Warfarin Doxorubicin

Clinically important, potentially hazardous interactions with doxorubicin, warfarin... 

Similarly, green tea Camellia sinensis), a commonly consumed dietary supplement in many Asian countries, contains catechins, which have been shown to inhibit the activity of P-glycoprotein (26) and the efflux of doxorubicin by a carcinoma cell line (27). Although currently there is no literature report of an interaction between green tea and prescription or over-the-counter drug based on modulation of P-glycoprotein, a potential interaction between green tea and warfarin was reported and is described in Chapter 6. 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

C9 Barbiturates, especially phenobarbital, phenytoin, primidone, rifampin Barbiturates, chloramphenicol, doxorubicin, ibuprofen, phenytoin, chlorpromazine, steroids, tolbutamide, warfarin... 

A number of case reports describe an increase in the effects of warfarin, accompanied by bleeding in some cases, caused by an-tineoplastic regimens containing carboplatin, chlormethine, cyclophosphamide, doxorubicin, etoposide, gefitinib, gemcitabine, ifosfamide with mesna, methotrexate, procarbazine, trastuzum-ab, vincristine or vindesine. A decrease in the effects of warfarin has been seen with azathioprine, cyclophosphamide, mercaptop-urine and mitotane, a decrease in the effects of acenocoumarol has been seen with mercaptopurine, and a decrease in the effects of phenprocoumon have l n seen with azathioprine. 

Etretinate. A man with T-cell lymphoma who had recently been given chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) was anticoagulated with warfarin after developing a pulmonary embolism. About three weeks later, he started etretinate 40 mg daily and it was found necessary to increase his warfarin dosage from 7 to 10 mg daily. His liver function tests were normal. This patient had also recently started taking co-proxamol , (p.436), tolbutamide , (p.380) and cimeti-dine , (p.412) , but all of these have been reported to only rarely increase the effect of warfarin. 

Sorafenib levels may be reduced by inhibitors of CYP3A4. Antacids may reduce the absorption of sorafenib. Siorafenib may increase docetaxel and doxorubicin levels. Isolated cases of raised ENRs and bleeding have been reported in patients taking warfarin with sorafenib. 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

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