Active Ingredients: Gabapentin
The AUC of 1800 mg of Gralise is slightly less than 1800 mg of the standard formulation.
In addition, the average maximum concentration Cmax of Gralise is slightly higher than 1800 mg of the standard form, and minimum concentration Cmin is slightly lower.
Finally, Tmax is increased in the extended-release form. The recommended maintenance dose is 600 mg twice a day. Doses greater than 1200 mg daily are not recommended, as side effects increase without a corresponding increase in efficacy. It is absorbed through the small intestine through a proton-linked monocarboxylate transporter MCT-1.
Unlike the original formulation, absorption of gabapentin enacarbil is not saturated at high doses, as MCT-1 is expressed in high levels in the intestinal tract.
The drug undergoes near-complete first pass hydrolysis to gabapentin by non-specific carboxylesterases mainly in enterocytes, as well as in the liver to a lessor degree. Consumption of alcohol increases the release of gabapentin enacarbil from the extended-release tablet.
Therefore, alcohol should be avoided when taking Horizant due to increased risk of side effects.
All forms of gabapentin must be adjusted in renal dysfunction, similar to standard formulations. When discontinuing gabapentin it is recommended to taper the dose over a week at least.
As with all antiepileptic drugs, increased risk of suicidal ideation is possible. Based on studies of gabapentin and pregabalin in epilepsy, the EC 50 values of pregabalin and gabapentin were estimated to be about 9.
Using studies in postherpetic neuralgia, the EC 50 values of pregabalin and gabapentin were estimated to be about 4. Based on these values, pregabalin was estimated to be about 2. One study analyzed data from phase 2 trials of gabapentin and pregabalin and created a pharmacodynamic model.
One cohort study reviewed the utility of switching patients with neuropathic pain due to peripheral neuropathy from gabapentin to pregabalin. Patients taking pregabalin also had improved pain control compared with those who remained on gabapentin.
Switching to pregabalin resulted in improved pain relief and also fewer adverse events. This was particularly true for patients who previously responded to gabapentin.
Patients who experienced adverse events with gabapentin were more likely to also experience adverse events with pregabalin.
These patients were also more likely to discontinue use of pregabalin than those who responded well to both gabapentin and pregabalin.
Additional study is needed to establish optimal dosing.