RLS patients experience a range of symptoms
The International RLS Rating Scale measures the range of symptoms
HORIZANT significantly reduced "mean International RLS Rating Scale total score" score in the 12-week pivotal trial1
In the REST Study, patients with RLS reported sensory and sleep symptoms as most troublesome.
The table at right shows the specific symptoms reported as most troublesome by more than 5% of patients in the REST Study (n=416); 3.4% of patients did not report a most troublesome symptom.
RLS discomfort in arms or legs
Urge to move
Movement brings relief
Severity of RLS sleepiness
Overall severity of RLS
Frequency of symptoms
Severity on an average day
Impact on daily activities
The International RLS (IRLS) Rating Scale is used to assess the severity of a patient’s RLS symptoms. The patient answers 10 questions in which they rate their symptoms from 0 to 4, with 0 being the absence of symptoms and 4 being very severe. A patient’s total score ranges from 0 to 40. The IRLS Rating Scale was validated in a controlled study and found to have high levels of internal consistency, interexaminer reliability, and test-retest reliability.2
In the 12-week pivotal trial, HORIZANT 600 mg reduced mean IRLS scores from baseline of 23.1 (severe) to 9.3 (mild), a 13.8‑point reduction (vs a 9.8‑point reduction for placebo; P<0.0001).
IRLS rating scale—total score by visit
In clinical trials of HORIZANT, the most common adverse reactions (≥5% and at least 2 times the rate of placebo) in patients with RLS were somnolence/sedation and dizziness.
The recommended dosage of HORIZANT for RLS is 600 mg taken once daily with food. A daily dose of 1200 mg provided no additional benefit compared with the 600-mg dose and caused an increase in adverse reactions.
Responders on the CGI-I Scale were defined as having a rating of "much improved" or "very much improved," last observation carried forward.
% responders on CGI-I scale
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
WARNINGS AND PRECAUTIONS
Effects on Driving
HORIZANT may cause significant driving impairment. The duration of driving impairment after starting therapy is unknown. 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 the emergence or worsening of 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 the emergence or worsening of the signs 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 (incidence >10% and at least 2 times the rate of placebo) were somnolence/sedation and dizziness.
The most common adverse reactions for patients with PHN (incidence >10% and greater than placebo) were dizziness, somnolence, and headache.
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
Pregnancy Category C. There are no adequate and well-controlled studies with HORIZANT in pregnant women. In nonclinical studies in rat and rabbits, administration of gabapentin enacarbil was developmentally toxic when administered to pregnant animals at doses and gabapentin exposures greater than those used clinically. HORIZANT should be used during pregnancy only if potential benefit justifies potential risk to fetus.
It is not known whether gabapentin derived from HORIZANT is secreted in human milk; however, gabapentin is secreted into human milk following oral administration of gabapentin products. Because of the potential for adverse reactions in nursing infants from HORIZANT, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness of HORIZANT in pediatric patients have not been studied.
Gabapentin is known to be almost exclusively excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. The dose of HORIZANT should be adjusted in patients with renal impairment based upon creatinine clearance. HORIZANT is not recommended for treatment of RLS in patients receiving hemodialysis.
For additional safety information, consult the HORIZANT full Prescribing Information here.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Horizant [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals, LLC.
The International Restless Legs Syndrome Study Group. Validation of the International Restless Legs Syndrome Study. Group Rating Scale for restless legs syndrome. Sleep Med. 2003;4(2):121-132.
Allen RP, Walters AS, Montplaisir J, et al. Restless Legs Syndrome prevalence and impact: REST General Population Study. Arch Intern Med. 2005;165:1286-1292.
Lee DO, Ziman RB, Perkins AT, Poceta JS, Walters AS, Barrett RW, for the XP053 Study Group. A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with Restless Legs Syndrome. J Clin Sleep Med. 2011;7(3):282-292.
Cundy KC, Sastry S, Luo W, Zou J, Moors TL, Canafax DM. Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin. J Clin Pharmacol. 2008;48(12):1378-1388.
García-Borreguero D, Kohnen R, Silber MH, et al. The long-term treatment of Restless Legs Syndrome/Willis–Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance. A report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013:14:675-684.
Kushida CA, Becker P, Ellenbogen AL, Canafax DM, Barrett RW, for the XP052 Study Group. Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS. Neurology. 2009;72(5):439-446.
Comella CL. Treatment of restless legs syndrome. Neurotherapeutics 2014;11(1):177-187.