Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review / Diálise peritoneal com múltiplas trocas bem-sucedida em paciente com grave toxicidade hematológica por metotrexato: relato de caso e revisão de literatura

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.

Resumo Apesar de sua toxicidade, o metotrexato é um medicamento eficaz no controle de várias doenças. A mielossupressão, um de seus principais efeitos adversos, aumenta em gravidade e frequência nos pacientes com insuficiência renal. Apresentamos o caso de um homem de 68 anos de idade com doença renal terminal relacionada à vasculite associada ao ANCA em diálise peritoneal, que recebeu a medicação em dose baixa em função da atividade da doença e que teve como complicação pancitopenia grave com mucosite, tratada com medidas de suporte e diálise peritoneal com múltiplas trocas. Revisamos 20 casos publicados até o presente momento sobre pancitopenia associada a metotrexato em pacientes em diálise. Foi identificada alta morbidade e mortalidade, razão pela qual seu uso nesse tipo de paciente não é recomendado. No entanto, quando esta complicação ocorre, uma opção terapêutica pode ser o uso de diálise peritoneal com múltiplas trocas, além da terapia de suporte para toxicidade medicamentosa. Maiores estudos são necessários para demonstrar o papel da diálise peritoneal com múltiplas trocas na remoção desse medicamento.

The effect of methotrexate and azathioprine on the serum levels of IgA-alfa1-antitrypsin complex in juvenile chronic arthritis

In the present study we investigated the influence of methotrexate (MTX) and azathioprine (AZA) on the serum levels of the IgA-alpha1-antitypsin (IgA-AT) complex in patients with the systemic form of juvenile chronic arthritis (JCA). Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immuno-suppressive agent) were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg(-1) week(-1) while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months) whereas AZA for 11 months (SD = 6 months). The average value of the complex was higher in JCA patients than in both control groups (0.74 + 0.73 U vs 0.37 + 0.13 U (control children), P<0.001 and vs 0.23 + 0.12 U (control adults), P<0.001). Values exceeding the normal range were found in twenty-two JCA patients (39.4 percent). Serum IgA-AT level was lowest in the MTX group compared to AZA and non-treated patients (0.56 + 0.24 U, 0.76 + 0.43 U, 0.95 + 0.52 U, respectively, P<0.05). IgA values exceeding normal levels for age were found in 14 percent of the patients. A correlation between the levels of the IgA-AT complex and C-reactive protein (r = 0.43, P<0.01), alpha1-acid-glycoprotein (r = 0.45, P<0.01), alpha1-antichymotrypsin (r = 0.52, P<0.01), alpha1-antitrypsin (r = 0.40, P<0.01) and IgA (r = 0.56, P<0.01) was established.

Disposition and clinical efficacy of methotrexate in patients with rheumatoid arthritis following weekly low intramuscular dosing

In sixteen patients with rheumatoid arthritis [RA], plasma concentrations of methotrexate [MTX] were monitored for 24 hours following the intramuscular [im] dosing with 10 mg per week for at least six weeks. Peak concentrations [0.7 +/- 0.5 mumol/l] were achieved 15 minutes following im injection of the drug, while immeasurable drug levels were observed after 24 hours following its injection. Total body clearance [CL/F] and apparent volume of distribution [V/F] averaged 157 ml/min and 0.64 L/kg, respectively. The elimination half-life was 3.0 +/- 1.1 hours. Clinical assessment of the patients showed less pronounced morning stiffness, improved functional capacity and significant reduction in both articular index score and joint swelling. Nausea was the most common side effect of MTX in this dosage regimen. It was concluded that MTX [10 mg im/week] possess a favorable benefit/risk ratio for the treatment of RA and in such patients the pharmacokinetic parameters are variable but comparable to literature data. There is no relation between the serum level of the drug and its efficacy in RA when administered once weekly