Pregabalin

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Dosage-adjustment-in-renal-failure 6 Pharmacokinetics 7 Adverse-effects 8 Drug-interactions 9 Mechanism-of-action 10 Notes 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

Introduction

• Tradename: Lyrica ( FDA-approved in 2004) DEA-controlled substance: class 5

Indications

• diabetic neuropathy [6]
• post-herpetic neuralgia [7]
• fibromyalgia [3,9,11] FDA-approved 06/2007
• spinal cord injury
• partial seizures [4]
• anxiety [9] {investigational}

Contraindications

• combined use gabapentin & pregabalin not indicated [10] combination not studied in controlled trials gabapentin & pregabalin synergistic in an animal model [10]

Dosage

• (adults, not recommended for children)
• start 50 mg PO TID
• increase to PO 100 mg TID, after 1 week if tolerated
• increase to PO 200 mg TID, after 2 weeks if tolerated
• avoid abrupt discontinuation, taper over 1 week [5]
• maximum dose = 600 mg/day

Dosage-adjustment-in-renal-failure

• reduce dose for creatinine clearance < 60 mL/min
• give supplemental dose after hemodialysis

Pharmacokinetics

• bioavailabiility is 90%, not affecte by food
• time to peak concentration after oral dose is 1 hour
• 98% unchanged by the kidneys
• not protein bound
• t1/2 is about 6 hours

Adverse-effects

• most adverse effects are mild to moderate [3,6] & dose- dependent
• dizziness (24-34%)
• somnolence (22-41%)
• dry mouth (5%)
• peripheral edema, weight gain (11%)
• blurred vision, amblyopia
• difficulty with concentration or attention, amnesia, confusion (7%)
• 600 mg daily adversely affects cognition [12]
• euphoria, some patients feel 'high' (4%) [4,6]
• accidental injury (4%)
• constipation (7%)
• may be withdrawal is stopped abruptly

• headache, nausea [4]

Drug-interactions

• no cyt P450 interactions

Mechanism-of-action

• GABA analog
• more potent than gabapentin
• binds to alpha-2 delta subunit of voltage-gated Ca+2 channel
• does NOT bind GABA receptors
• may improve both pain & sleep in fibromyalgia [11]

Notes

• Manufacturer: Pfizer

More General Terms

• analgesic (antalgic)

Additional Terms

• gabapentin (Neurontin, Gralise)
• voltage-dependent Ca+2 channel alpha-2/delta

Internet Database

PubChem: 125889

References

1. Prescriber's Letter 11(10): 2004
2. Prescriber's Letter 12(2): 2005 New Drugs Approved by the FDA in 2004 Detail-Document#: [1] (subscription needed) [2]
3. Internal Medicine News, June 2005, pg 12
4. Prescriber's Letter 12(8): 2005 New Drug: Lyrica (Pregabalin) Detail-Document#: [3] (subscription needed) [4]
5. Monthly Prescribing Reference [5]
6. Lesser H et al, Pregabalin relieves symptoms of painful diabetic neuropathy. A randomized controlled trial. Neurology 2004, 63:2104 PMID: [6]
7. Dworkin RH et al, Pregabalin for the treatment of postherpetic neuralgia. A randomized, placebo-controlled trial. Neurology 2003, 60:1274 PMID: [7]
8. Beydoun A et al, Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology 2005, 64:475 PMID: [8]
9. Prescriber's Letter 14(5): 2007 Lyrica (Pregabalin) Update Detail-Document#: [9] (subscription needed) [10]
10. Prescriber's Letter 14(10): 2007 Combined use of Gabapentin (Neurontin) and Pregablin (Lyrica) Detail-Document#: [11] (subscription needed) [12]
11. Mease PJ et al, A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol 2008, 35:502 PMID: [13]
12. Salinsky M et al Cognitive effects of pregabalin in healthy volunteers: A double-blind, placebo-controlled trial. Neurology 2010 Mar 2; 74:755 PMID: [14]

pregabalin (Lyrica,'son of gabapentin')