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Home / Drugs / Starting with D / Doxorubicin
 
Doxorubicin
 

indication

For the treatment of Koposi's sarcome connected to AIDS.

pharmacology

Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific.

mechanism of action

Doxorubicin has antimitotic and cytotoxic activity through a number of proposed mechanisms of action: Doxorubicin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes.

toxicity

LD50=21800 ug/kg (rat, subcutaneous)

half life

55 hours

route of elimination

Plasma clearance is in the range 324 to 809 mL/min/m2 and is predominately by metabolism and biliary excretion.

drug interactions

Dabigatran etexilate: P-Glycoprotein inducers such as doxorubicin may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.

Digoxin: The antineoplasic agent decreases the effect of digoxin

Telithromycin: Telithromycin may reduce clearance of Doxorubicin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Doxorubicin if Telithromycin is initiated, discontinued or dose changed.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Doxorubicin. Consider alternate therapy or monitor for therapeutic/adverse effects of Doxorubicin if Terbinafine is initiated, discontinued or dose changed.

Trastuzumab: Trastuzumab may increase the cardiotoxicity of Doxorubicin. Signs and symptoms of cardiac dysfunction should be monitored for frequently. Increased risk of heart failure. Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of doxorubicin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxorubicin if voriconazole is initiated, discontinued or dose changed.

Zidovudine: Additive myelosuppression may occur. Doxorubicin may decrease the efficacy of zidovudine. Concomitant therapy should be avoided.