Rapamune

Sirolimus

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 w/ cyclosporine therapy Usual oral loading dose: 6 mg administered as soon as possible after transplantation, followed by 2 mg once daily. The dose should then be individualized 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 & Rapamune dose should be adjusted 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 ⅓ to ½.

May be taken with or without food: Take consistently, either w/ or w/o meal. Avoid grapefruit juice.

Hypersensitivity.

Hypersensitivity reactions eg, 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. Excess mortality, graft loss & hepatic artery thrombosis in combination w/ tacrolimus in liver transplant patients. Bronchial anastomotic dehiscence when used as part of an immunosuppressive regimen in lung transplant patients. Closely monitor renal function during co-administration w/ cyclosporine. Lymphocele; hyperlipidemia; rhabdomyolysis; ILD; latent viral infections eg, BK virus associated nephropathy & JC virus associated progressive multifocal leukoencephalopathy (PML). Impaired or delayed wound healing & fluid accumulation. Patients w/ BMI <30 kg/m². Limit exposure to sunlight & UV light. Patients w/ delayed graft function. Periodic quantitative monitoring of urinary protein excretion is recommended. Conversion from calcineurin inhibitors to Rapamune & de novo use of Rapamune w/o calcineurin inhibitor in renal transplant patients. Concomitant use w/ calcineurin inhibitor may increase the risk of calcineurin inhibitor-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. 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. Cyclosporine w/drawal in high-risk renal transplant patients. Severe hepatic impairment. Women of childbearing potential should initiate effective contraception before, during & for 12 wk after therapy. Pregnancy & lactation. Childn <13 yr.

Thrombocytopenia, anaemia, 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 & blood creatinine, abnormal LFT (including increased ALT & AST); hypokalemia, hypophosphatemia, hyperlipidemia (including hypercholesterolemia), hyperglycemia, hypertriglyceridemia, fluid retention, DM; arthralgia; headache; proteinuria; menstrual disorder (including amenorrhoea & menorrhagia); rash, acne; HTN, lymphocele. Hemolytic uremic syndrome, neutropenia; pericardial effusion; pancreatitis, stomatitis, ascites; hypersensitivity (including angioedema, anaphylactic & anaphylactoid reaction); sepsis, pyelonephritis, CMV infection, herpes zoster; osteonecrosis; squamous & basal cell carcinoma; ovarian cyst; pulmonary embolism, pneumonitis, pleural effusion, epistaxis; venous thrombosis (including DVT).

May have increased levels w/ CYP3A4 inhibitors eg, 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. May have decreased levels w/ CYP3A4 inducers eg, 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. Possible HUS/TTP/TMA w/ calcineurin inhibitor. Immunosuppressants may affect response to vaccination. Bioavailability is affected by concomitant food intake after administration.

Immunosuppressants

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

POM