tacrolimus and Gingival-Hyperplasia

This 24-week, open, single-arm, prospective, multicenter study evaluated the effects of conversion from ciclosporin to Tacrolimus QD in adult kidney transplant patients. Stable patients receiving ciclosporin were converted to Tacrolimus QD at 0.1mg/kg/day. Relative change in renal function (primary endpoint) was assessed using estimated creatinine clearance (eCrCl) with a noninferiority margin set at -10%. A total of 346 patients were enrolled; and 301 patients were treated per protocol (PPS) in the hyperlipidemia (n=42), hypertrichosis (n=106), hypertension (n=77) and gingival hyperplasia (n=76) groups. Relative change in eCrCl was -0.6% in all PPS patients (95% CI, -2.2; 0.9) and -5.3% in the hyperlipidemia (CI, -9.59; -0.97), 0.9% in the hypertrichosis (CI, -2.59; 4.45), -0.1% in the hypertension (CI, -3.8; 3.68), and -1% in the gingival hyperplasia groups (CI, -4.63; 2.65) (PPS), meeting noninferiority criteria. There was no acute rejection. Decreases in serum lipids and blood pressure were moderate but without meaningful change in the number of treatment medications. Substantial decreases in severity of ciclosporin-related cosmetic side effects were evident from investigator and patient self-report of symptoms. Renal function remained stable after conversion to Tacrolimus QD. The effect of conversion on cardiovascular parameters was not clinically meaningful, however, marked improvement in ciclosporin-related cosmetic side effects was observed. (ClinicalTrials.gov number: NCT00481481).

Topics: Adult; Aged; Creatinine; Cyclosporine; Female; Gingival Hyperplasia; Humans; Hyperlipidemias; Hypertension; Hypertrichosis; Immunosuppressive Agents; Kidney Transplantation; Lipids; Male; Middle Aged; Prospective Studies; Tacrolimus

The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.

Topics: Adult; Cyclosporine; Esthetics; Female; Gingival Hyperplasia; Humans; Hyperlipidemias; Hypertension; Hypertrichosis; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Retreatment; Tacrolimus; Treatment Outcome

Cyclosporin A (CsA) is widely used to prevent liver transplantation failure. CsA-induced gingival overgrowth is a common side effect. However, the effect of cirrhotic liver disease, liver transplantation, and immunosuppressive therapy on the periodontium is yet unclear. The aim of the present cross-sectional study was to examine the effect of liver cirrhosis, transplantation, and immunosuppressive therapy on the periodontium.. The experimental group (LC) consisted of 13 liver cirrhosis patients. A second experimental group (PT) included 24 patients, post-liver transplantation, receiving immunosuppressive therapy. Seventeen healthy subjects formed a control group. The Ramfjord index teeth were recorded for plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and gingival overgrowth (GO).. Mean PI and mean GI for the LC, PT, and C groups were not statistically different (P >0.05). Mean PD for the LC (3.32+/-0.24 mm) and PT group (3.41+/-0.13 mm) was significantly higher (P = 0.0001, ANOVA) compared to the C group (2.45+/-0.16 mm). Likewise, CAL for the LC (4.89+/-0.47 mm) and PT group (4.68+/-0.47 mm) was significantly higher (P = 0.001, ANOVA) than the C group (2.78+/-0.23 mm). Patients in the PT group exhibited the greatest mean GO scores (0.88+/-0.09) compared to the LC group (0.37+/-0.07) and the C group (0.09+/-0.02). All 3 groups were significantly different from each other (P = 0.0001) despite great variability within the groups. GO in the CsA-treated patients (1.1+/-0.09) was significantly higher (P = 0.0001) than in those treated with tacrolimus (0.57+/-0.1).. Liver cirrhosis patients demonstrated greater pocketing and attachment loss compared to healthy matched controls. These same differences were observed in patients post-transplantation. Gingival overgrowth occurred as a result of the immunosuppressive therapy with CsA, while to a lesser degree with tacrolimus. Replacement of CsA by tacrolimus in patients manifesting gingival overgrowth might be recommended whenever possible to overcome this problem.

Topics: Analysis of Variance; Cyclosporine; Female; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Statistics, Nonparametric; Tacrolimus

Topics: Cyclosporine; Female; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Tacrolimus

Topics: Adult; Aged; Anticholesteremic Agents; Cyclosporine; Fatty Acids, Monounsaturated; Female; Fluvastatin; Gingival Hyperplasia; Hirsutism; Humans; Hyperlipidemias; Immunosuppressive Agents; Indoles; Kidney Transplantation; Lovastatin; Male; Middle Aged; Pravastatin; Tacrolimus

Topics: Cyclosporine; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Kidney Transplantation; Prospective Studies; Tacrolimus

Topics: Cyclosporine; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Tacrolimus

Topics: Administration, Topical; Adult; Calcineurin Inhibitors; Gingival Hyperplasia; Humans; Male; Tacrolimus

An infant boy with steroid-resistant nephrotic syndrome (idiopathic membranous glomerulonephropathy) achieved remission with ciclosporin but developed eosinophilia and high IgE levels (max 19 000  iU/mL). Conversion to tacrolimus resulted in chronic diarrhoea (eosinophilic gastroenteritis), muscle weakness, polyserositis and failure-to-thrive. In contrast, a trial without tacrolimus resulted in a ciclosporin-responsive relapse, therapy-resistant focal seizures with generalised spikes, worsening muscle weakness and diarrhoea. The patient was weaned off of ciclosporin and completely normalised. In vitro testing demonstrated decreased viability of the patient's cells when incubated with calcineurin inhibitors (ciclosporin, 70%; tacrolimus, 80% compared to control cells), supporting their role in this adverse drug reaction.

Topics: Cell Survival; Cyclosporine; Deprescriptions; Drug Substitution; Enteritis; Eosinophilia; Failure to Thrive; Gastritis; Gingival Hyperplasia; Glomerulonephritis, Membranous; Humans; Hypertrichosis; Immunosuppressive Agents; In Vitro Techniques; Infant; Kidney Glomerulus; Male; Microscopy, Electron; Muscle Weakness; Seizures; Serositis; Tacrolimus; Vasculitis

The CONCERTO study results showing the beneficial effects of conversion from cyclosporine to tacrolimus prolonged-release (tacrolimus PR) in stabilised patients after kidney transplantation, were first published in 2011. This communication describes our first experience of conversion from cyclosporine to tacrolimus PR in stabilised kidney transplant patients. The aim was to determine whether it could be used in routine clinical practice in the Czech and Slovak Republics.. Evaluation was carried out at five transplantation centres in the Czech Republic and Slovakia. In all participating Centres, the drug conversion was conducted according to the ICH/GCP guidelines. A total of 104 patients stabilised after kidney transplantation were converted from maintenance therapy with cyclosporine to treatment with tacrolimus PR. The data were collected 26 weeks after the switch. The primary endpoint was change in kidney graft function measured from the estimated glomerular filtration rate (GFR). The effect of conversion on blood pressure, metabolic parameters and cosmetic changes was also recorded. Special attention was paid to the safety and tolerability of treatment with tacrolimus PR.. GFR increased after six months by 10 % (P = 0.040). In addition a significant decrease in serum creatinine and triglycerides level was found together with major reduction in the incidence and severity of gingival hyperplasia and hirsutism. 3% of patients developed new onset of diabetes mellitus. Otherwise, the switch was very well-tolerated, without serious adverse events or acute rejections.. Conversion from cyclosporine to tacrolimus PR was shown to be a safe therapeutic alternative with patient benefits.

Topics: Cyclosporine; Delayed-Action Preparations; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Substitution; Dyslipidemias; Female; Gingival Hyperplasia; Glomerular Filtration Rate; Hirsutism; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Tacrolimus; Treatment Outcome

Aplastic anemia (AA) is a rare disorder in children, usually treated with immunosuppressive therapy (IST) including antithymocyte globulin (ATG) and cyclosporin A. There are no current widely used alternative therapies with comparable efficacy. We describe a child with severe aplastic anemia (SAA), who developed severe gingival hyperplasia secondary to cyclosporin A, unresponsive to intensive dental intervention. When IST was changed to tacrolimus there was a significant improvement in the gingival hyperplasia, but equally important, he achieved complete response of his AA within several months. The use of tacrolimus in children with AA may be a potential modality of treatment.

Topics: Anemia, Aplastic; Anemia, Refractory; Child; Cyclosporine; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Male; Tacrolimus

Tacrolimus and Cyclosporine A (CyA) are cornerstones in immunosuppressive therapy. Cyclosporine side eff ects include hypertension and hypercholesterolemia both of which may increase the risk of cardiovascular mortality, gingival hyperplasia and hirsutism are known to reduce quality of life. The aim of this prospective study was to evaluate changes in cardiovascular risk profile and cosmetic side eff ects after conversion from CyA to tacrolimus.. 25 stable kidney transplant recipients (9 male, 16 female) were converted from a CyA to a tacrolimus--based regimen. Mean age was 45.7 +/- 13.5 years. Time to switch following transplantation was 4.7+/-1.7 years. Reasons for conversion were multiple: arterial hypertension (9), hypertrichosis (3), gingival hyperplasia (3), hyperlipidemia (14).. 19/25 patients completed the one year study period. One patient died, two returned to hemodialysis, two were switched back to CyA and one patient was lost to follow-up. There were statistically significant changes (p = < 0.05) in systolic and diastolic pressure and antihypertensive medication could be reduced in 13 patients. The dose of lipid-lowering agents could be reduced in the majority of the recipients and a complete withdrawal was achieved in 7 patients. Hypertrichosis and gingival hyperplasia resolved in all patients. Further, there was a significant improvement (p = <0.05) in urea and serum creatinine levels. Adverse events were consistent with the established safety profile for tacrolimus.. Conversion to a tacrolimus-based regimen led to an improvement in the cardiovascular risk profile. Further, cosmetic side eff ects which may lead to non-compliance, resolved after the switch.

Topics: Adult; Cardiovascular Diseases; Cyclosporine; Female; Gingival Hyperplasia; Humans; Hyperlipidemias; Hypertension; Hypertrichosis; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Risk Factors; Tacrolimus

To estimate the prevalence of gingival overgrowth in kidney allograft recipients in southern Switzerland and to determine the factors associated with it. We hypothesized that poor oral hygiene was a risk factor.. We assessed the level of oral hygiene among renal transplant patients and determined whether a good level of information and regular dental checkups in addition to good oral hygiene could prevent gingival hyperplasia. Seventy-six adults who had undergone kidney transplantation were examined. The level of oral hygiene, gender, age, time elapsed from transplantation, medication and dose were recorded.. In general the level of oral hygiene was average. We found a significant association between the severity of gingival overgrowth and the level of oral hygiene. No statistical relationship between gingival hyperplasia and the other recorded variables was detected. Patients on tacrolimus had a tendency to have less gingival hyperplasia. Patient education, along with regular dental checkups and a good level of oral hygiene, should prevent gingival hyperplasia or maintain it at an acceptable level.. Intensive motivation of patients to maintain good oral hygiene is necessary to reduce the incidence of gingival hyperplasia.

Topics: Adult; Aged; Calcineurin Inhibitors; Cross-Sectional Studies; Cyclosporine; Female; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Oral Hygiene; Patient Education as Topic; Risk Factors; Severity of Illness Index; Switzerland; Tacrolimus

Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies.. The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats.. Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar.. After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P>0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the Vf and Vcf (P<0.05).. Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related.

Topics: Animals; Cell Count; Collagen; Connective Tissue; Epithelium; Fibroblasts; Gingiva; Gingival Hyperplasia; Gingival Overgrowth; Immunosuppressive Agents; Injections, Subcutaneous; Male; Mouth Mucosa; Random Allocation; Rats; Rats, Sprague-Dawley; Tacrolimus; Time Factors

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

Topics: Anemia, Aplastic; Azithromycin; Cyclosporine; Female; Gingival Hyperplasia; Humans; Middle Aged; Tacrolimus

The use of cyclosporine for immunosuppression in renal transplantation allograft recipients is associated with hypertrichosis, gingival hyperplasia, and hypercholesterolemia. Conversion of patients to tacrolimus may lead to an improvement in these effects with minimal risk of rejection or allograft dysfunction.. Sixteen renal transplant recipients were prospectively converted from CsA to tacrolimus and followed for 1 year. Gingival hyperplasia index, total cholesterol, and blood pressure were recorded at the outset, 4-, 8-, and 12-month intervals. Glomerular filtration rate was checked before conversion and 1 year later. Photographs documenting hypertrichosis were taken before conversion and 1 year later. Adverse effects from tacrolimus were recorded at 4, 8, and 12 months.. Twelve patients with hypertrichosis noted rapid improvement. Mean gingival hyperplasia index decreased from 24 to 6; mean total cholesterol decreased from 237 to 195. Glomerular filtration rate was essentially unchanged (56 to 54). One episode of rejection occurred, three patients developed diarrhea, three noted headaches, and one had a tremor.. If carefully monitored, patients suffering adverse effects secondary to cyclosporine may be converted to tacrolimus with minimal risk of allograft dysfunction or rejection.

Topics: Adolescent; Adult; Cyclosporine; Diarrhea; Female; Gingival Hyperplasia; Humans; Hypercholesterolemia; Hypertrichosis; Immunosuppressive Agents; Male; Middle Aged; Tacrolimus; Time Factors

Gingival Hyperplasia (GH) and hypertrichosis (HT) are two sides effects associated with the usage of cyclosporine (CyA) but not with tacrolimus (FK 506). The aim of this study is to evaluate the efficacy and security of the conversion from CsA to FK 506 to treat those two complications. From August 1996 to May 1997, 15 patients (9 males, 6 females) aged from 23 to 63 years old (38 +/- 14, mean +/- SD) were switched from CsA to FK 506, 12 for GH, 2 for HT and one for combined presentation. FK 506 was first initiated at a dose of 0.15 mg/kg/day and then adjusted to a level target of 8 ng/ml. The conversion was done on an out patient basis at average 35 (5-83) months after transplantation. Patients were followed prospectively for 12 months. There was a significant reduction in GH in all patients within 3 months. Five out 13 patients had a complete resolution of GH within three months of conversion, 9/12 within 6 months and all by 12 months. HT resolved completely within 6 months. No rejection episode occurred and the serum creatinin remain stable over one year post conversion. Conversion from CsA to FK 506 is thus a safe and valid option to treat CsA induced GH and HT.

Topics: Adult; Creatinine; Cyclosporine; Drug Monitoring; Female; Gingival Hyperplasia; Graft Rejection; Humans; Hypertrichosis; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Tacrolimus

Topics: Adult; Aged; Cholesterol; Creatinine; Cyclosporine; Gingival Hyperplasia; Humans; Hypertrichosis; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Prednisone; Tacrolimus; Triglycerides

During immunosuppression with cyclosporine, gingival overgrowth, a minor secondary effect, may appear in the first weeks of treatment. In certain cases it may affect the function and/or esthetic appearance in a manner intolerable to the patient. A new immunnosuppressive molecule, tacrolimus, presently used as a treatment of second choice to control acute corticoresistant rejection, may bring oral comfort to these patients, since it reduces gingival overgrowth to negligible levels.

Topics: Cyclosporine; Gingival Hyperplasia; Gingival Overgrowth; Graft Rejection; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Tacrolimus

Topics: Adult; Female; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Tacrolimus

Topics: Child, Preschool; Cyclosporine; Female; Gingival Hyperplasia; Heart Transplantation; Humans; Immunosuppressive Agents; Tacrolimus

The evolution and the improvement of the surgical techniques and pharmacological therapies brought to new patients categories, also in odontoiatric field for example patients who underwent organ transplantation. Among the patients, we wanted to dwell our attention on pediatric patients after liver transplantation, by light of the new therapeutic outlines modifications. In fact in these young patients it is possible to observe, besides the severe systemic consequences, also the involvement of the oral cavity. After the transplantation, the immunosuppressive therapy is set up and it is based on the use of cyclosporine with the possible azotiopine or steroid association. The cyclosporine side-effects are well known and, among these, the gingival hyperplasia. FK506 is a drug recently introduced, it is a strong immunosuppressor. Therefore we began to estimate patients who assumed FK 506, in order to compare the effect at the gingival level among patients who follow a cyclosporine therapy.

Topics: Child; Child, Preschool; Cyclosporine; Drug Therapy, Combination; Female; Gingiva; Gingival Hyperplasia; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Tacrolimus

Orthotopic liver transplantation is now a widely used treatment for patients with end-stage liver disease. Lifelong pharmacologic immunosuppression renders these patients susceptible to many infections. The purpose of this article is to provide guidelines for treating the patient with end-stage liver disease, both before and after transplantation. In addition, we shall discuss some of the medical implications associated with end-stage liver disease and their clinical presentations and appropriate presurgical management. Adverse side effects of long-term immunosuppression and their effect on the oral and maxillofacial region shall also be discussed. Last, a brief discussion of FK506, the latest immunosuppressant, will be presented together with the implications of its use on our surgical treatment of these patients.

Topics: Anti-Bacterial Agents; Candidiasis, Oral; Chronic Disease; Cyclosporins; Gingival Hyperplasia; Humans; Immunosuppression Therapy; Liver Diseases; Liver Transplantation; Partial Thromboplastin Time; Prothrombin Time; Tacrolimus