INDICATIONS: HORIZANT® (gabapentin enacarbil) Extended-Release Tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults.
HORIZANT is not recommended for patients who are required to sleep during the daytime and remain awake at night.
HORIZANT® (gabapentin enacarbil) Extended-Release Tablets are indicated for the management of postherpetic neuralgia (PHN) in adults.
IMPORTANT SAFETY INFORMATION
Effects on Driving
HORIZANT may cause significant driving impairment. Patients should not drive until they have enough experience on HORIZANT to know if it impairs their driving. Patients’ ability to assess their driving competence and degree of somnolence caused by HORIZANT can be imperfect.
Somnolence/Sedation and Dizziness
HORIZANT causes somnolence/sedation and dizziness. Patients should not drive or operate other complex machinery until they have enough experience on HORIZANT to know if it impairs their ability to perform these tasks.
Lack of Interchangeability With Gabapentin
HORIZANT is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles. The same dose of HORIZANT results in different plasma concentrations of gabapentin relative to other gabapentin products. The safety and effectiveness of HORIZANT in patients with epilepsy have not been studied.
Suicidal Behavior and Ideation
HORIZANT is a prodrug of gabapentin, an antiepileptic drug (AED). AEDs increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. As a prodrug of gabapentin, HORIZANT also increases this risk. Patients treated with any AED for any indication should be monitored for new or worsening depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Anyone considering prescribing HORIZANT must balance the risk of suicidal thoughts or behavior with the risk of untreated illness.
Patients, caregivers, and families should be informed that HORIZANT increases the risk of suicidal thoughts and behavior and should be advised of the need to be alert for new or worsening signs of and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts of self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including gabapentin. HORIZANT is a prodrug of gabapentin. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy,
in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved.
It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. HORIZANT should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Discontinuation of HORIZANT
When discontinuing HORIZANT, patients with RLS receiving 600 mg or less once daily can discontinue the drug without tapering. If the recommended dose is exceeded, the dose should be reduced to 600 mg daily for 1 week prior to discontinuation to minimize the potential of withdrawal seizure.
In patients with PHN receiving HORIZANT twice daily, the dose should be reduced to once daily for 1 week prior to discontinuation to minimize the potential of withdrawal seizure.
In an oral carcinogenicity study, gabapentin enacarbil increased the incidence of pancreatic acinar cell adenoma and carcinoma in male and female rats. The clinical significance of this finding is unknown.
The most common adverse reactions for patients with RLS receiving HORIZANT 600 mg, 1,200 mg, and placebo, respectively, were somnolence/sedation (20%, 27%, and 6%), dizziness (13%, 22%, and 4%), headache (12%, 15%, and 11%), nausea (6%, 7%, and 5%), and fatigue (6%, 7%, and 4%). A daily dose of 1,200 mg provided no additional benefit compared with the 600-mg dose, but caused an increase in adverse reactions.
The most common adverse reactions for patients with PHN taking HORIZANT 1,200 mg and placebo, respectively, were dizziness (17% and 15%), somnolence/sedation (10% and 8%), headache (10% and 9%), nausea (8% and 5%), and fatigue (6% and 1%).
A daily dose greater than 1,200 mg/day provided no additional benefit, but caused an increase in adverse reactions.
Gabapentin enacarbil is released faster from HORIZANT Extended-Release tablets in the presence of alcohol. Consumption of alcohol is not recommended when taking HORIZANT.
HORIZANT taken in conjunction with morphine causes increased somnolence/sedation, dizziness, and nausea.
USE IN SPECIAL POPULATIONS
Pregnancy and Lactation
Based on animal data, HORIZANT may cause fetal harm. There are no adequate and well-controlled studies of HORIZANT in pregnant women. HORIZANT should be used during pregnancy only if potential benefit justifies potential risk to fetus.
HORIZANT is converted to gabapentin, which is secreted into human milk. Discontinue nursing or discontinue HORIZANT, taking into account the importance of HORIZANT to the mother, due to potential for adverse reactions in nursing infants.
In patients with RLS who have compromised renal function, HORIZANT should be dosed based
upon creatinine clearance (CrCl): 30 to 59 mL/min, start with 300 mg per day and increase to
600 mg as needed; 15 to 29 mL/min, use 300 mg per day; <15 mL/min, use 300 mg every other day. HORIZANT is not recommended for use in patients receiving hemodialysis.
In patients with PHN who have compromised renal function, HORIZANT should be dosed based
upon creatinine clearance (CrCl): 30 to 59 mL/min, a titration dose of 300 mg in AM for 3 days, increase to maintenance dose of 300 mg twice daily at Day 4 and increase to 600 mg twice daily as needed, tapering requirement of reduced current maintenance dose to once daily in AM for 1 week; 15 to 29 mL/min, a titration dose of 300 mg in AM on Day 1 and Day 3, use 300 mg in AM as maintenance therapy and increase to 300 mg twice daily if needed, tapering requirement necessary if taking 300 mg twice daily, reduce to 300 mg once daily in AM for 1 week, if taking
300 mg once daily, no tapering needed; <15 mL/min, no titration dose, 300 mg every other day in AM and increase to 300 mg once daily in AM if needed, no tapering needed; <15 mL/min on hemodialysis, no titration dose, 300 mg following every dialysis and increase to 600 mg following every dialysis if needed, no tapering needed.