Dosing and uses of Neurontin, Gralise (gabapentin)
Adult dosage forms and strengths
capsule
- 100mg
- 300mg
- 400mg
tablet
- 300mg (Gralise)
- 600mg (Gralise, Neurontin)
- 800mg (Neurontin)
oral solution
- 250mg/5mL
Partial Seizures
Neurontin
- Adjunctive therapy for partial seizures with or without secondary generalization
- Initial: 300 mg PO q8hr
- May increase up to 600 mg PO q8hr; up to 2400 mg/day administered and tolerated in clinical studies; up to 3600 mg administered for short duration and tolerated
Postherpetic Neuralgia
Neurontin
- Day 1: 300 mg PO qDay
- Day 2: 300 mg PO q12hr
- Day 3: 300 mg PO q8hr
- Maintenance: Subsequently titrate as needed up to 600 mg PO q8hr; doses >1800 mg/day have demonstrated no additional benefit
Gralise
- Titrate gradually to 1800 mg/day PO; take qDay with evening meal
- Day 1: 300 mg PO qDay
- Day 2: 600 mg PO qDay
- Days 3-6: 900 mg PO qDay
- Days 7-10: 1200 mg PO qDay
- Days 11-14: 1500 mg PO qDay
- Day 15 and after (maintenance): 1800 mg PO qDay
Dosing considerations
- Gralise tablets swell in gastric fluid and gradually release gabapentin
Restless legs syndrome (Off-label)
100-300 mg PO 2 hr before bedtime on first day; may titrate every 2 weeks until symptom relieve achieved (range 300-1800 mg/day)
Cocaine withdrawal (Off-label)
800-1500 mg/day PO in divided doses for up to 9 months
Insomnia (Off-label)
Up to 1800 mg PO evenings for up to 9 weeks
Diabetic Neuropathy (Off-label)
900 mg/day PO initially; may increase gradually q3Days to 1800-3600 mg/day
Tremors in multiple sclerosis (Off-label)
1200-1800 mg/day PO as monotherapy
Hot flashes-cancer related (Off-label)
200-1600 mg PO qDay to q6hr for 4-8 weeks
Amyotrophic Lateral Sclerosis (Orphan)
Neurontin
Orphan indication sponsor
- Warner-Lambert Company, Parke-Davis Pharmaceutical Research Division; 2800 Plymouth Road; Ann Arbor, MI 48105
Dosing Modifications
Renal impairment (Neurontin)
- CrCl >60 mL/min: 300-1200 mg PO TID
- CrCl 30-60 mL/min: 200-700 mg q12hr
- CrCl 15-29 mL/min: 200-700 mg qDay
- CrCl <15 mL/min: 100-300 mg qDay
- Hemodialysis (CrCl <15 mL/min): Administer supplemental dose (range 125-350 mg) posthemodialysis, after each 4 hr dialysis interval; further dose reduction should be in proportion to CrCl (eg, CrCl of 7.5 mL/min should receive one-half daily posthemodialysis dose)
Renal impairment (Gralise)
- CrCl ≥60 mL/min: 1800 mg qDay with evening meal
- CrCl 30-59 mL/min: 600-1800 mg qDay with evening meal
- CrCl <30 mL/min or hemodialysis: Do not administer
Administration
Reducing the dose, discontinuing the drug, or substituting an alternative medication should be done gradually over a minimum of 1 week or longer
Swallow Gralise tablets whole; do not cut, crush, or chew them
Pediatric dosage forms and strengths
capsule
- 100mg
- 300mg
- 400mg
tablet
- 300mg (Gralise)
- 600mg (Gralise, Neurontin)
- 800mg (Neurontin)
oral solution
- 250mg/5mL
Partial Seizures
Neurontin
- Adjunctive therapy for partial seizures with or without secondary generalization in patients older than 12 years of age with epilepsy; also indicated as adjunctive therapy for partial seizures in pediatric patients aged 3-12 years
- <3 years: Safety and efficacy not established
- 3-12 years (initial dose): 10-15 mg/kg/day PO divided q8hr initially; titrate up in approximately 3 days to effective maintenance dose
- 3-4 years (maintenance dose): 40 mg/kg/day PO divided q8hr
- 5-12 years (maintenance dose): 25-35 mg/kg/day PO divided q8hr
- >12 years (initial dose): 300 mg PO q8hr; may increase up to 600 mg PO q8hr
Geriatric dosage forms and strengths
Dosing Considerations
Gralise tablets swell in gastric fluid and gradually release gabapentin
Dosing Modifications
Renal impairment: Gabapentin dose reduction may be required, depending on renal function
Neurontin, Gralise (gabapentin) adverse (side) effects
>10%
Ataxia (1-13%)
Dizziness (16-20%)
Drowsiness (5-21%)
Fatigue (11-15%)
Somnolence (16-20%)
1-10%
Diplopia (6-10%)
Nystagmus (6-10%)
Tremor (6-10%)
Amblyopia (1-5%)
Back pain (1-5%)
Constipation (1-5%)
Depression (1-5%)
Dry mouth (1-5%)
Dysarthria (1-5%)
Dyspepsia (1-5%)
Hostility (5-8% children)
Hyperkinesia (3-5%)
Increased appetite (1-5%)
Leukopenia (1-5%)
Myalgia (1-5%)
Nervousness (1-5%)
Peripheral edema (1-5%)
Pharyngitis (1-5%)
Pruritus (1-5%)
Rhinitis (1-5%)
Vasodilation (1-5%)
Weight gain (1-5%)
Abnormal vision (>1%)
Anorexia (>1%)
Arthralgia (>1%)
Asthenia (>1%)
HTN (>1%)
Malaise (>1%)
Paresthesia (>1%)
Purpura (>1%)
Vertigo (>1%)
Postmarketing Reports
Angioedema
Blood glucose fluctuation
Breast enlargement
Erythema multiforme
Elevated liver function tests
Fever
Hyponatremia
Jaundice
Stevens-Johnson syndrome
Adverse events following abrupt discontinuation have also been reported; the most frequently reported events have been anxiety, insomnia, nausea, pain, and sweating
Postmarketing reports
Changes in libido, ejaculation disorders, and anorgasmia
Warnings
Contraindications
Hypersensitivity
Cautions
Increased blood CPK levels and rhabdomyolysis reported
Antiepileptic drugs increase risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor for emergence or worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
Anaphylaxis and angioedema reported after first dose or at any time during treatment; instruct patients to discontinue therapy and seek medical care should they experience signs or symptoms of anaphylaxis or angioedema
May cause CNS depression, which may impair ability to operate heavy machinery; advise patients not to drive until they have gained enough experience to assess whether therapy will impair ability to drive
Extended release formulation (Garlise) not studied in the treatment of seizures
Extended release formulation (Garlise), not interchangeable with immediate release
May potentiate effects of other sedatives or ethanol when administered concomitantly
Do not discontinue abruptly (may increase seizure frequency); gradually taper over a minimum of 1 week
Ages 3-12 years: Risk of neuropsychiatric adverse events, including emotional lability, hostility, thought disorders, and hyperkinesia
Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, reported; some of these events have been fatal or life-threatening; typically presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement (eg, hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) and may resemble an acute viral infection
Pregnancy and lactation
Pregnancy category: C
Lactation: Enters breast milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Neurontin, Gralise (gabapentin)
Mechanism of action
GABA analogue; structurally related to neurotransmitter GABA, but has no effect on GABA binding, uptake, or degradation; presence of gabapentin binding sites throughout the brain reported; mechanism for analgesic and anticonvulsant activity unknown
Absorption
Variable from proximal small bowel by L-amino transport system
Neurontin
- Bioavailability: Inversely proportion to dose; 60% (900 mg/day); 47% (1200 mg/day); 34% (2400 mg/day); 33% (3600 mg/day); 27% (4800 mg/day)
- Peak plasma time: 2-4 hr
- Peak plasma concentration: 8536 ng/mL
- AUC: 141,301 ng•hr/mL
Gralise
- Bioavailability: Increased with high fat meal
- Peak plasma time: 8 hr
- Peak plasma concentration: 9585 ng/mL (1800 mg qDay)
- AUC: 132,808 ng•hr/mL
Distribution
Neurontin and Gralise
- Protein bound: <3%
- Vd: 58 L
Metabolism
Gabapentin is not appreciably metabolized in humans
Not a substrate, inducer, or inhibitor of CYP450 isoenzymes
Elimination
Neurontin and Gralise
- Half-life: 5-7 hr
- Dialyzable: Yes
- Renal clearance: 225 mL/min; 125 mL/min (if older than 70 y)
- Total body clearance: Proportional to CrCl
- Excretion: Urine
