Lyrica - Drug Monograph

Introduction

Lyrica (pregabalin) is a prescription medication classified as a gamma-aminobutyric acid (GABA) analog. Initially approved by the FDA in 2004, it has become a widely used agent for various neurological and pain conditions. Pregabalin is a Schedule V controlled substance due to its potential for abuse and dependence.

Mechanism of Action

Pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system. This binding reduces calcium influx at nerve terminals, which subsequently decreases the release of several excitatory neurotransmitters, including glutamate, norepinephrine, and substance P. The result is a reduction in neuronal excitability and synaptic transmission, which underlies its anticonvulsant, analgesic, and anxiolytic effects. Unlike traditional GABAergic drugs, pregabalin does not directly act on GABA receptors.

Indications

FDA-approved indications:

• Neuropathic pain associated with diabetic peripheral neuropathy
• Postherpetic neuralgia
• Adjunctive therapy for adults with partial-onset seizures
• Fibromyalgia
• Neuropathic pain associated with spinal cord injury
• Generalized anxiety disorder (approved outside the US in some countries)

Dosage and Administration

• Initiate at 150 mg/day divided into 2-3 doses
• May increase to 300 mg/day within 1 week based on efficacy and tolerability
• Maximum dose: 600 mg/day (300 mg BID)

• Renal impairment: Dose reduction required based on creatinine clearance
• Elderly: Consider reduced doses due to decreased renal function
• Hepatic impairment: No dose adjustment needed
• Pediatrics: Safety and effectiveness not established under age 18

• Oral administration with or without food
• Should be tapered gradually when discontinuing (over at least 1 week)

Pharmacokinetics

• Absorption: Rapid and extensive (>90% bioavailability), not affected by food
• Distribution: Volume of distribution approximately 0.5 L/kg, minimal protein binding
• Metabolism: Negligible hepatic metabolism; not a substrate, inhibitor, or inducer of CYP450 enzymes
• Elimination: Primarily excreted unchanged in urine (90%), elimination half-life of 6 hours
• Steady-state: Achieved within 24-48 hours with repeated dosing

Contraindications

• Known hypersensitivity to pregabalin or any product components
• Concomitant use with thiazolidinedione antidiabetic agents (increased risk of peripheral edema and weight gain)

Warnings and Precautions

• Potential for abuse, misuse, and dependence

• Angioedema: Reports of life-threatening angioedema
• Hypersensitivity reactions: Including skin redness, blisters, hives, rash, and dyspnea
• Driving impairment: Dizziness, somnolence, blurred vision, and concentration difficulties
• Suicidal behavior and ideation: Increased risk in patients taking antiepileptic drugs
• Peripheral edema: May occur, particularly in elderly patients and those with cardiac conditions
• Weight gain: Can be significant and may increase cardiovascular risk
• Tumorigenic potential: Pancreatic acinar cell tumors observed in rat studies
• Withdrawal symptoms: Abrupt discontinuation may cause insomnia, nausea, headache, and anxiety

Drug Interactions

• CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids, and other sedating agents
• Thiazolidinediones: Increased risk of peripheral edema and weight gain
• Angiotensin-converting enzyme inhibitors: Potential increased risk of angioedema

Adverse Effects

• Dizziness (29%)
• Somnolence (22%)
• Dry mouth (11%)
• Peripheral edema (11%)
• Blurred vision (8%)
• Weight gain (8%)
• Difficulty with concentration/attention (8%)

• Angioedema
• Hypersensitivity reactions
• Suicidal ideation and behavior
• Respiratory depression (particularly with concomitant opioid use)
• Rhabdomyolysis
• Severe dizziness and syncope

Monitoring Parameters

• Efficacy: Pain scales, seizure frequency, anxiety assessment tools
• Safety: Renal function (serum creatinine and calculation of CrCl at baseline and periodically)
• Weight: Regular monitoring, particularly in patients with diabetes or cardiac conditions
• Mental status: Assessment for depression, suicidal thoughts, or unusual behavior changes
• Edema: Monitoring for peripheral edema, particularly in elderly patients
• Ophthalmologic: Visual acuity testing recommended for patients reporting visual changes
• Abuse/misuse potential: Regular assessment, particularly in patients with substance use history

Patient Education

• Take medication exactly as prescribed; do not suddenly stop without medical supervision
• Be aware of potential dizziness, drowsiness, and blurred vision; avoid driving or operating machinery until effects are known
• Report any swelling, breathing difficulties, or skin reactions immediately
• Monitor weight regularly and report significant changes
• Avoid alcohol and other CNS depressants while taking pregabalin
• Inform all healthcare providers about pregabalin use, particularly before surgery
• Use caution when rising from sitting or lying position due to dizziness risk
• Store medication securely to prevent misuse by others
• Report any mood changes, depression, or suicidal thoughts promptly

References

1. FDA Prescribing Information: Lyrica (pregabalin). Revised January 2023. 2. Bockbrader HN, et al. Clinical pharmacokinetics of pregabalin in healthy volunteers. J Clin Pharmacol. 2010;50(8):941-950. 3. Tölle T, et al. Pregabalin for the treatment of neuropathic pain: a comprehensive review. Expert Opin Pharmacother. 2016;17(5):663-677. 4. Moore RA, et al. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;(3):CD007076. 5. Zaccara G, et al. Safety and efficacy of pregabalin in epilepsy: a systematic review. Seizure. 2018;57:36-43. 6. Häuser W, et al. Efficacy, tolerability and safety of pregabalin in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials. Rheumatology. 2018;57(12):2145-2153.