Alternate Name(s):
FK506, PROGRAF
Classification:
Immunosuppressive Agent - NON-CYTOTOXIC HAZARDOUS
Original Date:
August 2005
Revised Date:
December 2019
Indications:
- Prevention and treatment of solid organ transplant rejection
- Other autoimmune diseases and the prevention of graft-vs-host disease following bone marrow transplantation
Reconstitution and Stability:
- Available as tacrolimus 5 mg/mL in 1 mL ampoules
- Store ampoules at room temperature
- Dilute with NS or D5W to a concentration of 0.004-0.02 mg/mL in a glass polyethylene (non-PVC), or polypropylene container
- Diluted solution is stable at room temperature for 24 hours
- DEHP-free tubing and non-PVC containers must be used
Compatibility:
- Solutions Compatible: D5W, NS
- Y-site Compatible: KCL, morphine, TPN (amino acids/dextrose)
Administration:
(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)
| SC | NO |
| IM | NO |
| IV Direct | NO |
| IV Intermittent Infusion |
YES; Not a recommended parenteral route due to increased risk of adverse effects associated with increased plasma tacrolimus concentrations Usual dilution: 0.004-0.02 mg/mL |
| IV Continuous Infusion |
YES, recommended parenteral route |
Dosage:
(For neonatal dosages, refer to Neonatal IV Drug Manual.)
- The optimal dosage and interval of tacrolimus has not been firmly established in pediatrics
- Suggested dosage range: 0.03-0.15 mg/kg/day as a continuous infusion
- For patients with hepatic or renal insufficiency, doses at the lower end of the dosing range should be used
- Conversion to oral therapy should occur as soon as possible
- Conversion from oral to IV:
- Oral dose = 4 x IV dose; administer the first dose 8-12 hours after the IV has been discontinued
Potential hazards of parenteral administration:
- CNS (most common): headache, tremor, insomnia, paresthesia, hyperesthesia, numbness, nightmares (greater with IV than oral)
- Blurred vision and photophobia have been reported with IV therpay
- Anaphylaxis: most likely related to the IV vehicle (castor oil) since oral administration does not carry the same risk
- Potential for higher risk or nephrotoxicity and CNS symptoms with infusion durations less than 24 hours (related to high peak concentration)
- Other adverse effects: nephrotoxicity, neurotoxicity, nausea, vomiting, diarrhea, infectious complications, anemia, leukocytosis, thrombocytopenia, hyperglycemia, hyperkalemia, hyperuricemia, hypomagnesemia
Notes:
- Monitoring guidelines for the first dose: monitor vital signs Q 5 minutes for the first 15 minutes of infusion, then Q 30 minutes x 1, then Q 1 hour thereafter x 3 hours, then Q 4 hours while infusion
- Monitor whole blood concentrations 2-3 times during the first week of therapy in the morning
- Target concentration are 5-20 mcg/L (monoclonal assay); concentrations in excess of 25 mcg/L should be asessed prior to administering
- If tacrolimus is being administered through a single lumen venous catheter, the sample should be drawn peripherally
- Oral administration is the usual route
- Do not administer to patients allergic to castor oil
- DO NOT ADMINISTER WITH CYCLOSPORINE (increased risk of nephrotoxicity)
- Cyclosporine must be discontinued 24-48 hours before starting tacrolimus and vice-versa; dosing may be further delayed in presence of high levels
- Additive nephrotoxicity when administered with other nephrotoxic drugs (e.g. amphotericin B, aminoglycosides, acylcovir, ganciclovir)
- Blood concentration of tacrolimus may be altered by drugs which increase or decrease hepatic microsomal enzyme activity (e.g. phenytoin, phenobarbital, cimetidine, rifampin, ketoconazole, erythromycin)