATION
For all indications, begin dosing at 150 mg/day.
Dosing recommendations:

Dose should be adjusted in patients with reduced renal function.

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®:

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®:

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 ®:

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

Non-Induced Adults and Adolescents 12 Years or Older:

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 :

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 ≥2 years of age with seizures associated with Lennox-Gastaut syndrome (LGS).

Migraine: Treatment for adults for prophylaxis of migraine headache.

DOSAGE AND ADMINISTRATION

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 UPDATES:  TROKENDI 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 UPDATES:  QUDEXY ® 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 ®:

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 (≤ 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: ≤ 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.

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®:

zonisamide - Zonegran®:

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]