Multiple drugs
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Various toxicities: case report A 63-year-old woman developed Covid-19 pneumonia during immunosuppressant therapy with mycophenolate mofetil and ciclosporin. Subsequently, she developed nephrotoxicity during concomitant administration of lopinavir/ritonavir and ciclosporin. Additionally, she exhibited lack of efficacy to hydrocortisone, lopinavir/ritonavir, oseltamivir and hydroxychloroquine during treatment for Covid-19 pneumonia [not all routes stated]. The woman, who had hypertension, had undergone deceased donor kidney transplantation. She was hospitalised for cough and dyspnoea. She had been receiving immunosuppressive therapy with mycophenolate mofetil [Cell Cept] 500mg twice a day and ciclosporin [cyclosporin] 75mg twice daily. Physical examination showed body temperature of 37.1°C, respiratory rate was 22/min, pulse rate was 80 beats/minute, oxygen saturation was 83% and BP was 120/80mm Hg. Laboratory tests indicated a total WBC count of 9100 per mL with 15.2% of lymphocytes, 81.1% of polymorphonuclear leukocytes, platelet count was 314 000 per mL with a PTT of 37, INR 1, PT 12.5, BUN 64, creatinine 2.8 mg/dL, LDH 560 U/L, sodium level was 139, potassium level was 4.5, ESR was 81mm/h, CRP was 60 mg/L and the urine protein dipstick value was 2+. A chest CT demonstrated the areas of solid and groundglass confluent consolidation in both lungs suggestive of a diagnosis of Covid-19 pneumonia, and immunosuppressive treatment (mycophenolate mofetil and ciclosporin) was considered as a risk factor for Covid-pneumonia. The woman was treated with a single oral dose of hydroxychloroquine 400mg and she also started receiving oral lopinavir/ ritonavir [Kaletra] 400mg/100mg twice daily along with oral oseltamivir 75mg daily and cefepime. The dose of mycophenolate mofetil was reduced to 50mg twice a day. An echocardiography revealed pericardial effusion with an ejection fraction of 60% and an abdomino-pelvic ultrasound showed increased parenchymal echogenicity in the transplanted kidney. The next day of hospitalisation, her serum creatinine was found to be increased to 3.1 mg/dL, and the oxygen saturation decreased to 78%. Vancomycin was added to treatment medications. On the day 4, despite these treatments, she developed respiratory distress with increased difficulty in breathing, oliguria and dyspnoea. Therefore, she was intubated and underwent 24 hour telemetry. Her CRP level was 78 mg/L, creatinine was increased to 3.4 mg/dL, ESR was 85, PT was 14.5 second, PTT was 40 seconds and platelet count was 387 000 per mL. Her treatment with ciclosporin and mycophenolate mofetil were stopped and hydrocortisone was started. On day 5, she developed respiratory acidosis and foamy bloody discharge through endotracheal tube. Her creatinine was further elevated to 4.4 mg/dL. Subsequently, she became bradycardic and developed cardio-pulmonary arrest. She underwent cardiopulmonary resuscitation, but it was unsuccessful and she died. Her nephrotoxicity was attributed to drug-drug interaction between lopinavir/ritonavir and ciclos
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