Interferons Zidovudine

INTERFERON ZIDOVUDINE t adverse effects with zidovudine Additive toxicity Monitor FBC and renal function closely. 1 doses as necessary. Use of pyrimethamine as prophylaxis seems to be tolerated... 

Fernandez-Cruz E, Lang JM, Frissen J, Fumer V, Chateauvert M, Boucher CA, Dowd P, Stevens J (1995) Zidovudine plus interferon-alpha versus zidovudine alone in HIV-infected symptomatic or asymptomatic persons with CD4+ cell counts > 150 x 10(6)/L results of the Zidon trial. AIDS 9 1025-1035... 

Fischl MA, Richman DD, Saag M, Meng TC, Squires KE, Holden-Wiltse J, Meehan PM (1997) Safety and antiviral activity of combination therapy with zidovudine, zalcitabine, and two doses of interferon-alpha2a in patients with HIV. J Acquit Immune Deflc Syndr Hum Retrovirol 16 247-253... 

Gendelman HE, Baca LM, Turpin J, Kalter DC, Hansen B, Orenstein JM, Dieffenbach CW, Friedman RM, Meltzer MS (1990) Regulation of HIV rephcation in infected monocytes by IFN-alpha. Mechanisms for viral restriction. J Immunol 145 2669-26676 Giovannini M, Zuccotti GV, Biasucci G, Locatelh V, Riva E (1992) Combined zidovudine and interferon-alpha 2a therapy in children with acquired immune deficiency syndrome. J Int Med Res 20 295-301... 

Kozlowski A, Charles SA, Harris JM (2001) Development of pegylated interferons for the treatment of chronic hepatitis C. BioDrugs 15 419 29 Krown SE, AeppU D, Balfour HH Jr (1999) Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol 20 245-254 LaFleur DW, NardeUi B, Tsareva T, Mather D, Feng P, Semenuk M, Taylor K, Buergin M, Chinchilla D, Roshke V, Chen G, Ruben SM, Pitha PM, Coleman TA, Moore PA (2001) Interferon-kappa, a novel type I interferon expressed in human keratinocytes. J Biol Chem 276 39765-39771... 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Drug Interactions According to the product label, interactions between Intron A and other drugs have not been fully evaluated. Caution should be exercised when administering Intron A therapy in combination with other potentially myelo-suppressive agents such as zidovudine. Concomitant use of alfa interferon and theophylline decreases theophylline clearance, resulting in a 100% increase in serum theophylline levels. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

The safety and activity of subcutaneous GM-CSF (300 micrograms/day for 1 week and 150 micrograms twice weekly for 11 weeks) has been compared with no treatment in 244 leukopenic HIV-infected patients (62). Adverse effects were reported in most of the patients treated with GM-CSF and consisted of flu-like symptoms (98%), bone pain (42%), and injection site reactions (85%). There was a two-fold increase in serum transaminase and alkaline phosphatase activities in 5.7% of patients. There was a moderate, but not significant, increase in HIV p24 antigen concentration. The few relevant clinical trials have provided no convincing evidence that GM-CSF enhances HIV replication or accelerates HIV-associated diseases (for example infections or neoplasms) in patients with AIDS (63). Only one patient with AIDS and ultrasonographic confirmation of enhanced Kaposi s sarcoma lesions temporally related to GM-CSF used for interferon- and zidovudine-related severe neutropenia has been reported (SEDA-19, 343). 

Synergistic hemotoxicity has sometimes resulted from the combination of interferon alfa with zidovudine in AIDS-associated Kaposi s sarcoma, but this regimen is considered to be relatively safe (421,422). 

Krown SE, Gold JW, Niedzwiecki D, Bundow D, Flomenberg N, Gansbacher B, Brew BJ. Interferon-alpha with zidovudine safety, tolerance, and clinical and virolo-gic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med 1990 112(11) 812-21. 

Albendazole, ag interferon, anti-CD5 antibody, azathioprine, dimercaprol, hycanthone, interferon, interleukin 2, iron dextran, ivermectin, ketoconazole, lansoprazole, metoprolol, nalidixic acid, OKT3, pefloxacin, tiabendazole, zidovudine... 

Zidovudine is rapidly absorbed from the G1 tract with peak serum concentrations occurring within 30 to 90 minutes. It binds to plasma proteins to the extent of 35 to 40%. Zidovudine is rapidly metabolized in the liver to the inactive 3 -azido-3 -deoxy-5 -0-beta-D-glucopyranuronosylthymi-dine (GAZT), which has an apparent elimination half-life of 1 hour. Zidovudine undergoes glomerular filtration and active tubular secretion. Coadministration of zidovudine with agents such as dapsone, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin, and interferon with potential to cause nephrotoxicity or cytotoxicity to hematopoietic elements, enhance its risk of adverse effects. Probenecid will inhibit the renal excretion of zidovudine. 

Interferon alfa does not alter the pharmacokinetics of didanosine or lamivudine to a clinically relevant extent. Interferon alfa and, particularly, interferon beta can cause an increase in the serum levels of zidovudine. HIV-positive patients infected with hepatitis C and treated with interferon alfa and ribavirin may be at special risk of NRTI-associated lactic acidosis. Interleukin-2 appears not to interact significantly with zidovudine. 

Interferon beta appears to inhibit the metabolism (glucuronidation) of the zidovudine by the liver. 

Nokta M, Loh JP, Douidar Ahmed AE, Pollard RB. Metabolic interaction of recombinant interferon-p and zidovudine in AIDS patients. JInterferon Res (1991) 11,159-64. 

Diaz C, Yogev R, Rodriguez J, Rege A, George W, Lertora J. ACTG-153 Zidovudine pharmacokinetics when used in combination with interferon alpha. Intersci Corf Antimicrob Agents Chemother( 99A) 34, 79. 

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