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Tacrolimus dosing guidelines

Genotype-based tacrolimus dosing guidelines: with or without CYP3A4*22? Pharmacogenomics. 2017 Nov;18(16):1473-1480. doi: 10.2217/pgs-2017-0131. Epub 2017 Nov 2. Authors Laure Elens 1 2 , Vincent Haufroid 2 3 Affiliations 1 Department of Integrated. Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 genotype and Tacrolimus Dosing (July 2015) Updates since publication: No updates on dosing recommendations since publication. Tables provided in the main manuscript of the guideline: Table 1. Assignment of likely metabolism phenotypes based on CYP3A5 diplotypes Table 2. Dosing. Tacrolimus may be initiated at least 24 hours after stopping cyclosporine; however, dosing should be delayed if cyclosporine blood levels are elevated. -Dosing should be titrated based on clinical assessments of rejection and tolerability, and to maintain recommended trough concentration ranges a. Assess tacrolimus trough level for correlation with tremors or headache b. If trough level is above goal, adjust tacrolimus dose and follow up with patient after the subsequent tacrolimus lab draw c. No dose adjustment is recommended if trough level within target range i. Follow up with patient in 1 week if no dose adjustment is made d

0.3 mg/kg/day PO in 2 divided doses, every 12 hours. If cell depleting induction treatment is administered, initiate tacrolimus at 0.1 mg/kg/day PO. Adjust dose as needed based on tacrolimus trough whole blood concentrations. Administer the initial dose no sooner than 6 hours after transplantation b Eligible participants in the PROGRAF Copay Card Program (Program) may receive annual savings up to $3000 for PROGRAF. Patients must have prescription drug coverage for PROGRAF. However, this Program offer is not valid for patients whose prescription claims are reimbursed, in whole or in part, by any federal or state-government funded prescription drug benefit program including but not.

Name: TACROLIMUS (Renal Transplant)Shared Care Guideline Page 2 of 7 Version: 1.0 Issue Date: December 2013 Review Date: December 2015 The initial dose of tacrolimus normal-release is titrated to achieve the desired trough blood level. The level required to prevent rejection without causing toxicity i ATG 1.5mg/kg IV daily. Total cumulative ATG dose of 6.0 to 7.5mg/kg Antimicrobial Dosing Guidelines Peak therapeutic ranges vary depending on the severity of infection i.e higher peaks for more severe infections (e.g. cystic Tacrolimus (Prograf®, Hecoria) Within 30 - 60 minutes before AM dose 3 doses 5-15 mcg/L Valproic Acid (Depakote®, Depakene® The calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the backbone of immunosuppression for most kidney transplant recipients. Despite many years of experience, protocols that optimize efficacy with minimal toxicity remain a subject of debate. Nevertheless, studies of the pharmacokinetic properties of the CNI, particularly cyclosporine, have led to improved dosing strategies The Clinical Pharmacogenetics Implementation Consortium recently published guidelines for initial tacrolimus dosing. The guidelines recommend increasing the starting dose by 1.5-2 times in extensive metabolizers (CYP3A5*1/*1) and intermediate metabolizers (CYP3A5*1/*3, *1/*6, *1/*7), and standard dose in poor metabolizers (CYP3A5*3/*3, *6/*6.

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Tacrolimus dose after thoracic transplantation is usually adjusted based on C 0 levels, mainly targeting the ranges proposed almost 20 years ago for kidney and liver transplant recipients: 15-20 ng/mL for the first 2 months, 10-15 ng/mL from months 3-6, and 8-10 ng/mL after 6 months following heart transplantation 5; and 10-25 ng/mL. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing KA Birdwell1,2, B Decker3, JM Barbarino4, JF Peterson2,5, CM Stein2,6, W Sadee7, D Wang7, AA Vinks8,9, YHe10, JJ Swen11, JS Leeder12, RHN van Schaik13, KE Thummel14, TE Klein4, KE Caudle15 and IAM MacPhee16 Tacrolimus is the mainstay immunosuppressant drug used afte The CPIC dosing guideline for tacrolimus recommends increasing the starting dose by 1.5 to 2 times the recommended starting dose in patients who are CYP3A5 intermediate or extensive metabolizers, though total starting dose should not exceed 0.3 mg/kg/day. Therapeutic drug monitoring should also be used to guide dose adjustments

The recommended starting dose of PROGRAF injection is 0.03-0.05 mg/kg/day in kidney and liver transplant and 0.01 mg/kg/day in heart transplant given as a continuous intravenous infusion. Adult patients should receive doses at the lower end of the dosing range. Concomitant adrenal corticosteroid therapy is recommended early post-transplantation Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations Bodyweight-based tacrolimus dosing followed by dose titration based on whole-blood concentrations, a practice known as therapeutic drug monitoring (TDM), is standard clinical care after solid organ transplantation. 1 According to the manufacturer's instructions, the tacrolimus starting dose should be 0.1-0.2 mg/kg bodyweight per day. 2 However, the available evidence to support this.

Genotype-based tacrolimus dosing guidelines: with or

To evaluate whether adaption of tacrolimus dosing according to CYP3A5 genotype would allow earlier achievement of target blood concentrations of tacrolimus in renal transplant recipients, Thervet et al. conducted a randomized controlled trial in a cohort of 280 kidney transplant patients to compare two dosing strategies: the 0.2 mg/kg/day. Whole blood tacrolimus concentration was 19 ng/ml in the patient who received an overdose on three consecutive dosing occasions, and concentrations ranged from 51.6 to 197 ng/ml in the remaining cases. All signs and symptoms resolved within a few days with no sequelae • Tacrolimus requires individual dose titration to achieve a satisfactory balance between maximizing efficacy and minimizing serious dose-related toxicity; Therapeutic drug monitoring is routinely employed to facilitate tacrolimus dose titration; and • Tacrolimus has small to medium within subject variability For patients carrying the CYP3A5*3/*3 allele and with 30% HCT, the required TAC dose to achieve target trough concentrations of 10-15 ng/ml was 4 mg twice daily (q12h) The dosage recommendations given below for oral administration should act as a guideline. Tacrolimus doses should be adjusted according to individual patient requirements. Tacrolimus is normally administered together with other immunosuppressive drugs. Tacrolimus should not be given concurrently with cyclosporin

CPIC® Guideline for Tacrolimus and CYP3A5 - CPI

Tacrolimus Dosage Guide + Max Dose, Adjustments - Drugs

Roger JELLIFFE | Professor of Medicine Emeritus

  1. A modified initial tacrolimus dosing on the basis of CYP3A5 metabolizer status is suggested if the genotype is known. In patients who express one or two functional copies of CYP3A5 ( e.g. , *1 combinations; normal or intermediate metabolizers), guidelines recommend a starting dose 1.5-2.0 times higher than the typical starting dose, not to.
  2. Prograf (tacrolimus, FK506) is a potent immunosuppressant indicated for the prophylaxis of organ rejection in allogeneic liver transplant patients. We report here a summary of 12 cases of acute overdoses received by Fujisawa USA, Inc. since the drug became commercially available in April 1994. In 11 cases, overdosage occurred with a single dose.
  3. a) In a second smaller trial, the initial dose of tacrolimus was 0.15-0.2 mg/kg/day and observed tacrolimus concentrations were 6-16 ng/mL during months 1-3 and 5-12 ng/mL during months 4-12 [see Clinical Studies ()]. Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower tacrolimus dosages than the recommended initial dosage may be sufficient as.
  4. ed by calculating what the ideal FK level would be post-transplant, and then having a total FK

Video: Prograf (tacrolimus) dose, indications, adverse effects

PROGRAF® (tacrolimus) Dosin

  1. The study used the institutional protocols for tacrolimus dose adjustments. To reach therapeutic tacrolimus levels, the patient had to be within the target range on 2 consecutive testings at least 24 hours apart. RESULTS: Overall, 63 (26.7%) patients achieved target therapeutic levels within 3 days of conversion from IV to oral dosing of.
  2. Supporting Evidence. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. This link will take you to the main page on the CPIC website relating to CYP3A5 and tacrolimus.On the site, you will find links to the main guideline publication and all supplementary information including a table that reports variant frequencies across.
  3. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 Suppl 3:S1. Budde K, Bunnapradist S, Grinyo JM, et al. Novel once-daily extended-release tacrolimus (LCPT) versus twice-daily tacrolimus in de novo kidney transplants: one-year results of Phase III, double-blind, randomized trial
  4. Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this.

In dosing regimens using sublingual administration of the contents of IR tacrolimus capsules, the sublingual to oral dosing ratio has ranged from 1:3 to 1:1 (Collin 2010; Nasiri-Toosi 2012). However, most studies suggest a dosing ratio of 1:2 (or 50% of the oral dose given sublingually), and most centers use this approach in practice. Contraindications. Hypersensitivity to tacrolimus or any component of the formulation, including castor oil (Prograf) Cautions. Hypersensitivity reactions, including anaphylaxis reported with injection formulation, which contains polyoxyl 60 hydrogenated castor oil (HCO-60), a castor oil derivative; limit IV use to patients unable to take orally; monitor patient for 30 min after initiation of. Antifungal therapy with voriconazole or fluconazole in combination with the calcineurin inhibitor tacrolimus exhibits significant CYP3A4 drug interaction potential in allogeneic hematopoietic cell transplant (HCT) recipients. The package insert for voriconazole has dosing recommendations for tacrolimus when voriconazole is started, but these do not apply to patients already receiving. While guidelines on dosage and target trough concentrations for tacrolimus have been reported in different transplant groups, there is a paucity of information for the elderly. No rigorous studies have been performed specifically to identify acceptable target drug concentrations in this population

Therapeutic Monitoring of Calcineurin Inhibitors for the

Please see the attached document for dosing guidelines for LMWHs at UW Medicine. NOTE: anectodal clinical and pharmacokinetic evidence at UW Medicine dating back to the early 1990s suggests that the clearance of enoxaparin is compromised in the presence of the calcineurin inhibitors (CNI) cyclosporine and tacrolimus.. It is our practice to reduce full dose enoxaparin by one level (from 1mg/kg. of 9 (IQR 7-11) days of tacrolimus, with a median time from symptom onset to tacrolimus administration of 11 days (IQR 9-17). Median tacrolimus dose per kg bodyweight was 0.0375 mg/kg twice daily (IQR 0.0276-0.05), and it was 0.0025 mg/kg every other day (IQR 0.0024-0.0029) when receiving concomitant lopinavir-ritonavir. Tacrolimus median. Tacrolimus can be safely combined with MMF or sirolimus. In a tacrolimus plus MMF combination regimen, MPA exposure is higher than with a similar dose of MMF in combination with ciclosporin. Concentrations of tacrolimus are decreased by concomitant therapy with prednisolone or with sirolimus at doses of 2 mg/day or higher Administration of Sublingual Tacrolimus in Renal Transplant Patients who are Nil By Mouth Clinical Guideline V1.0 Page 2 of 11 Summary Yes NG tube available Patient nil by mouth No Suspend the capsule contents in water and administer via NG tube Is the patient usually on: Prograf/Adoport Advagraf Envarsus Administer the same dose as the oral. Tacrolimus was started immediately after transplantation as continuous intravenous infusion at a dose of 0.015 mg/kg/day and oral tacrolimus was administered at a dose of 0.1 to 0.3 mg/kg/day with subsequent dose adjustments to target trough levels of 12 to 15 nanogram/mL in the first month and 9 to 12 nanogram/mL thereafter

Renal Dose Adjustment Guidelines for Antimicrobials . CRRT Dosing Recommendations . CRRT Background: • When a patient is initiated on CRRT, antimicrobial therapy often requires adjustment to ensure adequate drug concentrations are achieved . • CVVHD removes solutes (including drugs) via diffusion. An electrolyte solution (dialysate The first dose of tacrolimus capsules should be given 8 to 12 hours after discontinuing the intravenous infusion. The recommended starting dose of tacrolimus injection is 0.03 to 0.05 mg/kg/day in kidney and liver transplant and 0.01 mg/kg/day in heart transplant given as a continuous intravenous infusion Tacrolimus at oral doses of 0.32 and 1 mg/kg during organogenesis in rabbits was associated with maternal toxicity as well as an increase in incidence of abortions; these doses are equivalent to 0.5 to 1X and 1.6 to 3.3X the recommended clinical dose range (0.1 to 0.2 mg/kg) based on body surface area corrections

Tacrolimus may be an effective alternative to high-dose steroids as first-line treatment for adults with minimal change nephrotic syndrome (MCNS), according to investigators. A 24-week open-label. Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug.After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis.For example, it is prescribed for severe. In addition to standard TDM, adjusting the starting dose of tacrolimus based on CYP3A5 genotype may allow for a more rapid achievement of therapeutic drug concentrations. In the newly published guidelines, CPIC recommends increasing the starting dose by 1.5 to 2 times the recommended starting dose in CYP3A5 extensive and intermediate metabolizers

Genotype-guided tacrolimus dosing in African American

  1. Background:The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use.Objective:This study quantified the drug interaction between low-dose fluconaz..
  2. Most recent guideline publication: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Human Leukocyte Antigen-B (HLA-B) Genotype and Allopurinol Dosing (February 2013) Updates since publication: June 2015 update: Guideline authors reviewed additional literature and concluded that none of the evidence would change the therapeutic recommendations in the 2013 guideline.

Cao Z, Linder MW, Jevans AW, Brown G, Valdes Jr R, Comparison of Tacrolimus concentrations measured by the Imx Tacrolimus vs the PROTRAC II FK506 ELISA assays, Clinical Chemistry 1999;45:1868-1870. 2 In a second smaller trial, the initial dose of tacrolimus was 0.15-0.2 mg/kg/day and observed tacrolimus concentrations were 6-16 ng/mL during month 1-3 and 5-12 ng/mL during month 4-12 [see Clinical Studies]. Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower PROGRAF dosages than the recommended. Tacrolimus ointment is used to treat the symptoms of eczema (atopic dermatitis; a skin disease that causes the skin to be dry and itchy and to sometimes develop red, scaly rashes) in patients who cannot use other medications for their condition or whose eczema has not responded to another medication Blood will be collected at baseline prior to the first dose of tacrolimus, and will will consist of 2 tubes of 5 mL blood (one for PK and one pharmacogenetics). Then, serial blood sampling will occur at 0.5, 1, 2, 4, 6, and 10h after the first tacrolimus dose Tacrolimus daily dose requirement when stable tacrolimus therapeutic trough concentrations were achieved (mg.kg −1.d −1) can be estimated by the following equation: exp(−1.25 - 0.05 × age.

Therapeutic Drug Monitoring of Tacrolimus-Personalized

Tacrolimus for the management of psoriasis: clinical utility and place in therapy Nina Malecic,1,2 Helen Young2 1Manchester Medical School, 2The Dermatology Research Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Abstract: Psoriasis affects 1%-3% of the population in the United Kingdom and can convey significant detriment to the physical and. Tacrolimus was started as continuous intravenous infusion at a dose of 0.05 mg/kg/day and oral tacrolimus was administered at a dose of 0.1 to 0.3 mg/kg/day with subsequent dose adjustments to target trough levels of 12 to 15 ng/ml. The 1-year survival rates were 73.1% in the tacrolimus versus 79.2% in the ciclosporin group Study dose: In 14 children, average oral tacrolimus dose was 0.16 mg/kg/day. Doses ranging from 0.036 to 0.3 mg/kg/day, were based on clinical signs, and were targeted to a trough level of 5 to 11 nanograms/mL. Astagraf XL(R) extended-release capsules are not interchangeable or substitutable for Prograf(R) immediate-release capsules

PharmGK

  1. Aims: Tacrolimus has extensive pharmacokinetic variability among patients and a narrow therapeutic window. The U.S. Clinical Pharmacogenetics Implementation Consortium recommends a starting dose for tacrolimus of 0.15-0.3 mg/kg/day, which is much higher compared with 0.05-0.15 mg/kg/day used in China
  2. The pharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations. The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus.
  3. istration The dose will be adjusted by the specialist according to individual requirements and trough tacrolimus levels. The patient will be commenced on a dose of 30 - 80 micrograms/kg per day in two divided doses
  4. The dose and number of drugs are gradually tapered depending on the occurrence or likelihood of rejection, nephrotoxicity or other drug Drug monitoring and any tacrolimus dose adjustments. Investigate, as appropriate, where symptoms suggest viral or fungal infections or possible If treatment is required follow guidelines but do not use.
  5. Medscape - Indication-specific dosing for Protopic (tacrolimus ointment), frequency-based adverse effects, comprehensive interactions, contraindications, pregnancy & lactation schedules, and cost information

Prograf Dosage Guide - Drugs

Tacrolimus does not work immediately. It may be up to 4 months before you notice any benefit. When and how to take tacrolimus Tacrolimus is given as a capsule. Usually you will be advised to take a dose twice a day with a full glass of water. The dose should be taken whole (not crushed or chewed) on an empty stomach, preferably at least Tacrolimus granules for oral suspension 0.2 and 1 mg product-specific bioequivalence guidance EMA/CHMP/159744/2016 Page 3/3 Number of studies: one single dose study Analyte parent metabolite both plasma/serum blood urine Enantioselective analytical method: yes n The major role of CYP3A5 in tacrolimus clearance and the association between CYP3A5*1 allele and blood concentration or dose-requirement of tacrolimus in transplant patients were consistently demonstrated. 7, 27, 37 The Clinical Pharmacogenetics Implementation Consortium provided dosing recommendations based on CYP3A5 genotype; notably for.

dosing interval and might, therefore, serve as an intermediate therapeutic end-point for guiding dosage adjustment. Pharmacokinetic variability in the liver trans­ plant group is partly a result of incomplete and erratic absorption of tacrolimus (mean bio­ availability 25%, range 4-89%).24 Both the rate and the extent of absorption of. establish the correlation between dose per kilogram of body weight and the level and concentration of tacrolimus with respect to post-transplant time (0 to 6.5 months). Figure 1. Relationship between steady-state blood tacrolimus concentration and weight-normalized the daily dosage of the drug in 13 patients. 0 5 10 15 20 25 30 0.000 0.050 0. Tacrolimus has a narrow therapeutic range and adverse effects are common, particularly at high dose and concentrations, making therapeutic drug monitoring essential. Since 90% of tacrolimus is in the cellular components of blood, especially erythrocytes, whole blood is the preferred specimen for analysis of trough concentrations Therapeutic Serum Concentrations and Sampling Guidelines 1 . THERAPEUTIC SERUM CONCENTRATIONS AND SAMPLING GUIDELINES Drug Usual Sample Time Therapeutic Serum Concentration Physicians' Routine Inpatient Orders Comments Amikacin Pre: 0-30 min. prior to next dose 2.5-10 mg/L Initial: Pre and Post with third regular dose. Maintenance: Pre and Post tacrolimus bioavailability was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very small in very fast, fast, slow, and very slow metabolizers, respectively. These categories are derived from distribution statistics and the calculation of quartiles of C/D ratio. Dose-adjusted tacrolimus.

The median weight-based dose of tacrolimus XR that achieved a therapeutic level among the cohort was 0.158 mg/kg/day (Q1-Q3: 0.0587-0.221), which was about 80% of the original median weight-based immediate-release tacrolimus dose. Therapeutic dosing strategies were widely variable, represented by an R 2 of 0.33 on linear regression. There was a. In case of a missed dose, it was observed that: (i) a single forgotten dose can greatly impact exposure: up to 49% decrease for tacrolimus trough concentration and 70% for AUC 0-12 h in patients with the highest clearance values; (ii) patients with a minimized exposure are the most affected by a missed dose; and (iii) a dose of 1.5 times the. Tacrolimus is used as a primary immunosuppressant and as secondary treatment for rejection following transplantation

Clinical Pharmacogenetics Implementation Consortium (CPIC

touse dosage regimen table to guide clinicians with drug dosing was created. Conclusion The final population model could provide information for the individualised dosing of tacrolimus for cardiac transplant recipients. InTrOduCTIOn Organ transplantation is the treatment of choice for patients with end-stage organ failure. Kidne Tacrolimus Dosage. Tacrolimus mediation is taken by mouth or given by injection. The oral medication is available in 1-mg (white) capsules and 5-mg (pink) capsules. How to Properly Take Tacrolimus. Take tacrolimus on a regular schedule, at the same time each day. Usually tacrolimus is taken twice a day, 12 hours apart, such as at 8 a.m. and 8 p. The pharmacokinetics of tacrolimus in patients with renal impairment was similar to that in healthy volunteers with normal renal function. However, consideration should be given to dosing tacrolimus at the lower end of the therapeutic dosing range in patients who have received a liver or heart transplant and have pre-existing renal impairment Before conversion, median trough level of tacrolimus was 6.4 ng/mL (range 2.3-8.1) and median daily dosage was 4.5 mg/day. 1-14 After conversion, median trough level of CyA was 68 ng/mL (range 37-128) and median daily dosage was 200 mg/day (100-300). Dosage of mycophenolate mofetil was not significantly modified during follow-up: 1.5 g/day in.

Avoiding Tacrolimus Underexposure and Overexposure with a

The mean sublingual tacrolimus dose of 0.116 ± 0.096 mg/kg daily corresponded to a mean AUC of 230 ± 74.1 ng · hr/mL (n = 4), while a mean oral dose of 0.414 ± 0.246 mg/kg daily was needed to achieve a similar AUC of 252 ± 92.7 ng · hr/mL (n = 5). The relative exposure of sublingual to oral tacrolimus translates to a dosing conversion. regimen consisted of basiliximab, tacrolimus (target trough 6-12 ng/mL for 3 months, thereafter 4-8 ng/mL), mycophenolate mofetil, and prednisolone that was reduced to a maintenance dosage of 5 mg once daily (q.d.) at 3-6 months. Patient data were collected from the hospital's electronic health records Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease (IBD). However, little is known about the effectiveness of topical tacrolimus in this patient population. The aim of this systematic review was to evaluate the current state of literature to evaluate the safety and effectiveness. Confusion when dispensing more than one strength for the patient's dose. With variable tacrolimus dosing based on the patient's weight, type of organ transplant, response to therapy, adjuvant immunosuppressants, and other factors, any of the available capsule or tablet strengths might be needed to fill a prescription

Aromatase Inhibitor Pathway (Multiple TissuesBertrand PONS | Medical Doctor | Université des Antilles

Tacrolimus (FK506) and cyclosporine A are 2 common immunosuppressants that have been shown to affect blood pressure. Thus, elucidation of mechanisms that contribute to posttransplant hypertension has major clinical implications. In general, the type of immune response evoked by a particular set of antigens, such as that associated with organ. Tacrolimus is the primary immunosuppression drug used in kidney and liver transplant patients. It is also a drug with a narrow therapeutic index. Such drugs are defined by a narrow distance between the dosage that induces a desired effect and that dosage which already has a toxic effect [1] The tacrolimus starting dose should be higher in CYP3A5 expressers, younger patients and those with a higher body surface area (BSA). It should be lower in patients carrying the CYP3A4*22 allele. The starting dose model can be used to individualize the tacrolimus starting dose following kidney transplantation Anglicheau D, Verstuyft C, Laurent-Puig P, et al. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J Am Soc Nephrol 2003; 14:1889