Class: Anticonvulsant Gabapentin enacarbil
- Tablets, ER, oral 600 mg
- Tablets, oral 300 mg
- Tablets, oral 600 mg
- Tablets, oral 600 mg
- Tablets, oral 800 mg
- Capsules, oral 100 mg
- Capsules, oral 300 mg
- Capsules, oral 400 mg
- Solution, oral 250 mg per 5 mL
CO Gabapentin (Canada)
Mechanism unknown; gabapentin enacarbil is a prodrug of gabapentin.
Bioavailability for the immediate-release tablets decreases as dose increases; bioavailability is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1,200, 2,400, 3,600, and 4,800 mg/day given in 3 divided doses, respectively. Food has only a slight effect on rate and extent of absorption (14% increase in AUC and C max ). Bioavailability for the ER tablets is approximately 75% (with food) and 42% to 65% (fasting). T max was 7.3 h (with food) and 5 h (fasting).
Less than 3% bound to plasma proteins. Vd is approximately 58 L (immediate release) and 76 L (ER).
Gabapentin enacarbil is hydrolyzed primarily in the intestines to the active metabolite gabapentin, which is not significantly metabolized in humans.
Excreted as unchanged gabapentin in the urine. Half-life is 5 to 7 h. Renal Cl ranged from 5 to 7 L/h (ER).
Special PopulationsRenal Function Impairment
In CrCl less than 30 mL/min, half-life is approximately 52 h (immediate release). In moderate and severe renal impairment, Cl was decreased to 3 and 1 L/h, respectively, compared with 5 to 7 L/h in nonrenal impairment patients (ER).Hemodialysis
The half-life is approximately 132 h on nondialysis days; during dialysis, half-life is reduced to 3.8 h (immediate release). Gabapentin is significantly removed by hemodialysis. Treatment with gabapentin enacarbil is not recommended for patients on hemodialysis (ER).Hepatic Function Impairment
Studies have not been performed.Elderly
Renal Cl decreases as a result of age-related decline in renal function.Children
Children between 1 mo and younger than 5 y achieved approximately 30% lower exposure (AUC) than that observed in those 5 y and older. Gabapentin elimination half-life averaged 4.7 h and was similar across the age groups studied. Higher oral Cl values were observed in children younger than 5 y compared with those observed in children 5 y and older, when normalized per body weight. The Cl was highly variable in infants younger than 1 y.Gender
No clinical meaningful differences in pharmacokinetics were found between men and women.Race
The effect of race was not studied.
Indications and Usage
Adjunctive therapy in treatment of partial seizures with or without secondary generalization in patients older than 12 y with epilepsy (immediate release); adjunctive therapy for partial seizures in children 3 to 12 y of age; management of postherpetic neuralgia in adults (immediate release); treatment of moderate to severe primary restless legs syndrome in adults (ER).
Agitation in dementia; alcohol withdrawal; bipolar disorder; cocaine withdrawal; diabetic neuropathy; fibromyalgia; headaches; hiccups (singultus); hot flashes (cancer- and/or postmenopausal-related); hyperhidrosis; nausea (cancer-related); neuralgia/neuropathy/chronic pain; prevention of migraine; pruritus (brachioradial/cholestatic/uremic); rectal administration; restless legs syndrome (immediate release); tremors in multiple sclerosis.
Hypersensitivity to the drug or its ingredients.
Dosage and AdministrationEpilepsy (Immediate Release)
Adults and Children older than 12 y
PO 300 mg 3 times daily initially. May increase as necessary to 900 to 1,800 mg/day (divided 3 times daily).Children 5 to 12 y of age
PO Initiate therapy at 10 to 15 mg/kg/day in 3 divided doses and titrate dose upward over a period of approximately 3 days to effective dose. Effective dosage is 25 to 35 mg/kg/day in 3 divided doses.Children 3 to 4 y of age
PO Initiate therapy at 10 to 15 mg/kg/day in 3 divided doses and titrate dose upward over a period of approximately 3 days to effective dose. Effective dosage is 40 mg/kg/day in 3 divided doses.Postherpetic Neuralgia (Immediate Release)
PO Start with a single 300 mg dose on day one, 600 mg on day two (divided twice daily), and 900 mg on day three (divided 3 times daily). Subsequently, titrate the dose upward as needed for pain relief to a daily dose of 1,800 mg (divided 3 times daily).Restless Legs Syndrome (ER)
PO 600 mg once daily taken at approximately 5 PM.Renal Function Impairment
Adults and Children older than 12 y (immediate release) CrCl 60 mL/min or higher
Total daily dose range, 900 to 3,600 mg/day.CrCl 30 to 59 mL/min
Total daily dose range, 400 to 1,400 mg/day.CrCl 16 to 29 mL/min
Total daily dose range, 200 to 700 mg/day.CrCl 15 mL/min
Total daily dose range, 100 to 300 mg/day.CrCl less than 15 mL/min
Reduce dose in proportion to CrCl (eg, patients with CrCl 7.5 mL/min should receive half the daily dose of patients with CrCl 15 mL/min).Adults (ER) CrCl 30 to 59 mL/min
600 mg on days 1 and 3, and every day thereafter.CrCl less than 30 mL/min
Use is not recommended.Patients on hemodialysis
Immediate release Maintenance doses based on CrCl as recommended, plus a supplemental posthemodialysis dose administered after each 4 h of hemodialysis as follows: If maintenance dose is 100 mg daily, postdialysis dose is 125 mg; if maintenance dose is 125 mg daily, postdialysis dose is 150 mg; if maintenance dose is 150 mg daily, postdialysis dose is 200 mg; if maintenance dose is 200 mg daily, postdialysis dose is 250 mg; if maintenance dose is 300 mg daily, postdialysis dose is 350 mg.
Gabapentin available under the trade names Gralise (R) and Horizant (R) is contraindicated in patients receiving hemodialysis.
ER Use is not recommended.
- Administer with food. Tablets should be swallowed whole and should not be cut, crushed, or chewed.
- May discontinue drug without tapering when receiving recommended dose. When recommended dose is exceeded, reduce dosage to 600 mg daily for 1 wk prior to discontinuation.
- If the dose is not taken at the recommended time, the next dose should be taken the following day as prescribed.
- Immediate release
- Tablets, capsules, and oral solution are interchangeable on a mg-to-mg basis.
- Max time between doses in 3-times-daily schedule should not exceed 12 h.
- Administer without regard to meals. Administer with food if GI upset occurs.
- If 600 or 800 mg scored tablet is split to administer a half-tablet, administer unused half-tablet at next dose. Discard any half-tablet not used within several days of splitting.
- Measure and administer prescribed dose of oral solution using dosing syringe, dosing spoon, or dosing cup.
- Reduce dose gradually over a minimum of 1 wk if gabapentin is discontinued.
Store tablets and capsules between 59° and 86°F. Store oral solution between 36° and 46°F.
May reduce bioavailability of gabapentin. Gabapentin should be taken 2 h after antacid.Cimetidine
Renal Cl of gabapentin may be reduced slightly. This interaction is not expected to be clinically important.Hormonal contraceptives
Norethindrone plasma levels may be increased by 13%, which is not expected to be clinically important.Hydrocodone
The AUC of gabapentin may be increased by 14% while the hydrocodone C max and AUC are decreased by gabapentin in a dose-dependent manner. Observe the clinical response of the patient when starting, stopping, or changing the gabapentin dose. If an interaction is suspected, adjust the hydrocodone dose as needed.Morphine
The AUC of gabapentin may be increased by morphine. The magnitude of this interaction at various gabapentin doses has not been evaluated. Observe the clinical response of the patient when starting, stopping, or changing the gabapentin dose. If an interaction is suspected, adjust the gabapentin dose as needed.Naproxen
In lower than therapeutic doses, gabapentin absorption was increased 12% to 15% by naproxen. The magnitude of this interaction within the recommended dose ranges of either drug is not known. Observe the clinical response of the patient when starting, stopping, or changing the dose of either drug. If an interaction is suspected, adjust the gabapentin dose as needed.
Laboratory Test Interactions
False-positive readings for Ames N-Multistix SG dipstick test when gabapentin is added to other antiepileptic drugs. Sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.
Hypertension (at least 1%); vasodilation (1%);
Dizziness (28%); sedation, somnolence (27%); headache (15%); ataxia (13%); fatigue (11%); hostility, nystagmus (8%); tremor (7%); asthenia (6%); emotional lability, irritability (4%); abnormal thinking, depression, feeling abnormal, feeling drunk, hyperkinesia, vertigo (3%); abnormal gait, amnesia, dysarthria, incoordination, libido decreased, nervousness (2%); balance disorder, lethargy (less than 2%); anxiety, confusion, malaise, paresthesia (at least 1%); abnormal coordination, hypesthesia, twitching (1%); aura disappeared, occipital neuralgia, sleepwalking; movement disorder (postmarketing).
Abrasion, pruritus, rash (1%); erythema multiforme, Stevens-Johnson syndrome (postmarketing).
Diplopia (6%); amblyopia, rhinitis (4%); pharyngitis (3%); abnormal vision (at least 1%); conjunctivitis, otitis media (1%).
Nausea/vomiting (8%); diarrhea (6%); dry mouth (5%); constipation (4%); abdominal pain, flatulence (3%); dental abnormalities, dry mouth or throat, dyspepsia, increased appetite (2%); anorexia, gingivitis (at least 1%).
Impotence (2%); breast hypertrophy (postmarketing).
Purpura (at least 1%); decreased WBC, leukopenia (1%); coagulation defect.
Hepatitis; elevated LFTs, jaundice (postmarketing).
Peripheral edema (8%); weight gain (3%); hyperglycemia (1%); dehydration; blood glucose fluctuations, hyponatremia (postmarketing).
Back pain, myalgia (2%); arthralgia, decreased or absent reflexes, increased reflexes (at least 1%); fracture (1%).
Bronchitis, respiratory tract infection (3%); coughing (2%); pneumonia (at least 1%); hoarseness, pseudocroup.
Viral infection (11%); fever (10%); infection (5%); accidental injury (3%); face edema (at least 1%); infectious mononucleosis; angioedema (postmarketing).
Monitor patients for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy or at times of dose changes (either increases or decreases), and during discontinuation of therapy.
Category C .
Excreted into breast milk.
Effectiveness as adjunctive therapy in the treatment of partial seizures in children younger than 3 y not established; safety and efficacy in management of postherpetic neuralgia and restless legs syndrome in children not established.
Because of age-related renal impairment, adjust dose based on CrCl.
Adjust dose based on CrCl.
May have carcinogenic potential.
May cause significant driving impairment, dizziness, drowsiness, somnolence, sedation, and other symptoms of CNS depression.
Emotional lability, hostility, thought disorders, and hyperkinesia have been reported with increased frequency in patients 3 to 12 y of age with epilepsy.
Gabapentin enacarbil is not interchangeable with other gabapentin products.
Serious adverse reactions
During clinical trials, some patients experienced status epilepticus, and 8 sudden, unexplained deaths occurred. The association of these reactions with gabapentin use is unclear.
Antiepileptic drugs increase the risk of suicidal thinking and behavior in patients taking these drugs for any indication.
Do not discontinue antiepileptic drugs abruptly because of possible increased seizure frequency from drug withdrawal. ER tablets, if used at the recommended dose, may be discontinued without tapering.
Diarrhea, dizziness, double vision, drowsiness, lethargy, slurred speech, somnolence/sedation.
- Advise patient or caregiver to read the Medication Guide before starting therapy and with each refill.
- Counsel patients, families, or caregivers that antiepileptic drugs may increase the risk of suicidal thoughts and behavior and to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm, and to immediately report any of these symptoms to their health care provider.
- Instruct patients with epilepsy to continue to take other medications for seizures unless advised otherwise by their health care provider.
- Advise patients or caregivers that medication will be started at a low dose and then increased as tolerated until maximum benefit has been obtained.
- Instruct patients or caregivers to take or administer gabapentin exactly as prescribed and not to change the dose or discontinue therapy unless advised by their health care provider.
- Advise patients or caregivers to take the immediate-release tablets without regard to meals but to take with food if stomach upset occurs. Inform patients that the ER tablets should be taken with food at approximately 5 PM.
- Advise patient or caregiver that maximum time between doses in the 3-times-daily schedule should not exceed 12 h.
- Advise patient or caregiver that if they split the 600 or 800 mg scored immediate-release tablet to administer a half-tablet dose, they should take the unused half-tablet at the next dose. Half-tablets not used within several days of splitting should be discarded.
- Inform patients that the ER tablet should be swallowed whole and not cut, crushed, or chewed.
- Advise patients or caregivers using oral solution to measure and administer prescribed dose using dosing syringe, spoon, or cup.
- Advise patients or caregivers that if the immediate-release tablet needs to be discontinued, it will be slowly withdrawn over a period of 1 wk or more unless safety concerns (eg, rash) require a more rapid withdrawal. The ER tablet, if used at the recommended dose, does not require tapering.
- Caution patient that drug may cause dizziness, drowsiness, or incoordination, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
- Instruct patients or caregivers to contact their health care provider if seizures worsen or if new types of seizures occur.
- Advise patients or caregivers to inform their health care provider if any of the following occur: emotional lability, hostility, thought disorders or abnormal thinking, restlessness or hyperactivity, excessive dizziness or drowsiness, swelling in the feet or ankles, any unexplained symptom or feeling.
- Inform patients that doses of gabapentin enacarbil and other gabapentin products are not interchangeable.
- Advise patient with epilepsy to carry medical identification (eg, card, bracelet) indicating medication usage and epilepsy.
- Advise pregnant patients taking gabapentin to enroll in the North American Antiepileptic Drug Pregnancy Registry. This can be done by calling 1-888-233-2334.
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