Temsirolimus

Aiother SRL derivative, temsirolimus, is in clinical trials for the treatment of various leukemias. 

Temsirolimus (35 Sirolimus (34) Macrolide Semi-synthetic Microbial Anticancer Leads to cell cycle 337-350... 

Temsirolimus (35 ToriseF, CCI-779 Wyeth, 2007), a semi-synthetic derivative of sirolimus (34), is an intravenous drug for the treatment of renal cell carcinoma (RCC) ° developed by Wyeth Pharmaceuticals... 

Gu J, Ruppen ME, Cai P. (2005) Lipase-catalyzed regioselective esterification of rapamycin Synthesis of temsirolimus (CCl-779). Org Lett 7 3945-3948. 

Gore ME. (2007) Temsirolimus in the treatment of advanced renal cell carcinoma Ann Oncol 18(Suppl 9) ix87-ix88. 

Belhnunt J, Szczylik C, Feingold J, Strahs A, Berkenblit A. (2008) Temsirolimus safety profile and management of toxic effects in patients with advanced renal ceU carcinoma and poor prognostic features. Ann Oncol 19 1387-1392. 

Panitumumab (Vectibix) Pemetrexed (Alimta) Rasburicase (Elitek) Sorafenib (Nexavar) Sunitinib (Sutent) Temsirolimus (Torisel Kit)... 

Temsirolimus (Torisel Kit) [mTOR Inhibitor] Uses Advanced RCC Action mTOR inhibitor Dose 25 mg IV over 30-60 min x 1 wk continue until tox or progression pre med w/ 25-50 mg Benadryl 30 min before Caution [D, -] w/ CYP3A4 inhib/inducers (Table VI-8), avoid grapefruit juice, vaccines, immediately postop Contra None Disp IV SE Hypersensitivity Rxn, rash, asthenia, mucositis, N, edema, anorexia, poor wound healing, bowel perfusion EMS May T glucose OD May cause NA, abd pain, HA, confusion, melana, and Szs symptomatic and supportive... 

The promising second oral therapy is Temsirolimus (Wyeth Pharm). Temsirolimus is believed to block the proliferation of immune T cells activated by interleukin, IL-2. The phase It clinical trial of Temsirolimus was also an international double blind placebo controlled trial. The trial involved 296 patients with either RR MS or SP MS with relapses. Participants received one of three doses of oral temsirolimus or placebo daily for 9 months. The primary outcome measure was the number of enhancing lesions after 9 months in study. By 32 w eeks into the study, those in the highest treatment dose had 47.8% fewer new enhancing lesions compared to those on placebo. The high dose group also had 51 % fev er relapses than the placebo group. Side effects included mouth ulceration or inflammation, menstrual dysfunction, hyperlipidemia and rashes. 

Calcineurin inhibitors ciclosporin, everolimus, pimecrolimus, sirolimus, tacrolimus, temsirolimus. 

Clinically important, potentially hazardous interactions with bepridil, cisapride, dasatinib, dofetilide, ergot derivatives, etravirine, fentanyl, fesoterodine, garlic, indinavir, irinotecan, ixabepilone, lapatinib, lovastatin, marihuana, midazolam, pimozide, proton-pump inhibitors, raltegravir, rifampin, ritonavir, sildenafil, simvastatin, solifenacin, St John s wort, temsirolimus, triazolam... 

Clinically important, potentially hazardous interactions with acetylcysteine, adenosine, aprepitant, aripiprazole, buprenorphine, caffeine, charcoal, clarithromycin, clobazam, dorazepate, clozapine, darunavir, dasatinib, delavirdine, dexamethasone, diltiazem, doxacurium, erythromycin, felodipine, fesoterodine, fosamprenavir, imatinib, influenza vaccines, lacosamide, lapatinib, levetiracetam, lopinavir, methylprednisolone, midazolam, nelfinavir, nilotinib, piracetam, prednisolone, propoxyphene, ritonavir, rivaroxaban, rufinamide, solifenacin, St John s wort, telithromycin, temsirolimus, terbinafine, tolvaptan, troleandomycin, verapamil, voriconazole... 

Clinically important, potentially hazardous interactions with alprazolam, aprepitant, astemizole, atorvastatin, benzodiazepines, carbamazepine, chlordiazepoxide, cilostazol, clonazepam, clorazepate, colchicine, conivaptan, cyclosporine, dabigatran, dasatinib, diazepam, digoxin, dihydroergotamine, disopyramide, ergot alkaloids, fesoterodine, fluoxetine, flurazepam, fluvastatin, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lorazepam, lovastatin, methylprednisolone, methysergide, midazolam, nilotinib, oxazepam, paroxetine, pimozide, pravastatin, prednisone, quazepam, repaglinide, rimonabant, rivaroxaban, sertraline, silodosin, simvastatin, solifenacin, temazepam, temsirolimus, tolvaptan, trabectedin, triazolam, warfarin, zidovudine... 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Clinically important, potentially hazardous interactions with aprepitant, astemizole, buspirone, dasatinib, eszopiclone, fesoterodine, isocarboxazid, ivabradine, ixabepilone, lapatinib, MAO inhibitors, phenelzine, pimozide, rimonabant, selegiline, sibutramine, solifenacin, St John s wort, sumatriptan, temsirolimus, tolvaptan, tramadol, tranylcypromine, trazodone... 

Clinically important, potentially hazardous interactions with amiodarone, anisindione, anticoagulants, azithromycin, corticosteroids, cyclosporine, dapsone, delavirdine, dicumarol, fosamprenavir, lapatinib, lopinavir, midazolam, oral contraceptives, ritonavir, solifenacin, tacrolimus, temsirolimus, tolvaptan, voriconazole... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Clinically important, potentially hazardous interactions with atorvastatin, carbamazepine, cisapride, cyclosporine, digoxin, dihydroergotamine, ergotamine, fesoterodine, hexobarbital, ixabepilone, lapatinib, lovastatin, metoprolol, midazolam, nilotinib, phenobarbital, phenytoin, pimozide, rifampin, rimonabant, simvastatin, sirolimus, tacrolimus, temsirolimus, tolvaptan, triazolam, warfarin... 

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