Miscellaneous Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Tacrolimus is a macrolide immunosuppressant, used to prevent solid organ rejection after transplantation (Scott et al., 2003). Tacrolimus decreases T-cell production through binding to an immunophilin, FK506 binding protein (FKBP), inhibiting calcineurin phosphatase. This inhibits downstream calcium-dependent events, such as interleukin-2 gene transcription, nitric oxide synthase activation, cell degranulation, and apoptosis, inhibiting T-cell production. Several small case series or case reports of the use of tacrolimus during pregnancies of transplant patients are published (Jain et al., 1993; Laifer et al., 1994; Yoshimura et al., 1996). No birth defects or adverse pregnancy outcomes were reported, except for slightly reduced birth weight and transient immunocompromise.
Tacrolimus
Anton C. de Groot in Monographs in Contact Allergy, 2021
Tacrolimus is a macrolide immunosuppressive drug obtained from the fermentation broth of a Japanese soil sample that contained the bacterium Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus is used orally after allogenic organ transplantation for immunosuppression to reduce the risk of organ rejection. It is also widely utilized topically for the treatment of atopic dermatitis, severe refractory uveitis after bone marrow transplantation, and vitiligo (1).
Antifungal management in risk groups: Solid organ transplant recipients
Mahmoud A. Ghannoum, John R. Perfect in Antifungal Therapy, 2019
Of the echinocandins, caspofungin and anidulafungin are not metabolized by the human cytochrome P450 system. Micafungin demonstrates weak Cyp3A4 inhibition. In general, these drugs are well tolerated and have few adverse effects. Transient elevation of liver transaminases has been reported in healthy volunteers and in SOT patients concomitantly administered caspofungin and calcineurin inhibitors. The coadministration of caspofungin with cyclosporine led to an increase in the AUC of caspofungin by about 35% without increase in maximum concentration (Cmax). The levels of cyclosporine were not increased. The manufacturer recommends caution when coadministering these agents, and they stress the importance of evaluating the risk–benefit ratio prior to use. Monitoring of liver enzymes during concomitant therapy with these agents is recommended. The administration of caspofungin with tacrolimus does not affect caspofungin pharmacokinetics but may reduce tacrolimus concentration by 25%. Careful monitoring of tacrolimus dosages and levels is required to maintain therapeutic concentrations.
Advagraf® with or without an induction therapy for de novo kidney-transplant recipients
Published in Expert Review of Clinical Immunology, 2018
Johan Noble, Thomas Jouve, Lionel Rostaing, Paolo Malvezzi
Tacrolimus is a cornerstone immunosuppressive agent used to prevent organ rejection following transplantation. The SYMPHONY study reported that the best combined immunosuppression therapy for kidney-transplant recipients with regard to biopsy-proven acute rejection (BPAR) and kidney-allograft function was based on low-exposure tacrolimus (Prograf®), i.e. with trough levels of ~7 ng/mL. Most kidney-transplant programs worldwide now use tacrolimus-based immunosuppression [1,2]. Although typically administered twice daily (Prograf®), a modified extended-release once-daily formulation (Advagraf®, Astagraf XL®) has been developed and licensed for use in many countries as prophylaxis for transplant rejection in adult recipients of a de novo kidney transplant. In this brief review, we focus on the use of Advagraf® for de novo kidney-transplant recipients who have or have not received an induction therapy.
Impact of body composition on pharmacokinetics of tacrolimus in liver transplantation recipients
Published in Xenobiotica, 2020
Lu Chen, Xiaoqing Lu, Guijun Tan, Liqin Zhu, Yihe Liu, Mengxue Li
This is the first study to investigate the effect of body composition on tacrolimus PK in liver transplantation recipients. Tacrolimus is a first-line immunosuppressant which is widely used in solid organ transplantation patients to prevent the rejection of transplanted organs (Wallemacq et al., 2009). Despite its success in preventing graft rejection, tacrolimus has a negative impact on long-term graft function. The dosage regimens of tacrolimus in clinical setting is complicated because of its wide inter-individual and intra- individual variability and narrow therapeutic index (Staatz et al., 2002; Zahir et al., 2005). This wide variability may result in sub-therapeutic concentrations which could carry the risk of graft rejection or high concentrations which may cause severe adverse effects, such as hypertension, diabetes, nephrotoxicity, gastrointestinal disturbance, neurotoxicity and infections (Han et al., 2012; Jalil et al., 2014). To reduce side effects and increase patients and graft survival after liver transplantation, TDM for tacrolimus is usually performed as a guidance of dose adjustment. However, the usefulness of monitoring the trough concentration to individualize tacrolimus therapy remains in doubt due to wide inter-individual and intra-individual variability in tacrolimus PK (Zahir et al., 2005). Therefore, it is necessary to investigate the factors which affect tacrolimus PK in individualizing therapy of tacrolimus. The purpose of our study was to investigate the relation between body composition and pharmacokinetics of tacrolimus in liver transplant patients.
Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists
Published in Seminars in Ophthalmology, 2022
Tacrolimus is a T cell inhibitor, that acts by a mechanism similar to cyclosporine.66,67 Topical tacrolimus is available in concentrations of 0.005%, 0.03%, and 0.1% while oral tacrolimus is administered in a dose for 0.05−0.1 mg/kg/day (2–12 mg/day) in two divided doses. The whole blood level of tacrolimus should be maintained between 1 and 12 µg/L, to avoid toxicity. 68 There is no consensus on duration of treatment, and therapy can last from anywhere between 6 to 18 months.68–70 Side effects reported with use of oral tacrolimus include hypertension, renal toxicity, gastrointestinal intolerance, paresthesia, pancreatitis, and lymphopenia.68,70 Monitoring for tacrolimus toxicity is similar to that of cyclosporine, with the addition of initial weekly measurement of CBC, blood glucose, liver enzymes, bilirubin, electrolytes (calcium, magnesium, and phosphate), and a lipid profile, the frequency of which may be reduced to monthly after stabilization of the dose.4
Related Knowledge Centers
- Cyp3A4
- Topical Medication
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