ASTAGRAF XL Dosage & Rx Info | Uses, Side Effects

Astagraf Xl Generic Name & Formulations

Legal Class

General Description

Tacrolimus 0.5mg, 1mg, 5mg; ext-rel caps.

Pharmacological Class

Immunosuppressant (calcineurin-inhibitor).

How Supplied

Ext-rel caps—30

Manufacturer

Astellas Pharma US, Inc.

Generic Availability

Mechanism of Action

Tacrolimus inhibits T-lymphocyte activation and proliferation. Experimental evidence suggests that tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin inhibited.

Astagraf Xl Indications

Indications

Organ rejection prophylaxis in kidney transplant patients, in combination with mycophenolate mofetil (MMF) and corticosteroids, with or without basiliximab induction.

Astagraf Xl Dosage and Administration

Adult

Swallow whole. Take once daily in the morning, preferably on an empty stomach. If previously on Prograf IV infusion, initial oral dose may be given 8–12hrs after discontinuing infusion. With basiliximab induction: initially 0.15-0.2mg/kg/day; give first dose prior to or within 48hrs after transplantation; but may be delayed until renal function has recovered; without induction (pre-op): 0.1mg/kg/day; give dose within 12hrs prior to reperfusion when used with MMF and corticosteroids; without induction (post-op): 0.2mg/kg/day; give first dose within 12hrs after reperfusion but not less than 4hrs after pre-op dose when used with MMF and corticosteroids. Black patients may require higher doses. Renal or hepatic impairment: use lowest effective dose. See full labeling.

Children

<4yrs: not established. ≥4yrs: with basiliximab induction: initially 0.3mg/kg/day; give dose within 24hrs after reperfusion.

Astagraf Xl Contraindications

Not Applicable

Astagraf Xl Boxed Warnings

Boxed Warning

Malignancies and serious infections in transplant patients. Increased mortality in female liver transplant patients.

Astagraf Xl Warnings/Precautions

Warnings/Precautions

Not interchangeable or substitutable with tacrolimus extended-release or immediate-release products. Not indicated for use in liver transplantation. Increased risk of lymphomas and other malignancies (eg, skin). Avoid sun, UV light. Increased risk of infections (eg, bacterial, viral, fungal, protozoal, cytomegalovirus), opportunistic infections including polyoma virus. Monitor Epstein-Barr virus serology, development of infections during therapy. Risk of new onset diabetes after transplant (esp. Hispanic and black patients); monitor blood glucose. Avoid in congenital long QT syndrome. CHF, bradyarrhythmias, concomitant antiarrhythmic drugs, or electrolyte disturbances; consider obtaining ECGs and monitor electrolytes periodically. Hepatic or renal impairment; monitor and consider dose reduction. Obtain tacrolimus whole blood concentrations (see full labeling), serum creatinine, serum potassium, and fasting glucose periodically. Risk for thrombotic microangiopathy (including hemolytic uremic syndrome and thrombotic thrombocytopenic purpura) esp. in those with severe infections, GVHD, HLA mismatch. Complete required immunizations prior to transplantation and treatment. Elderly. Labor & delivery. Advise females and males of reproductive potential to use appropriate conception prior to initiation. Pregnancy. Nursing mothers.

Astagraf Xl Pharmacokinetics

Distribution

Plasma protein bound: ~99%; mainly bound to albumin and alpha-1-acid glycoprotein.

Metabolism

Extensively by the mixed-function oxidase system (primarily CYP3A4 and CYP3A5).

Elimination

Fecal (92.6 ± 30.7%), renal (2.3 ± 1.1%). Half-life: 38 ± 3 hours. Clearance: 0.172 ± 0.088 L/hr/kg.

Astagraf Xl Interactions

Interactions

Concomitant sirolimus (in liver/heart transplant), live vaccines: not recommended. Concomitant mTOR inhibitors (eg, sirolimus, everolimus) may increase risk of thrombotic microangiopathy. Concomitant mycophenolic acid (MPA) products; monitor and reduce the dose of these as needed. Concomitant strong CYP3A4 inhibitors/inducers or substrates: must adjust dosing regimen, closely monitor tacrolimus blood concentrations and for QT prolongation. Caution with potassium-sparing diuretics, ACEIs, ARBs. Avoid grapefruit/grapefruit juice, alcohol. Additive nephrotoxicity with aminoglycosides, ganciclovir, amphotericin B, cisplatin, ritonavir; if concomitant use, monitor renal function and tacrolimus blood levels; adjust doses of both drugs. May be potentiated by calcium channel blockers (eg, verapamil, diltiazem, nifedipine, nicardipine), antifungals (eg, voriconazole, posaconazole, itraconazole, fluconazole, ketoconazole), macrolides (eg, troleandomycin, clarithromycin, erythromycin), lansoprazole, omeprazole, chloramphenicol, cimetidine, clotrimazole, amiodarone, danazol, ethinyl estradiol, protease inhibitors (eg, nelfinavir, telaprevir, boceprevir, ritonavir), nefazodone, letermovir, schisandra sphenanthera extracts, magnesium-aluminum-hydroxide, metoclopramide. May be potentiated by cannabidiol; consider tacrolimus dose reduction and monitor closely. May be antagonized by carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. Johns wort, methylprednisolone, prednisone, caspofungin. Monitor closely with direct acting antiviral therapy; may need to adjust dose.

Astagraf Xl Adverse Reactions

Adverse Reactions

Diarrhea, constipation, nausea, peripheral edema, tremor, anemia, headache, abdominal pain, insomnia, hypertension, renal dysfunction, infections (viral, cytomegalovirus, polyoma virus), hypophosphatemia, hyperkalemia, hypomagnesemia, hyperglycemia, nephrotoxicity or neurotoxicity (esp. in high doses), JC virus-associated progressive multifocal leukoencephalopathy, post-transplant diabetes mellitus, posterior reversible encephalopathy syndrome (consider reduced dose or discontinue), malignancies (lymphomas, skin), post-transplant lymphoproliferative disorder, pure red cell aplasia (consider discontinuation), Torsade de Pointes.

Astagraf Xl Clinical Trials

See Literature

Astagraf Xl Note