Tacrolimus

Administration

• Type: immunosuppressant
• Dosage Forms: 0.5,1,5
• Routes of Administration: PO, topical, IV
• Common Trade Names:Prograf

Adult Dosing

Heart transplant rejection prophylaxis

• 0.075mg/kg/day PO divided q12h
• Start: >6h post-transplant; Info: adjust dose based on serum levels

Liver transplant rejection prophylaxis

• 0.1-0.15mg/kg/day PO divided q12h
• Start: >6h post-transplant; Info: adjust dose based on serum levels

Kidney transplant rejection prophylaxis

• 0.1-0.2mg/kg/day PO divided q12h
• Start: within 24h post-transplant; delay if renal function not adequate; Info: adjust dose based on serum levels

Pediatric Dosing

Liver transplant rejection prophylaxis

• 0.15-0.2mg/kg/day PO divided q12h
• Start: >6h post-transplant; Info: adjust dose based on serum levels

Special Populations

• Pregnancy Rating: Pregnancy Category C
• Lactation risk: possibly unsafe

Renal Dosing

• Adult:
  • kidney transplant: give lowest recommended dose, may consider further dose decrease; postop oliguria: start 6-24h post-transplant; may delay until renal function adequate; HD: not defined
  • all other transplants: give lowest recommended dose, may consider further dose decrease; HD: not defined
• Pediatric: give lowest recommended dose, may consider further dose decrease; HD: not defined

Hepatic Dosing

• Adult: give lowest recommended dose, may consider further dose decrease; Child-Pugh Score >10: decrease dose, amount not defined
• Pediatric: give lowest recommended dose, may consider further dose decrease; Child-Pugh Score >10: decrease dose, amount not defined

Contraindications

• Allergy to class/drug
• hypersensitivity to castor oil derivatives (IV form)
• liver transplant use (ER cap form)
• electrolyte abnormalities, uncorrected
• congenital long QT syndrome
• caution if QT prolongation
• caution if QT prolongation family history
• caution if torsades de pointes history
• caution if ventricular arrhythmias
• caution if bradycardia
• caution if recent MI
• caution if CHF
• caution in female patients
• caution in Black patients
• caution in Hispanic patients
• caution if renal impairment
• caution if hepatic impairment

Adverse Reactions

Serious

• immunosuppression
• malignancy
• lymphoma
• post-transplant lymphoproliferative disorder
• infection, severe
• CMV
• PML
• BK virus-assoc. nephropathy
• Stevens-Johnson syndrome
• toxic epidermal necrolysis
• anaphylaxis
• nephrotoxicity
• neurotoxicity
• posterior reversible encephalopathy syndrome
• seizures
• myocardial hypertrophy
• pericardial effusion
• QT prolongation
• torsades de pointes
• hyperkalemia, severe
• hypertension, severe
• diabetes mellitus
• myelosuppression
• DIC
• thrombocytopenic purpura
• hemolytic anemia
• pure red cell aplasia

Common

• tremor
• diarrhea
• headache
• hypertension
• Creatinine increase
• infection
• nausea/vomiting
• insomnia
• pain
• hypophosphatemia
• constipation
• asthenia
• edema, peripheral
• hypomagnesemia
• fever
• anemia
• diabetes mellitus/hyperglycemia
• paresthesia
• LFTs elevated
• hyperlipidemia
• hyperkalemia
• anorexia
• dyspepsia
• arthralgia
• dyspnea
• pruritus/rash
• hypokalemia
• dizziness
• cough
• leukopenia
• photosensitivity
• bronchitis

Pharmacology

• Half-life: 3.5-40.6h; 23.6h (heart transplant patients), 18.8h (kidney transplant patients), 11.7h (liver transplant patients); Info: prolonged half-life in hepatic impairment
• Metabolism: liver extensively; CYP450: 3A4 substrate
• Excretion:feces 92.4%, urine 2.3% (<1% unchanged)

Mechanism of Action

Macrolide calcineurin inhibitor, inhibits T-lymphocyte activation

References

epocrates

Authors

Jung-Eun Lim, Claire, Daniel Ostermayer, Ross Donaldson, Neil Young