Practical considerations in the use of intravenous tacrolimus in hematopoietic stem cell transplantation patients
Notice bibliographique
Résumé
Graft-versus-host-disease (GvHD) is the most frequent and important complication after allogeneic hematopoietic stem cell transplantation (HSCT). Despite aggressive immunosuppressive prophylaxis, GvHD can still occur even when the donor is a perfectly matched sibling. Prevention and treatment of GvHD remain a major challenge in allogeneic stem cell transplantation. Most centres use a combination of a calcineurin inhibitor (cyclosporine or tacrolimus) in conjunction with a short course methotrexate as prophylaxis of GvHD. Methylprednisolone in combination with a calcineurin inhibitor is the first-line treatment for acute GvHD. Patients with failure of initial therapy will receive a secondary treatment with tacrolimus, mycophenolate mofetil, sirolimus, anti-thymocyte globulin or monoclonal antibodies among others. Tacrolimus is a macrolide antibiotic isolated from the Streptomyces tsukubaensis. It inhibits calcineurin, resulting in the inhibition of interleukin-2 production and the formation of cytotoxic lymphocytes, which are mainly responsible for graft rejection and GvHD. Tacrolimus (Prograft , Astellas Pharma, UK, USA) is commercially available in two different forms: capsules for oral administration and a sterile solution for intravenous (IV) administration. The latter contains the equivalent of 5mg anhydrous tacrolimus in 1mL. Each mL contains polyoxyl 60 hydrogenated castor oil (HCO-60) 200mg, and dehydrated alcohol, USP, 80.0% v/v. Tacrolimus injection must be diluted within the range 0.004–0.02mg/ml with 0.9% sodium chloride or 5% dextrose before administration. In addition, due to the non-commercial availability, many centers prepare an oral tacrolimus suspension. Currently, the recommended method of administration of IV tacrolimus is continuous (24 h) infusion because of high rates of neurologic and renal toxicities seen with rapid or short infusions twice daily. However, when using continuous infusion, a dedicated central venous line is advised and this reduces the number of access ports required for administration of other drugs such as antibiotics or parenteral nutrition. Due to this logistic problem, some centers prefer the intermittent administration of tacrolimus which is considered to be a safe and effective alternative to continuous infusion in children. When administrating tacrolimus intravenously, there are some major concerns. As tacrolimus is prepared and administered with IV tubing, syringes and other equipment containing polyvinylchloride (PVC), it can be absorbed by the PVC. In addition, castor oil, as part of the excipients for the IV tacrolimus solution, may leach phthalates from PVC-phthalate containing equipment. Therefore, it is advised to use PVC-free and phthalate-free containers, tubing and syringes, in order to maintain a consistant blood concentration. Our research question was guided by an allogeneic transplanted patient who received cyclosporine and low-dose methotrexate for the prevention of GvHD as routinely performed in our hospital. Due to an insufficient response (skin rash suggestive for GvHD) in combination with methylprednisolone, cyclosporine was switched to tacrolimus after a few days of treatment. The administration of tacrolimus in continuous infusion was complicated by large fluctuation in blood levels. For this patient, due to absorption problems, the
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
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Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,009 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».