Estudos

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GABAPENTINA

Combate central e periférico com elevada seletividade pelo receptor específico

DESCRIÇÃO

A Gabapentina é um análogo do ácido γ-aminobutírico (GABA), usado como adjuvante na terapia anticonvulsivante, neuralgia e afecções psiquiátricas.

MECANISMO DE AÇÃO As subunidades α2δ, dos canais de cálcio dependentes de voltagem, localizadas no encéfalo e tronco cerebral desempenham um papel importante em condições de inflamação e dor neuropática, aumentando a excitabilidade neuronal através do influxo intensificado de cálcio. A ligação da Gabapentina à subunidade proteica α2δ leva à diminuição do influxo de cálcio nos neurônios e, consequentemente, à inibição da liberação de neurotransmissores excitatórios (glutamato) importantes na produção da dor.

INDICAÇÕES

Adjuvante anticonvulsivante; Neuralgias e dores; Enxaqueca (profilaxia); Afecções psiquiátricas; Epilepsias.

DOSE USUAL Recomendação oral de 300 a 1800mg de Gabapentina ao dia para adultos; de 10 a 15mg/kg/d de Gabapentina ao dia para crianças de 3 a 12 anos.

SUGESTÕES DE FÓRMULAS

PRINCIPAIS REFERÊNCIAS D'AMICO, D. Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials. Neurol Sci. doi: 10.1007/s10072-010-0268-7. 2010. Disponível em:< http://www.ncbi.nlm.nih.gov/pubmed/23218533>. Acesso em: 14/09/2016, às 17:27. MEDAWAR, C. V.; MATHEUS, M. E. Antidepressivos Tricíclicos e Gabapentinóides: uma análise do perfil farmacológico no tratamento da dor neuropática. Rev. Bras. Farm. v. 93, n. 3, p. 290-297. 2012. Disponível em:< http://www.rbfarma.org.br/files/rbf-2012-93-3-4.pdf>. Acesso em: 15/09/2016, às 09:36.

Gabapentina........................................................... 5% Baclofeno................................................................. 5% Cetoprofeno........................................................... 10% Lidocaína................................................................. 5% Gel transdérmico qsp............................................. 1mL

Modo de uso: aplicar 1mL, 3 a 4 vezes ao dia na região dolorida e/ou no local de origem da dor. Na

fibromialgia a dose deve ser dividida entre os “pontos gatilho” da dor.

Indicação: dor neuropática.

Gabapentina..................................................... 300mg

Modo de uso: 1 dose, 3 vezes ao dia. Indicação: dor crônica.

GABAPENTINA

ESTUDOS CLÍNICOS

Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. OBJECTIVES: Effective postoperative pain management is crucial in the care of surgical patients. Opioids, which are commonly used in managing postoperative pain, have a potential for tolerance and addiction, along with sedating side effects. Gabapentin's use as a multimodal analgesic regimen to treat neuropathic pain has been documented as having favorable side effects. This meta-analysis examined the use of preoperative gabapentin and its impact on postoperative opioid consumption. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify randomized control trials that evaluated preoperative gabapentin on postoperative opioid consumption. The outcomes of interest were cumulative opioid consumption following the surgery and the incidence of vomiting, somnolence, and nausea. RESULTS: A total of 1,793 patients involved in 17 randomized control trials formed the final analysis for this study. Postoperative opioid consumption was reduced when using gabapentin within the initial 24 hours following surgery (standard mean difference -1.35, 95% confidence interval [CI]: -1.96 to -0.73; P<0.001). There was a significant reduction in morphine, fentanyl, and tramadol consumption (P<0.05). While a significant increase in postoperative somnolence incidence was observed (relative risk 1.30, 95% CI: 1.10-1.54, P<0.05), there were no significant effects on postoperative vomiting and nausea. CONCLUSION: The administration of preoperative gabapentin reduced the consumption of opioids during the initial 24 hours following surgery. The reduction in postoperative opioids with preoperative gabapentin increased postoperative somnolence, but no significant differences were observed in nausea and vomiting incidences. The results from this study demonstrate that gabapentin is more beneficial in mastectomy and spinal, abdominal, and thyroid surgeries. Gabapentin is an effective analgesic adjunct, and clinicians should consider its use in multimodal treatment plans among patients undergoing elective surgery. Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials. Chronic migraine is an important public health problem. The aim of treatment should be to reduce migraine frequency and its negative impact on functioning, as well as to limit the use of acute medications. These goals may be accomplished by introducing effective prophylaxis. The aim of the present article is to critically review the published evidence on the pharmacological prophylaxis of chronic migraine, analysing published double-blind, placebo-controlled studies on adult patients. The results of the review indicate that tizanidine, gabapentin, valproic acid, and particularly topiramate are effective prophylactics against chronic migraine, with improvements in several endpoints that were significantly superior to those achieved by placebo. However, the different results found by different trials, as well as several methodological problems inherent in the trials, suggest the need for further research to provide clear indications from large, multicentre, controlled trials with homogeneous inclusion criteria and adequate endpoints. Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial. OBJECTIVE: To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients. METHODS: A 12-week randomised open label control trial was conducted at the Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January to March 2011 involving 80 outpatients who had a history of migraine. The sample was divided into two equal groups. Primary efficacy measure was changed into mean monthly migraine frequency. Secondary efficacy measure included reduction in severity and average duration of an attack. Chi square test and paired t-test were used to analyse the data through SPSS 15. RESULT: Reduction in mean monthly migraine frequency (10.67 +/- 4.25 to 1.82 +/- 2.02) in the topiramate group was significantly greater compared with (11.97 +/- 4.452 to 2.73 +/- 2.59) that in the gabapentin group (p < 0.001). Reduction in severity from 6.60 +/- 2.122 to 1.03 +/- 0.92 in the topiramate group was also significantly greater compared with 6.93 +/- 1.90 to 1.18 +/- 1.01 in the gabapentin group (p < 0.001). Reduction in the average duration of attacks from 25.77 +/- 22.32 hours to 1.05 +/- 1.06 hours in the topiramate group was significantly greater compared with 22.20 +/- 20.72 to 1.08 +/- 1.40 hours in the gabapentin group (p < 0.001). Weight loss and numbness were common adverse effects in the topiramate group.

Dizziness, weight gain and somnolence were reported in the gabapentin group. CONCLUSION: Gabapentin appeared well tolerated in 30 (75%) patients compared to topiramate in 23(57.5%) patients. Both drugs were equally effective in migraine prophylaxis. Efficacy of gabapentin in migraine prophylaxis. OBJECTIVE: To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura). STUDY DESIGN AND TREATMENT: After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a three-times-a-day dosing regimen. METHODS: The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor. RESULTS: At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P =.006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P =.013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin. CONCLUSION: Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness. Antidepressivos Tricíclicos e Gabapentinóides: uma análise do perfil farmacológico no tratamento da dor neuropática. A dor crônica é uma condição incapacitante, capaz de se estender de vários meses a anos e não envolve somente a experiência física, mas também diversas dimensões humanas como afeto, cognição, comportamento e relação social, sendo uma das causas mais frequentes da procura por assistência médica. A dor neuropática está inserida no contexto da dor crônica e é causada por uma lesão ou doença que afeta o sistema somatossensorial, porém os mecanismos neurobiológicos envolvidos nessa condição ainda não estão completamente esclarecidos. Os antidepressivos tricíclicos e os gabapentióides são os fármacos de primeira linha para o tratamento farmacológico da dor neuropática. Este estudo faz uma breve análise do perfil farmacológico dessas classes e avalia suas vantagens e desvantagens na terapia da dor neuropática, utilizando como método de avaliação a leitura de artigos, revisões bibliográficas e diretrizes terapêuticas que abordam esta condição. Através da análise dos fármacos, conclui-se que, apesar dos medicamentos apresentarem comprovação de eficácia, muitas vezes os mesmos são empregados de forma inadequada, havendo ainda a necessidade de um maior diálogo entre médico e paciente, além de mais estudos voltados para as ações de tais fármacos no organismo.

Therapeutic Reviews: Anti-epileptic Drugs. Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com). The use of gabapentin in the management of postoperative pain after total hip arthroplasty: a meta-analysis of randomised controlled trials. BACKGROUND: Pain management after total hip arthroplasty (THA) varies and has been widely studied in recent years. Gabapentin as a third-generation antiepileptic drug that selectively affects the nociceptive process has been used for pain relief after THA. This meta-analysis was conducted to examine the efficacy of gabapentin in THA. METHODS: An electronic-based search was conducted using the following databases: PubMed, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled trials (RCTs) involving gabapentin and a placebo for THA were included. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Five trials met the inclusion criteria. The cumulative narcotic consumption and the visual analogue scale (VAS) scores at 24 and 48 h postoperatively were used for postoperative pain assessment. There was a significant decrease in morphine consumption at 24 h (P = 0.00). Compared with the control group, the VAS score (at rest) at 48 h was less in the gabapentin group (P = 0.00). CONCLUSION: The administration of gabapentin is effective in decreasing postoperative narcotic consumption and the VAS score. The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty: A Meta-Analysis. The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) and non-RCTs was to evaluate the efficacy and safety of gabapentin versus placebo for pain control after total knee arthroplasty (TKA).In December 2015, a systematic computer-based search was conducted in the Medline, Embase, PubMed, Cochrane Controlled Trials Register (CENTRAL), Web of Science, Google, and Chinese Wanfang databases. This systematic review and meta-analysis were performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria. The primary endpoint was the visual analogue scale (VAS) score after TKA with rest or mobilization at 24 and 48 hours, representing the efficacy of pain control after TKA. Cumulative morphine consumption via patient controlled anesthesia (PCA) was also assessed to determine the morphine-spare effect. Complications such as dizziness, pruritus, vomiting, nausea, and sedation were also compiled to assess the safety of gabapentin. Stata 12.0 software was used for the meta-analysis. After testing for publication bias and heterogeneity across studies, the data were aggregated for random-effects modeling whenever necessary.Six studies involving 769 patients met the inclusion criteria. Our meta-analysis revealed that gabapentin resulted in superior pain relief compared to the control group in terms of VAS score with rest at 24 hours (mean difference [MD] = -3.47; 95% confidence interval [CI] -6.16 to -0.77; P = 0.012) and at 48 hours postoperatively (MD = -2.25; 95% CI -4.21 to -0.30; P = 0.024). There was no statistically significant difference between the groups with respect to the VAS score at 24 hours postoperatively (MD = 1.05; 95% CI -3.31 to 5.42; P = 0.636) or at 48 hours (MD = 1.71; 95% CI -0.74 to 4.15; P = 0.171). These results indicated that the perioperative administration of gabapentin decreases the cumulative morphine consumption via PCA at 24 hours (MD = -8.28; 95% CI -12.57 to -3.99; P = 0.000) and 48 hours (MD = -4.50; 95% CI -10.98 to -3.61; P = 0.221). Furthermore, gabapentin decreased the rate of postoperative dizziness (relative risk [RR], 0.68; 95% CI 0.47-0.99, P = 0.044) and the occurrence of pruritus (RR, 0.50; 95% CI 0.37-0.67, P = 0.000).Based on the current meta-analysis, gabapentin exerts an analgesic and opioid-sparing effect in acute postoperative pain management without increasing the rate of dizziness and pruritus.

Retrospective Study on the Analgesic Activity of a Topical (TT-CTAC) Cream in Patients With Diabetic Neuropathy and Other Chronic Pain Conditions. Treatment of chronic pain in diabetic neuropathy or neuropathic pain of other origins is challenging. Compounded topical formulations have evolved as potential treatment options. The objective of this retrospective study was to evaluate the efficacy of a compounded topical cream (Transdermal Therapeutics). Two versions of TT-CTAC cream were evaluated: cream 6B and cream 7B. Both creams contain ketamine (10%), baclofen (2%), gabapentin (6%), amitriptyline (4%), bupivacaine (2%), and clonidine (0.2%). Additionally, one cream (7B) contains nifedipine (2%). The primary efficacy outcome was the change in numeric pain intensity score from pretreatment to posttreatment. Secondary outcomes were qualitative grading (excellent, good, poor, or no effect), reduction in oral medication, and avoiding referral to a pain specialist. Information on 283 patients was evaluated, 205 received the 7B and 78 received 6B creams. The pain score decreased by 2.4 ± 2.4 (35%) with the 6B cream (from 7.8 ± 1.6 to 5.4 ± 2.0, P < 0.001) and by 3.0 ± 2.4 (40%) with the 7B cream (from 7.5 ± 1.7 to 4.5 ± 2.2, P < 0.001). Excellent or good effects were reported in 82% of the patients in the 6B and in 70% in the 7B groups. Reduction in oral pain medication was seen in 35% of the patients in the 7B and in 20% in the 6B groups. In the opinion of the treating physicians, the cream therapy caused the avoidance of a pain specialist referral in 53% of the patients in the 6B and in 39% in the 7B groups. The creams were equally effective in diabetic neuropathy, neuropathic pain, or other chronic pain states. We conclude that both creams provided excellent pain relief in the majority of the patients studied and may be a useful modality for pain therapy. REFERÊNCIAS ARUMUGAM, S.; LAU, C. S.; CHAMBERLAIN, R. S. Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. J Pain Res. v. 12, n. 19, p. 631-640. 2016. Disponível em:< https://www.ncbi.nlm.nih.gov/pubmed/27672340>. Acesso em: 13/10/2016, às 12:19. BATISTUZZO, J. A O; ITAYA, M.; ETO, Y. Formulário Médico-Farmacêutico. 5 ed. São Paulo: Pharmabooks, 2015. D'AMICO, D. Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials. Neurol Sci. doi: 10.1007/s10072-010-0268-7. 2010. Disponível em:< http://www.ncbi.nlm.nih.gov/pubmed/23218533>. Acesso em: 14/09/2016, às 17:27. HAN, C. et al. The use of gabapentin in the management of postoperative pain after total hip arthroplasty: a meta-analysis of randomised controlled trials. J Orthop Surg Res. v. 11, n. 1. 2016. Disponível em:< https://www.ncbi.nlm.nih.gov/pubmed/27405805>. Acesso em: 13/10/2016, às 12:31. HOWARD, P. et al. Therapeutic Reviews: Anti-epileptic Drugs. Journal of Pain and Symptom Management. v. 45, n. 5, p. 788-804. 2011. Disponível em:< http://www.jpsmjournal.com/article/S0885-3924(11)00465-9/pdf>. Acesso em: 15/09/2016, às 10:01. MATHEW, N. T. et al. Efficacy of gabapentin in migraine prophylaxis. Headache. v. 41, n. 2, p. 119-128. 2001. Disponível em:< http://www.ncbi.nlm.nih.gov/pubmed/11251695>. Acesso em: 14/09/2016, às 17:36. MEDAWAR, C. V.; MATHEUS, M. E. Antidepressivos Tricíclicos e Gabapentinóides: uma análise do perfil farmacológico no tratamento da dor neuropática. Rev. Bras. Farm. v. 93, n. 3, p. 290-297. 2012. Disponível em:< http://www.rbfarma.org.br/files/rbf-2012-93-3-4.pdf>. Acesso em: 15/09/2016, às 09:36. ZAIN, S. et al. Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial. J Pak Med Assoc. v. 63, n. 1, p. 3-7. 2013. Disponível em:< http://www.ncbi.nlm.nih.gov/pubmed/23865122>. Acesso em: 14/09/2016, às 17:31. ZHAI, L.; SONG, Z.; LIU, K. The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty: A Meta-Analysis. Medicine (Baltimore). v. 95, n. 20. 2016. Disponível em:< https://www.ncbi.nlm.nih.gov/pubmed/27196473>. Acesso em: 13/10/2016, às 12:47. SOMBERG, J. C.; MOLNAR, J. Retrospective Study on the Analgesic Activity of a Topical (TT-CTAC) Cream in Patients With Diabetic Neuropathy and Other Chronic Pain Conditions. Am J Ther. v. 22, n. 3. 2015. Disponível em:< https://www.ncbi.nlm.nih.gov/pubmed/25859821>. Acesso em: 04/11/2016, às 12:26.