On the investigator-rated CGI (Clinical Global Impression), significantly more gabapentin enacarbil-treated patients (76.1%) responded than placebo (38.9%).
Patients treated with gabapentin enacarbil showed an improved international RLS (IRLS) total score (13.2) in contrast to placebo group (8.8) at 2 weeks. 3, 4 Statistically significant differences ( P<0.05) between the treatment groups receiving 600 and 1,200 mg of gabapentin enacarbil and the group receiving placebo were observed at Week 12. The effectiveness of gabapentin enacarbil in the treatment of moderate-to-severe primary RLS was demonstrated in two 12-week randomized, placebo-controlled clinical studies in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria. 1 HOW DID GABAPENTIN ENACARBIL PERFORM IN CLINICAL STUDIES? Gabapentin enacarbil is classified as Pregnancy Category C however, there are no adequate and well-controlled studies with gabapentin enacarbil in pregnant women.
Like all anti-epileptic drugs, gabapentin enacarbil carries the same FDA risk warning for increasing suicidal thoughts or behavior in patients taking these drugs for any indication. 1 The following adverse reactions were dose-related: somnolence/sedation, dizziness, feeling drunk, libido decreased, depression, headache, peripheral edema, and vertigo. The most commonly observed adverse reactions (5% and at least 2 times the rate of placebo) in these trials for the 600-mg dose were somnolence/sedation (20% on gabapentin enacarbil vs. Experience to date indicated that gabapentin is safe and relatively nontoxic.Eleven out of 163 patients (7%) treated with 600 mg of gabapentin enacarbil discontinued treatment due to adverse reactions compared with 10 of the 245 patients (4%) who received placebo.
The most common side effects include somnolence, dizziness, ataxia, and fatigue. In general, adverse effects with gabapentin are infrequent and usually resolve with continued treatment. Therefore, gabapentin serum concentrations are not changed following the addition or discontinuation of other common anticonvulsants (ie, phenobarbital, phenytoin, carbamazepine, or valproic acid), nor are their serum concentration altered upon the addition or discontinuation of gabapentin. In addition, the lack of hepatic metabolism eliminates the interactions with other hepatically cleared medications, which can induce/inhibit hepatic drug metabolizing enzyme systems (cytochrome P450s). Since gabapentin does not bind to serum proteins, it does not exhibit pharmacokinetic variability and interactions with other highly protein-bound medications (eg, phenytoin). The elimination half-life is 5 to 7 hours in patients with normal renal function. In addition, gabapentin does not undergo hepatic metabolism, unlike most other antiepileptic drugs, and is eliminated almost entirely by renal excretion with a clearance that approximates the glomerular filtration rate. In fact, the precise mechanism by which it exerts its analgesic and anticonvulsant effects is unknown.Īfter oral administration and absorption, gabapentin circulates essentially unbound to serum proteins. Although designed as a gamma amino butyric acid (GABA) analogue, gabapentin does not bind to GABA receptors, nor does it affect the neuronal uptake or degradation of GABA. Gabapentin is an antiepileptic drug that is effective in treating seizures, neuropathies, and a variety of neurological and psychological maladies.