CNS: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), SEIZURES, dizziness, headache, insomnia, tremor, abnormal dreams, agitation, anxiety, confusion, emotional lability, depression, hallucinations, psychoses, somnolence.
EENT: abnormal vision, amblyopia, tinnitus.
Resp: cough, pleural effusion, asthma, bronchitis, pharyngitis, pneumonia, pulmonary edema.
CV: hypertension, peripheral edema, QTc interval prolongation.
GI: GI BLEEDING, abdominal pain, anorexia, ascites, constipation, diarrhea, dyspepsia, ↑liver enzymes, nausea, vomiting, cholangitis, cholestatic jaundice, dysphagia, flatulence, ↑ appetite, oral thrush.
GU: nephrotoxicity, urinary tract infection.
Derm: pruritus, rash, alopecia, herpes simplex, hirsutism, sweating, photosensitivity.
Endo: hyperglycemia.
F and E: hyperkalemia, hyperlipidemia, hypokalemia, hypomagnesemia, hypophosphatemia, hyperphosphatemia, hyperuricemia, hypocalcemia, hyponatremia, metabolic acidosis, metabolic alkalosis.
Hemat: anemia, leukocytosis, leukopenia, thrombocytopenia, coagulation defects, pure red cell aplasia.
MS: arthralgia, hypertonia, leg cramps, muscle spasm, myalgia, myasthenia, osteoporosis.
Neuro: paresthesia, neuropathy.
Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS, fever, generalized pain, abnormal healing, chills, risk of lymphoma/skin cancer.
Because of the potential risk for anaphylaxis, the IV route of administration of tacrolimus should be reserved for those patients unable to take the drug orally. Extended-release capsules are not interchangeable with immediate-release capsules or other extended-release products.
African-American patients may require a higher dose to achieve desired tacrolimus trough concentrations.
Kidney Transplantation
- PO (Adults): Initial dose of immediate-release capsules (with azathioprine) — 0.2 mg/kg/day in 2 divided doses; titrate to achieve recommended whole blood trough concentration; Initial dose of immediate-release capsules (with mycophenolate mofetil and IL-2 antagonist) — 0.1 mg/kg/day in 2 divided doses; titrate to achieve recommended whole blood trough concentration; Extended-release capsules (Astagraf XL) (with basiliximab induction) — 0.15 mg/kg once daily (to be started either before or within 48 hr of completion of transplant); Extended-release capsules (Astagraf XL) (without basiliximab induction) — 0.1 mg/kg given as single dose preoperatively within 12 hr prior to reperfusion, followed by 0.2 mg/kg once daily started postoperatively at least 4 hr after preoperative dose and within 12 hr after reperfusion; Conversion from immediate-release capsules to extended-release capsules (Envarsus XR) — Initiate extended-release treatment with a once daily dose that is 80% of the total daily dose of the immediate-release product (also appropriate for African-American patients).
- PO (Children): Immediate-release capsules — 0.15–0.4 mg/kg/day in 2 divided doses.
- IV (Adults): Initial dose — 0.03–0.1 mg/kg/day as a continuous infusion; titrate to achieve recommended blood concentration.
- IV (Children): 0.03–0.15 mg/kg/day.
Liver Transplantation
- PO (Adults): Initial dose of immediate–release capsules — 0.1–0.15 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
- PO (Children): Initial dose of immediate–release capsules — 0.15–0.2 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
- IV (Adults and Children): Same as for kidney transplant.
Heart Transplanatation
- PO (Adults): Initial dose of immediate–release capsules — 0.075 mg/kg/day in 2 divided doses; titrate to achieve recommended blood concentration.
- IV (Adults): Initial dose of immediate–release capsules — 0.01 mg/kg/day as a continuous infusion; titrate to achieve recommended blood concentration.
Astagraf XL, Envarsus XR, Prograf
Therapeutic Classification: Immunosuppressant agents
Absorption: Absorption following oral administration is erratic and incomplete (5–67%).
Distribution: Crosses the placenta and enters breast milk.
Protein Binding: 99%.
Metabolism/Excretion: 99% metabolized by the liver; <1% excreted unchanged in the urine.
Half-life: Liver transplant patients — 11.7 hr; healthy volunteers — 21.2 hr.
