Rapamune

Prophylaxis of organ rejection in patients receiving renal transplants. Initially used in a regimen w/ cyclosporine & corticosteroids in patients at low to moderate immunologic risk.

Adult Combination w/ cyclosporine therapy Usual oral loading dose: Administer 6 mg as soon as possible after transplantation followed by 2 mg once daily, then individualize dose to obtain whole blood trough levels of 4-12 ng/mL. Maintenance regimen w/ cyclosporine w/drawal At 2-4 mth following transplantation, cyclosporine should be progressively discontinued over 4-8 wk & adjust Rapamune dose to obtain whole blood trough conc w/in 16-24 ng/mL for the 1st yr following transplantation, then target sirolimus conc should be 12-20 ng/mL thereafter. Patient at high immunologic risk Recommended to be taken 4 hr after cyclosporine microemulsion administration. Hepatic impairment Reduce maintenance dose by approx ¹/₃ to ½.

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

Hypersensitivity.

Hypersensitivity reactions including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis & hypersensitivity vasculitis. Increased susceptibility to infection & development of lymphoma & other malignancies particularly of the skin due to immunosuppression. Not recommended in liver or lung transplant patients. Associated excess mortality, graft loss & hepatic artery thrombosis in combination w/ tacrolimus in liver transplant recipients. Reported cases of bronchial anastomotic dehiscence when used as part of an immunosuppressive regimen in lung transplant patients. Closely monitor renal function during co-administration w/ cyclosporine or tacrolimus. Consider appropriate adjustment of immunosuppression regimen including discontinuation of Rapamune, cyclosporine &/or tacrolimus in patients w/ elevated or increasing serum creatinine levels. Lymphocele; ILD; latent viral infections (eg, BK virus-associated nephropathy & JC virus-associated progressive multifocal leukoencephalopathy). Consider appropriate post-op measures to minimize lymphocele. Impaired or delayed wound healing & fluid accumulation; patients w/ BMI >30 kg/m² may be at increased risk of abnormal wound healing. Limit exposure to sunlight & UV light by wearing protective clothing & using sunscreen. Monitor for hyperlipidemia; initiate subsequent interventions (eg, diet, exercise & lipid-lowering agents) if hyperlipidemia is detected. Monitor for elevated lipids during Rapamune therapy w/ or w/o cyclosporine; possible rhabdomyolysis & other adverse effects in concomitant use w/ HMG-CoA reductase inhibitor &/or fibrate. May delay recovery of renal function in patients w/ delayed graft function. Periodic quantitative monitoring of urinary protein excretion is recommended. Conversion from calcineurin inhibitor (CNI) to Rapamune in patients w/ GFR <40 mL/min; de novo use of Rapamune w/o CNI in renal transplant patients. Concomitant use w/ CNI may increase risk of CNI-induced hemolytic uremic syndrome/TTP/thrombotic microangiopathy (HUS/TTP/TMA). Elevated sirolimus levels w/ or w/o concomitant ACE inhibitors may potentiate angioedema. Administer antimicrobial prophylaxis for Pneumocystis carinii pneumonia for 1 yr following transplantation. Cytomegalovirus (CMV) prophylaxis is recommended for 3 mth after transplantation particularly for patients at increased risk for CMV infection. Cyclosporine w/drawal in high-risk renal transplant patients. Monitor whole blood sirolimus levels in all patients. Not recommended to be co-administered w/ strong inhibitors (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin) or strong inducers (eg, rifampin or rifabutin) of CYP3A4 &/or P-gp. Concomitant use w/ cannabidiol; other drugs known to impair renal function; other immunosuppressive agents. Severe hepatic impairment. Advise women of childbearing potential to initiate effective contraception before, during & for 12 wk after therapy. Use only if the potential benefit outweighs the potential risk to the embryo/fetus during pregnancy. Lactation; potential for adverse reaction in nursing infants. Safety & efficacy have not been established in ped patients <13 yr; monitor sirolimus whole blood through levels if used in ped patients <13 yr.

Thrombocytopenia, anemia, leukopenia; tachycardia; abdominal pain, constipation, diarrhea, nausea; edema, peripheral edema, pyrexia, pain, impaired healing; pneumonia, fungal, viral & bacterial infection, herpes simplex, UTI; increased blood LDH & creatinine, abnormal LFT (including increased ALT & AST); hypokalemia, hypophosphatemia, hyperlipidemia (including hypercholesterolemia), hyperglycemia, hypertriglyceridemia, fluid retention, DM; arthralgia; headache; proteinuria; menstrual disorder (including amenorrhea & menorrhagia); rash, acne; HTN, lymphocele. HUS, neutropenia; pericardial effusion; pancreatitis, stomatitis, ascites; hypersensitivity (including angioedema, anaphylactic & anaphylactoid reaction); sepsis, pyelonephritis, CMV infection, herpes zoster; osteonecrosis; squamous cell carcinoma of skin, basal cell carcinoma; ovarian cyst; pulmonary embolism, pneumonitis, pleural effusion, epistaxis; venous thrombosis (including DVT).

Increased levels w/ CYP3A4 & P-gp inhibitors; Ca channel blockers (eg, diltiazem, nicardipine, verapamil), antifungals (eg, clotrimazole, fluconazole, itraconazole, ketoconazole, voriconazole), antibiotics (eg, clarithromycin, erythromycin, telithromycin, troleandomycin), GI prokinetics (eg, cisapride, metoclopramide), bromocriptine, cimetidine, cyclosporine, danazol, letermovir, PIs (eg, ritonavir, indinavir, boceprevir, telaprevir), grapefruit juice. Decreased levels w/ CYP3A4 & P-gp inducers; anticonvulsants (eg, carbamazepine, phenobarb, phenytoin), antibiotics (eg, rifabutin, rifampicin, rifapentine), herbal prep (eg, St. John's wort). Increased C_max, t_max & AUC w/ diltiazem, verapamil, erythromycin & ketoconazole. Decreased AUC & C_max w/ rifampicin. Monitor for rhabdomyolysis development when used concomitantly w/ cyclosporine together w/ HMG-CoA reductase inhibitor &/or fibrate. Increased C_max & AUC w/ cyclosporine. Increased sirolimus blood levels when used concomitantly w/ cannabidiol. Reported HUS/TTP/TMA w/ CNI. Immunosuppressants may affect response to vaccination; avoid use of live vaccines during treatment. Bioavailability is affected by concomitant food intake.

Immunosuppressants

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

POM