Usual Adult Dose for Epilepsy

Initial dose: 300 mg orally 3 times a day
Maintenance dose: 300 to 600 mg orally 3 times a day
Maximum dose: 2400 to 3600 mg/day

Comments:

• Doses up to 2400 mg/day have been well tolerated in long-term studies; doses of 3600 mg/day have be used in a small number of patients for a relatively short duration and have been well tolerated.
• The maximum time between doses should not exceed 12 hours.
• The safety and effectiveness of gabapentin available under the trade name Gralise or Horizant have not been studied in patients with epilepsy.

Use: Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization

Usual Adult Dose for Postherpetic Neuralgia

Immediate-release:
Initial dose:
Day 1: 300 mg orally once
Day 2: 300 mg orally 2 times day
Day 3: 300 mg orally 3 times a day

• Titrate dose as needed for pain relief

Maintenance dose: 900 to 1800 mg/day orally in 3 divided doses
Maximum dose: 1800 mg per day

Extended-release: Gralise (gabapentin) 24-hour extended-release tablets:
Initial dose:
Day 1: 300 mg orally with the evening meal
Day 2: 600 mg orally with the evening meal
Days 3 through 6: 900 mg orally with the evening meal
Days 7 through 10: 1200 mg orally with the evening meal
Days 11 through 14: 1500 mg orally with the evening meal
Maintenance dose (Day 15 and onward): 1800 mg orally with the evening meal

Extended-release: Horizant (gabapentin enacarbil) extended release tablets:
Initial dose:
Day 1 to Day 3: 600 mg orally once a day
Maintenance dose (Day 4 and onward): 600 mg orally twice a day
Maximum dose: 1200 mg/day

Comments:

• The extended-release products Gralise and Horizant are not interchangeable with each other or other gabapentin products due to differing pharmacokinetic profiles.
• In clinical trials, exceeding maximum doses have not shown additional benefits, but higher doses have resulted in increase in adverse reactions.

Use: For the management of postherpetic neuralgia.

Usual Adult Dose for Restless Legs Syndrome

600 mg orally once daily with food at about 5 PM
Maximum dose: 600 mg

Comment:

• Gabapentin enacarbil available under the trade name Horizant is the only gabapentin product approved for treatment of Restless Legs Syndrome (RLS).
• A daily dose of 1200 mg provided no additional benefit compared with the 600 mg dose, but caused an increase in adverse reactions.
• This drug is not recommended for patients who are required to sleep during the daytime and remain awake at night.

Use: For the treatment of moderate-to-severe primary RLS in adults.

Usual Pediatric Dose for Epilepsy

Age: 3 to 11 years:
Initial dose: 10 to 15 mg/kg/day orally in 3 divided doses
Maintenance dose:
Age: 3 to 4 years: 40 mg/kg/day orally and in 3 divided doses (3 times a day)
Age: 5 to 11 years: 25 to 35 mg/kg/day in 3 divided doses (3 times a day)
Maximum dose: Doses up to 50 mg/kg/day have been well tolerated in a long term clinical study

Age: 12 years or older:
Initial dose: 300 mg orally 3 times a day
Maintenance dose: 300 to 600 mg orally 3 times a day
Maximum dose: 2400 to 3600 mg/day; doses up to 2400 mg/day have been well tolerated in long-term studies; doses of 3600 mg/day have be used in a small number of patients for a relatively short duration and have been well tolerated.

Comments:

• Initial doses should be titrated over 3 days to the recommended maintenance doses.
• The maximum time between doses should not exceed 12 hours.
• The safety and effectiveness of gabapentin available under the trade name Gralise or Horizant have not been studied in pediatric patients and patients with epilepsy.

Use: Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization in patients 3 years of age and older.

Renal Dose Adjustments

Immediate release:
12 years or older: Doses should be divided and administered 3 times a day

• CrCl 60 mL/min or greater: 900 to 3600 mg/day
• CrCl 30 to 59 mL/min: 400 to 1400 mg/day
• CrCl 15 to 29 mL/min: 200 to 700 mg/day
• CrCl 15 mL/min: 100 to 300 mg/day (reduce daily dose in proportion to CrCl)

Less than 12 years: Data not available

Extended release: Gralise (24-hour extended-release tablets):

• CrCl greater than or equal to 60 mL/min: No adjustment recommended
• CrCl 30 to 60 mL/min: 600 to 1800 mg orally with the evening meal
• CrCl less than 30 mL/min: Not recommended

Extended-release: Horizant (gabapentin enacarbil extended-release tablets):
RESTLESS LEGS SYNDROME:

• CrCl greater than or equal to 60 mL/min: No adjustment recommended
• CrCl 30 to 59 mL/min: Initial dose: 300 mg orally once a day and increase to 600 mg as needed
• CrCl 15 to 29 mL/min: 300 mg orally once a day
• CrCl less than 15 mL/min: 300 mg orally every other day

POSTHERPETIC NEURALGIA:

• CrCl 60 mL/min or greater: No adjustment recommended
• CrCl 30 to 59 mL/min: Initial dose: 300 mg orally once a day for 3 days, then 300 mg orally 2 times a day; increase to 600 mg orally 2 times a day as needed
• CrCl 15 to 29 mL/min: Initial dose: 300 mg orally in the morning on day 1 and day 3; then 300 mg once a day in the morning; may increase to 300 mg orally 2 times a day if needed
• CrCl less than 15 mL/min: 300 mg orally every other day; increase to 300 mg orally once daily if needed

Liver Dose Adjustments

Data not available

Dose Adjustments

Geriatric Patients: Because elderly patients are more likely to have decreased renal function, the dose of this drug should be adjusted based on CrCl values.

Drug Withdrawal:

• The drug should be gradually withdrawn
• If immediate-release dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber)
• If Gralise is discontinued, this should be discontinued over a minimum of 1 week or longer
• If Horizant is discontinued in patient receiving 600 mg/day or less, discontinuation may be done without tapering
• If Horizant is discontinued in patients receiving this drug twice a day, reduce to once daily for 1 week prior to discontinuation

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to active substance or any product excipients

Safety and efficacy have not been established in patients younger than 18 years in the management of postherpetic neuralgia or Restless Leg Syndrome.
Safety and efficacy have not been established in patients younger than 3 years in the adjunctive treatment of partial seizures.
Safety and efficacy have not been established in patients younger than 18 years for gabapentin available under the trade names Gralise or Horizant.

Consult WARNINGS section for additional precautions.

Dialysis

Immediate-release: 12 years or older:

• Adjust dose based on CrCl and provide post-hemodialysis supplemental dose after each 4 hours of hemodialysis: See manufacturer product labeling for post-hemodialysis supplemental dose

Extended-release:

• Gralise: Hemodialysis: Not recommended
• Horizant (gabapentin enacarbil):

RESTLESS LEGS SYNDROME:

• CrCl less than 15 mL/min on hemodialysis: Not recommended

POSTHERPETIC NEURALGIA:

• CrCl less than 15 mL/min on hemodialysis: 300 mg orally following every dialysis; increase to 600 mg orally following every dialysis if needed

Other Comments

Administration advice:
Immediate-release:

• Take orally with or without food
• Swallow capsules whole with water
• If 600 mg or 800 mg tablets are scored to administer half-tablet, the unused half-tablet should be used as next dose; if half-tablet is not used within 28 days of dividing, the scored tablet should be discarded

Extended-release:

• Horizant (gabapentin enacarbil): Take orally once a day about 5 PM for Restless Leg Syndrome or twice a day in the morning and evening for Postherpetic Neuralgia; swallow tablets whole with food; do not cut, crush, or chew tablets
• Gralise extended-release tablets should be taken once daily with the evening meal; do not cut, crush, or chew tablets
• Horizant and Gralise are not interchangeable with each other or other gabapentin products

MISSED DOSES:
Horizant: If a dose is missed, skip the missed dose and take the next dose at the scheduled time
Gralise: If a dose is missed, take with food as soon as they remember; if it is almost time for the next dose, skip the missed dose and take the next dose at the regular time; do not take two doses at the same time

Storage:

• Oral Solution: Store in the refrigerator (2C to 8C [36F to 46F])

General:

• If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.

Monitoring:

• Monitor for respiratory depression in at-risk patients (patients with respiratory impairment and/or on concomitant CNS depression medications)
• Monitor for the emergence of worsening depression, suicidal thoughts, or behavior, and/or any unusual changes in mood or behavior

Patient Advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Medication Guide).
• Patients, families, and caregivers should understand that this drug may increase the risk of suicidal thoughts and behavior and they should be instructed to report any unusual change in mood or behavior, worsening of depression, or suicidal thoughts or behaviors to their healthcare provider immediately.
• Patients, families, and caregivers should be instructed to report a rash or other signs or symptoms of hypersensitivity, such as fever or lymphadenopathy as this may signal a more serious event; patients should be instructed to stop therapy and seek medical care if they develop signs or symptoms of anaphylaxis or angioedema.
• Patients should be counseled on concomitant alcohol use; patients on taking Horizant should be instructed to avoid alcohol as alcohol may cause the drug to be released faster from its extended-release tablet.
• Patients, families, and caregivers should understand that this drug may cause respiratory depression, especially in patients with underlying respiratory impairment and/or concomitant use of CNS depressants.
• Women of childbearing potential should speak with their healthcare provider if they become or intend to become pregnant, and if they intend or are breastfeeding.
• Patients should be instructed not to drive a car or perform hazardous tasks until they gain sufficient experience with this drug to understand how it affects their mental and/or motor performance.