[Hepatotoxicity probably associated with gabapentin]. / Hepatotoxicidad probablemente asociada a gabapentina.

BACKGROUND: Gabapentin is an anticonvulsant medication used as an adjuvant in the treatment of neuropathic pain; few cases have been reported in which it causes acute liver injury. CLINICAL CASE: 56-year-old male patient with a history of chronic kidney disease on hemodialysis and narrowing of the spinal canal under treatment with gabapentin, who presented acute liver injury probably secondary to a dose of gabapentin; however, it remitted with the suspension of said drug. CONCLUSION: Gabapentin lacks liver metabolism; the mechanism by which it produces liver injury is still unknown; however, there are reports of hepatotoxicity associated with its administration, so its use must be individualized for each patient.

INTRODUCCIÓN: la gabapentina es un fármaco anticonvulsivante utilizado como adyuvante en el tratamiento del dolor neuropático; se han reportado pocos casos en los cuales es causa de lesión hepática aguda. CASO CLÍNICO: paciente masculino de 56 años de edad con antecedente de enfermedad renal crónica en hemodiálisis y diagnóstico de canal lumbar estrecho en tratamiento con gabapentina, quien presentó lesión hepática aguda, probablemente secundaria a la dosis de gabapentina; sin embargo, remitió posterior a la suspensión de dicho fármaco. CONCLUSIÓN: la gabapentina carece de metabolismo hepático; el mecanismo por el cual produce lesión hepática aún es desconocido; sin embargo, existen reportes de hepatotoxicidad asociada a su administración, por lo que su utilización deberá individualizarse para cada paciente.

Doneness preferences, meat and meat-derived heterocyclic amines intake, and N-acetyltransferase 2 polymorphisms: association with colorectal adenoma in Japanese Brazilians.

Intake of heterocyclic amines (HCAs) and other mutagenic compounds formed during cooking has been hypothesized to be responsible for the positive association observed between red meat and colorectal cancer. We evaluated whether well-done/very well-done preferences for various meat and fish items, higher intakes of meat and fish, and meat-derived and fish-derived HCA are associated with the risk of colorectal adenoma (CRA) in a Japanese-Brazilian population. We selected 302 patients with adenoma and 403 control individuals who underwent total colonoscopy between 2007 and 2013, and collected information on aspects of meat intake using a detailed questionnaire. We also estimated HCA intake of the study participants using an HCA database that matched the cooking methods of this population. Latent class analysis on the basis of response to doneness preferences for different cooking methods of commonly consumed meat and fish items identified four distinct subgroups. Compared with the subgroup characterized by a preference for rare/medium well-done cooking for most meat and fish items, the odds ratio of CRA for the well-done/very well-done preference subgroup was 1.19 (95% confidence interval: 0.51-2.75). High intake of mixed-meat dishes was suggestively associated inversely with CRA, whereas a high intake of poultry was associated positively with CRA. No clear association with intake of total or specific HCAs and no effect modification by N-acetyltransferase 2 acetylation genotype were observed. We found no statistically significant associations between meat and HCA intake and CRA. These findings do not support a positive association between meat and meat-derived HCA intake and the risk of CRA.

Comparative mutagenic activity of atmospheric particulate matter from limeira, stockholm, and kyoto.

Atmospheric particulate matter (PM) organic fractions from urban centers are frequently mutagenic for the Salmonella/microsome assay. This mutagenicity is related to both primary and secondary pollutants, and meteorological conditions have great influence on the secondary pollutant's formation. Our objective was to compare the mutagenicity of atmospheric total suspended particulates (TSP) from three cities with marked different meteorological conditions and TSP concentrations: Limeira (Brazil) with 99.0 µg/m3 , Stockholm (Sweden) with 6.2 µg/m3 , and Kyoto (Japan) with 28.0 µg/m3 . For comparison, we used the same batch of filters, sample extraction method, and Salmonella/microsome testing protocol with 11 strains of Salmonella with and without metabolic activation. Samples were collected during winter and pooled into one single extract representing each city. All samples were mutagenic for all tested strains, except for TA102. Based on the strain's selectivity, nitroarenes, polycyclic aromatic hydrocarbons, and aromatic amines play a predominant role in the mutagenicity of these samples. The mutagenic potencies expressed by mass of extracted organic material (EOM; revertants/µg EOM) were similar (~twofold difference) among the cities, despite differences in meteorological conditions and pollution sources. In contrast, the mutagenic potencies expressed by air volume (rev/m3 ) varied ~20-fold, with Limeira > Kyoto ≈ Stockholm. These results are the first systematic assessment of air mutagenicity from cities on three continents using the same protocols. The results confirm that the mutagenic potency expressed by EOM mass is similar regardless of continent of origin, whereas the mutagenic potency expressed by air volume can vary by orders of magnitude. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc.

Gabapentin acutely increases the apnea-hypopnea index in older men: data from a randomized, double-blind, placebo-controlled study.

Although drugs with sedative properties may increase the risk of airway collapse during sleep, their acute effects on the apnea-hypopnea index in older adults are under-reported. We investigated the acute effects of gabapentin (GABA) on sleep breathing in older men without sleep apnea. A double-blind, randomized, placebo-controlled cross-over pilot study using a bedtime dose of gabapentin 300 mg was conducted in eight non-obese older men. Polysomnography measured the effects of the intervention. The apnea-hypopnea index was higher in the gabapentin arm than in the placebo arm (22.4 ± 6.1 versus 12.2 ± 4.3, P ≤ 0.05, d: 0.67), as was the oxygen desaturation index (20.6 ± 5.8 versus 10.8 ± 3.9, P ≤ 0.05, d: 0.68). The number needed to harm was four. A subset analysis demonstrated that differences in sleep respiratory parameters were present only during non-rapid eye movement sleep, as well as only in the supine position. No adverse events were reported. Hence, gabapentin worsened sleep breathing acutely compared with placebo. Long-term clinical trials are warranted to elucidate the clinical relevance of these findings for the safety profile of GABAergic agents.

An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and Opioids.

We report a retrospective case series of 19 infants exposed to both opioids and gabapentin prenatally. We describe a unique behavioral phenotype in 15 of these infants and report a treatment strategy.

Clinical Trial Assessing the Efficacy of Gabapentin Plus B Complex (B1/B12) versus Pregabalin for Treating Painful Diabetic Neuropathy.

INTRODUCTION: Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN. METHOD: Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment. RESULTS: Both drugs showed reduction of pain intensity, without significant statistical difference (P = 0.900). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P = 0.014. CONCLUSIONS: Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298.

Gabapentin Use in the Neonatal Intensive Care Unit.

Gabapentin was used for the treatment of term and preterm infants with suspected visceral hyperalgesia caused by a variety of neurologic and gastrointestinal morbidities. Improved feeding tolerance and decreased irritability were seen, as well as decreased usage of opioids and benzodiazepines. Adverse events occurred with abrupt discontinuation of this medication.

Joint association of fruit, vegetable, and heterocyclic amine intake with DNA damage levels in a general population.

OBJECTIVE: To assess joint effects of heterocyclic amine (HCA), fruit, and vegetable intake on DNA damage in a general population. METHODS: A cross-sectional survey (ISA-Capital) was performed among adults and older adults in Brazil. We selected 73 participants with high HCA intake and 73 sex- and age-matched participants with non-HCA intake (n = 146) for the present study. Diet was assessed by a 24-h dietary recall and a structured questionnaire with cooking methods and levels of meat doneness. DNA damage was measured by 8-oxo-2'-deoxyguanosine (8-OHdG). The association between DNA damage and dietary intake was analyzed by linear regression models. RESULTS: Fruit intake showed significantly inverse association with 8-OHdG (ß, -0.787; P = 0.035), whereas HCA intake was significantly associated with increased DNA damage (ß, 1.621; P = 0.036) after adjusting for covariates, including sex, age, body mass index, energy intake, smoking, physical activity, and C-reactive protein. Vegetable intake was not significantly associated with 8-OHdG. We also found a significant association between joint fruit and HCA intake and DNA damage, and the difference in 8-OHdG levels was significantly higher between participants with the lowest fruit intake and highest HCA intake and those with the highest fruit intake and non-HCA intake (P = 0.049). CONCLUSIONS: Lower intake of fruits and higher intake of HCAs were associated with higher DNA damage levels and showed an additive effect pattern.

Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin.

INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.

Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin / Prurido urêmico em pacientes em hemodiálise: tratamento com desloratidina versus gabapentina

INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.

INTRODUÇÃO: Prurido urêmico é comum entre pacientes em diálise. Tratamentos eficazes não estão disponíveis até o momento. Provas recentes com anti-histamínicos e gabapentina indicam vários efeitos. OBJETIVO: Comparar a eficiência e os efeitos colaterais da gabapentina e da desloratadina em pacientes com prurido na diálise. MÉTODOS: Estudo prospectivo, aberto e comparativo com 22 pacientes em hemodiálise crônica com prurido constante durante um período de pelo menos 60 dias. Após uma semana, submetemos os pacientes a três semanas de gabapentina 300 mg, três vezes por semana, ou desloratadina 5 mg três vezes por semana. Após um período de eliminação de uma semana, os pacientes trocaram de regime por mais três semanas. O objetivo primário do estudo foi a mudança na escala visual analógica (EVA) de prurido. RESULTADOS: Dezenove indivíduos completaram os dois tratamentos e foram submetidos à análise. Os escores da EVA caíram com ambos os tratamentos (5,95 para 4,6 com gabapentina, p = 0,07; 5,89 para 3,4 com desloratadina, p = 0,004), mas somente a desloratadina teve significância estatística. Nenhuma diferença foi observada ao comparar o escore final do prurido com gabapentina e desloratadina (4,6 versus 3,4, p = 0,16). Excesso de sedação foi comum com gabapentina. A desloratadina teve alto nível de tolerância. CONCLUSÃO: A desloratadina dá alívio significante do prurido urêmico quando comparada a nenhum tratamento. A gabapentina tem eficiência marginal. A desloratadina tem maior nível de tolerância em relação à gabapentina.

Gabapentin for postoperative pain after photorefractive keratectomy: a prospective, randomized, double-blind, placebo-controlled trial.

PURPOSE: To determine whether treatment with oral gabapentin reduces postoperative pain after photorefractive keratectomy (PRK). METHODS: This prospective, randomized, double-blind, placebo-controlled study comprised 40 patients scheduled for bilateral PRK. Exclusion criteria were previous refractive surgery; diseases that could affect epithelial healing; use of antihistamines, nonsteroidal anti-inflammatory drugs, or steroids; and use of mitomycin C during PRK. Patients were divided into two groups: 20 patients received gabapentin capsules (300 mg) and 20 patients received identical placebo capsules. Visual acuity, slit-lamp examination, and a 12-question, 10-point visual numerical scale questionnaire were evaluated at each postoperative follow-up. Main outcome measures were the severity of pain at each follow-up and during the previous 24 hours. Secondary outcome measures were maximum and minimum severity of pain, healing time, uncorrected distance visual acuity, and the rating of other symptoms and potential side effects. RESULTS: The gabapentin group had less pain during the first 72 hours (P=.024 to .001). A significant difference in favor of gabapentin was found for the first 48 hours regarding minimum pain severity (P=.005 and .01 for 24 and 48 hours, respectively) and for the first 72 hours for maximum pain severity (P=.014, .007, and .001 for 24, 48, and 72 hours, respectively). No significant differences were observed for side effects, symptoms, or healing time except discomfort in favor of gabapentin during the first 24 hours (P=.043). CONCLUSIONS: Gabapentin significantly reduced postoperative pain after PRK compared to placebo, with no increase in reported side effects.

Gabapentin vs. low-dose transdermal estradiol for treating post-menopausal women with moderate to very severe hot flushes.

BACKGROUND: Gabapentin (GPT), a widely used drug in neurology, has been proposed as a non-hormonal option for the management of hot flushes in menopausal women with contraindications for estrogen therapy. OBJECTIVE: To compare GPT versus low-dose transdermal estradiol (E(2)) for treating post-menopausal women with moderate to very severe hot flushes. METHODS: A total of 45 post-menopausal women with moderate to very severe hot flushes were prospectively and single-blinded randomised to receive oral GPT 600 mg/night or transdermal 25 microg/day E(2) per week. Hot flush intensity and frequency were assessed with the Menopause Rating Scale and a numeric scale respectively at baseline and at 1, 4 and 8 weeks. Side effects were also assessed. RESULTS: Hot flush intensity and frequency significantly decreased for both groups at 1, 4 and 8 weeks of treatment as compared to baseline; however, this decrease was statistically more evident for the E(2) group. Although the percentage of hot flush intensity and frequency reduction at the end of the treatment was higher for E2, this was not statistically significant (68.2% vs. 60.6% for intensity and 70.1% vs. 58.9% for frequency, respectively, p > 0.05, NS). Encountered side effects included: drowsiness, dizziness, fatigue (GPT group) and mastodynia, vaginal spotting and a local allergic reaction (E(2) group). Compliance to treatment was 95.6% (GPT group) as compared to 90.9% for the E(2) group. CONCLUSION: Despite statistical significant differences, from a clinical point of view oral GPT 600 mg was as effective as low-dose transdermal E(2) in controlling moderate to severe hot flushes in post-menopausal women, and should be recommended as an alternative option in those with contraindications to estrogen therapy. More research is warranted in this regard.

Novel long-term anticonvulsant treatment with gabapentin without causing memory impairment in mice.

We previously reported that administration of a single dose of gabapentin (GBP) immediately after training improves memory of mice in an inhibitory avoidance task (IA), whereas GBP administered repeatedly for 7 days impairs memory. This is in accordance with the observation that long-term clinical treatment with GBP may be associated with adverse cognitive side effects. In the present work we used a GBP-loaded poly(epsilon-caprolactone) implant, allowing controlled release of the drug and maintenance of constant plasma levels over 1 week. When GBP-loaded implants were inserted subcutaneously into mice, immediately after training in the IA task, memory consolidation was enhanced. Moreover, GBP released from implants had an anticonvulsant action against pentylenetetrazole-induced seizures. These results suggest that maintenance of stable GBP plasma levels could protect against seizures without causing memory impairment. Hence, the adverse cognitive effects might be avoided by stabilizing plasma levels of the drug.

[Efficacy and safety of gabapentin in Borderline Personality Disorder: a six-month, open-label study]. / Eficacia y seguridad de Gabapentina en el Trastorno Límite de Personalidad: estudio abierto de seis meses de duración.

Anticonvulsants are showing to be helpful in the treatment of Borderline Personality Disorder and are widely used in clinical settings, although few studies have been published and their role in different borderline patients is not completely outlined. Gabapentin pharmacologic profile and its documented efficacy in anxiety disorders and drug abuse withdrawal were the basis for this open label multicenter six-month follow-up trial in borderline patients not enough responsive to previous therapies. DSM-IV Borderline Personality diagnosis was confirmed by the Diagnostic Interview for Borderlines-Revised. Outcome measures were changes in scores on Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Beck Depression Inventory, Barratt Impulsivity Scale and Clinical Global Impression Scale of Severity and Improvement. A global improvement, especially in anxious and depressive symptomatology, was observed; no adverse events were reported. Gabapentin showed to be efficacious and safe in Borderline Personality Disorder's treatment.

Economic evaluation of oral treatments for neuropathic pain.

UNLABELLED: The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for the treatment of neuropathic pain has been demonstrated, but it is unknown which one is the most cost-effective. We designed a cost-utility analysis of a hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The perspective of the economic evaluation was that of a third-party payor. For effectiveness and safety estimates, we performed a systematic review of the literature. For direct cost estimates, we used average wholesale prices, and the American Medicare and Clinical Laboratory Fee Schedules. For utilities of health states, we used the Health Utilities Index. We modeled 1 month of therapy. For comparisons among treatments, we estimated incremental cost per utility gained. To allow for uncertainty from variations in drug effectiveness, safety, and amount of medication needed, we conducted a probabilistic Monte Carlo simulation. Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were equally beneficial. Gabapentin was the most expensive as well as the least beneficial. A multivariable probabilistic simulation produced similar results to the base-case scenario. In summary, amitriptyline and carbamazepine are more cost-effective than tramadol and gabapentin and should be considered as first-line treatment for neuropathic pain in patients free of renal or cardiovascular disease. PERSPECTIVE: Prescription practices should be based on the best available evidence, which includes the evaluation of the medication's cost-effectiveness. This does not mean that the cheapest or the most expensive, but rather the most cost-effective medication should be chosen-the one whose benefits are worth the harms and costs. We report a cost-effectiveness evaluation of treatments for neuropathic pain.

Treatment of diabetic neuropathic pain with gabapentin alone or combined with vitamin B complex. preliminary results.

Neuropathic pain is a syndrome that affects around 1% of population. This condition can be severely disabling and traditional analgesics are useless against this type of pain. Several adjuvants such as the anticonvulsive agent gabapentin have been used to treat diabetic neuropathy with several degrees of effectiveness, but it is characterized of a high incidence of dizziness, somnolence and ataxia. Previously we have found a functional synergistic interaction after co-administration of gabapentin and B vitamins by using a neuropathic pain model in the rat. In order to evaluate the efficacy of gabapentin and B vitamins in the treatment of diabetic neuropathy in humans we carried out a comparative trial. In this study are presented preliminary results from 6 patients assigned to two groups: group A (n=3) received gabapentin, and group B (n=3) received gabapentin plus B vitamins. In both groups, the dose was increased at weekly intervals, and characteristics of pain and some parameters of quality of life were assessed. Both treatments significantly reduced pain and improved quality of life in the patients. Dizziness was the main adverse event observed in both groups. Data suggest that the combination of gabapentin and B vitamins could be an alternative treatment for diabetic neuropathic patients.

Review on meat consumption and cancer in South America.

Consumption of red meat and its heterocyclic amines (HCA) content has been associated with an increased risk for colorectal cancer and, with less consistency, with stomach, oesophagus, pancreas, breast, prostate and kidney cancers. Uruguay and Argentina's rates for breast and colon cancer are among the highest in the world. The main type of meat consumed in these countries is beef, of which consumption rank first and second, respectively in the world, with about 60 kg per year per capita. Beef is cut in different ways following the customs of different countries and regions. The predominant consumption of different cuts and ways of cooking, are described for different regions within Argentina as well as frequencies of consumption of different kinds of meats. These differences reflect not only habits and customs but also socioeconomic variations among regions.A review of epidemiological studies performed in South American countries related to meat consumption, ways of cooking, HCA, and different cancers is presented. It is concluded that comparisons among studies generated in countries or regions with different meat types, beef cuts consumption usage and cooking methods must be very careful. Hence, future research for the verification of the observed associations between HCA and cancer, should be conducted through in-depth, chemically validated questionnaires based on local data.

Case-control study on the role of heterocyclic amines in the etiology of upper aerodigestive cancers in Uruguay.

To examine the risk of upper aerodigestive tract cancers (UADC: oral cavity, pharynx, larynx, and esophagus) associated with dietary heterocyclic amine (HCA) exposure, a case-control study involving 140 cases and 286 controls was conducted in Montevideo, Uruguay. Beef and red meat intakes were positively associated with risk of UADC [odds ratio (OR) for red meat intake = 2.8, 95% confidence interval (CI) = 1.4-6.0], whereas no association was observed with white meat (poultry plus fish) intake. When meat intake was examined by cooking method, no association was observed for fried meat. On the other hand, broiled and boiled meat were associated with a significant increase in risk of UADC (OR for broiled meat = 2.0, 95% CI = 1.0-4.3). Total HCA intake was associated with an increased risk (OR = 2.2, 95% CI = 1.1-4.2) of UADC. The HCA effect was similar among the different cancer sites.