Pregabalin

drugbox
IUPAC_name = ("S")-3-(aminomethyl)-5-methylhexanoic acid


width = 152px
CAS_number = 148553-50-8
ATC_prefix = N03
ATC_suffix = AX16
PubChem = 5486971
DrugBank = APRD01198
C=8|H=17|N=1|O=2
molecular_weight = 159.23 g.mol^-1
smiles = NC [C@H] (CC(C)C)CC(=O)O
bioavailability = ≥90%
protein_bound = Nil
metabolism = Negligible
elimination_half-life = 5–6.5 hours
excretion = Renal
pregnancy_category = B3 (Au), C (U.S.)
legal_status = S4 (Au), POM (UK), Schedule V (U.S.)
routes_of_administration = Oral

Pregabalin (INN) (pronEng|prɨˈgæbəlɨn) is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adultsBenkert, O., Hippius, H. et al.: Kompendium der Psychiatrischen Pharmakotherapie, 6. Auflage, Springer Medizin Verlag, Heidelberg, 2007. (german) ISBN 9783540344018] . It has also been found effective for generalized anxiety disorder and is (as of 2007) approved for this use in EuropeBenkert, O., Hippius, H. et al.: Kompendium der Psychiatrischen Pharmakotherapie, 6. Auflage, Springer Medizin Verlag, Heidelberg, 2007. (german) ISBN 9783540344018] . 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 [cite journal |author=Crofford LJ, Rowbotham MC, Mease PJ, "et al." |title=Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial |journal=Arthritis Rheum |volume=52 |issue=4 |pages=1264–73 |year=2005 |pmid=15818684 |doi=10.1002/art.20983 [http://www3.interscience.wiley.com/cgi-bin/fulltext/110438360/HTMLSTART Free full text] ] and spinal cord injury. [cite journal |author=Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK |title=Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial |journal=Neurology |volume=67 |issue=10 |pages=1792–800 |year=2006 |pmid=17130411 |doi=10.1212/01.wnl.0000244422.45278.ff] In June 2007, pregabalin became the first medication approved by the U.S. Food and Drug Administration specifically for the treatment of fibromyalgia.cite press release | url = http://www.fda.gov/bbs/topics/NEWS/2007/NEW01656.html | title = FDA Approves First Drug for Treating Fibromyalgia | publisher = U.S. Food and Drug Administration | date = June 21 2007 | accessdate = 2008-01-14]

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.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]

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.Fact|date=August 2008

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.Fact|date=August 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 (Australian Medicines Handbook).

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.Fact|date=August 2008
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.Fact|date=August 2008
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.Fact|date=August 2008
Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Renal clearance of pregabalin is 73 mL/minute.Fact|date=August 2008

Indications/Uses

Nerve Pain after Herpes, Diabetic Complication causing Injury to some Body Nerves, Additional Medication to Treat Partial Seizures, Disorder characterized by Stiff, Tender & Painful MusclesLyrica Oral may also be used to treat:Neuropathic PainThis medication is used to treat pain caused by nerve damage due to diabetes and shingles (herpes zoster) infection. It is also used to treat pain in people with fibromyalgia.It is also used with other medications to treat certain types of seizures (partial onset seizures).

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).cite press release |url=http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/03-27-2006/0004327379 |title=Pfizer's Lyrica Approved for the Treatment of Generalized Anxiety Disorder (GAD) in Europe |accessdate=2007-07-04 |format= |work=]

ide effects

Common side effects: (Especially in Patients with Kidney Disease) Hallucinations/Vivid Dreams/Weakness/Fever/ Low Blood Pressure/Dehydration can occur. Close Observation Highly Recommended. *Severe Drowsiness *Severe,Uncoordinated *Severe, Fluid Retention in the Legs, Feet, Arms or Hands *Severe,Dizzy *Less Severe,

Infrequent side effects:Disease of the Nerves *Severe,Blurred Vision *Severe,Sensation of Spinning or Whirling *Severe,Weight Gain *Severe,Infection *Severe,Dry Mouth *Less Severe,Incomplete or Infrequent Bowel Movements *Less Severe,Pain *Less Severe,Head Pain *Less Severe,Injury *Less Severe,Feeling Weak *Less Severe,

Rare side effects:

Double Vision *Severe,
Pink eye *Severe,Middle Ear Infection *Severe,Ringing in the Ears *Severe,Hemorrhage of Blood Under the Skin *Severe,Inflammation of Lining of the Stomach and Intestines *Severe,Hives *Severe,Small Skin Blister *Severe,Muscle Spasm *Severe,Voluntary Movement Difficulty *Severe,Rash *Severe,Visible Water Retention *Severe,Puffy Face from Water Retention *Severe,Difficulty Speaking *Severe,Wheezing *Severe,Trouble Breathing *Severe,Chest Pain *Severe,Problems with Bladder Control *Severe,Giant Hives *Severe,Reaction due to an Allergy *Severe,Numbness and Tingling *Severe,Low Blood Sugar *Severe,Decreased Blood Platelets *Severe,Confused *Severe,Having Thoughts of Suicide *Severe,Extreme Sense of Well Being *Less Severe,Problems with Eyesight *Less Severe,Involuntary Eye Movement *Less Severe,Sinus Irritation and Congestion *Less Severe,Bronchitis *Less Severe,Inability to have an Erection *Less Severe,Itching *Less Severe,Fingernail and/or Toenail Disease *Less Severe,Joint Pain *Less Severe,Backache *Less Severe,Abnormal Increase in Muscle Tone *Less Severe,Muscle Weakness *Less Severe,Muscle Pain *Less Severe,Leg Cramps *Less Severe,Cannot Focus Thoughts *Less Severe,Loss of Memory *Less Severe,Stupor *Less Severe,Fever *Less Severe,Low Energy *Less Severe,Involuntary Quivering *Less Severe,Twitching *Less Severe,Abnormal Manner of Walking *Less Severe,Numbness *Less Severe,Increased Hunger *Less Severe,Feel Like Throwing Up *Less Severe,Throwing Up *Less Severe,Gas *Less Severe,Diarrhea *Less Severe,Frequent Urination *Less Severe,Stomach Cramps *Less Severe,Swelling of the Abdomen *Less Severe,Nervous *Less Severe,Anxious *Less Severe,Loss of One's Own Sense of Reality or Identity *Less Severe,Sexual Problems *Less Severe,Altered Interest in Having Sexual Intercourse *Less Severe,

Adverse effects

Adverse drug reactions associated with the use of pregabalin include: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]
*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).

References

External links

* http://www.webmd.com/drugs/drug-93965-Lyrica+Oral.aspx?drugid=93965&drugname=Lyrica+Oral
* [http://www.lyrica.com Pfizer website for Lyrica]
* [http://www.pfizer.com/pfizer/download/uspi_lyrica.pdf U.S. prescribing information]
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