(ĐTĐ) - The US Food and Drug Administration (FDA) has approved gabapentin enacarbil (Horizant, GlaxoSmithKline) extended-release tablets for the management of postherpetic neuralgia in adults.
The drug, approved in April 2011 for the treatment of restless legs syndrome (RLS), is now approved to treat postherpetic neuralgia (PHN) at a dose of 600 mg twice daily, notes a joint statement from GlaxoSmithKline (GSK) and Xenoport Inc.
The drug, a prodrug of gabapentin, was discovered and developed by XenoPort. Gabapentin enacarbil uses the body's nutrient transport mechanisms, through which it is thought to be absorbed into the body, the companies' statement notes. Once absorbed, it is converted to gabapentin and binds to a specific calcium channel but not other common receptors. The exact mechanism by which it treats RLS or manages PHN is unknown, they write.
Gabapentin enacarbil (Horizant)
"Horizant is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles," the statement points out. "The same dose of Horizant results in different plasma concentrations of gabapentin relative to the same dose of other gabapentin products."
The efficacy and safety of the drug in the setting of PHN was evaluated in a 12-week principal efficacy trial, along with 2 supportive studies that all met their primary endpoints. The 3 studies included 574 adult patients from the United States, Canada, and Germany.
In the 12-week controlled study, the most frequently reported side effects were somnolence and dizziness: somnolence was reported in 10% of those taking 1200 mg of gabapentin enacarbil per day vs 8% of those receiving placebo; and dizziness was reported by 17% of treated patients vs 15% of those taking placebo. Headache occurred in 10% and 9%, respectively; nausea in 8% vs 5% of placebo patients; and fatigue/asthenia in 6% of treated patients vs 1% of placebo patients.
Initiation of treatment should be at a dose of 600 mg in the morning for 3 days, followed by the recommended full dose of 600 mg twice daily (1200 mg per day) beginning on day 4, they note. Doses must be adjusted in patients with impaired renal function.
Postherpetic neuralgia occurs in about 10% of those recovering from an outbreak of herpes zoster, commonly known as shingles.
The statement includes the following safety information:
- Effects on driving: The drug causes significant driving impairment, and treated patients "should not drive until they have sufficient experience to know whether their ability to drive is impaired." The patient's own ability to assess their driving competence and the degree of somnolence caused by the drug "can be imperfect," they note.
- Suicidal behavior and ideation: Gabapentin enacarbil is a prodrug of gabapentin, an antiepileptic drug (AED). AEDs increase the risk of suicidal thoughts or ideation, and as a prodrug of gabapentin, gabapentin enacarbil also increases this risk. Patients should be monitored for new or worsening depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior. Patients, caregivers, and their families should be advised of this risk and report any behaviors of concern to their healthcare provider. "Anyone considering prescribing Horizant must balance the risk of suicidal thoughts or behavior with the risk of untreated illness," the statement notes.
The safety and effectiveness of gabapentin enacarbil has not been studied in patients with epilepsy.
- Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity: This condition has been reported with other AEDs and is a risk with this new agent; some 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," the statement notes. "Eosinophilia is often present. Because the disorder is variable in its expression, other organ systems not noted here may be involved."
- Discontinuation: In patients with PHN receiving gabapentin enacarbil twice daily, the dose should be reduced to once-daily for 1 week prior to discontinuation to minimize the potential for withdrawal seizure.
Complete prescribing information is available at www.gsk.com.
Gabapentin enacarbil is not approved outside of the United States for this indication. It is also approved for moderate to severe RLS in adults but is not recommended for those who need to sleep during the day and remain awake at night.
Horizant is a registered US trademark of GSK. In association with GSK's first commercial sale of the product after approval for PHN, XenoPort is entitled to a milestone payment of $10 million from GSK.