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Lyrica is one of four drugs which a subsidiary of Pfizer in 2009 pleaded guilty to misbranding "with the intent to defraud or mislead". Pfizer agreed to pay $2.3 billion (£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer illegally promoted the drugs and caused false claims to be submitted to government healthcare programs for uses that were not medically accepted.<ref>[http://news.bbc.co.uk/2/hi/business/8234533.stm Pfizer agrees record fraud fine]</ref>
Lyrica is one of four drugs which a subsidiary of Pfizer in 2009 pleaded guilty to misbranding "with the intent to defraud or mislead". Pfizer agreed to pay $2.3 billion (£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer illegally promoted the drugs and caused false claims to be submitted to government healthcare programs for uses that were not medically accepted.<ref>[http://news.bbc.co.uk/2/hi/business/8234533.stm Pfizer agrees record fraud fine]</ref>

Pregabalin is available in 25, 50, 75, 100, 150, 200, 225, and 300 mg capsules, and recently a strawberry flavoured oral solution has been developed, containing 20mg/mL with an added sweetening agent (sucrose) to mask the chemical's bitter taste.<ref>http://www.rxlist.com/lyrica-drug.htm</ref><ref>http://priorartdatabase.com/IPCOM/000187748</ref>


==History==
==History==

Revision as of 23:52, 30 October 2010

Pregabalin
Clinical data
License data
Pregnancy
category
Routes of
administration		Oral(main), IV, Insufflation
ATC code
Legal status
Legal status
  • S4 (Au), POM (UK), Schedule V (U.S.)
Pharmacokinetic data
Bioavailability≥90%
Protein bindingNil
MetabolismNegligible
Elimination half-life5–6.5 hours
ExcretionRenal
Identifiers
  • (S)-3-(aminomethyl)-5-methylhexanoic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.119.513 Edit this at Wikidata
Chemical and physical data
FormulaC8H17NO2
Molar mass159.23 g.mol-1 g·mol−1
3D model (JSmol)
  • NC[C@H](CC(C)C)CC(=O)O
  (verify)

Pregabalin (INN) (Template:Pron-en) is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults.[1] It has also been found effective for generalized anxiety disorder and is (as of 2007) approved for this use in the European Union.[1] 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[2] and spinal cord injury.[3] In June 2007, pregabalin became the first medication approved by the U.S. Food and Drug Administration specifically for the treatment of fibromyalgia.[4]

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.[5]

Lyrica is one of four drugs which a subsidiary of Pfizer in 2009 pleaded guilty to misbranding "with the intent to defraud or mislead". Pfizer agreed to pay $2.3 billion (£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer illegally promoted the drugs and caused false claims to be submitted to government healthcare programs for uses that were not medically accepted.[6]

Pregabalin is available in 25, 50, 75, 100, 150, 200, 225, and 300 mg capsules, and recently a strawberry flavoured oral solution has been developed, containing 20mg/mL with an added sweetening agent (sucrose) to mask the chemical's bitter taste.[7][8]

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 neuropathic pain, and post-herpetic neuralgia in December 2004, and appeared on the U.S. market in fall 2005.[9]

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.[citation needed]

Indications

Pregabalin is indicated for:

Its therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally unlike benzodiazepines it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.[12][13]

It has not been found to be effective for HIV-associated peripheral neuropathy.[14]

Adverse effects

Adverse drug reactions associated with the use of pregabalin include:[15][16]

Pregabalin may also cause withdrawal effects after long-term use if discontinued abruptly. When prescribed for seizures, quitting "cold turkey" can increase the strength of the seizures and possibly cause the seizures to reoccur. Withdrawal symptoms include restlessness, insomnia, and anxiety. Pregabalin should be reduced gradually when finishing treatment.[citation needed]

Overdosage

Several renal failure patients developed myoclonus while receiving pregabalin, appparently as a result of gradual accumulation of the drug. Acute overdosage may be manifested by somnolence, tachycardia and hypertonicity. Plasma, serum or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients.[18][19][20]

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. Pregabalin also decreases the release of neurotransmitters such as glutamate, noradrenaline, and substance P (Australian Medicines Handbook). Pregabalin increases neuronal GABA levels by producing a dose-dependent increase in glutamic acid decarboxylase activity.[1] Glutamic acid decarboxylase (GAD) is the enzyme that converts the excitatory neurotransmitter glutamate into the inhibitory GABA in a single step. For this reason, pregabalin greatly potentiates benzodiazepines, barbiturates & other depressants.

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. Administration with food, though, has no clinically significant effect on the extent of absorption.[21]

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.[21]

Metabolism: Pregabalin undergoes negligible metabolism in humans.[22] Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The N-methyl pregabalin is the major metabolite.[21]

Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.[21] Renal clearance of pregabalin is 73 mL/minute.[verification needed]

Drug interactions

No pharmacokinetic interactions have been demonstrated in vivo. The manufacturer notes some potential pharmacological interactions with opioids (pregabalin is synergistic with opioids in lower doses), benzodiazepines, barbiturates, ethanol (alcohol), and other drugs that depress the central nervous system.[15]

Misuse

Pregabalin is a Schedule V drug, classified as a CNS depressant. The potential for abuse of pregabalin is significantly less than the potential with benzodiazepines.[23]

References

  1. ^ a b Benkert, O., Hippius, H. et al.: Kompendium der Psychiatrischen Pharmakotherapie, 6. Auflage, Springer Medizin Verlag, Heidelberg, 2007. (german) ISBN 9783540344018
  2. ^ 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:10.1002/art.20983. PMID 15818684. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) Free full text
  3. ^ 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:10.1212/01.wnl.0000244422.45278.ff. PMID 17130411.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ "FDA Approves First Drug for Treating Fibromyalgia" (Press release). U.S. Food and Drug Administration. June 21, 2007. Retrieved 2010-10-30.
  5. ^ 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
  6. ^ Pfizer agrees record fraud fine
  7. ^ http://www.rxlist.com/lyrica-drug.htm
  8. ^ http://priorartdatabase.com/IPCOM/000187748
  9. ^ Dworkin RH, Kirkpatrick P (2005). "Pregabalin" (PDF on free subscription). Nature Reviews Drug Discovery. 4 (6): 455–6. doi:10.1038/nrd1756. PMID 15959952. {{cite journal}}: Unknown parameter |month= ignored (help)
  10. ^ "Pfizer's Lyrica Approved for the Treatment of Generalized Anxiety Disorder (GAD) in Europe" (Press release). Retrieved 2007-07-04.
  11. ^ Bandelow, B.; Wedekind, D.; Leon, T. (2007). "Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention". Expert Rev Neurother. 7 (7): 769–81. doi:10.1586/14737175.7.7.769. PMID 17610384. {{cite journal}}: Unknown parameter |month= ignored (help)
  12. ^ Bandelow, B.; Wedekind, D.; Leon, T. (2007). "Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention". Expert Rev Neurother. 7 (7): 769–81. doi:10.1586/14737175.7.7.769. PMID 17610384. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Owen, RT. (2007). "Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety". Drugs Today (Barc). 43 (9): 601–10. doi:10.1358/dot.2007.43.9.1133188. PMID 17940637. {{cite journal}}: Unknown parameter |month= ignored (help)
  14. ^ Simpson DM, Schifitto G, Clifford DB; et al. (2010). "Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial". Neurology. 74 (5): 413–20. doi:10.1212/WNL.0b013e3181ccc6ef. PMC 2816006. PMID 20124207. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ a b Pfizer Australia Pty Ltd. Lyrica (Australian Approved Product Information). West Ryde: Pfizer; 2006.
  16. ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  17. ^ Medication Guide
  18. ^ Murphy NG, Mosher L. Severe myoclonus from pregabalin (Lyrica) due to chronic renal insufficiency. Clin. Tox. 46: 594, 2008.
  19. ^ Yoo L, Matalon D, Hoffman RS, Goldfarb DS. Treatment of pregabalin toxicity by hemodialysis in a patient with kidney failure. Am. J. Kidney Dis. 54: 1127-1130, 2009.
  20. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1296-1297.
  21. ^ a b c d "Summary of product characteristics" (PDF). European Medicines Agency. 19 August 2009. Retrieved 8 September 2009.
  22. ^ Susan L. McElroy,. Antiepileptic Drugs to Treat Psychiatric Disorders. p. 370.{{cite book}}: CS1 maint: extra punctuation (link)}
  23. ^ Chalabianloo, F (2009). "Pregabalin and its potential for abuse". Journal of the Norwegian Medical Association. 129 (3): 186–187. doi:10.4045/tidsskr.08.0047. PMID 19180163. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
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