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tacrolimus (Rx)Brand and Other Names:Prograf, Astagraf XL, more...Hecoria, Envarsus XR

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, immediate-release (Prograf, Hecoria, generics)

  • 0.5mg
  • 1mg
  • 5mg

capsule, extended-release (Astagraf XL)

  • 0.5mg
  • 1mg
  • 5mg

tablet, extended-release (Envarsus XR)

  • 0.75mg
  • 1mg
  • 4mg

injectable solution

  • 5mg/mL
more...

Heart Transplant

Prophylaxis of organ rejection in patients receiving allogeneic transplants; use with azathioprine or mycophenolate mofetil (MMF) recommended

IV: 0.01 mg/kg/day by continuous infusion initially 

PO (immediate-release): 0.075 mg/kg/day divided q12hr initially  

Dosing considerations

  • Administer initial dose no sooner than 6 hr after transplantation
  • Dosage adjusted according to clinical response and trough tacrolimus concentration
  • Trough level (months 1-3): 10-20 ng/mL
  • Trough level (months >3): 5-15 ng/mL
  • Monitor serum potassium

Liver Transplant

Prophylaxis of organ rejection in patients receiving allogeneic transplants

IV: 0.03-0.05 mg/kg/day by continuous infusion initially 

PO (immediate-release): 0.1-0.15 mg/kg/day divided q12hr initially  

Dosing considerations

  • Dosage adjusted according to clinical response and trough tacrolimus concentration
  • Trough level (months 1-12): 5-20 ng/mL
  • Monitor serum potassium

Kidney Transplant

Prograf

  • Prophylaxis of organ rejection in patients receiving allogeneic kidney transplants; used concomitantly with azathioprine or MMF or interleukin (IL)-2 receptor antagonist (eg, basiliximab or daclizumab) and corticosteroids
  • PO (with azathioprine): 0.2 mg/kg/day divided q12hr initially  
  • PO (with MMF/IL-2 receptor antagonist): 0.1 mg/kg/day divided q12hr initially
  • IV: 0.03-0.05 mg/kg/day IV by continuous infusion initially 

Astagraf XL

  • Prophylaxis of organ rejection in patients receiving kidney transplants; used concomitantly with MMF and corticosteroids, with or without basiliximab induction
  • With basiliximab induction
    • MMF, corticosteroids, and initial tacrolimus dose may be administered before or within 48 hr after completion of renal transplantation but may be delayed until renal function has recovered
    • 15 mg/kg PO once daily
  • Without induction
    • When agent is used with MMF and corticosteroids, preoperative dose should be given as single dose within 12 hr before reperfusion; initial postoperative dose should be given ≥4 hr after preoperative dose and ≤12 hr after reperfusion
    • Preoperative: 0.1 mg/kg PO once daily
    • Postoperative: 0.2 mg/kg PO once daily
    • Postoperative oliguria: Initial postoperative dose should be administered ≥6 hr and ≤48 hr after transplantation but may be delayed until renal function shows evidence of recovery

Envarsus XR

  • Indicated for the prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate-release formulations in combination with other immunosuppressants
  • Not interchangeable or substitutable with other tacrolimus products
  • Conversion from immediate-release tacrolimus
    • Administer an Envarsus XR dose that is 80% of the total daily dose of the tacrolimus immediate-release product
    • Monitor whole blood tacrolimus levels and titrate to achieve target whole blood trough concentration ranges of 4-11 ng/mL

Dosing considerations

  • Dosage adjusted according to clinical response and observed tacrolimus whole-blood trough concentrations
  • Trough level, Prograf with azathioprine (months 1-3): 7-20 ng/mL
  • Trough level, Prograf with azathioprine (months 4-12): 5-15 ng/mL
  • Trough level, Prograf with MMF/IL-2 receptor antagonist (months 1-12): 4-11 ng/mL
  • Trough level, Astragraf XL with basiliximab induction (days 1-60): 5-17 ng/mL
  • Trough level, Astragraf XL with basiliximab induction (months 3-12): 4-12 ng/mL
  • Trough level, Astragraf XL without induction (days 1-60): 6-20 ng/mL
  • Trough level, Astragraf XL without induction (months 3-12): 6-14 ng/mL
  • Monitor serum potassium

Dosage Modifications

CYP3A5*1 allele

  • African-American patients, compared to Caucasian patients, may need to be titrated to higher dosages to attain comparable trough concentrations
  • ~80% of the African-American patients are carriers of the active, wild type CYP3A5*1 allele, resulting in a higher rate of tacrolimus clearance because of rapid metabolism

Renal impairment

  • Use lower end of dosing range
  • Monitor renal function and adjust dose according to whole blood concentrations and tolerability

Hepatic impairment

  • Mild: No dosage adjustment required
  • Moderate: Monitor whole blood concentrations and adjust dose accordingly
  • Severe (mean Child-Pugh score >10): Mean clearance of tacrolimus was substantially lower compared with normal hepatic function; dosage reduction recommended; administer 80% of preconversion daily dose of immediate release dosage form when converting from tacrolimus immediate release to extended release

Graft-Versus-Host Disease (Orphan)

Prophylaxis

Orphan indication sponsor

  • Fujisawa USA, Inc, 3 Parkway North Center, Deerfield, IL 60015

Pulmonary Arterial Hypertension (Orphan)

Orphan designation for treatment of pulmonary arterial hypertension

Sponsor

  • Selten Pharma, Inc; 14435C Big Basin Way #246; Saratoga, CA 95070

Dosage Forms & Strengths

capsule, immediate-release

  • 0.5mg
  • 1mg
  • 5mg

injectable solution

  • 5mg/mL
more...

Liver Transplant

Prophylaxis of organ rejection in patients receiving liver transplants without preexisting renal or hepatic impairment

IV: 0.03-0.05 mg/kg/day by continuous infusion initially 

PO (immediate-release): 0.15-0.2 mg/kg/day divided q12hr initially  

Dosing considerations

  • Use lower end of dosing range
  • Dosage adjusted according to clinical response, tolerability, and observed whole-blood tacrolimus concentrations
  • Trough level (months 1-12): 5-20 ng/mL
  • Monitor serum potassium
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Interactions

Interaction Checker

tacrolimus and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (selected)

            Diarrhea (25-72%)

            Headache (24-64%)

            Insomnia (30-64%)

            Abdominal pain (29-59%)

            Tremor (15-56%)

            Nephrotoxicity (36-52%)

            Asthenia (11-52%)

            Hypertension (38-50%)

            Hypophosphatemia (49%)

            Hypomagnesemia (16-48%)

            Hyperglycemia (22-47%)

            Hyperlipemia (10-31%)

            Nausea (32-46%)

            Increased serum creatinine (24-45%)

            Hyperkalemia (13-45%)

            Paresthesia (17-40%)

            Constipation (23-35%)

            Anorexia (34%)

            Urinary tract infection (16-34%)

            Increased blood urea nitrogen (BUN) (30%)

            Vomiting (14-29%)

            Hypokalemia (13-29%)

            Dyspepsia (28%)

            Dizziness (19%)

            Edema (18%)

            Oliguria (18%)

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            Warnings

            Black Box Warnings

            Should be prescribed only by physicians who have experience with immunosuppression in transplant recipients and can provide necessary follow-up and appropriate monitoring

            Increased risk of fungal, viral, bacterial, and protozoal infections and lymphoma due to immunosuppression

            Astagraf XL: Increased mortality in female transplant recipients was observed in clinical trial of liver transplantation; use of extended release formulation in liver transplantation is not recommended

            Contraindications

            Hypersensitivity to tacrolimus or castor oil (Prograf)

            Cautions

            Increased risk of infections and lymphoma, including latent virus activation (eg, BK virus-induced nephropathy)

            Risk of posttransplant diabetes mellitus, especially in black and Hispanic patients

            Black patients may require higher doses in kidney transplant

            Discontinue cyclosporine 24 hours before starting tacrolimus

            Combination immunosuppressant therapy

            Hypertension may occur; may treat with antihypertensives that are non-potassium-sparing diuretics

            Use caution with concurrent administration of nephrotoxic agents, calcium-channel blocking agents

            Mild-to-severe hyperkalemia may occur; avoid use of potassium sparing diuretics

            Myocardial hypertrophy reported (reversible with dose reduction or discontinuation)

            QT prolongation reported; consider obtaining electrocardiograms and monitoring electrolytes in patients at high risk

            Use with strong CYP3A inhibitors and inducers: Adjust tacrolimus dose and monitor trough concentrations and for occurrence of adverse reactions, including QT prolongation

            Cases of pure red-cell aplasia reported; if this is diagnosed, consider discontinuing tacrolimus

            Gastrointestinal perforation; all reported cases were considered a complication of transplant surgery or accompanied by infection, diverticulum, or malignant neoplasm

            African-Americans may need to be titrated to higher dosages to achieve the target tacrolimus concentrations

            Graft rejection and other serious adverse effects have resulted from medication errors with extended release dosage form; patients and caregivers are advised to recognize appearance extended release tablets

            Monitor blood glucose; new onset of diabetes after transplants reported

            Acute and or chronic nephrotoxicity reported with therapy; monitor renal function; consider dosage reduction

            Neurotoxicity including risk of posterior reversible encephalopathy syndrome (PRES) reported; monitor for neurologic abnormalities; reduce dosage or discontinue

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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Drug is excreted in breast milk; not recommended

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

            more...
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            Pharmacology

            Mechanism of Action

            Calcineurin inhibitor; inhibits T-cell activation and proliferation, humoral immunity

            Macrolide antibiotic; potent immunosuppressant

            Absorption

            Bioavailability: 7-55% (children); 7-32% (adults)

            Peak plasma time: 0.5-6 hr

            Distribution

            Protein bound: 99%

            Vd: 0.5-4.7 L/kg (children); 0.55-2.47 L/kg (adults)

            Metabolism

            Metabolized in liver by CYP3A4

            Metabolites: 13-O-demethyl tacrolimus (major)

            P-gp substrate

            Elimination

            Half-life: 23-46 hr (immediate release); 34.5-41 hr (extended release)

            Excretion: Feces (94%); urine (<1%)

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            Administration

            IV Incompatibilities

            Y-site: Acyclovir, ganciclovir

            IV Compatibilities

            Solution: D5W(?), NS(?)

            Additive: Cimetidine

            Y-site (partial list): Ampicillin, ampicillin-sulbactam, calcium gluconate, cefazolin, ciprofloxacin, dopamine, fluconazole, furosemide, heparin, lorazepam, metoclopramide, metronidazole, morphine sulfate, multivitamins, penicillin G potassium, potassium chloride, propranolol, sodium bicarbonate, trimethoprim-sulfamethoxazole, vancomycin

            IV Preparation

            Dilute with NS or D5W to 0.004-0.02 mg/mL

            IV Administration

            Administer by IV continuous infusion only (use infusion pump)

            Tacrolimus is dispensed in 50-mL glass container with no overfill

            Use polyolefin administration sets, especially for low drug concentrations; polyvinyl chloride (PVC) sets may be used for concentrations >100 mg/mL, but significant absorption may occur with these sets at concentrations >50 mg/mL

            Oral Administration

            PO suspension of 0.5 mg/mL requires extemporaneous compounding by pharmacist

            Immediate-release capsules: Administer consistently with or without food

            Extended-release capsules or tablets: Take preferably on an empty stomach

            Extended-release capsules or tablets: Swallow whole; do not chew, divide, or crush

            Missed doses

            • Once daily extended-release: Take it as soon as possible within 14 hr (Astagraf XL) or 15 hr (Envarsus XR) after missing the dose; beyond the 14-hr or 15-hr time frame, wait until the usual scheduled time to take the next regular daily dose; do not double the next dose

            Storage

            Before dilution, store at 5-25°C (41-77°F)

            Admixtures prepared in D5W or NS should be stored in polyolefin containers and glass bottles (PVC containers absorb significant amounts of drug)

            Infusion through PVC tubing does not result in decreased concentrations; however, loss by absorption may be more important with lower concentrations

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            Images

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            Formulary

            FormularyPatient Discounts

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            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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