Rapamune

Sirolimus

Prophylaxis of organ rejection in patients receiving renal transplant. Initially in regimen w/ cyclosporine & corticosteroids in patients w/ low to moderate immunological risk. In combination w/ cyclosporine (CsA) & corticosteroids for the 1st yr following transplantation in patients at high immunologic risk (black transplant recipients &/or repeat renal transplant recipients who lost previous allograft for immunologic reason &/or patients w/ high-panel reactive Abs).

Patient at low to moderate immunologic risk Combination therapy w/ CsA Loading dose: 6 mg post-transplantation for de novo transplant recipients. Maintenance: 2 mg daily. Dose should be increased to obtain whole blood trough conc (w/in range of 16-24 ng/mL) at 2-4 mth following transplantation while CsA should be w/drawn. Target conc: 12-20 ng/mL (chromatographic method). Patient at high immunologic risk Combination w/ tacrolimus Initial loading dose: Up to 10 mg on days 1 & 2 post-transplantation. Initial maintenance dose of 5 mg daily starting on day 3. Starting dose of tacrolimus: Up to 0.2 mg/kg daily in divided doses & should be adjusted to achieve whole blood trough conc of 10-15 ng/mL for 14 days, 5-10 ng/mL from day 15 to end of wk 26, & 3-5 ng/mL from wk 27 to end of wk 52. Administer prednisone at min of 5 mg/day. Combination w/ CsA therapy Loading dose: Up to 15 mg on day 1 post-transplantation. Initial maintenance: 5 mg daily starting on day 2. Starting dose of CsA: Up to 7 mg/kg daily in divided doses & should be subsequently adjusted to achieve whole blood trough conc of 200-300 ng/mL for 14 days, 150-200 ng/mL from day 15 to the end of wk 26 & 100-150 ng/mL from wk 27 to end of wk 52. Administer prednisone at min of 5 mg/day. Renal allograft recipient Max: 40 mg daily. Ped patient ≥13 yr weighing <40 kg Initial loading dose: 3 mg/m². Maintenance: Adjust based on BSA to 1 mg/m² daily. Patient w/ hepatic impairment Maintenance dose: Reduce by approx ⅓ to ½.

May be taken with or without food: Take consistently either always w/ or always w/o meals. Do not crush/chew/split tab. Avoid grapefruit juice.

Hypersensitivity.

Hypersensitivity reactions eg, anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis & hypersensitivity vasculitis. Not recommended as immunosuppressive therapy in liver or lung transplant patients. Increased susceptibility to opportunistic infections including activation of latent viral infections (BK virus-associated nephropathy & JC virus-associated progressive multifocal leukoencephalopathy), sepsis & fatal infections; development of lymphoma & other malignancies, particularly of the skin; serum cholesterol & triglycerides. Excess mortality, graft loss & hepatic artery thrombosis; bronchial anastomotic dehiscence in de novo liver transplant patients. Impaired or delayed wound healing including lymphocele & wound dehiscence. Fluid accumulation including peripheral edema, lymphedema, pleural effusion & pericardial effusions (hemodynamically significant effusions). Angioedema. ILD including pneumonitis & bronchiolitis obliterans w/ organizing pneumonia & pulmonary fibrosis. Patient w/ BMI >30 kg/m². Limit exposure to sun & UV light; wear protective clothing & use sunscreen w/ high protective factor. Monitor for hyperlipidemia; elevated lipids, & possible development of rhabdomyolysis & other adverse effects in patients administered w/ HMG-CoA reductase inhibitor &/or fibrate; renal function during co-administration w/ tacrolimus or CsA. Consider discontinuation of immunosuppressive regimen in patients w/ elevated serum creatinine levels. Continuation of combination therapy w/ CsA >4 mth after transplantation in patients at low to moderate immunologic risk. May delay recovery of renal function in patients w/ delayed graft function. Periodic quantitative monitoring of urinary protein excretion. Conversion to sirolimus in patients w/ GFR <40 mL/min. De novo use w/o calcineurin inhibitor. Administer prophylaxis for Pneumocystis carinii pneumonia (1 yr after transplantation) & cytomegalovirus (3 mth after transplantation). Concomitant use w/ calcineurin inhibitor may increase risk of calcineurin inhibitor-induced HUS/TTP/TMA & w/ ACE inhibitors may result in angioneurotic edema-type reactions. W/drawal of CsA in high-risk renal transplant patients. Avoid use of live vaccines during treatment. Patients w/ Banff 93 grade III acute rejection or vascular rejection prior to CsA w/drawal, those who are dialysis-dependent or w/ serum creatinine >4.5 mg/dL, Black patients, renal re-transplants, multi-organ transplants & w/ a high panel of reactive Abs. Monitor sirolimus whole blood trough levels in patients w/ hepatic impairment. Contraception must be initiated before therapy & maintained during therapy & for 12 wk after therapy has been stopped. Pregnancy & lactation. Childn <13 yr.

Sepsis, pneumonia, mycobacterial infection (including TB), pyelonephritis, herpes zoster, herpes simplex, UTI, fungal, cytomegalovirus, EBV, viral & bacterial infection; lymphoma, neuroendocrine skin carcinoma, malignant melanoma, post-transplant lymphoproliferative disorder, squamous cell carcinoma of skin, basal cell carcinoma; pancytopenia, TTP, hemolytic uremic syndrome, neutropenia, thrombocytopenia, anemia, leukopenia; hypersensitivity (including angioedema, anaphylactic & anaphylactoid reactions); hypokalemia, hypophosphatemia, hyperlipidemia (including hypercholesterolemia), hyperglycemia, hypertriglyceridemia, fluid retention, DM; posterior reversible encephalopathy syndrome, headache; pericardial effusion, tachycardia; venous thrombosis (including DVT), HTN, lymphoedema, lymphocele; pulmonary hemorrhage & embolism, alveolar proteinosis, pneumonitis, pleural effusion, epistaxis; pancreatitis, stomatitis, ascites, abdominal pain, constipation, diarrhea, nausea; exfoliative dermatitis, hypersensitivity vasculitis, rash, acne; osteonecrosis, arthralgia; nephrotic syndrome, focal segmental glomerulosclerosis, proteinuria; menstrual disorder (including amenorrhea & menorrhagia), ovarian cyst; impaired healing, edema, peripheral edema, pyrexia, pain; abnormal LFT (including increased ALT & AST), increased blood creatinine & blood LDH.

Not recommended w/ strong CYP3A4 inhibitors (eg, ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin) or CYP3A4 inducers (eg, rifampin, rifabutin). Increased conc w/ P-gp inhibitors & CYP3A4 inhibitors eg, Ca channel blockers (diltiazem, nicardipine, verapamil), antifungals (clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole), antibiotics (clarithromycin, erythromycin, telithromycin, troleandomycin), GI prokinetic agents (cisapride, metoclopramide), bromocriptine, cimetidine, CsA, danazol, letermovir, PIs (eg, for HIV & hepatitis C eg, ritonavir, indinavir, boceprevir & telaprevir), grapefruit juice. Decreased conc w/ P-gp inducers & CYP3A4 inducers eg, anticonvulsants (carbamazepine, phenobarb, phenytoin), antibiotics (rifabutin, rifampicin, rifapentine), St. John's Wort (Hypericum perforatum). Increased bioavailability w/ diltiazem. Significantly affected rate & extent of absorption & increased C_max, t_max & AUC of both drugs w/ verapamil, erythromycin & ketoconazole. Monitor for the development of rhabdomyolysis w/ CsA, HMG-CoA reductase inhibitors &/or fibrates. Increased blood levels w/ cannabidiol. Calcineurin-induced hemolytic uremic syndrome/TTP/thrombotic microangiopathy w/ calcineurin inhibitor. Avoid use of live vaccines. Reduced CYP3A4-mediated metabolism w/ grapefruit juice.

Immunosuppressants

L04AH01 - sirolimus ; Belongs to the class of mammalian target of rapamycin (mTOR) kinase inhibitors. Used as immunosuppressants.

Rx