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Pregabalin

From Pharmacopedia

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Summary
Common uses
Postherpetic neuralgia (FDA)0, Diabetic peripheral neuropathy (FDA)0, Fibromyalgia (FDA; the only gabapentinoid with FDA approval for this indication)0, Partial-onset seizures (FDA, adjunct)0, Spinal-cord-injury neuropathic pain (FDA)0, Generalized anxiety disorder (EU approval; off-label in US)0, Social anxiety disorder (EU; off-label in US)0
Pharmacy
Starting dose
Neuropathic pain: 75 mg PO BID, titrate to 150 mg BID after 1 week. Fibromyalgia: 75 mg PO BID, titrate to 150 mg BID. Anxiety (off-label): 75-150 mg/day divided BID-TID
Preparations
Capsules 25, 50, 75, 100, 150, 200, 225, 300 mg; oral solution 20 mg/mL; Lyrica CR tablets 82.5, 165, 330 mg
US FDA Max
600 mg/day (seizures); 450 mg/day (fibromyalgia and neuropathic pain)
Pharmacology
Routes
Oral
Onset
Neuropathic pain and fibromyalgia effect emerges over 1-2 weeks
Duration
BID-TID dosing for IR; once-daily for CR
Half-life
6.3 hours[1]
Bioavailability
≥90% (linear pharmacokinetics, distinguishing it favorably from gabapentin's saturable LAT-1 absorption)[1]
Pregnancy
Some signal for major congenital malformations; limited human data.[citation needed]
Legal status
Schedule V controlled substance in US (federally), distinct from gabapentin which remains federally unscheduled[1]
Purported mechanism
Binds the α2δ-1 auxiliary subunit of voltage-gated calcium channels with approximately 6-fold higher affinity than gabapentin, reducing presynaptic Ca²⁺ influx and excitatory neurotransmitter release (glutamate, substance P, norepinephrine, calcitonin gene-related peptide). Despite the gabapentinoid class name, pregabalin does not bind GABA receptors or affect GABA reuptake.0 Linear pharmacokinetics across the dosing range with non-saturable transport, in sharp contrast to gabapentin where bioavailability falls steeply with dose. Renally eliminated essentially unchanged; dose adjustment required in renal impairment[1].

References

  1. 1.0 1.1 1.2 1.3 FDA Prescribing Information, Lyrica (pregabalin), Pfizer, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021446s035,022488s013lbl.pdf