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Pregabalin
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| Systematic (IUPAC) name | |
| (S)-3-(aminomethyl)-5-methylhexanoic acid | |
| Identifiers | |
| CAS number | |
| ATC code | N03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C8H17NO2 |
| Mol. mass | 159.23 g.mol-1 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ≥90% |
| Protein binding | Nil |
| Metabolism | Negligible |
| Half life | 5–6.5 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status |
S4 (Au), POM (UK), Schedule V (U.S.) |
| Routes | Oral |
Pregabalin (INN) (pronounced /prɨˈgæbəlɨn/) is an anticonvulsant drug used for neuropathic pain, as an adjunct therapy for partial seizures. It has also been found effective for generalized anxiety disorder. It was designed as a more potent successor to gabapentin. Pregabalin is marketed by Pfizer under the trade name Lyrica.
Recent studies have shown that pregabalin is effective at treating chronic pain in disorders such as fibromyalgia[1] and spinal cord injury.[2] In June 2007, pregabalin became the first medication approved by the U.S. Food and Drug Administration specifically for the treatment of fibromyalgia.[3]
It is considered to have a low potential for abuse, and a limited dependence liability if misused, and is thus classified as a Schedule V drug in the U.S.[4]
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History
Pregabalin was initially developed by medicinal chemist Richard Bruce Silverman at Northwestern University in the United States. The drug was approved in the European Union in 2004. Pregabalin received U.S. Food and Drug Administration (FDA) approval for use in treating epilepsy, diabetic neuropathy pain and post-herpetic neuralgia pain in June 2005, and appeared on the U.S. market in fall 2005.
In June 2007 the FDA approved Lyrica as a treatment for fibromyalgia. It was the first drug to be approved for this indication and remained the only one, until duloxetine (Cymbalta) gained FDA approval for the treatment of fibromyalgia in June 2008.
Pharmacology
Pharmacodynamics
Like gabapentin, pregabalin binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system. This reduces calcium influx into the nerve terminals and decreases the release of neurotransmitters such as glutamate, noradrenaline and substance P.
Pharmacokinetics
Absorption: Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within one hour. Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 to 30% and a delay in Tmax to approximately 2.5 hours.
Distribution: Pregabalin has been shown to cross the blood brain barrier in mice, rats and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the volume of distribution of pregabalin for an orally administered dose is approximately 0.56 L/kg and is not bound to plasma proteins.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methy pregabalin is the major metabolite.
Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Renal clearance of pregabalin is 73 mL/minute.
Clinical use
Indications
Pregabalin is indicated for:
- Treatment of neuropathic pain in adults
- Adjunctive therapy in adults with partial seizures with or without secondary generalization
- Fibromyalgia pain
- Generalized anxiety disorder (approved in the European Union).[5]
Adverse effects
Adverse drug reactions associated with the use of pregabalin include:[6][7]
- Very common (>10% of patients): dizziness, drowsiness
- Common (1–10% of patients): visual disturbance (including blurred vision, diplopia), ataxia, dysarthria, tremor, lethargy, memory impairment, euphoria, constipation, dry mouth, peripheral edema, loss or decrease of libido, erectile dysfunction, weight gain
- Infrequent (0.1–1% of patients): depression, confusion, agitation, hallucinations, myoclonus, hypoaesthesia, hyperaesthesia, tachycardia, excessive salivation, sweating, flushing, rash, muscle cramp, myalgia, arthralgia, urinary incontinence, dysuria, thrombocytopenia, Kidney calculus
- Rare (<0.1% of patients): neutropenia, first degree heart block, hypotension, hypertension, pancreatitis, dysphagia, oliguria, rhabdomyolysis
Drug interactions
No pharmacokinetic interactions have been demonstrated in vivo. The manufacturer notes some potential pharmacological interactions with oxycodone, lorazepam and ethanol (alcohol). Concurrent use may increase the central nervous system effects of these medications (e.g. drowsiness, effects on concentration).[6]
References
- ^ Crofford LJ, Rowbotham MC, Mease PJ, et al. (2005). "Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial". Arthritis Rheum 52 (4): 1264–73. doi:. PMID 15818684. Free full text
- ^ Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK (2006). "Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial". Neurology 67 (10): 1792–800. doi:. PMID 17130411.
- ^ U.S. Food and Drug Administration (June 21, 2007). "FDA Approves First Drug for Treating Fibromyalgia". Press release. Retrieved on 2008-01-14.
- ^ Drug Enforcement Administration, Department of Justice. Schedules of controlled substances: placement of pregabalin into schedule V. Final rule. Fed Regist 2005;70(144):43633-5. PMID 16050051
- ^ "Pfizer's Lyrica Approved for the Treatment of Generalized Anxiety Disorder (GAD) in Europe". Press release. Retrieved on 2007-07-04.
- ^ a b Pfizer Australia Pty Ltd. Lyrica (Australian Approved Product Information). West Ryde: Pfizer; 2006.
- ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
External links
- Lyrica (pregabalin) drug label/data at Daily Med from U.S. National Library of Medicine, National Institutes of Health.
- Pfizer website for Lyrica
- U.S. prescribing information
