tacrolimus and Headache

To determine if future studies of coenzyme Q(10) and GPI-1485 in Parkinson disease (PD) may be warranted.. We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold.. The primary outcome measure (change in total Unified Parkinson's Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed.. Coenzyme Q(10) and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies.

Topics: Aged; Coenzymes; Double-Blind Method; Female; Headache; Humans; Male; Middle Aged; Nausea; Parkinson Disease; Tacrolimus; Ubiquinone

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

Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares.. Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion.. BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously.. Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively).. There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months.. Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroids.

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Dermatitis, Atopic; Double-Blind Method; Emollients; Emulsions; Female; Follow-Up Studies; Headache; Humans; Infant; Life Tables; Male; Patient Dropouts; Pharyngitis; Severity of Illness Index; Tacrolimus; Treatment Outcome

Tacrolimus (FK506, Prograf) is marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation. A previously conducted, randomized, 24-subject, crossover bioavailability study of 1 and 5 mg capsules (one period each) failed to demonstrate bioequivalence. A single-dose, four-period, four-sequence, randomized, crossover, replicate study (N = 32) was therefore used to evaluate the bioequivalence of the marketed 1 and 5 mg capsules in healthy volunteers. Tacrolimus blood concentrations were measured serially over 72 hours using a commercially available ELISA assay. Noncompartmental pharmacokinetic parameters were determined. Ninety percent CIs of log-transformed parameter ratios were 90.5-101.9, 87.1-101.7, and 89.7-103.8 for Cmax, AUC0-t, and AUC0-infinity, respectively. Since all values were within 80% to 125%, the capsules are bioequivalent. Based on %CVs, intersubject variability was approximately two to three times greater than intrasubject variability. The safety of single 5 mg oral tacrolimus doses administered to healthy volunteers at 7-day intervals was also ascertained.

Topics: Abdominal Pain; Adult; Area Under Curve; Arthralgia; Capsules; Cross-Over Studies; Diarrhea; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Knee Joint; Male; Purpura; Tacrolimus; Therapeutic Equivalency

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

Topics: Cyclosporine; Drug Therapy, Combination; Graft Rejection; Headache; Humans; Immunosuppression Therapy; Liver Transplantation; Neurotoxins; Retrospective Studies; Seizures; Sleep Wake Disorders; Tacrolimus; Tremor

Tacrolimus-induced encephalopathy presents with acute neurological symptoms such as headache, seizures, visual disturbances, hemiplegia, and altered mental status. A 60-year-old woman, presented to our clinic with a 4-month history of severe headache. She recently underwent kidney transplantation and was taking tacrolimus. MRI scan showed diffuse and symmetric alterations involving both supratentorial and infratentorial white matter. Cerebral spinal fluid assessment for infectious diseases were negative but elevated total protein level and oligoclonal bands positivity were reported. Treatment with steroid bolus, along with tacrolimus tapering, provided clinico-radiological improvement. This is the first case of tacrolimus-induced neurotoxicity strongly suggestive of an immune-mediated pathogenesis.

Topics: Female; Headache; Humans; Immunosuppressive Agents; Leukoencephalopathies; Middle Aged; Tacrolimus

Reversible cerebral vasoconstriction syndrome (RCVS) is a transient cerebrovascular disorder putatively caused by some immunosuppressive agents.. We recently encountered a 47-year-old female patient diagnosed with dilated cardiomyopathy who developed RCVS after heart transplantation. A triple-drug regimen consisting of tacrolimus, mycophenolate mofetil, and a corticosteroid was started after surgery. On postoperative day (POD) 11, the patient developed a severe headache, although computed tomography of the head demonstrated no signs of hemorrhage or infarction. At first, both a painkiller and migraine drugs were regularly administered to the patient. On POD 21, however, she developed an unbearable headache with a visual field defect and mild hemiparesis of the right hand. Magnetic resonance imaging (MRI) of the brain revealed a cerebral infarction in the left occipital lobe with diffuse vasoconstriction of both the middle and posterior cerebral arteries. A diagnosis of RCVS was made and tacrolimus, a drug suspected to cause RCVS, was discontinued. In its place, two doses of basiliximab followed by everolimus, both of which are alternatives for tacrolimus, were given. The corticosteroid dose was also increased. Furthermore, to release vasoconstriction, both verapamil and diltiazem were administered. On POD 27, cerebrovascular constrictions were shown to be relieved on brain MRI and the patient's neurological symptoms subsequently almost completely diminished.. RCVS should always be considered as a cause of headache in heart transplant recipients because tacrolimus, an immunosuppressive agent, may trigger RCVS. This will allow rapid intervention that is essential for avoiding irreversible neurological deficits.

Topics: Female; Headache; Heart Transplantation; Humans; Immunosuppressive Agents; Middle Aged; Tacrolimus; Vasospasm, Intracranial

Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.. The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).. Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.. Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.

Topics: Adolescent; Adult; Aged; Confusion; Dose-Response Relationship, Drug; Drug Monitoring; Female; Graft Rejection; Headache; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Psychotic Disorders; Renal Insufficiency, Chronic; Retrospective Studies; Seizures; Tacrolimus; Tremor; Young Adult

Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible symptoms including headache, visual disturbances, focal neurological deficits, altered mentation, and seizures. It has been associated with circumstances that may affect the cerebrovascular system, such as hypertension, eclampsia, and immunosuppression with calcineurin inhibitors. The underlying etiology of PRES has remained unclear; however, cerebrovascular autoregulatory dysfunction, hyperperfusion, and endothelial activation have been implicated.. We describe a case of a young patient with lung transplant, who presented with headache, acute binocular blindness, and seizure immediately after infusion of saline through a peripherally inserted central catheter line, which inadvertently terminated cephalad in the left internal jugular vein, near the jugular foramen. Subsequent brain magnetic resonance imaging revealed vasogenic edematous lesions in a pattern consistent with PRES--a diagnosis supported by his constellation of symptoms, history of lung transplantation on tacrolimus immunosuppression, and relative hypertension.. This is the first reported case describing the development of PRES after the insertion of a peripherally inserted central catheter line. The development of PRES in a typical high-risk patient immediately after cerebral venous outflow obstruction implicates the role of the cerebral venous system and provides potential insight into the mechanism of this disorder that remains of unclear pathogenesis.

Topics: Adult; Blindness; Brain; Catheterization, Central Venous; Headache; Humans; Hypertension; Immunosuppression Therapy; Lung Transplantation; Magnetic Resonance Imaging; Male; Posterior Leukoencephalopathy Syndrome; Seizures; Tacrolimus; Treatment Outcome

There is little precedent for a medication-induced spontaneous intracranial hypotension/cerebrospinal fluid (CSF) hypovolemia (SIH). This case history of a woman with low CSF pressure, orthostatic headache, and radiographic findings consistent with SIH but without a detectable leak was notable for its association, both onset and resolution, with the use of the calcineurin inhibitor tacrolimus (FK506). A literature review for potential causes of a tacrolimus-induced CSF hypotension suggests many potential mechanisms of action, including effects on blood brain barrier and dural compliance, and supports further vigilance for this condition in the medically complex setting of tacrolimus use.

Topics: Cerebrospinal Fluid Leak; Cerebrospinal Fluid Rhinorrhea; Female; Graft Rejection; Headache; Humans; Hypovolemia; Immunosuppressive Agents; Intracranial Hypotension; Liver Transplantation; Middle Aged; Tacrolimus

Serial changes in the circulating and cerebrospinal fluid (CSF) cytokine levels were assessed in a patient with Sjogren's syndrome (SS)-associated meningoencephalomyelitis. A 16-yr-old girl diagnosed as having primary SS at 8 yr of age presented headache and vomiting. CSF studies revealed lymphocyte-dominant pleocytosis and high IgM index, but no evidence of infection. Disturbed consciousness and diffuse slow waves on electroencephalogram led to the diagnosis of SS-meningoencephalitis. The clinical condition subsided after a cycle of dexamethasone therapy, however, 2 months later urinary retention and paresthesia of the lower body developed. Craniospinal magnetic resonance imaging (MRI) showed extensive intraparenchymal lesions with high T2-weighted signal intensity adjacent to the posterior left horn of lateral ventricle of the brain and the longitudinal lesion from C5 to T10 of the spinal cord. High-dose methyl-prednisolone and subsequent tacrolimus therapy has effectively controlled the activity of SS-meningoencephalomyelitis. Monitoring of systemic and CSF cytokine levels during the course of illness revealed that CSF interleukin-6, but not interferon-gamma or tumor necrosis factor-alpha levels were the sensitive indicator of disease activity. The unique cytokine profile, differing from those of infectious meningitis may be useful for predicting the central nervous system involvement in autoimmune disease.

Topics: Adolescent; Anti-Inflammatory Agents; Biomarkers; Brain; Cytokines; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Interleukin-6; Magnetic Resonance Imaging; Meningoencephalitis; Methylprednisolone; Monitoring, Physiologic; Myelitis; Predictive Value of Tests; Sjogren's Syndrome; Spinal Cord; Tacrolimus; Treatment Outcome; Vomiting

To classify the headache syndromes under treatment with calcineurin inhibitors and to investigate whether the latter influence the nitric oxide production of human brain microvascular cells (HBMEC).. Single cases of cyclosporine-induced headaches have been reported. Since calcineurin inhibitors are known to influence the renal metabolism of NO, a key molecule in tension-type headache and migraine, we were interested whether calcineurin inhibitors might change NO metabolism in HBMEC as well.. Headache symptoms of 74 patients receiving cyclosporine and/or tacrolimus for organ transplantation were retrospectively assessed. Furthermore, the effect of cyclosporine and tacrolimus on nitric oxide production in human brain microvascular endothelial cells was investigated after incubation.. Only 18 of the 74 patients reported no headache 1-36 months after liver, lung, or bone-marrow transplantation, 28 reported a new headache, and 17 an increase in the frequency or intensity of a pre-existing headache. The headache was generally classified as migraine without aura (IHS 1.1) or migraine-like headache (IHS 1.6). Furthermore, we found significantly increased NO production after co-incubation of calcineurin inhibitors with human brain microvascular endothelial cells.. The pathophysiological mechanism of these headaches may be connected with an endothelial dysfunction in terms of increased production of NO.

Topics: Adult; Aged; Brain; Calcineurin Inhibitors; Cells, Cultured; Cyclosporine; Endothelial Cells; Female; Headache; Humans; Immunosuppressive Agents; Male; Middle Aged; Nitric Oxide; Retrospective Studies; Tacrolimus; Transplants

A 24 year old woman presented with a sudden excruciating headache mimicking an acute vascular event. She had undergone a lung transplantation because of cystic fibrosis and was receiving maintenance treatment with tacrolimus and prednisone. Ancillary investigation excluded vascular causes. Magnetic resonance imaging demonstrated hyperintense lesions in the infratentorial and parieto-occipital regions consistent with posterior leucencephalopathy syndrome. Both her clinical condition improved and the lesions disappeared completely after withdrawal of tacrolimus, suggesting that her condition could be explained by a tacrolimus encephalopathy.

Topics: Acute Disease; Adult; Brain; Brain Diseases; Cyclosporine; Cystic Fibrosis; Diagnosis, Differential; Drug Therapy, Combination; Female; Headache; Humans; Image Enhancement; Immunosuppressive Agents; Lung Transplantation; Magnetic Resonance Imaging; Neurologic Examination; Postoperative Complications; Prednisone; Recurrence; Tacrolimus

A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.

Topics: Adult; Anemia, Aplastic; Anticonvulsants; Blood-Brain Barrier; Bone Marrow Transplantation; Brain Diseases; Brain Edema; Ceftazidime; Cerebral Hemorrhage; Cyclosporine; Diagnosis, Differential; Diuretics; Endothelium, Vascular; Epilepsy, Generalized; Female; Fluconazole; Graft vs Host Disease; Headache; Humans; Immunosuppressive Agents; Intracranial Hypertension; Magnetic Resonance Imaging; Tacrolimus; Transplantation Conditioning; Transplantation, Homologous

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

Topics: Cyclosporine; Female; Headache; Humans; Middle Aged; Tacrolimus