definition of Wikipedia
|Systematic (IUPAC) name|
|Licence data||US Daily Med:|
|Pregnancy cat.||B3 (Au), C (U.S.)|
|Legal status||S4 (Au), POM (UK), Schedule V (U.S.)|
|Routes||Oral(main), IV, Insufflation|
|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. 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 and diabetic peripheral neuropathy, fibromyalgia, et al. Sales reached a record $3.063 billion in 2010.
Recent studies have shown that pregabalin is effective at treating chronic pain in disorders such as fibromyalgia and spinal cord injury. In June 2007, pregabalin became the first medication approved by the U.S. Food and Drug Administration specifically for the treatment of fibromyalgia.
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 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 20 mg/mL with an added sweetening agent (sucrose) to mask the chemical's bitter taste. The maximum daily recommended dose for pregabalin is 600 mg. Dosages must be monitored and increases should be based on patient's tolerance.
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 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.
Usually physicians will start the patient on a low dose of pregabalin and increase it gradually, depending on the patient's evaluation. 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.
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 post-herpetic 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 (Cymbalta) 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 Lyrica drug.
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. Because of complication risk associated with certain common side-effects in patients affected by other health issues, Pregabalin should not be used without regular medical supervision and any side effect should immediately be reported.
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 (alpha2delta) subunit of the voltage-dependent calcium channel in the central nervous system. Pregabalin decreases the release of neurotransmitters including glutamate, noradrenaline, substance P and calcitonin gene-related peptide. However, unlike anxiolytic compounds (eg, benzodiazepines) which exert their therapeutic effects through binding to GABAA, GABAB, and benzodiazepine receptors, pregabalin neither binds directly to these receptors nor augments GABAA currents or affects GABA metabolism (Pfizer Inc. 2006).
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, 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. Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methyl pregabalin.
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.
Pregabalin has been assigned to pregnancy category C by the FDA. Animal studies have revealed increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity including lethality, growth retardation, and both nervous and reproduction system functional impairment. Animal studies have reported that pregabalin crosses the placenta and have shown an increased risk in male-mediated teratogenicity. There are no controlled data in human pregnancy. Pregabalin should only be given during pregnancy when there are no alternatives and benefit outweighs risk.
Pregabalin is a Schedule V drug, classified as a CNS depressant. The potential for abuse of pregabalin is less than the potential with benzodiazepines; additionally the mild euphoric effects of pregablin disappear with prolonged use.
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