DOCSLIB.ORG

Influence of Co-Medication with Sirolimus Or Cyclosporine On

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Influence of Co-Medication with Sirolimus Or Cyclosporine On American Journal of Transplantation 2005; 5: 2937–2944 Copyright C Blackwell Munksgaard 2005 Blackwell Munksgaard doi: 10.1111/j.1600-6143.2005.01107.x Influence of Co-Medication with Sirolimus or Cyclosporine on Mycophenolic Acid Pharmacokinetics in Kidney Transplantation ∗ D. Cattaneoa,b, ,S.Merlinia,b,S.Zenonia,b, Introduction S. Baldellia,b,E.Gotti a,G.Remuzzia,b and N. Pericoa,b Mycophenolic acid (MPA), the active form of the pro-drug mycophenolate mofetil (MMF) and the new mycopheno- aDepartment of Immunology and Transplantation, late sodium, is part of standard immunosuppressive reg- Ospedali Riuniti–Mario Negri Institute for Pharmacological imens in organ transplantation (1). MMF is commonly Research, Bergamo, Italy administered in a fixed daily dose as adjunctive therapy bCenter for Research on Organ Transplantation ‘Chiara in combination with a calcineurin inhibitor and corticos- Cucchi De Alessandri e Gilberto Crespi’, Bergamo, Italy ∗ teroids. Recent evidence, however, suggests that a fixed Corresponding author: Dario Cattaneo, dose regimen—adopted in the majority of transplant units [email protected] worldwide—no longer might be the best approach for the management of transplant patients, since wide inter- The pharmacokinetics of mycophenolic acid (MPA)— patient variability in drug exposure has been observed in the active metabolite of mycophenolate mofetil kidney transplant recipients given the fixed daily MMF dose (MMF)—is significantly influenced by co-medications. (2). Therefore, therapeutic drug pharmacokinetic monitor- The impact of sirolimus on daily MPA exposure, how- ing is advised (3–6). A significant predictive value for acute ever, has not been investigated so far. As a part of the rejection (3,5,6), renal function (2) and drug-related side ef- study aimed at investigating the efficacy of Campath- fects (7,8) has been found for the 12-h dose interval MPA 1H induction therapy in a steroid-free regimen in kid- area under the concentration-time curve (AUC − ) and for ney transplantation, MPA plasma levels were seri- 0 12 ally measured in 21 patients treated with low-dose the predose trough MPA concentration (C0). sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full Following oral administration, MPA is converted to inac- pharmacokinetic profiles were compared at month 6 tive metabolites by glucuronidation mediated by the uridine and 12 post-surgery. Mean dose-adjusted MPA trough diphosphate glucuronosyltransferase (UDP-GT) enzyme levels were 4.4-fold higher in patients on combined family (1,9). The main metabolite, 7-hydroxy-glucuronide SRL and MMF than in those given CsA and MMF. Phar- (MPAG), is excreted in the urine but may also contribute to macokinetic studies demonstrated that mean MPA the enterohepatic recirculation of MPA after excretion into Cmax and Tmax were comparable in the two groups, the bile and hydrolysis in the gastrointestinal tract (10). Re- while mean MPA AUC − was higher in SRL than CsA 0 12 cently, three carboxyl-linked additional glucuronides have treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent also been detected in vitro and in vivo (11). with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different ef- Concomitant immunosuppressive therapy significantly in- fects on MPA metabolism and/or excretion eventually fluences MPA exposure. In particular glucocorticoids, affecting its immunosuppressive property and/or tox- by inducing UDP-GT expression, interfere with MMF icity. CsA, but not SRL, inhibits MPA enterohepatic re- metabolism (12). Others reported a significant increase circulation, reducing MPA daily exposure. in plasma MPA concentrations in patients treated with MMF plus tacrolimus (13,14), attributed to the inhibition Key words: Cyclosporine, drug-drug interactions, kid- of MPA glucuronidation by tacrolimus (13,15). At variance, ney transplantation, mycophenolic acid, pharmacoki- combining MMF with the other calcineurin inhibitor cy- netics, sirolimus closporine (CsA) reduced MPA exposure (16). Recently, Received 9 June 2005, revised 13 July 2005 and ac- experimental animal studies have shown that CsA inhibits cepted for publication 9 August 2005 the multidrug resistance-associated protein 2 (MRP2)—a protein expressed at the apical surface of hepatocytes— which excretes conjugation products of drug metabolites, as MPA glucuronides, into bile (17,18). Therefore CsA, by blocking the transport of MPA metabolites into bile from 2937 Cattaneo et al. hepatocytes, reduces enterohepatic recirculation of MPA, were given MMF at the oral low-dose of 500 mg twice a day starting on ultimately leading to a decrease in MPA concentrations in day 1 post-operatively, with no specific MPA targets. During the study, the MMF dose was adjusted by the attending physicians, which were unaware the 4 to 12-h window of the AUC profile (AUC4−12) (17). of the MPA concentrations. Modifications of MMF doses were mainly per- Sirolimus (SRL) is a new immunosuppressant character- formed taking into account blood leukocyte count as well or other clinical ized by a unique mechanism of action and a potential ca- conditions related to drug tolerability and adverse effects. pacity to synergize with other antirejection drugs (19). In The administration of prokinetic drugs, resins or any agent known to inter- the clinical practice, SRL is usually given in association with fere with MPA absorption, distribution, metabolism and/or elimination was calcineurin inhibitors and steroids or antimetabolites such not allowed during all the study period. as MMF and azathioprine (20). Preliminary retrospective evidence indicates that concomi- Study design and pharmacokinetic measurements tant SRL therapy enhances MPA trough level as compared This prospective study examined the effects of SRL and CsA on dose- with CsA (21,22). However, there are no prospective stud- adjusted MPA trough levels measured every 5 days starting from day 5 ies, with strict drug monitoring and full pharmacokinetic post-Tx—when patients reached steady-state of drug distribution—up to evaluations aimed at formally assessing the effects of SRL day 90 and then at month 4, 6 and 12 post-surgery. and CsA on MPA exposure. Moreover, at month 6 and 12 post-transplant, all patients underwent a 12-h The current study—which is part of a protocol aimed at in- MPA pharmacokinetic profile. On the morning of the pharmacokinetic stud- ies, blood samples were collected for routine hematological, biochemical vestigating the efficacy of Campath-1H induction therapy in analysis as well as estimation of glomerular filtration rate by iohexol clear- a steroid-free regimen in kidney transplant patients—was ance (23) and for the determination of trough levels of plasma MPA and designed to compare prospectively the effects of SRL- or blood SRL or CsA. Then patients were given the morning dose of MMF and CsA-coadministration with MMF on MPA exposure. Given SRL or CsA. MPA pharmacokinetic analysis was based on EDTA-collected its potent effect of depleting both T and B lymphocytes, blood samples from antecubital vein at 20, 40, 75, 120 minutes and 3, 4, 5, Campath-1H should allow the minimization of maintenance 6, 7, 8, 10 and 12 h after drug administration. Samples were centrifuged at anti-rejection therapy. We have, therefore, planned to use 3000 g, plasma separated and stored at −20◦Cuntil analysis. For SRL and very low doses of CsA or SRL, in combination with low- CsA pharmacokinetics, blood samples were collected in heparinized tubes ◦ doses of MMF. In the present study, we sought to : (1) se- at 0.5, 1, 2, 3, 4, 5, 6, 8, 10 and 12 h after dosing and stored at −20 C un- rially monitor MPA trough levels in patients given low-dose til analysis. All drug measurements were performed by high-performance liquid-chromatography (HPLC) as previously described (2,24,25). MPA, SRL SRL or low-dose CsA both in addition to low-dose MMF as and CsA concentration-time profile was recorder for all patients, together maintenance immunosuppression over 12 months post- with the time to reach the maximum concentration (Tmax)andthe maxi- operatively; (2) compare 12-h MPA pharmacokinetic pro- mum drug concentration (Cmax). The AUC from time equal to 0 to the last files in both groups at month 6 and 12 after surgery and (3) sampling point (12 h) was calculated by the trapezoidal rule. examine the effects of SRL and CsA on MPA enterohepatic recirculation, expressed as MPA AUC4−12. To study the different effect, if any, of SRL and CsA on MPA bioavailabil- ity, we measure MPA AUC0−2,asasurrogate marker of MPA absorption. Additionally, to test the hypothesis that CsA may decrease the MPA en- Methods terohepatic recirculation (17), we also estimated the MPA AUC from 4 h to 12 h after drug administration (AUC4−2), a time interval corresponding to the Patients appearance of a secondary MPA peak due to enterohepatic recirculation, re- Twenty-one patients (13 men; 8 women) with end-stage renal disease lated to the reabsorption of MPA glucuronidated metabolites as MPA. Both who underwent primary kidney transplant were enrolled under an Ethics MPA AUC0−2 and AUC4−12 were estimated using the trapezoidal rule. Committee-approved protocol at the Ospedali Riuniti Bergamo, Italy, follow- ing written informed consent. They were allocated to one of the following two study groups according to a randomization design: Group 1 (n = 11) Statistical analysis was assigned to Campath-1H, low-dose SRL and low-dose MMF; group 2 Results are reported as means ±SD. Correlation between MPA trough lev- (n = 10) entered a regimen with Campath-1H, low-dose CsA and low-dose els and the corresponding AUC0−12 was performed in both groups (SRL MMF. and CsA) by linear regression analysis. To take into account the confound- ing factor of MMF drug dose changes, MPA trough levels and pharma- Campath-1 (Alemtuzumab, Schering Plough, Milano, Italy) was given as cokinetic parameters were adjusted for the daily MMF dose.
Load more

Recommended publications
  • PPE Requirements Hazardous Drug Handling
    This document’s purpose is only to provide general guidance. It is not a definitive interpretation for how to comply with DOSH requirements. Consult the actual NIOSH hazardous drugs list and program regulations in entirety to understand all specific compliance requirements. Minimum PPE Required Minimum PPE Required Universal (Green) - handling and disposed of using normal precautions. PPE Requirements High (Red) - double gloves, gown, eye and face protection in Low (Yellow) - handle at all times with gloves and appropriate engineering Hazardous Drug Handling addition to any necessary controls. engineering controls. Moderate (Orange) -handle at all times with gloves, gown, eye and face protection (with splash potential) and appropirate engineering controls. Tablet Open Capsule Handling only - Contained Crush/Split No alteration Crush/Split Dispensed/Common Drug Name Other Drug Name Additional Information (Formulation) and (NIOSH CATEGORY #) Minimum PPE Minimum PPE Minimum PPE Minimum PPE Required required required required abacavir (susp) (2) ziagen/epzicom/trizivir Low abacavir (tablet) (2) ziagen/epzicom/trizivir Universal Low Moderate acitretin (capsule) (3) soriatane Universal Moderate anastrazole (tablet) (1) arimidex Low Moderate High android (capsule) (3) methyltestosterone Universal Moderate apomorphine (inj sq) (2) apomorphine Moderate arthotec/cytotec (tablet) (3) diclofenac/misoprostol Universal Low Moderate astagraf XL (capsule) (2) tacrolimus Universal do not open avordart (capsule) (3) dutasteride Universal Moderate azathioprine
    [Show full text]
  • Drug-Induced Sexual Dysfunction in Men and Women
    VOLUME 36 : NUMBER 2 : APRIL 2013 ARTICLE Drug-induced sexual dysfunction in men and women Helen M Conaglen whether the clinician is willing to ask about sexual Clinical psychologist and SUMMARY issues and does so in a sensitive way.7,8 Senior research fellow Many medical conditions and their treatments Patients on long-term medications may not be John V Conaglen aware that their sexual problems have developed Endocrinologist and contribute to sexual dysfunction. as a result of their treatment. Conversely some may Associate professor in Commonly implicated drugs include Medicine blame their drugs for sexual problems which are due Sexual Health Research Unit antihypertensives, antidepressants, to relationship difficulties or other stressors. Some Waikato Clinical School antipsychotics and antiandrogens. doctors consider that asking patients if they had Faculty of Medical and Understanding the potential for drug-induced noticed any sexual adverse effects from their drugs Health Sciences University of Auckland sexual problems and their negative impact may ‘suggest’ them to the patient, and possibly result on adherence to treatment will enable the in non-adherence. Patients attributing their sexual clinician to tailor treatments for the patient problems to their drugs are less likely to continue the Key words treatment even when necessary for their health.9 The antidepressants, and his or her partner. consultation should include discussion of the patient’s antihypertensives, Encouraging a discussion with the patient sexual issues so these can be considered in treatment antipsychotics, arousal, about sexual function and providing erectile dysfunction, decisions. hypoactive sexual desire strategies to manage the problem are critical disorder, male impotence, to good clinical care.
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Corticosteroid Interactions with Cyclosporine, Tacrolimus, Mycophenolate, and Sirolimus: Fact Or Fiction?
    Transplantation Corticosteroid Interactions with Cyclosporine, Tacrolimus, Mycophenolate, and Sirolimus: Fact or Fiction? Stefanie Lam, Nilufar Partovi, Lillian SL Ting, and Mary HH Ensom he discovery and use of 4 classes of Timmunosuppressive agents (ie, cal- OBJECTIVE: To review the current clinical evidence on the effects of corticosteroid cineurin inhibitors, mammalian target of interactions with the immunosuppressive drugs cyclosporine, tacrolimus, myco- rapamycin [mTOR], antimetabolites, phenolate, and sirolimus. corticosteroids) have led to tremendous DATA SOURCES: Articles were retrieved through MEDLINE (1966–February 2008) improvements in short-term outcomes of using the terms corticosteroids, glucocorticoids, immunosuppressants, cyclo- solid organ transplantation. The goal of sporine, tacrolimus, mycophenolate, sirolimus, drug interactions, CYP3A4, P- glycoprotein, and UDP-glucuronosyltransferases. Bibliographies were manually immunosuppression is to prevent rejec- searched for additional relevant articles. tion of the transplanted organ while min- STUDY SELECTION AND DATA EXTRACTION: All English-language studies dealing imizing drug-related toxicity. The cal- with drug interactions between corticosteroids and cyclosporine, tacrolimus, cineurin inhibitors, cyclosporine and mycophenolate, and sirolimus were reviewed. tacrolimus, are potent inhibitors of T cells, DATA SYNTHESIS: Corticosteroids share common metabolic and transporter acting at a point of activation between re- pathways, the cytochrome P450 and P-glycoprotein (P-gp/ABCB1)
    [Show full text]
  • Medical Therapy for Pediatric Vascular Anomalies
    79 Medical Therapy for Pediatric Vascular Anomalies Judith F. Margolin, MD1 Heather Mills Soni, CPNP1 Sheena Pimpalwar, MD2 1 Baylor College of Medicine, Texas Children’sCancerandHematology Address for correspondence Judith F. Margolin, MD, Department of Service, Houston, Texas Pediatrics, Baylor College of Medicine, Texas Children’sCancerand 2 Division of Interventional Radiology, Department of Radiology, TCH, Hematology Service, Suite 1510, Clinical Care Center, 6701 Fannin Baylor College of Medicine, Houston, Texas Street, Houston, Texas 77030 (e-mail: [email protected]). Semin Plast Surg 2014;28:79–86. Abstract Vascular anomalies (VAs) comprise a large variety of individual diagnoses that in different phases of treatment require a diverse number of medical specialists to provide optimal care. Medical therapies include agents usually associated with cancer chemo- therapy, such as vincristine, as well more immunomodulatory types of drugs, such as Keywords glucocorticoids and sirolimus. These immunomodulating drugs are being successfully ► vascular anomalies applied in cases that are typically categorized as vascular tumors, including kaposiform ► chemotherapy hemangioendothelioma (KHE) and tufted angioma (TA), as well as some of the more ► sirolimus invasive types of vascular malformations (i.e., microcystic lymphatic malformations and ► kaposiform blue rubber bleb nevus syndrome (BRBNS). These therapies need to be combined with hemangio- good supportive care, which often involves anticoagulation, antimicrobial prophylaxis, endothelioma
    [Show full text]
  • Diapositiva 1
    4CPS-082 BACKGROUND: • Nephrogenic diabetes insipidus (NDI) results from the inability of the late distal tubules and collecting ducts to respond to vasopressin. • The lack of ability to concentrate urine results in polyuria and polidipsia. • NDI is almost always drug induced; however, there are other causes of it that are acquired, such as electrolyte abnormalities as hypokalemia or hypercalcemia. OBJECTIVE: • To describe a case of nephrogenic diabetes insipidus (NDI) associated with the long-term use and high-dose liposomal amphotericin B. METHODS: • Data were obtained from electronic medical records RESULTS: A 39 years old man diagnosed with diffuse large B-cell non-Hodgkin Lymphoma underwent an allogeneic bone marrow transplant. After a few months, the disease’s progression was detected and immunosuppressive treatment was suspended (February 2014). Rescue treatment was: Gemcitabine and Vinorelbine. In May, the patient was admitted to the hospital with graft-versus-host disease grade III, intestinal form. He was treated with: cyclosporine, micophenolate, sirolimus, methylprednisolone, oral and rectal beclametasone. Additionally, as antimicrobial prophylaxis were meropenem, acyclovir, levofloxacine, cotrimoxazole and caspofungine. In June, serum galactomannan antigen test was positive and invasive pulmonary aspergillosis was diagnosed. Aspergillus fumigatus and Aspergillus flavus were isolated. The patient was started on liposomal amphotericin B 6mg/kg (440 mg) daily during 41 days (accumulated dosage: 18.04g). Voriconazol was rejected because of concomitant treatment with sirolimus. During the treatment, his serum potassium was decreased <1.5mEq/L and it was difficult to maintain >3 mEq/L during the treatment with significant polyuria (urine output was >6litr/day). Nephrogenic diabetes insipidus(NDI) was diagnosed.
    [Show full text]
  • Sirolimus, Everolimus) Symptom Management Oxygen Rehab/Exercise Antidepressants/Anxiolytics Inhalers Lung Transplant Roadmap
    Drug Therapy for LAM Maryl Kreider, MD Director, ILD Program, Penn Lung Center, Philadelphia, PA (Drug) Therapy For LAM Disease Modifying MTOR inhibitors (sirolimus, everolimus) Symptom Management Oxygen Rehab/exercise Antidepressants/Anxiolytics Inhalers Lung transplant Roadmap Sirolimus What is it? Why in LAM? Nuts and Bolts Old therapies Future therapies Sirolimus Rapamycin = Rapamune = Sirolimus First of a class of medications called mTOR inhibitors Discovered in a soil sample on Easter Island – initially used as an antibiotic Now most common use is as a immunosuppressant in patients who have had transplants Also used in heart stents to stop them from getting clogged and as a cancer therapy (kidney cancer and some lymphomas) Sirolimus mTOR is an enzyme that lives in human cells and is part of a long and complex chain of interactions that control cell growth Blocking mTOR should reduce the growth of cells that are rapidly dividing Taveira-DaSilva and Moss. Rev Port Pneumol. Doesn’t kill the cells – 2012;18:142-4 just slows growth Sirolimus Other mTOR inhibitors Everlimus (Affinitor) Temsirolimus SIROLIMUS IN LAM Why sirolimus? Tuberous sclerosis complex is a genetic disorder with know abnormalities of TSC1 and TSC2 genes that lead to abnormal TSC1 and 2 proteins Some patients with TSC develop LAM We know that TSC1 and 2 stimulate the mTOR enzyme So the theory was if you block mTOR perhaps you would effect LAM CAST Trial Cincinnati Angiomyolipoma Sirolimus Trial (CAST) Looked at the effect of taking sirolimus for a year on the size of the AMLs (kidney growths) CAST Bissler et al.
    [Show full text]
  • CVS Specialty® Pharmacy Distribution Drug List Providing One of the Broadest Offerings of Specialty Pharmaceuticals in the Industry
    July 2021 Updated Quarterly CVS Specialty® Pharmacy Distribution Drug List Providing one of the broadest offerings of specialty pharmaceuticals in the industry The CVS Specialty Pharmacy Distribution Drug List is a guide of medications available and distributed through CVS Specialty. Our goal is to help make your life better. With more than 40 years of experience, CVS Specialty provides quality care and service. Our network of pharmacies includes certifications and accreditations from the Joint Commission, Utilization Review Accreditation Commission (URAC), the National Association of Boards of Pharmacy (NABP) and the Accreditation Commission for Health Care (ACHC). These nationally recognized symbols reflect an organization’s commitment to meet highest standards of quality, compliance and safety. This list is updated quarterly. Below brand-name products are in CAPS, and generic products are shown in lowercase italics. Prospective Patients: Ready to get started? Enroll to get your medications from CVS Specialty. Health Care Providers: Visit the CVS Specialty website to download enrollment forms or call 1-800-237-2767 (TTY: 711). Therapy Class Brand Name Generic Name Acromegaly BYNFEZIA PEN octreotide acetate (SANDOSTATIN) SANDOSTATIN SANDOSTATIN LAR SOMATULINE DEPOT SOMAVERT Alcohol/Opioid Dependency PROBUPHINE IMPLANT KIT SUBLOCADE VIVITROL Allergen Immunotherapy ORALAIR PALFORZIA Alpha-1 Antitrypsin Deficiency ARALAST NP GLASSIA ZEMAIRA Amyloidosis ONPATTRO VYNDAMAX VYNDAQEL Anemia ARANESP EPOGEN PROCRIT REBLOZYL RETACRIT Asthma CINQAIR DUPIXENT FASENRA NUCALA XOLAIR Atopic Dermatitis DUPIXENT Botulinum Toxins DYSPORT MYOBLOC XEOMIN Cardiac Disorders ARCALYST dofetilide (TIKOSYN) TIKOSYN Specialty and non-specialty products distributed by CVS Specialty, as well as products covered by a member’s prescription or medical benefit plan, may change from time to time.
    [Show full text]
  • Rapamycin: Drug Repurposing in SARS-Cov-2 Infection
    pharmaceuticals Review Rapamycin: Drug Repurposing in SARS-CoV-2 Infection Jiri Patocka 1,2 , Kamil Kuca 2,3,* , Patrik Oleksak 3 , Eugenie Nepovimova 3, Martin Valis 4, Michal Novotny 4 and Blanka Klimova 4 1 Institute of Radiology, Toxicology and Civil Protection, Faculty of Health and Social Studies, University of South Bohemia Ceske Budejovice, 37005 Ceske Budejovice, Czech Republic; [email protected] 2 Biomedical Research Centre, University Hospital, 50003 Hradec Kralove, Czech Republic 3 Department of Chemistry, Faculty of Science, University of Hradec Kralove, 50003 Hradec Kralove, Czech Republic; [email protected] (P.O.); [email protected] (E.N.) 4 Department of Neurology, Charles University, Faculty of Medicine and University Hospital Hradec Kralove, 50003 Hradec Kralove, Czech Republic; [email protected] (M.V.); [email protected] (M.N.); [email protected] (B.K.) * Correspondence: [email protected]; Tel.: +420-603-289-166 Abstract: Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world’s acknowledged databases Web of Science, PubMed, Springer and Scopus were involved.
    [Show full text]
  • CYTOTOXIC and NON-CYTOTOXIC HAZARDOUS MEDICATIONS
    CYTOTOXIC and NON-CYTOTOXIC HAZARDOUS MEDICATIONS1 CYTOTOXIC HAZARDOUS MEDICATIONS NON-CYTOTOXIC HAZARDOUS MEDICATIONS Altretamine IDArubicin Acitretin Iloprost Amsacrine Ifosfamide Aldesleukin Imatinib 3 Arsenic Irinotecan Alitretinoin Interferons Asparaginase Lenalidomide Anastrazole 3 ISOtretinoin azaCITIDine Lomustine Ambrisentan Leflunomide 3 azaTHIOprine 3 Mechlorethamine Bacillus Calmette Guerin 2 Letrozole 3 Bleomycin Melphalan (bladder instillation only) Leuprolide Bortezomib Mercaptopurine Bexarotene Megestrol 3 Busulfan 3 Methotrexate Bicalutamide 3 Methacholine Capecitabine 3 MitoMYcin Bosentan MethylTESTOSTERone CARBOplatin MitoXANtrone Buserelin Mifepristone Carmustine Nelarabine Cetrorelix Misoprostol Chlorambucil Oxaliplatin Choriogonadotropin alfa Mitotane CISplatin PACLitaxel Cidofovir Mycophenolate mofetil Cladribine Pegasparaginase ClomiPHENE Nafarelin Clofarabine PEMEtrexed Colchicine 3 Nilutamide 3 Cyclophosphamide Pentostatin cycloSPORINE Oxandrolone 3 Cytarabine Procarbazine3 Cyproterone Pentamidine (Aerosol only) Dacarbazine Raltitrexed Dienestrol Podofilox DACTINomycin SORAfenib Dinoprostone 3 Podophyllum resin DAUNOrubicin Streptozocin Dutasteride Raloxifene 3 Dexrazoxane SUNItinib Erlotinib 3 Ribavirin DOCEtaxel Temozolomide Everolimus Sirolimus DOXOrubicin Temsirolimus Exemestane 3 Tacrolimus Epirubicin Teniposide Finasteride 3 Tamoxifen 3 Estramustine Thalidomide Fluoxymesterone 3 Testosterone Etoposide Thioguanine Flutamide 3 Tretinoin Floxuridine Thiotepa Foscarnet Trifluridine Flucytosine Topotecan Fulvestrant
    [Show full text]
  • Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology
    pharmaceutics Article Sirolimus Pharmacokinetics Variability Points to the Relevance of Therapeutic Drug Monitoring in Pediatric Oncology Amelia-Naomi Sabo 1,2, Sarah Jannier 3 , Guillaume Becker 2,4, Jean-Marc Lessinger 1, Natacha Entz-Werlé 3,5,* and Véronique Kemmel 1,2,* 1 Laboratoire de Biochimie et Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France; [email protected] (A.-N.S.); [email protected] (J.-M.L.) 2 Laboratoire de Pharmacologie et Toxicologie Neurocardiovasculaire, Unité de Recherche 7296, Faculté de Médecine de Maïeutique et des Métiers de la Santé, Centre de Recherche en Biomédecine de Strasbourg (CRBS), 67085 Strasbourg, France; [email protected] 3 Unité d’Onco-Hématologie Pédiatrique, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France; [email protected] 4 Service de la Pharmacie, Hôpitaux Universitaires de Strasbourg, 67200 Strasbourg, France 5 Unité Mixte de Recherche (UMR) 7021, Centre National de la Recherche Scientifique (CNRS), Laboratoire de Bioimagerie et Pathologies, Signalisation Tumorale et Cibles Thérapeutiques, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France * Correspondence: [email protected] (N.E.-W.); [email protected] (V.K.); Tel.: +33-(0)-3-8812-7533 (V.K.) Abstract: Sirolimus is widely used in transplantation, where its therapeutic drug monitoring (TDM) is well established. Evidence of a crucial role for sirolimus in the PI3K/AkT/mTor pathway has Citation: Sabo, A.-N.; Jannier, S.; stimulated interest in its involvement in neoplasia, either as monotherapy or in combination with Becker, G.; Lessinger, J.-M.; other antineoplastic agents. However, in cancer, there is no consensus on sirolimus TDM.
    [Show full text]
  • Cyclophosphamide Improves Engraftment in Patients with SCD and Severe Organ Damage Who Undergo Haploidentical PBSCT
    REGULAR ARTICLE Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT Courtney D. Fitzhugh,1,2 Matthew M. Hsieh,2 Tiffani Taylor,2 Wynona Coles,2 Katherine Roskom,1 Delon Wilson,1 Elizabeth Wright,3 Neal Jeffries,4 Christopher J. Gamper,5 Jonathan Powell,5 Leo Luznik,5 and John F. Tisdale2 1Sickle Cell Branch, National Heart, Lung, and Blood Institute (NHLBI), 2Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and NHLBI, 3Office of the Clinical Director, NIDDK, and 4Division of Cardiovascular Sciences, Office of Biostatistics Research, NHLBI, National Institutes of Health, Bethesda, MD; and 5Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD Peripheral blood stem cell transplantation (PBSCT) offers a curative option for sickle cell Key Points disease (SCD). Although HLA-matched sibling transplantation is promising, the vast majority • Patients with SCD and of patients lack such a donor. We sought to develop a novel nonmyeloablative HLA- severe organ damage haploidentical PBSCT approach that could safely be used for patients with severe organ can tolerate non- damage. Based on findings in our preclinical model, we developed a phase 1/2 trial myeloablative condi- using alemtuzumab, 400 cGy total body irradiation, and escalating doses of posttransplant tioning with no cyclophosphamide (PT-Cy): 0 mg/kg in cohort 1, 50 mg/kg in cohort 2, and 100 mg/kg in cohort transplant-related b mortality. 3. A total of 21 patients with SCD and 2 with -thalassemia received a transplant.
    [Show full text]