tacrolimus and Fatigue

The impact of different immunosuppression regimes on the health-related quality of life (HRQoL) and the severity of fatigue in liver transplant recipients is largely unknown. We investigated the impact of a sirolimus-based regimen compared with a tacrolimus (TAC)-based regimen on the HRQoL and the severity of fatigue.. In this multicenter, open-label, randomized, controlled trial, 196 patients were randomized 90 d after transplantation to (1) once daily normal-dose TAC or (2) once daily combination therapy of low-dose sirolimus and TAC. HRQoL was measured with the EQ-5D-5L questionnaire, the EQ-visual analog scale, and the severity of fatigue questionnaire Fatigue Severity Score (FSS). The EQ-5D-5L scores were translated to societal values. We examined the HRQoL and the FSS over the course of the study by fitting generalized mixed-effect models.. Baseline questionnaires were available for 87.7% (172/196) of the patients. Overall, patients reported the least problems in the states of self-care and anxiety/depression and the most problems in the states of usual activities and pain/discomfort. No significant differences in HrQol and FSS were seen between the 2 groups. During follow-up, the societal values of the EQ-5D-5L health states and the patient's self-rated EQ-visual analog scale score were a little lower than those of the general Dutch population in both study arms.. The HRQoL and FSS were comparable in the 36 mo after liver transplantation in both study groups. The HRQoL of all transplanted patients approximated that of the general Dutch population, suggesting little to no residual symptoms in the long term after transplantation.

Topics: Fatigue; Health Status; Humans; Immunosuppression Therapy; Liver Transplantation; Quality of Life; Surveys and Questionnaires; Tacrolimus

The safety and pharmacokinetics of anidulafungin coadministered with tacrolimus were investigated using a single-sequence, open-label design. Healthy volunteers received 5 mg tacrolimus orally on days 1 and 13 of the study. Anidulafungin (200 mg) was administered intravenously on day 4, followed by 100-mg doses on days 5 through 13. Key pharmacokinetic parameters, including C(max), AUC, t((1/2)), CL, and V(ss), were derived from concentration-time data. The 90% confidence intervals (CIs) of the ratios of mean pharmacokinetic parameters of anidulafungin plus tacrolimus to each drug alone were well within the 80% to 125% bioequivalence range, indicating no pharmacokinetic interaction. This ratio was 101.6 (90% CI: 92.77-111.22) for tacrolimus AUC(0-infinity) and 107.2 (90% CI: 105.1-109.4) for anidulafungin AUC(ss). The 2 drugs were well tolerated, and no drug-related serious adverse events were reported. Because of its lack of pharmacokinetic interaction with key immunosuppressive agents, anidulafungin is an important option for the prevention and treatment of invasive fungal infections in transplant recipients.

Topics: Administration, Oral; Adolescent; Adult; Alanine Transaminase; Anidulafungin; Antifungal Agents; Area Under Curve; Aspartate Aminotransferases; Creatine Kinase; Dizziness; Drug Interactions; Echinocandins; Fatigue; Half-Life; Headache; Humans; Immunosuppressive Agents; Infusions, Intravenous; Male; Middle Aged; Nocturia; Peptides, Cyclic; Tacrolimus; Therapeutic Equivalency; Thrombophlebitis

We have taken the opportunity of a clinical trial of the potential efficacy and safety of FK 506 (tacrolimus) in chronic progressive multiple sclerosis (MS) to examine the influence of this potent new immunosuppressant on circulating T-lymphocytes in an otherwise healthy non-transplant population. Peripheral blood levels of subsets of CD4+ T lymphocytes expressing the activation molecule interleukin-2 receptor (p55 alpha chain; CD25) or the CD45RA isoform were determined sequentially in 19 patients that were treated continuously with oral FK 506 (starting dose 0.15 mg/kg/day) for 12 months. No significant change in the proportion of circulating CD25+ CD4+ cells was observed over the study period in which the mean trough plasma FK 506 level rose from 0.3 +/- 0.2 to 0.5 +/- 0.4 ng/ml. There was also no significant effect of FK 506 on the percentage of CD45R+ CD4+ cells in the peripheral blood at 12 months compared with pretreatment values. Analysis of a subgroup of 7 patients, who showed a sustained reduction in CD25+ CD4+ cells and a reciprocal increase in CD45RA+ CD4+ cells for at least 6 months after start of treatment, did not reveal any difference in disability at one year compared with the treatment group as a whole. The side effects of FK 506 were mild and the overall degree of disability estimated by the mean Kurtzke expanded disability status scale (EDSS) score or the ambulation index did not deteriorate significantly in the 19 patients studied over the 12 months of FK 506 administration.

Topics: Administration, Oral; Adult; Aged; CD4-Positive T-Lymphocytes; Fatigue; Feeding and Eating Disorders; Female; Humans; Leukocyte Common Antigens; Male; Middle Aged; Multiple Sclerosis; Pilot Projects; Receptors, Interleukin-2; Tacrolimus; Tremor

Gitelman syndrome (GS) is a rare autosomal recessive inherited salt-losing tubulopathy (SLT). Here, we report, for the first time, a case of GS overlapping nephrotic syndrome (NS) related to PLA2R-associated membranous nephropathy (MN).. We described a male patient had a 4-year history of recurrent fatigue. Serum biochemistry revealed hypokalemia with renal potassium wasting, hypomagnesemia, metabolic alkalosis, hyperreninemia, hypocalciuria, as well as nephrotic-range proteinuria, hypoalbuminemia, and elevated serum anti-phospholipase A2 receptor (PLA2R) antibody. Gene sequencing identified compound heterozygous mutations in SLC12A3 [c.536T > A(p.V179D) and c.1456G > A(p.D486N)]. The unusual association of SLTs and nephrotic-range glomerular proteinuria prompted us to perform a renal biopsy. Renal biopsy showed idiopathic MN. Due to the potential to activate the sodium-chloride co-transporter (NCC) and cause hyperkalemia, tacrolimus was selected to treat NS. Following treatment with potassium chloride, magnesium oxide, low-dose glucocorticoid combined with tacrolimus, the fatigue significantly improved, and concurrently hypokalemia, hypomagnesemia were corrected and NS was remitted.. Renal biopsy should be warranted for GS patients with moderate to nephrotic-range proteinuria. Tacrolimus was preferred to the management of GS patients with NS.

Topics: Fatigue; Gitelman Syndrome; Glomerulonephritis, Membranous; Humans; Hypokalemia; Magnesium; Male; Potassium; Proteinuria; Solute Carrier Family 12, Member 3; Tacrolimus

Topics: Abdominal Pain; Aged; Fatigue; Female; Humans; Lupus Erythematosus, Systemic; Pancytopenia; Panniculitis, Lupus Erythematosus; Panniculitis, Peritoneal; Prednisolone; Tacrolimus; Tomography, X-Ray Computed

During the novel coronavirus pandemic, organ transplant recipients represent a frail susceptible category due to long-term immunosuppressive therapy. For this reason, clinical manifestations may differ from general population and different treatment approaches may be needed. We present the case of a 36-year-old kidney-transplanted woman affected by Senior-Loken syndrome diagnosed with COVID-19 pneumonia after a contact with her positive mother. Initial symptoms were fatigue, dry cough, and coryza; she never had fever nor oxygen supplementation. Hydroxychloroquine and lopinavir/ritonavir were started, and the antiviral drug was replaced with darunavir/cobicistat after 2 days for diarrhea. Immunosuppressant levels were closely monitored, and we observed very high tacrolimus trough levels despite initial dose reduction. The patient was left with steroid therapy alone. The peculiarity of clinical presentation and the management difficulties represent the flagship of our case report. We stress the need for guidelines in transplant recipients with COVID-19 infection with particular regard to the management of therapy.

Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; Ciliopathies; Cobicistat; Common Cold; Coronavirus Infections; Cough; COVID-19; COVID-19 Drug Treatment; Cytochrome P-450 CYP3A Inhibitors; Darunavir; Deprescriptions; Drug Combinations; Drug Interactions; Enzyme Inhibitors; Fatigue; Female; Glucocorticoids; Graft Rejection; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Leber Congenital Amaurosis; Lopinavir; Methylprednisolone; Optic Atrophies, Hereditary; Pandemics; Pneumonia, Viral; Ritonavir; SARS-CoV-2; Severity of Illness Index; Tacrolimus

Topics: Antihypertensive Agents; Cyclophosphamide; Cyclosporine; Drug Substitution; Drug Therapy, Combination; Fatigue; Glomerulosclerosis, Focal Segmental; Gynecomastia; Humans; Hypertension; Male; Mastodynia; Middle Aged; Muscle Weakness; Mycophenolic Acid; Prednisone; Proteinuria; Tacrolimus

To discuss a comprehensive diagnostic approach to an active duty patient presenting with dyspnea on exertion, fatigue, and pallor. A 50-year-old active duty E-6 white male in Al Udeid, Qatar, presented with progressive dyspnea on exertion, fatigue, and new pallor. This case illustrates the course of events from Al Udeid to the Walter Reed Army Medical Center, where the final diagnosis was made. Along the way, questions with discussions explore the various diagnostic and management aspects of his case and highlight military relevant issues that include efficient diagnostic algorithms in the field and transfusion of scarce blood products.

Topics: Algorithms; Anemia, Aplastic; Antilymphocyte Serum; Bone Marrow Examination; Cyclosporins; Decision Trees; Diagnosis, Differential; Drug Therapy, Combination; Dyspnea; Fatigue; Humans; Immunosuppressive Agents; Male; Middle Aged; Military Medicine; Military Personnel; Pallor; Qatar; Tacrolimus; United States

The presence of severe and mild neurotoxicity in our pediatric renal transplant recipients treated with tacrolimus was determined by chart review (severe neurotoxicity) and patient survey (mild neurotoxicity). 14 patients were studied (mean age 15 yr, 5 month, +/- 4.4 yr). 1 patient experienced seizures, felt to be related to malignant hypertension. No other episode of severe neurotoxicity was documented. Most patients (12/14) reported at least one mild neurologic symptom, and half stated their symptoms were present at least 'most of the time'. The most frequent complaints were myalgias (7/14, 50%) and tremors (7/14, 50%) followed by fatigue (5/14, 38%). Severe neurotoxicity may be relatively infrequent in pediatric renal transplant patients treated with tacrolimus. Milder neurologic complaints may be commonly seen in this population, but in general are not severe enough to cause discontinuation of tacrolimus.

Topics: Adolescent; Adult; Child; Evaluation Studies as Topic; Eye; Fatigue; Follow-Up Studies; Headache; Humans; Hyperesthesia; Hypertension, Malignant; Immunosuppressive Agents; Kidney Transplantation; Muscle, Skeletal; Pain; Peripheral Nervous System Diseases; Retrospective Studies; Seizures; Sleep Initiation and Maintenance Disorders; Tacrolimus; Tremor