scholarly journals Tacrolimus Dose-Conversion Ratios Based on Switching of Formulations for Patients with Solid Organ Transplants

2021 ◽  
Vol 74 (4) ◽  
Author(s):  
Wen-Yuan Johnson Kuan ◽  
Nathalie Châteauvert ◽  
Vincent Leclerc ◽  
Benoît Drolet
Keyword(s):  
Organ Transplant ◽  
Oral Formulation ◽  
Conversion Ratio ◽  
Oral Suspension ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Blood Concentrations ◽  
Electronic File ◽  
Before And After ◽  
Using Data

Background: Tacrolimus may be administered during hospitalization as an IV formulation or oral suspension. However, literature suggesting appropriate ratios for conversion from these formulations to capsules is limited. Objective: To evaluate conversion ratios after a switch in formulation of tacrolimus for solid-organ transplant recipients. Methods: This single-centre observational longitudinal study involved hospitalized patients who underwent a switch in formulation of tacrolimus according to 1 of 3 possible scenarios: IV to oral suspension, IV to capsule, or oral suspension to capsule. Data were collected from the earliest accessible electronic file (January 2009) to January 1, 2019. Conversion ratios were calculated for each of the 3 groups using data for blood concentrations and doses before and after the switch. The calculated ratios were then compared with recommended conversion ratios: 1:5 (i.e., 1 mg of IV tacrolimus is converted to 5 mg of oral tacrolimus, expressed as “5”) for either of the switches involving an IV formulation and 1:1 (i.e., same amount, expressed as “1”) for the switch from oral formulation to capsules. Results: For the group who underwent switching from the IV formulation to oral suspension, the mean calculated conversion ratio was 3.04, which was significantly different from the recommended ratio of 5. For the group who underwent switching from the IV formulation to capsules, the calculated conversion ratio was 5.18, which was not significantly different from the recommended ratio of 5. For the group who underwent switching from oral suspension to capsules, the calculated conversion ratio was 1.17, which was not significantly different from the recommended ratio of 1. Conclusion: In this small retrospective study of tacrolimus therapy, the calculated conversion ratio was significantly different from the recommended ratio for patients who were switched from IV administration to oral suspension, but not for those switched from IV administration or oral suspension to capsules. Therapeutic drug monitoring therefore appears indispensable, regardless of conversion ratios. RÉSUMÉ Contexte : Le tacrolimus peut être administré par IV ou sous forme de suspension orale pendant une hospitalisation. Cependant, il existe peu de documents qui proposent des ratios appropriés pour convertir ces formulations en capsules. Objectif : Évaluer les ratios de conversion après un changement de formulation du tacrolimus pour les bénéficiaires de greffes d’organes solides. Méthodes : Cette étude observationnelle longitudinale unicentrique impliquait des patients hospitalisés, pour qui la formulation de tacrolimus changeait en fonction de chacun des trois scénarios possibles : passage de l’administration par IV à la suspension orale, passage de l’administration par IV aux capsules ou passage de l’administration par suspension aux capsules. Le recueil des données a été effectué à partir du plus ancien dossier électronique accessible (janvier 2009) jusqu’au 1er janvier 2019. Les ratios de conversion ont été calculés pour chacun des trois groupes à l’aide de données pour les concentrations de sang et des doses avant et après le changement. Les ratios calculés ont ensuite été comparés avec les ratios de conversion recommandés : 1:5 (c.-à-d., 1 mg de tacrolimus administré par IV est converti en 5 mg de tacrolimus par voie orale, conversion exprimée par le nombre « 5 ») pour chacun des changements impliquant une formulation IV et 1:1 (c.-à-d. même quantité, conversion exprimée par le nombre « 1 ») pour le passage de la formulation orale aux capsules. Résultats : Dans le groupe dont l’administration par IV est passée à une suspension orale, le ratio de conversion moyen calculé était de 3,04, ce qui était significativement différent par rapport au ratio recommandé de 5. Pour le groupe dont l’administration par IV est passée à des capsules, le ratio de conversion moyen calculé était de 5,18, ce qui n’était pas significativement différent par rapport au ratio recommandé de 5. Pour le groupe dont l’administration est passée de la suspension orale aux capsules, le ratio de conversion moyen calculé était de 1,17, ce qui n’était pas significativement différent par rapport au ratio recommandé de 1. Conclusion : Dans cette petite étude rétrospective de la thérapie à l’aide du tacrolimus, le ratio de conversion calculé était significativement différent du ratio recommandé pour les patients qui passaient d’une administration IV à une suspension orale, mais pas pour ceux qui passaient d’une administration par IV ou d’une suspension orale à des capsules. La surveillance thérapeutique des médicaments semble donc indispensable, quels que soient les ratios de conversion.

scholarly journals Tacrolimus Intrapatient Variability After Switching From Immediate or Prolonged-Release to Extended-Release Formulation, After an Organ Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Arnaud Del Bello ◽  
Clotilde Gaible ◽  
Nathalie Longlune ◽  
Anne-Laure Hebral ◽  
Laure Esposito ◽  
...  
Keyword(s):  
Extended Release ◽  
Organ Transplant ◽  
Immediate Release ◽  
Prolonged Release ◽  
Solid Organ ◽  
Safe Procedure ◽  
Release Formulation ◽  
Blood Concentrations ◽  
Extended Release Formulation ◽  
Before And After

Background and Purpose: Several formulations of tacrolimus are available, but evidence of the benefit of changing to the most recent formulations is lacking. Tacrolimus intra-patient variability (tacrolimus IPV) is an emerging risk factor associated with poor graft outcomes after solid organ transplantations. Here, we examined the modifications of tacrolimus IPV after switching to a different formulation of tacrolimus.Experimental Approach: We identified 353 solid organ transplant recipients that were switched in our center from immediate-release (IR-tacrolimus) or prolonged-release tacrolimus (PR-tacrolimus) to extended-release, LCP-tacrolimus (LCP-tacrolimus). Among them, 54 patients underwent at least 3 available tacrolimus blood concentrations before and after the switch, allowing us to investigate tacrolimus IPV.Key Results: The switch was considered as a safe procedure since only four of the 353 patients presented a graft rejection after the switch, and no patient was hospitalized for tacrolimus overdose. The tacrolimus IPV estimated by the coefficient of variation (CV-IPV) was stable before and after the switch to LCP-tacrolimus (CV-IPV: 29.0% (IQR 25–75 (15.5; 38.5) before and 24.0% (15.8; 36.5) after the switch, p = 0.65).Conclusion and Implications: Switching from IR- or PR-tacrolimus to LCP-tacrolimus is a safe procedure. However, the CV-tacrolimus IPV was not impacted by the change of formulation.

scholarly journals P0428CYTOMEGALOVIRUS INFECTION IN PATIENTS WITH GLOMERÜLER DISEASE TREATED WITH CYCLOPHOSPHAMIDE: A SINGLE-CENTER EXPERIENCE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gizem Kumru Şahin ◽  
Şahin Eyüpoğlu ◽  
Rezzan Eren Sadioğlu ◽  
Güle Çınar ◽  
Kenan Ateş ◽  
...  
Keyword(s):  
Risk Factors ◽  
Antiviral Treatment ◽  
Low Density Lipoprotein ◽  
Clinical Status ◽  
Organ Transplant ◽  
Density Lipoprotein ◽  
Solid Organ ◽  
Cmv Infection ◽  
Single Center Experience ◽  
Before And After

Abstract Background and Aims Cytomegalovirus (CMV) infection is an important complication in immunocompomised patients. Although approach to CMV infection is well-defined in stem cell and solid organ transplant recipients, less is known about the frequency and risk factors of CMV disease in patients with glomerulonephritis (GN). As few studies have shown that cyclophosphamide (CYC) treatment is a risk factor for CMV infection in GN patients, we aimed to describe the frequency and risk factors of CMV infection in GN patients treated with CYC. Method 268 patients diagnosed GN between January 2017 and November 2019 in Ankara University İbni Sina Hospital, Nephrology Department. We recruited 43 GN patients who were treated with CYC and screened all patients for viral DNA monthly. CMV infection defined by CMV DNA detected >500 copies/µl. Patients developed CMV and no-CMV infection were compared for age, sex, glomerular pathology, renal function and clinical status before and after treatment. Results CMV infection was detected in 10 (23,3%) patients at 2±1 (min:1 max:3) months of CYC treatment (Table-1). 7 patients were treated for CMV infection with parenteral ganciclovir, while the other 3 patients with low CMV DNA level (509, 538 and 540 copies/ml) and no disease symptoms were monitored without antiviral treatment. Patients with CMV infection had higher serum creatinine (4,2±3,2 vs. 1,9±1,8 mg/dl, p=0,006), lower estimated glomerular filtration rate (29±11 vs. 65±8 (ml/min/1.73 m2, p=0.016), lower low-density lipoprotein (144±71 vs. 221±83 mg/dl, p=0,012) at diagnosis compared with no-CMV infection patients (Table-2). Also more patients were diagnosed with rapidly proggressive GN (80,0% vs. 27.3%, p=0,007), and secondary GN was the most common GN diagnosis (80,0% vs. 27.3%, p=0.007) in CMV infection group. Conclusion CMV infection is a common complication in GN patients treated with CYC. Routine monitoring and prophylaxis should be considered for the patients who have risk factors for CMV infection.

scholarly journals 2107. Azole Therapeutic Drug Monitoring (TDM) in a Multiracial Cohort with Varied Pharmacogenetics

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S713-S713
Author(s):  
Peijun Yvonne Zhou ◽  
Tze Peng Lim ◽  
Si Lin Sarah Tang ◽  
Yixin Liew ◽  
Nathalie Grace Sy. Chua ◽  
...  
Keyword(s):  
Hematological Malignancy ◽  
Organ Transplant ◽  
Drug Formulation ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Efficacy And Safety ◽  
Breakthrough Infection ◽  
Southeast Asians ◽  
Anti Fungal ◽  
Trough Levels

Abstract Background Voriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers. Methods All adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety. Results VOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L). Conclusion VOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis. Disclosures All authors: No reported disclosures.

scholarly journals Absence of chronic hepatitis E in a German cohort of common variable immunodeficiency patients

2012 ◽  
Vol 4 (1) ◽  
pp. 28 ◽  
Author(s):  
Sven Pischke ◽  
Ruediger Horn-Wichmann ◽  
Diana Ernst ◽  
Bjoern Georg Meyer ◽  
Regina Raupach ◽  
...  
Keyword(s):  
Common Variable Immunodeficiency ◽  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Before And After ◽  
Protective Antibodies ◽  
Solid Organ Transplant Recipients ◽  
Common Variable

Cases of chronic or prolonged hepatitis E virus (HEV) infections have been described in solid organ transplant recipients, HIV infected patients and in patients with malignancies or idiopathic CD4+ T lymphopenia. It is unknown if HEV infection also takes chronic courses in patients with common variable immunodeficiency (CVID). We studied a cohort of 73 CVID patients recruited in a low endemic Central European country. None of the subjects tested positive for HEV RNA or anti-HEV IgG. Immunoglobulin transfusions (n=10) tested negative for HEV RNA but all were anti-HEV positive. To verify that such pooled blood products contain anti-HEV protective antibodies we measured the anti-HEV IgG optical density (OD) values in patients before and after transfusion. Anti-HEV OD values increased after infusion but did not reach the cut-off considered as positive. Thus, chronic HEV infections seem to be rare events in CVID patients in Germany. Commercially available immuno globulin infusions contain anti HEV antibodies and may contribute to protection from HEV infection

scholarly journals 2112. Voriconazole for Primary Prophylaxis: A Decade of Trends and Outcomes

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S715-S715
Author(s):  
Ahmad Mourad ◽  
Melissa D Johnson ◽  
John R Perfect
Keyword(s):  
Drug Interactions ◽  
Fungal Infections ◽  
Primary Prophylaxis ◽  
Antifungal Prophylaxis ◽  
University Hospital ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Blood Concentrations ◽  
The Mean ◽  
Microbiological Data

Abstract Background Invasive fungal infections (IFI) continue to affect the immunocompromised patient population. Many of these patients require antifungal prophylaxis. Voriconazole is an azole antifungal that has been utilized for preventing IFIs but does not have an approved indication for prophylaxis. Methods Adult patients admitted to Duke University Hospital from January 1, 2005 to December 31, 2015 who had received at least 2 days of systemic voriconazole as primary prophylaxis were included in this retrospective medical records review. Demographics, underlying comorbidities, adverse events, drug interactions, voriconazole blood concentrations, and microbiological data were assessed. Results Our review identified 403 patients receiving voriconazole for primary prophylaxis. 220 (55.6%) were male, 303 (75.2%) were Caucasian, and the mean age was 46.0 ± 15.7 years. 233 (57.8%) had leukemia, and 63 (15.6%) had lymphoma. 301 (74.7%) underwent hematopoietic transplant (BMT), and 45 (11.2%) had a solid-organ transplant. 176 (43.7%) patients received chemotherapy and 261 (64.8%) received immunosuppressive drugs. The mean voriconazole total daily maintenance dose was 416.1 ± 65.9 mg (5.5 ± 1.6 mg/kg/day). Patients received inpatient voriconazole for a mean of 19.5 ± 16.5 days. 371 (92.1%) patients received a concomitant interacting drug. Only 140 (43.7%) patients had therapeutic drug monitoring. The mean first voriconazole serum concentration was 1.8 ± 1.7 mg/L. 87 (21.6%) patients discontinued voriconazole prematurely; 41 (10.2% overall) of these patients had an adverse event requiring discontinuation. 5 had breakthrough fungal infections with microbiological data identifying a fungal species, which included Rhizopus spp. among others. Conclusion Voriconazole is frequently used for primary prophylaxis of IFIs and most commonly in BMT. It appears to be relatively well tolerated with some adverse side-effects (~10%) despite many potential drug–drug interactions and provides appropriate fungal coverage for many immunosuppressed patients. However, few patients had breakthrough fungal infections while receiving voriconazole. In a real-world setting, voriconazole can provide antifungal prevention in certain high-risk patients. Disclosures All authors: No reported disclosures.

Interaction Between Cyclosporine and Palbociclib in a Renal Transplant Patient: Case Report and Pharmacokinetic Perspective

2019 ◽  
Vol 33 (6) ◽  
pp. 912-914 ◽  
Author(s):  
Jeremiah D. Momper ◽  
Jin Yang ◽  
Janice Kerr ◽  
Ila Saunders ◽  
Jennifer Smith ◽  
...  
Keyword(s):  
Viral Infections ◽  
Immunosuppressive Agents ◽  
Organ Transplant ◽  
Therapeutic Index ◽  
Time Dependent ◽  
Solid Organ ◽  
Close Monitoring ◽  
Transplant Recipients ◽  
Blood Concentrations ◽  
Living Related

Solid organ transplant recipients have increased cancer risk due in part to chronic immunosuppression and opportunistic oncogenic viral infections. The management of drug interactions in transplant recipients being treated for cancer is important both to minimize the likelihood of drug-related toxicities and to optimize therapeutic outcomes. We present a case of a 41-year-old woman with a stable living–related kidney transplant maintained on an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and prednisone, who was subsequently diagnosed with a metastatic lobular breast carcinoma and papillary thyroid cancer and started palbociclib, a time-dependent CYP3A inhibitor. After initiation of palbociclib, cyclosporine trough and peak concentrations were increased by 159% and 81%, respectively, relative to the average cyclosporine concentrations pre-palbociclib. Using the Drug Interaction Probability Scale (DIPS), the interaction between palbociclib and cyclosporine was rated as “probable.” Dose reductions of immunosuppressive agents that are CYP3A substrates are warranted if palbociclib is initiated, followed by close monitoring of blood concentrations. This report also highlights the challenges of coadministering a time-dependent inhibitor with a narrow therapeutic index drug that is metabolized by the same enzyme, particularly when the inhibitor is given in cycles with off-treatment periods.

scholarly journals Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Ryan M. Rivosecchi ◽  
Cornelius J. Clancy ◽  
Ryan K. Shields ◽  
Christopher R. Ensor ◽  
Michael A. Shullo ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Organ Transplant ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Dose Ratio ◽  
Transplant Patients ◽  
Daily Dose ◽  
Liver Transplant Recipients

ABSTRACT We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.

scholarly journals Achievement of clinical isavuconazole blood concentrations in transplant recipients with isavuconazonium sulphate capsules administered via enteral feeding tube

2020 ◽  
Vol 75 (10) ◽  
pp. 3023-3028 ◽  
Author(s):  
Erin K McCreary ◽  
M Hong Nguyen ◽  
Matthew R Davis ◽  
Jared Borlagdan ◽  
Ryan K Shields ◽  
...  
Keyword(s):  
Enteral Feeding ◽  
Feeding Tube ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Capsule Formulation ◽  
Blood Concentrations ◽  
Routes Of Administration ◽  
Enteral Feeding Tube ◽  
Academic Medical ◽  
The Usa

Abstract Background Isavuconazole is a triazole antifungal available in IV and capsule formulation. Prescribing information states that capsules should not be chewed, crushed, dissolved or opened because the drug was not studied in this manner. However, considering the pharmacokinetics of the capsules, we theorized opening and sprinkling the contents into an enteral feeding tube (EFT) would result in adequate absorption and systemic concentrations of isavuconazole. Objectives To determine whether patients receiving isavuconazonium sulphate capsules via EFT would achieve clinical blood concentrations of isavuconazole. Methods Nineteen solid organ and HCT recipients receiving isavuconazole via EFT for prevention or treatment of invasive fungal infection (IFI) were prospectively identified at four academic medical centres in the USA. Patients were included in this evaluation if they received isavuconazole via EFT for at least 5 days and therapeutic drug monitoring (TDM) was performed. Results TDM was performed after a median of 7 days (range 6–17) following EFT administration and 15 days (range 7–174) of isavuconazole therapy overall. Median isavuconazole concentration was 1.8 μg/mL (range 0.3–5.2). Median isavuconazole concentrations in patients with or without prior IV administration were 1.8 μg/mL (range 0.3–5.2) and 2.2 μg/mL (range 0.8–3.6; P = 0.896), respectively. Concentrations achieved with the EFT route were similar to or greater than the corresponding concentrations via the IV route in six patients who had TDM performed during both routes of administration. Conclusions It is reasonable to consider opening isavuconazonium sulphate capsules and administering the contents enterally for prevention and treatment of IFI.

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