Corticosteroids Aprepitant

Corticosteroids noted an increase in plasma levels of dexamethasone or methylprednisolone when given concurrently with aprepitant. Corticosteroids are substrates for CYP3A4 and the inhibition of this enzyme by high-dose aprepitant leads to raised plasma levels of corticosteroids. 

Dosage regimen Aprepitant is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose of aprepitant is 125... 

Neurokinin 1 (NKiJ-receptor antagonists have antiemetic properties that are mediated through central blockade in the area postrema. Aprepitant (an oral formulation) is a highly selective Nl -receptor antagonist that crosses the blood-brain barrier and occupies brain NKj receptors. It has no affinity for serotonin, dopamine, or corticosteroid receptors. Fosaprepitant is an intravenous formulation that is converted within 30 minutes after infusion to aprepitant. 

APREPITANT ANTICANCER AND IMMUNOMODULATING DRUGS-CORTICOSTEROIDS t dexamethasone and methylprednisolone levels Inhibition of CYP3A4-mediated metabolism of these corticosteroids Be aware... 

Clinically important, potentially hazardous interactions with alfuzosin, amiodarone, aprepitant, carbamazepine, celiprolol, corticosteroids, cyclosporine, epirubicin, erythromycin, mistletoe, moricizine, oxprenolol, ranolazine, simvastatin, sulpiride... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

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... 

Aprepitant is supplied in 80- and 125-mg capsules and is administered for 3 days in conjunction with highly emetogenic chemotherapy along with a 5-HT3-receptor antagonist and a corticosteroid. The recommended adult dosage of aprepitant is 125 mg administered 1 hour before chemotherapy on day one, followed by 80 mg once daily in the morning on days two and three of the treatment regimen. 

One of the fundamental features of aprepitant, and a major advantage it has over other chemotherapy-induced side-effect treatments, is that while it successfully antagonises the NKl receptors it has very little affinity over other receptors such as serotonin, dopamine, and corticosteroids. It is estimated that aprepitant is at least 3000 times more selective of NKl receptors compared to the other well-known neurotransmitter antagonists. 

The use of aprepitant has also been shown to increase the activity of the 5-HT3 receptor antagonist ondansetron and the corticosteroid dexamethasone, which are also used to prevent the acute phase of CINV caused by chemotherapy. 

When used for the treatment of chemotherapy-induced nausea and vomiting, aprepitant is given over 3 days as part of a combination antiemetic regimen that also includes a 5HT antagonist as well as a corticosteroid. The recommended dose is 125 mg orally 1 hour before chemotherapy on day 1 and 80 mg orally each morning on days 2 and 3. 

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