What is the generic name of Lyrica?

Lyrica Original Name

The generic name of Lyrica is pregabalin.

Lyrica is the brand name under which pregabalin was originally marketed by Pfizer. Pregabalin is a gamma-aminobutyric acid (GABA) analog that was developed as a second-generation α2δ ligand, structurally related to the earlier antiepileptic drug gabapentin (Neurontin). 1, 2

Chemical and Pharmacological Identity

• Chemical nomenclature: Pregabalin is chemically designated as S-(+)-3-isobutylGABA or (S)-3-(aminomethyl)-5-methylhexanoic acid. 3, 4
• Structural relationship: Pregabalin shares structural similarity with gabapentin but represents a refined molecule with improved pharmacokinetic properties. 2, 5

FDA Approval and Indications

• Initial FDA approval: Pregabalin received FDA approval in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia, making it the first drug approved in both the United States and Europe for these specific conditions. 3
• Expanded indications: In June 2005, pregabalin was approved as adjunctive treatment in adults with partial-onset seizures. 3
• Additional uses: Pregabalin has also been approved in Europe for the treatment of generalized anxiety disorder and has demonstrated efficacy in social anxiety disorder. 2, 3

Mechanism of Action

• Primary binding site: Pregabalin binds with high affinity to the alpha2-delta (α2δ) protein, an auxiliary subunit of voltage-gated calcium channels, which is the presumed site of action for its therapeutic effects. 1
• Neurotransmitter modulation: By binding to α2δ subunits, pregabalin subtly reduces the synaptic release of several neurotransmitters, including glutamate and GABA, thereby reducing neuronal excitability. 1, 4
• Vesicle release reduction: Pregabalin reduces the emptying of neurotransmitter vesicles from presynaptic sites in both GABAergic and glutamatergic neurons, affecting both calcium-dependent and calcium-independent release mechanisms. 4

Pharmacokinetic Profile

• Oral bioavailability: Pregabalin exhibits approximately 90% oral bioavailability, with peak plasma levels occurring approximately 1 hour after oral administration. 2
• Food effect: Food does not significantly affect the extent of absorption based on area-under-the-curve (AUC) data. 2
• Protein binding and metabolism: Pregabalin is not protein-bound and exhibits negligible hepatic metabolism, with approximately 95% of the oral dose appearing unchanged in the urine. 2
• Half-life: The plasma half-life is approximately 6 hours and is not dose-dependent. 2

Clinical Efficacy

• Diabetic peripheral neuropathy: In four clinical trials involving 1,068 patients, pregabalin 300–600 mg/day produced significantly greater improvement in mean pain scores compared to placebo (P ≤ 0.01). 3
• Postherpetic neuralgia: Patients receiving pregabalin 450–600 mg/day experienced significantly greater relief of pain and pain-related sleep interference than placebo recipients (P ≤ 0.002). 3
• Partial-onset seizures: Patients with refractory partial-onset seizures receiving pregabalin 150–600 mg/day concomitantly with other antiepileptic drugs had significantly fewer seizures than placebo recipients (P ≤ 0.001). 3
• Anxiety disorders: In three studies evaluating pregabalin 200–600 mg/day for generalized anxiety disorder or social anxiety disorder, patients had significantly greater reduction in Hamilton Anxiety Scale scores than placebo recipients (P ≤ 0.01). 3

Safety and Tolerability

• Common adverse effects: The most frequently reported adverse effects involve the central nervous system, including somnolence (≤50%), dizziness (≤49%), and headache (≤29%). 3
• Discontinuation rates: Adverse effects resulted in study withdrawal in ≤32% of patients across reviewed clinical trials. 3
• Overall safety profile: Pregabalin is considered a safe and well-tolerated treatment for neuropathic pain, epilepsy, and anxiety disorders. 2

Combination Therapy Considerations

• Synergistic potential: Although pregabalin and gabapentin share similar mechanisms of action, they have been used in combination in clinical and research settings, demonstrating a synergistic effect in pain control without clinically significant pharmacokinetic interactions. 5
• Dose optimization: Combined use may allow reduction of individual agent doses, potentially minimizing side effects while enhancing therapeutic response compared to monotherapy. 5
• Caution required: Pharmacokinetics, drug interactions, and adverse reactions must be carefully considered before proposing combination therapy as first-line treatment in refractory pain situations. 5