|Systematic (IUPAC) name|
|Trade names||Lyrica, Nervalin|
|Licence data||US Daily Med:|
|Pregnancy cat.||B3 (Au), C (U.S.)|
|Legal status||Prescription Only (S4) (AU) POM (UK), Schedule V (U.S.)|
|Mol. mass||159.23 g.mol-1|
|(what is this?)|
Pregabalin (INN) // is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is (as of 2007) approved for this use in the European Union and Russia. It was designed as a more potent successor to gabapentin. Pregabalin is marketed by Pfizer under the trade name Lyrica. Pfizer described in an SEC filing that the drug could be used to treat epilepsy, post-herpetic neuralgia, diabetic peripheral neuropathy and fibromyalgia. Sales reached a record $3.063 billion in 2010. In Bangladesh Pregabalin is sold under the brand of Nervalin by Beximco Pharma It is effective at treating some causes of chronic pain such as fibromyalgia but not others. It is considered to have a low potential for abuse, and a limited dependence liability if misused, but is classified as a Schedule V drug in the U.S.
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 approved by the U.S. Food and Drug Administration (FDA).
Pregabalin appears to be as effective as gabapentin for neuropathic pain; however costs more. It is effective for some people with postherpetic neuralgia and fibromyalgia. There is not enough data to state that it should be used in all neuropathic pain. It has not been found to be effective for HIV-associated peripheral neuropathy. It has not been shown to be useful for cancer related neuropathic pain. There is no evidence for use in acute pain. Pregabalin is also used for the treatment perioperative pain. There is no evidence for its use in the prevention of migraines and gabapentin has been found not to be useful.
- Very common (>10% of patients): dizziness, drowsiness.
- Common (1–10% of patients): blurred vision, diplopia, increased appetite and subsequent weight gain, euphoria, confusion, vivid dreams, changes in libido (increase or decrease), irritability, ataxia, attention changes, abnormal coordination, memory impairment, tremors, dysarthria, parasthesia, vertigo, dry mouth and constipation, vomiting and flatulence, erectile dysfunction, fatigue, peripheral oedema, drunkenness, abnormal walking, asthenia, nasopharyngitis, increased creatine kinase level.
- Infrequent (0.1–1% of patients): depression, lethargy, agitation, anorgasmia, hallucinations, myoclonus, hypoaesthesia, hyperaesthesia, tachycardia, excessive salivation, hypoglycaemia, 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, suicidal thoughts or behavior.
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 difficulty sleeping, nausea, anxiety, diarrhoea, flu or flu-like symptoms, headache, increased sweating, convulsions, pain, dizziness, nervousness, and depression. Pregabalin should be reduced gradually when finishing treatment.
Several renal failure patients developed myoclonus while receiving pregabalin, apparently 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.
Like gabapentin, pregabalin binds to the α2δ (alpha-2-delta) subunit of the voltage-dependent calcium channel in the central nervous system. Pregabalin decreases the release of neurotransmitters including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. However, unlike anxiolytic compounds (e.g., benzodiazepines) which exert their therapeutic effects through binding to GABAA, pregabalin neither binds directly to these receptors nor augments GABAA currents or affects GABA metabolism (Pfizer Inc., 2006). The half-life for pregabalin is 6.3 hours.
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 (time to reach Cmax) to approximately 2.5 hours. Administration with food, however, has no clinically significant effect on the extent of absorption.
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. In experiments using nuclear medicine techniques, it was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methylpregabalin.
Pregabalin was invented 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. FDA approval for use in treating epilepsy, diabetic neuropathic pain, and postherpetic neuralgia in December 2004, 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 gained FDA approval for the treatment of fibromyalgia in June 2008.
The patent for Lyrica currently expires in March 2018 (Silverman, R. B.; Andruszkiewicz, R. U. S. Pat. 6,197,819 B1 (March 6, 2001) “Gamma Amino Butyric Acid Analogs and Optical Isomers.”). This is the earliest possible date that a generic version of Lyrica could become available. However, there are other circumstances that could come up to extend the exclusivity period of Lyrica beyond 2018. These circumstances could include things such as lawsuits or other patents for specific Lyrica uses. Once Lyrica goes off patent, there may be several companies that manufacture a generic pregabalin drug.
Society and culture
In the United States, the Food and Drug Administration (FDA) has approved pregabalin for adjunctive therapy for adults with partial onset seizures, management of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy, and the treatment of fibromyalgia. Pregabalin has also been approved in the European Union and Russia (but not in US) for treatment of generalized anxiety disorder.
Pregabalin is a Schedule V drug, and its classified as a CNS depressant. The potential for abuse of pregabalin is less than the potential with benzodiazepines; additionally the euphoric effects of pregabalin disappear with prolonged use.
Lyrica is one of four drugs which Pharmacia & Upjohn, 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 approved by the U.S. Food and Drug Administration (FDA).
Anaesthesiology research fraud
Pregabalin is one of two Pfizer drugs that had become a mainstay in multimodal analgesia but the key research conducted by Scott Reuben between 1996 and 2009 which paved the way for these drugs has been found to be fraudulent. According to one source, this massive case of academic misconduct has left multimodal analgesia in a shambles. Many aspects of postoperative pain management concerning many of the drugs used, including pregabalin, will need to be reconsidered.
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- U.S. prescribing information
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