tacrolimus and Sleep-Initiation-and-Maintenance-Disorders

There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis.. Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis.. A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks.. The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations.. The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen.. Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.

Topics: Abdominal Pain; Adult; Aged; Blood Glucose; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Severity of Illness Index; Skin; Sleep Initiation and Maintenance Disorders; Statistics as Topic; Tacrolimus; Treatment Outcome

Topics: Confusion; Cyclosporine; Europe; Headache; Humans; Incidence; Kidney Transplantation; Liver Transplantation; Neurotoxins; Paresthesia; Prospective Studies; Sleep Initiation and Maintenance Disorders; Tacrolimus

Neurological complications were examined in a multicentre, randomized, parallel-group study of 545 patients undergoing primary liver transplantation to compare the efficacy and safety of FK 506- and cyclosporin A-based immunosuppressive regimens (CBIR). In an additional analysis, patients were divided into early and late randomized cohorts to detect the influence of protocol amendements that allowed for FK 506 dose reductions. Initial follow-up was for 6 months. Tremor, headache and insomnia were the most frequently reported adverse events involving the neurological system. Whereas these neurological symptoms were observed significantly more often in FK 506-treated patients (P < 0.05 vs. CsA for the overall population), this was no longer the case for the late FK 506 and CBIR cohorts. The risk of FK 506-treated patients developing tremor was related to the initial i.v. dose, the rate of administration of the i.v. dose and the daily dose (P < 0.01). Headache was significantly correlated with the FK 506 dose (P < 0.05), and insomnia was not related to any dosing variable. Major neurological symptoms, including psychosis, convulsion, coma, aphasia and intracranial haemorrhage, were reported with a low frequency (0.4-5.2%), and differences between both treatment groups were neither significant for the overall population nor for the early and late cohorts of FK 506 and CBIR. Data from the late cohorts showed no differences in the overall incidence of neurological adverse events between FK 506- and CBIR-treated patients.

Topics: Cyclosporine; Drug Therapy, Combination; Europe; Graft Rejection; Headache; Humans; Immunosuppressive Agents; Liver Transplantation; Muromonab-CD3; Nervous System Diseases; Sleep Initiation and Maintenance Disorders; Survival Rate; Tacrolimus; Time Factors; Tremor

Lung transplant recipients are at high risk of developing sleep disorders such as insomnia, but the prevalence and features are currently poorly characterized within this population. Since these disorders are associated with increased morbidity and mortality, it is important to identify them to optimize the care of lung transplant recipients. We sought to evaluate the prevalence of insomnia within our university-based lung transplant clinic and determine whether a relationship exists between insomnia and exposure to immunosuppressant medications following transplantation.. Participants were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (n = 92) completed the adult sleep history questionnaire, which included the Insomnia Severity Index (ISI) to assess for insomnia (defined as ISI score >10). Cumulative tacrolimus exposure was determined in 73 patients by performing an area under the curve calculation to assess for a potential relationship between tacrolimus exposure and insomnia.. The prevalence of insomnia was 40% within this population. Although no difference in time since transplant was found, cumulative mean ± standard error of the mean tacrolimus exposure was significantly higher in patients with insomnia versus those without insomnia (17 190 ± 1673 ng·d/mL vs 12 130 ± 1630 ng·d/mL, respectively; P = .04). Estimated tacrolimus exposure was not greater with increasing frequency of insomnia complaints (analysis of variance P = .54).. In our population, insomnia is common after lung transplantation, with prevalence greater than the general population. Higher cumulative exposure to tacrolimus may contribute to insomnia in this group. Future research should investigate the relationship between immunosuppressant therapy and development of sleep disorders.

Topics: Cross-Sectional Studies; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Prevalence; Sleep Initiation and Maintenance Disorders; Tacrolimus; Wisconsin

Complications following lung transplantation are common and significantly reduce quality of life, and increase morbidity and mortality. Increasing evidence suggests sleep disorders are prevalent following lung transplantation, but factors associated with their development are not known.. We sought to evaluate the prevalence of restless legs syndrome (RLS) in a lung transplant population and determine if a relationship exists between RLS and exposure to immunosuppressant medications.. Subjects were recruited through the University of Wisconsin Hospital and Clinics Lung Transplant Clinic (N = 125). Participants (N = 81) completed sleep questionnaires, including the four RLS diagnostic criteria, insomnia severity index, and Sheehan disability scale. Cumulative tacrolimus exposure was determined in 62 subjects by calculating an area under the curve (AUC) to assess for a relationship with restless legs syndrome.. Prevalence of RLS was 35 percent. Cumulative mean ± SEM tacrolimus exposure was similar in patients with RLS versus those without RLS (17446 ± 1855 ng days/mL vs. 15303 ± 1643 ng days/mL, respectively; p = 0.42). Insomnia severity index scores (12.5 ± 1.0 vs 6.8 ± 0.7, p < 0.0001) and Sheehan disability scores (7.8 ± 1.3 vs 3.6 ± 0.6, p = 0.003) were significantly higher in those with vs those without RLS symptoms, respectively.. Our data confirms increased prevalence of RLS following lung transplantation reported by previous studies. RLS symptoms were not related to estimated tacrolimus exposure. Predictors of RLS following lung transplantation need to be further investigated to better identify and control RLS symptoms and reduce associated insomnia and disability.

Topics: Area Under Curve; Female; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Prevalence; Restless Legs Syndrome; Risk Factors; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires; Tacrolimus

Calcineurin inhibition with tacrolimus has been used after renal transplantation (RTPL) as rescue therapy for insufficient immunological control or if cyclosporin A (CSA) toxicity occurred. Neurologic side-effects occur but are rare in children, usually presenting as tremor; however, serious complications, e.g. the posterior leukoencephalopathy syndrome are also documented. Twenty children (10 girls) were switched to tacrolimus: 11 (55%) for immunological reasons (n = 9: steroid-resistant rejection; n = 2: recurrent rejections) and nine for CSA side-effects. Tacrolimus was started at a median of 8 wk (range 10 d to 8.7 yr) after RTPL and was continued for a median of 2.5 yr (range 5 wk to 4.6 yr). Renal function significantly improved over a period of 12 months following conversion to tacrolimus (glomerular filtration rate 56 +/- 19 vs. 66 +/- 16 mL/min/1.73 m2; p < 0.03; n = 13). Fifteen of 20 (75%) patients tolerated tacrolimus well. The most frequent side-effects were neuropsychological and behavioral symptoms in three children, ranging from anorexia nervosa-like symptoms with weight loss, amenorrhea, depression and school problems to severe insomnia and to aggressive and anxious behavior in one child. Only the latter child was exposed to toxic tacrolimus blood levels. All side-effects were fully reversible after discontinuation of tacrolimus. In conclusion, tacrolimus had a beneficial effect on renal function and was well tolerated in the majority of pediatric patients. However, neuropsychologic and behavioral side-effects are important and maybe underrecognized in children.

Topics: Abdominal Pain; Adolescent; Aggression; Amenorrhea; Child; Child Behavior Disorders; Cyclosporine; Depression; Diabetes Mellitus; Drug Resistance; Female; Gingival Hyperplasia; Graft Rejection; Humans; Hypertrichosis; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Sleep Initiation and Maintenance Disorders; Tacrolimus; Weight Loss

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