Drug information of Everolimus

Mechanism of effect

Inhibitor of mammalian target of rapamycin (mTOR), which is a serine-threonine kinase. Everolimus binds to an intracellular protein, resulting in an inhibitory complex formation and inhibition of mTOR kinase activity.

Pharmacodynamic

Everolimus is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake

Pharmacokinetics

T max is 1 to 2 h. C max and AUC are approximately 11.1 ng/mL and 75 + 31 ng•h/mL, respectively, for a 0.75 mg twice-daily dosage in renal transplant patients Protein binding is approximately 74%. Vd is 107 to 342 L. Everolimus is a substrate for CYP3A4 and P-glycoprotein (P-gp). Elimination half-life is approximately 30 h. Recovery in the feces and urine is 80% and 5%, respectively.

Drug indications

advanced renal cell carcinoma , prophylaxis of organ rejection- kidney transplant

Dosage

Usual Adult Dose for Organ Transplant - Rejection Prophylaxis Kidney transplant: 0.75 mg orally twice a day Usual Adult Dose for Renal Cell Carcinoma 10 mg orally once a day Duration of therapy: Continue until disease progression or unacceptable toxicity occurs.

Drug contraindications

hypersensitivity to drug or its components.

Side effects

Migraine , Headache , insomnia , Dermatit , Tachycardia , dizziness , fatigue , Seizures , rash , asthenia , pruritus , Hypertension , Erythema , chronic heart failure , acne , Rhinitis , Urinary tract infection , edema , Cough , sinusitis , fever , anxiety , Infections , somnolence , malaise , Otitis media , conjunctivitis , Arthralgia , pain in the extremities , back pain , Upper respiratory tract infection , Hand-and-Foot Syndrome , diabetes mellitus , dry skin , nail disorders , pharyngitis , Epistaxis , pleural effusion

Interactions

Erythromycin , Itraconazole , Cyclosporine , Fluconazole , Phenobarbital , Phenytoin , Verapamil , Voriconazole , Captopril , Carbamazepine , Ketoconazole , Clarithromycin , Thymoglubin , Deferiprone , Zafirlukast , Glibenclamide , Lapatinib , Clozapine , Daclatasvir , ledipasvir and sofosbuvir , Rifabutin , Rifapentine , Atazanavir , Ranolazine , Darunavir , ritonavir , nelfinavir , mitotane , Meglumine Compound , Mefloquine , Golimumab , Hib vaccine , brigatinib , Fosinopril , Ramipril , Efavirenz , lumacaftor and Ivacaftor , Etravirine , Netilmicin , Darifenacin , Mibefradil , Nicardipine , cobicistat , Delavirdine , Oxiconazole , Canakinumab , Basiliximab , Alefacept , Letermovir , Diatrizoate (Amidotrizoic acid) , Butabarbital , Apalutamide , Valdecoxib , Ioxaglate , Rilonacept , Hepatitis B Vaccine , Lorlatinib , Troleandomycin , Oxaprozin , Gallium Nitrate , Iothalamate Meglumine , Glycerol Phenylbutyrate , Nitrendipine , oleandomycin , Typhoid vaccine (live), oral , Meningococcal conjugate vaccine , Rabies Vaccine , tucatinib , sirukumab , Ombitasvir, Paritaprevir, and Ritonavir

Alerts

1- Increased susceptibility to infection and the possible development of malignancies, such as lymphoma and skin cancer, may result from immunosuppression. 2- In renal transplant patients, use reduced doses of cyclosporine in combination with everolimus in order to reduce renal dysfunction. It is important to monitor the cyclosporine and everolimus whole blood trough concentrations 3- An increased risk of kidney arterial and venous thrombosis resulting in graft loss was reported, mostly within 30 days posttransplantation.

Points of recommendation

1- Administer at the same time each day, either consistently with or without food 2- Do not chew or crush tablets. 3- In patients receiving a renal transplant, initiate oral prednisone once oral medication is tolerated

Pregnancy level

D

Related drugs

Sirolimus