Certican

Everolimus

In combination w/ ciclosporin for microemulsion & corticosteroids for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving an allogenic renal or cardiac transplant. In combination w/ tacrolimus & corticosteroids for the prophylaxis of organ rejection in patients receiving a hepatic transplant.

Adult General kidney & heart transplant population Initially 0.75 mg twice daily administered as soon as possible after transplantation. Liver transplant population 1 mg twice daily w/ initial dose approx 4 wk after transplantation. Adjust dose at 4-5 days intervals based on achieved blood levels, tolerability, response, change in co-medications & clinical situation. Mild or moderate hepatic impairment (Child-Pugh Class A or B) Reduce dose to approx ½ of the normal dose. Recommended everolimus whole blood trough levels: 3-8 ng/mL.

May be taken with or without food: Take consistently either always w/ or always w/o meals. Swallow whole, do not chew/crush. Avoid grapefruit juice.

Hypersensitivity to everolimus, sirolimus.

Discontinue use if ILD occurs. Patients at high immunological risk. Combination w/ thymoglobulin induction. Increased risk of acute rejection, developing infections, lymphomas & other malignancies particularly in skin, kidney arterial & venous thrombosis, calcineurin inhibitor-induced haemolytic uraemic syndrome/TTP/thrombotic microangiopathy & new onset DM. Monitor blood trough levels, skin neoplasm. Not recommended in concomitant use w/ strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir) & inducers (eg, rifampicin, rifabutin). Minimize exposure to UV light, sunlight, & to use an appropriate sunscreen. Hyperlipidaemia/severe refractory hyperlipidaemia. Patients under HMG-CoA reductase inhibitor &/or fibrate treatment. Everolimus and calcineurin inhibitor-induced renal dysfunction. Angioedema; proteinuria. Impaired wound healing. Reversible azoospermia & oligospermia in patients treated w/ mTOR inhibitors. Not to be taken by patients w/ galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption. Black patients. Women of childbearing potential should use effective contraception during & up to 8 wk after therapy. Risk for male infertility in prolonged use. Not to be used during pregnancy. Lactating women should not breast feed. Childn & adolescents.

Viral, bacterial & fungal infections, URTI; leucopenia; pericardial effusion; hyperlipidaemia (cholesterol & triglycerides), new onset DM; HTN; pleural effusion; abdominal pain; peripheral oedema, incisional hernia. Sepsis, UTI, lower resp tract infection, wound infection; thrombocytopenia, pancytopenia, anaemia, coagulopathy, TTP/haemolytic uraemic syndrome; lymphocele, VTE, graft thrombosis; diarrhoea, nausea, pancreatitis, vomiting, stomatitis/mouth ulceration, oropharyngeal pain; angioneurotic oedema, acne, surgical wound complication; proteinuria; erectile dysfunction; pain, impaired healing; abnormal hepatic enzyme.

Absorption & subsequent elimination may be influenced by medicinal products that affect CYP3A4 &/or Pgp. Increased clearance, decreased C_max & AUC w/ rifampicin. Increased C_max & AUC w/ ketoconazole, erythromycin, verapamil. Increased bioavailability w/ ciclosporin. Increased C_min of octreotide. Increased C_max & AUCinf of midazolam. Increased metabolism & decreased blood levels w/ St. John's wort, anticonvulsants (eg, carbamazepine, phenobarb, phenytoin), anti HIV drugs (eg, efavirenz, nevirapine). Increased risk of angioedema w/ ACE inhibitors. Increased blood levels w/ antifungals (eg, fluconazole), Ca-channel blockers (eg, nicardipine, diltiazem) & PIs (eg, nelfinavir, indinavir, amprenavir). Decreased efflux & increased blood conc w/ P-gp inhibitors. Increased conc of CYP3A4 & CYP2D6 substrates w/ narrow therapeutic index. May affect response w/ live vaccines. Avoid grapefruit & grapefruit juice.

Immunosuppressants

L04AA18 - everolimus ; Belongs to the class of selective immunosuppressive agents. Used to induce immunosuppression.

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