Gabapentin Enacarbil
Gabapentin enacarbil is a prodrug of gabapentin designed to overcome gabapentin's erratic, saturable absorption. It is absorbed by high-capacity intestinal transporters and hydrolysed to gabapentin, giving more predictable, sustained exposure. It is approved for moderate-to-severe restless legs syndrome and postherpetic neuralgia, and shares gabapentin's dependence and withdrawal profile.
01 Overview
Marketed as Horizant, gabapentin enacarbil is absorbed via MCT-1 and other transporters throughout the intestine rather than the narrow duodenal window gabapentin relies on, yielding dose-proportional gabapentin levels and once- or twice-daily dosing.
Because it delivers gabapentin, its pharmacology, benefits and risks mirror the parent drug, including sedation, dizziness and a withdrawal syndrome on abrupt discontinuation. It should be tapered like gabapentin.
02 Mechanism
Enzymatically hydrolysed after absorption to release gabapentin, which binds the alpha-2-delta-1 subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Restless legs syndrome | 600 mg/day | Oral | 600 mg once daily around 5 pm with food. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Restless legs reliefReduces IRLS symptom scores and improves sleep in moderate-to-severe restless legs syndrome. | Moderate | Clinical | |
| Neuropathic pain reliefReduces postherpetic neuralgia pain with more stable exposure than immediate-release gabapentin. | Moderate | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Somnolence and dizzinessDrowsiness and dizziness, the leading adverse events in trials. | Mild | Very common | Clinical | |
| Withdrawal on abrupt cessationAnxiety, insomnia and autonomic symptoms if stopped suddenly. | Moderate | Common after chronic use | Clinical |