gabapentin enacarbil

gabapentin enacarbil


Pharmacologic class: 1-amino-methyl cyclohexoneacetic acid

Therapeutic class: Anticonvulsant

Pregnancy risk category C


Unknown. Possesses properties resembling those of other anticonvulsants, which appear to stabilize cell membranes by altering cation (sodium, calcium, and potassium) transport, thereby decreasing excitability and suppressing seizure discharge or focus.


Capsules: 100 mg, 300 mg, 400 mg

Oral solution: 250 mg/5 ml

Tablets: 300 mg, 600 mg, 800 mg

Tablets (extended-release): 300 mg, 600 mg

Indications and dosages

Adjunctive treatment of partial seizures

Adults and children older than age 12: Initially, 300 mg P.O. t.i.d. Usual range is 900 to 1,800 mg/day in three divided doses.

Children ages 5 to 12: Initially, 10 to 15 mg/kg/day P.O. in three divided doses, titrated upward over 3 days to 25 to 35 mg/kg/day in three divided doses

Children ages 3 to 4: Initially, 10 to 15 mg/kg/day P.O. in three divided doses, titrated upward over 3 days to 40 mg/kg/day in three divided doses

Postherpetic neuralgia

Adults: Initially, 300 mg P.O. as a single dose on day 1; then 600 mg in two divided doses on day 2 and 900 mg in three divided doses on day 3. Then titrate upward as needed to 1,800 mg/day given in three divided doses. Or, titrate to a maximum of 1,800 mg (Gralise) P.O. daily as 300 mg on day 1,600 mg on day 2, 900 mg on days 3 to 6, 1,200 mg on days 7 to 10, 1,500 mg on days 11 to 14, and 1,800 mg on day 15. Or initially, 600 mg (Horizant) P.O. in morning for 3 days; then increase to 600 mg b.i.d. beginning on day 4.

Moderate to severe primary restless legs syndrome

Adult: 600 mg (Horizant) P.O. daily with food in evening

Dosage adjustment

• Renal impairment

Off-label uses

• Bipolar disorder
• Migraine prophylaxis
• Tremor associated with multiple sclerosis


• Hypersensitivity to drug or its components (other than Horizant)


Use cautiously in:
• renal insufficiency
• creatinine clearance less than 15 ml/minute (Horizant) or less than 30 ml/minute (Gralise), patients on hemodialysis (avoid use)
• patients with suicidal thoughts or behavior
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 3 (safety not established for partial seizures)
• children (safety not established for Horizant)
• children younger than age 18 (safety not established for Gralise).


• Give with or without food (other than Horizant and Gralise).
• Give Gralise and Horizant whole with evening meal.
• Administer first dose at bedtime to reduce adverse effects (other than Gralise and Horizant).
• Don't give within 2 hours of antacids.
• Give daily doses no more than 12 hours apart (other than Gralise and Horizant).
• Be aware that seizures may increase in patients with seizure disorders if drug is rapidly discontinued. Withdraw drug gradually over a minimum of 1 week.
• Be aware that Gralise and Horizant aren't interchangeable with other forms of gabapentin and safety and effectiveness of Gralise in patients with seizures hasn't been established.

Adverse reactions

CNS: somnolence, headache, drowsiness, anxiety, dizziness, malaise, vertigo, weakness, ataxia, altered reflexes, hyperkinesia, paresthesia, tremor, amnesia, abnormal thinking, difficulty concentrating, hostility, emotional lability, suicidal thoughts or behavior

CV: hypertension, peripheral edema

EENT: abnormal vision, nystagmus, diplopia, amblyopia, rhinitis, pharyngitis, dry throat

GI: nausea, vomiting, constipation, flatulence, dyspepsia, anorexia, dry mouth

GU: erectile dysfunction

Hematologic: leukopenia

Musculoskeletal: joint, back, or muscle pain; fractures

Respiratory: cough

Skin: pruritus, abrasion

Other: dental abnormalities, gingivitis, facial edema, increased appetite, weight gain, multiorgan hypersensitivity


Note: Apply to all forms other than Horizant

Drug-drug.Antacids: decreased gabapentin absorption

Antihistamines, CNS depressants, sedative-hypnotics: increased risk of CNS depression

Hydrocodone: decreased hydrocodone Cmax and area under the curve (AUC), increased gabapentin AUC

Morphine: increased gabapentin concentration

Drug-diagnostic tests.Urinary protein dipstick test: false-positive result

White blood cells (WBCs): decreased count

Drug-behaviors.Alcohol use: increased risk of CNS depression

Patient monitoring

Evaluate neurologic status (including observing for emergence or worsening of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior) and motor function.
• Assess WBC count.
• Monitor blood pressure.

Monitor patients for early signs and symptoms of hypersensitivity, such as fever or lymphadenopathy (although rash may not present). Discontinue drug if an alternative etiology for the signs or symptoms can' be established.

Patient teaching

• Tell patient he may take with or without food and to take first dose at bedtime to reduce adverse effects (other than Gralise and Horizant).
• Tell patient taking Gralise or Horizant to take drug with evening meal, to swallow tablet whole, and not to crush, split, or chew tablets.

Caution patient not to stop taking drug suddenly. Dosage must be tapered to minimize seizure risk.
• Instruct patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, motor function, and vision.
• Tell patient that drug may cause joint pain, muscle aches, or bone pain. Encourage him to discuss activity recommendations and pain management with prescriber.

Advise patient or caregiver to immediately report emergence or worsening of depression, suicidal thoughts or behavior, or unusual changes in mood or behavior.

Instruct patient or caregiver to immediately report early signs and symptoms of hypersensitivity, such as fever or enlarged lymph nodes.
• Advise patient not to drink alcohol while taking gabapentin.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

References in periodicals archive ?
Bioavailability is greater in gabapentin enacarbil as compared to gabapentin.
Keywords: augmentation, gabapentin enacarbil, Horizant, Neupro, restless leg syndrome, RLS, rotigotine
Gabapentin enacarbil is available as long-acting, once-daily medication with one approved dosage for RLS.
The absorption of gabapentin occurs in a limited area of the small intestine and leads to individual responses to doses; gabapentin enacarbil is a prodrug with a novel mode of transport that allows absorption throughout the length of the intestine (Cundy et al.
Subjective improvement in time awake because of RLS symptoms, quality of sleep, and ability to function were noted in patients who received gabapentin enacarbil (Kushida et al.
Gabapentin enacarbil is primarily excreted as unchanged gabapentin by the kidneys and is effectively removed by hemodialysis (Xenoport, 2013).
Gabapentin enacarbil is also indicated for the treatment of postherpetic neuralgia with a dose of 1200 mg/day.
XenoPort holds all other world-wide rights to gabapentin enacarbil.
The suicidal thoughts/behavior warning was expected as gabapentin enacarbil is a prodrug of Pfizer's (NYSE: PFE) gabapentin, an antiepileptic drug (AED).
Horizant contains gabapentin enacarbil that becomes gabapentin, a drug used to treat seizures in people with epilepsy, when absorbed into the body.
In addition, prior to the end of the transition period, GSK will provide to XenoPort inventory of gabapentin enacarbil in GSK's possession that is not required for use by GSK in the manufacture of Horizant.
XenoPort holds all other world-wide rights and has co-promotion and certain development rights to gabapentin enacarbil in the United States.