Gabapentin Versus Pregabalin

Gabapentin and pregabalin are anticonvulsants utilized in a wide array of conditions. These drugs share a similar chemical structure and share many of the same uses, so let’s take a look at gabapentin versus pregabalin?

Mechanism of action: The precise mechanism of action of these drugs is not well known, but may rely on high-affinity binding to the α2δ subunit of voltage-activated calcium channels in the CNS and lead to a reduction in neurotransmitter release. They are both structurally similar to GABA – though they have no GABAergic activity – and share functional similarities to the amino acid leucine. 

Pharmacokinetics: Gabapentin has a slow oral absorption following oral administration, reaching peak plasma concentrations after about 3-4 hours. It also displays saturable absorption, which can lead to unpredictable kinetics (here’s what that means clinically). In contrast, pregabalin has a more predictable absorption following oral administration, quickly reaching peak levels within 60 minutes and exhibiting linear absorption, indicating that it likely has another route of absorption besides the facilitated transport through system L-amino acid transporters. Both drugs display fairly similar distribution characteristics. Neither are plasma protein-bound and have a fairly small apparent volume of distribution, with gabapentin estimated to be 0.8 L/kg and pregabalin at 0.5 L/kg. Both gabapentin and pregabalin have minimal metabolism in humans, with the N-methyl metabolite of each accounting for less than 1% of the dose. Neither drug is metabolized through the CYP450 enzyme systems and thus do not interact with the numerous drugs that rely on CYP enzymes.

Uses: Gabapentin is FDA approved for postherpetic neuralgia and as an adjunct therapy for partial seizures. Common off-label uses include PTSD, anxiety, bipolar disorder, resistant depression and other mood disorders, diabetic peripheral neuropathy, fibromyalgia, pruritus due to hemodialysis, hot sweats, and preemptive therapy for acute postoperative pain. Pregabalin is also approved for postherpetic neuralgia and adjunct treatment for partial seizures, as well as for pain due to diabetic peripheral neuropathy, fibromyalgia, and neuropathic pain secondary to spinal cord injury. Off-label uses include generalized anxiety disorder, social anxiety disorder, bipolar disorder, insomnia, and other chronic pain conditions. A majority of the use of these drugs is for off-label indications. One other difference between these medications is that pregabalin is classified as a schedule V drug federally, whereas gabapentin is not, however some states do have a more strict classification for gabapentin.

Dosing is a big differentiator when comparing gabapentin versus pregabalin. Pregabalin is more potent than gabapentin and thus requires much smaller doses. The dosing can vary largely between indications and may need to be increased over time due to tolerance or worsening of the patient’s condition. Both drugs are dosed multiple times daily for the immediate release versions, with gabapentin often being taken three times daily and pregabalin typically two or three times daily. Doses of 1200-3600 mg daily are common for gabapentin, while pregabalin’s total daily dose will often fall between 150 mg to 600 mg. Here’s an estimate of dosing and conversion between pregabalin and gabapentin. Gabapentin extended-release formulation, Gralise, is not interchangeable with other gabapentin products. There are approximate recommendations for dosing and conversion between immediate and extended-release formulations for both of these medications.

Tolerability: Both of these drugs are fairly well tolerated. The most common adverse reactions with gabapentin and pregabalin use include dizziness and somnolence. Gabapentin may also cause some confusion and peripheral edema, while pregabalin is sometimes associated with dry mouth, blurred vision, and peripheral edema.

Let’s compare the affordability of gabapentin versus pregabalin. Gabapentin has been available generically for almost 20 years, but pregabalin generics were just approved in 2019 so pregabalin cash price can be more expensive in some situations.

There are many similarities between gabapentin and pregabalin due to their highly similar chemical structure, and this is shown in their widespread use for many conditions. Overall, pregabalin may be the more effective treatment option (particularly at higher dosages) for postherpetic neuralgia and epilepsy, and potentially the off-label uses, as well as having a steeper dose-response curve and linear kinetics, allowing for lower doses to be used. 

This article was written by Lincoln Haiby in collaboration with Eric Christianson, PharmD, BCGP, BCPS

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Bockbrader, HN, et al. A Comparison of the Pharmacokinetics and Pharmacodynamics of Pregabalin and Gabapentin. Clinical pharmacokinetics. 2010;49(10):661-669. Accessed July 26, 2021.

Gabapentin. Micromedex DrugDex. IBM Micromedex. Accessed July 26, 2021.

Pregabalin. Micromedex DrugDex. IBM Micromedex. Accessed July 26, 2021.


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Written By Eric Christianson

August 25, 2021

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