Pregabalin should be avoided with a medication guide for the patient, which contains important information about its use and risks. Warnings include the risk of angioedema (swelling of the throat, head and neck), which may be associated with life-threatening airway impairment that requires emergency treatment. Hypersensitivity reactions such as hives, dyspnea (difficulty breathing) and wheezing may occur. An increased frequency of seizures or other side effects may occur if the medication is stopped quickly. Antiepileptic medications, including pregabalin, increase the risk of suicidal thoughts or behaviors. In addition, pregabalin may cause peripheral edema (swelling of the hands or legs), so caution should be exercised when administering antidiabetic drugs with thiazolidinedione. Pregabalin may cause dizziness and drowsiness and may affect the ability to drive or use machines. The endogenous α-amino acids L-leucine and L-isoleucine, which are very similar to pregabalin and other gabapentinoids in their chemical structure, are apparent ligands of the α2δ VDCC subunit with similar affinity to gabapentinoids (e.g. IC50 = 71 nM for L-isoleucine) and are present in human cerebrospinal fluid at micromolar concentrations (e.g. 12.9 μM for L-leucine, 4.8 μM for L-isoleucine). [76] It has been theorized that they could be the endogenous ligands of the subunit and that they can competitively antagonize the effects of gabapentinoids. [76] [77] Although gabapentinoids such as pregabalin and gabapentin have nanomolar affinities for the α2δ subunit, their in vivo potencies are in the low micromolar range, and competition for binding by endogenous L-amino acids is likely responsible for this discrepancy. [75] Another aspect to consider may be the risk of polymedication.
Pregabalin and gabapentin are usually prescribed with other painkillers, mainly opioids; Less than 50-70% were reported in a recently published paper (23). This combination may increase the risk of death from overdose (30). Otherwise, the usefulness of combining pregabalin and opioids to treat one type of pain is unclear, as some researchers have described that pregabalin combined with more severe opioids and higher oral doses of opioids; In addition, pregabalin use has not been associated with improvement in mental symptoms (31). Pregabalin undergoes little or no metabolism. [6] [20] [87] Experiments with nuclear medicine techniques have shown that approximately 98% of the radioactivity recovered in urine is unchanged pregabalin. [7] The main metabolite is N-methylpregabaline. [7] Studies involving human participants have been reviewed and approved by the Colorado Multiple Review Board (protocol number: 13-2394) and locally by the Parc de Salut Mar Ethics Committee (protocol number: 2017/7331/I). Written consent to participate in this study was given by the legal guardian or next of kin of the participants.
In the United States, the Food and Drug Administration (FDA) has approved pregabalin for adjunctive therapy in adults with partial seizures, the treatment of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy, and the treatment of fibromyalgia. [110] Pregabalin has also been approved in the European Union, the United Kingdom, and Russia for the treatment of generalized anxiety disorder. [100] [46] [111] Background: Non-medical use (NMU) of prescription GABA analogues (pregabalin and gabapentin) has been reported, particularly among opioid users. However, the prevalence of gabapentinoid NMU in the general population has not yet been adequately assessed. The objective of this research is to determine the prevalence of GABA prescription NGU-like and related demographic data in five European countries with particular details in Spain. Yasir Abbasi, consultant psychiatrist and clinical director of addiction services at Mersey Care NHS Foundation Trust, said the increase in prescriptions was worrying because pregabalin could be dangerous if misused. Pfizer`s lead patent for Lyrica for seizure disorders in the UK expired in 2013. In November 2018, the UK Supreme Court ruled that Pfizer`s second patent on the pain treatment drug was invalid because there was no evidence of the conditions it covered – central and peripheral neuropathic pain.
From October 2015, GPs were forced to switch from generic pregabalin to branded until the second patent expired in July 2017. This cost the NHS £502 million. [121] Pregabalin is excreted in the urine from the kidneys, mainly unchanged. [6] [7] It has a relatively short elimination half-life with a reported value of 6.3 hours. [6] Due to its short elimination half-life, pregabalin is administered 2-3 times daily to maintain therapeutic levels. [6] The renal clearance of pregabalin is 73 ml/minute. [4] A 2019 review found that pregabalin reduces symptoms and is generally well tolerated. [41] After abrupt or rapid cessation of pregabalin, some people have reported symptoms suggestive of physical dependence. The FDA noted that the pregabalin dependence profile, as measured by a personal physical withdrawal checklist, was quantitatively lower than that of benzodiazepines. [54] Even people who stopped using pregabalin in the short term experienced withdrawal symptoms such as insomnia, headache, nausea, anxiety, diarrhea, flu-like symptoms, nervousness, severe depression, pain, cramps, hyperhidrosis, and dizziness. [60] Pharmacologically, gabapentinoids selectively bind to the α2δ subunit of voltage-gated calcium channels in neuronal tissues of the central nervous system. This, in turn, increases GABA levels and decreases other excitatory neurotransmitters (5).
This mechanism is associated with their antinociceptive, anticonvulsant, anxiolytic and sleep-modulating effects (6). Gabapentinoids, despite their reputation as safe drugs, pose significant risks. Sedation, dizziness, gait instability and intoxication are common side effects; Up to one-third of patients taking therapeutic doses experience dizziness or drowsiness (7).