Retrovir

Nucleoside Reverse Transcriptase Inhibitor

Common Name: zidovudine (ZDV) or AZT

Brand Name: Retrovir

Class: nucleoside analog (also called nucleoside reverse transcriptase inhibitor, NRTI or nuke)

Standard dose: One 300 mg tablet twice a day (12 hours apart); two 100 mg capsules three times a day also available, no food restrictions (may be taken with or without food). Clear, strawberry-flavored liquid available for pediatric use. Take missed dose as soon as possible, but do not double up on your next dose. Generic is available.

AWP: $496.56 (generic $356.04) / month, $64.61 (generic $48.13) for 240 ml syrup

Manufacturer contact: GlaxoSmithKline,
www.treathiv.com, 1 (888) 825-5249

AIDSInfo:
1 (800) HIV-0440 (448-0440), www.aidsinfo.nih.gov

Potential side effects and toxicity: May include headaches, fever, chills, muscle soreness, fatigue, nausea, and fingernail discoloration. Zidovudine (AZT) has been associated with alteration of various cells in the blood through bone marrow suppression resulting in anemia (low red blood cell counts) and/or neutropenia (low white blood cell counts), particularly during the first three months in people with advanced HIV. Potential exists for severe anemia requiring blood transfusion, erythropoietin injections, or hospitalization when used on its own or in combination with hydroxyurea. Rare but potentially fatal toxicity with all NRTIs: hepatomegaly with steatosis (enlarged fatty liver) and lactic acidosis (accumulation of lactate in the blood and abnormal acid-base balance). Lactic acidosis has been seen in patients taking NRTIs, but is more common and more severe in women, people who are obese, and people who have been taking NRTIs for a long time; it is more common in people with liver disease, but can occur in people without a history of liver damage. People with lactic acidosis may experience persistent fatigue, abdominal pain or distension, nausea/vomiting, difficulty breathing or shortness of breath, and enlarged, fatty liver. Pancreatitis (inflammation of the pancreas) can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting, and bleeding. Risks for pancreatitis include: higher than recommended doses of NRTIs, advanced HIV, and alcohol use. The risk for pancreatitis with zidovudine is low compared to didanosine (Videx).

Potential drug interactions: Biaxin, Mycobutin, and rifampin (under various brand names) may decrease zidovudine blood levels. Benemid (probenecid), Dilantin (phenytoin), and Depakote (valproic acid) may increase zidovudine blood levels and decrease zidovudine clearance, but no dosing adjustments are recommended. Zidovudine and Zerit should not be used together due to evidence that one limits the other's effectiveness. Also, bone marrow suppression should be monitored with use of Cytovene (ganciclovir), Valcyte, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferon-alpha, ribavirin (Rebetol), and with cancer treatments such as hydroxyurea and doxorubicin. Ribavirin and zidovudine may cancel each other out, so this combination should be monitored closely. New Procrit or Epogen warning: if hemoglobin target is above manufacturer's recommendation (12 g/dL), the risk for serious and life-threatening cardiovascular complications significantly increases. For zidovudine patients, measure hemoglobin once a week after starting the anemia drugs until hemoglobin has stabilized. Notify health care provider if experiencing pain and/or swelling in the legs, worsening in shortness of breath, increases in blood pressure, dizziness or loss of consciousness, extreme tiredness, or blood clots in hemodialysis vascular access ports. Do not take with Combivir or Trizivir, since zidovudine is already in these medications.

Tips: The not-so-good news for people adding zidovudine: the fatigue and the potential anemia. You can start taking erythropoietin (Procrit or Epogen) for some anemias, but that's adding an expensive weekly injectable. Some doctors would prefer switching out the zidovudine for another drug. Also, some clinicians avoid the "T" drugs, or thymidine analogs (zidovudine and Zerit) because of their implication in lipoatrophy (fat loss, seen in the arms, legs, and face). Zidovudine has for years been associated with "AZT butt," a disheartening flatness that happens gradually. Taking with food may minimize upset stomach. Please see package insert for more complete potential side effects and interactions.

Doctor

Retrovir (zidovudine, known to most as AZT, generic form available in the U.S.) was the first antiretroviral developed and has had a significant impact on the course of HIV infection. Historically, AZT development has served as an example of a highly successful government and industry partnership to combat a lethal disease. In reality, conflict and controversy surrounded its development and can make some interesting reading if one so desires to explore this issue. The conflict and controversy surrounding this drug, however, led many patients to refuse AZT therapy. In our clinic, AZT is primarily used in the fixed dose combinations Combivir or Trizivir. Since the approval of other more powerful and convenient antiretrovirals, the use of AZT as a stand-alone drug (or in combination) in HAART therapy has decreased significantly. In developing countries, where the number of individuals infected with HIV is large but the antiretroviral choices small, AZT (alone or in fixed dose combination) is first-line therapy. My most vivid memory of AZT is its use as monotherapy in the first patients we treated many years ago in our clinic. We watched the CD4 count increase (marginally) for a few months (we didn't have HIV RNA at that time) and then drop to levels lower than when they started therapy. This was the first hint that a single drug would not be enough to treat HIV. While I would never advocate use of AZT as monotherapy, I have to be honest, I do have one patient who uses AZT as monotherapy (all of us have "that one patient"). This was his first therapy and his immune system is good, virus undetectable, and no adverse effects. I did convince him once to go off AZT ("he obviously didn't need it"). To prove that every individual is unique, when off the drug, his immune system decreased and virus appeared. There went my credibility as far as AZT monotherapy with this patient. -- Frank M. Graziano, M.D., Ph.D.

Activist

In the beginning, there was AZT. This failed oral chemotherapy was pulled out of the archives and received FDA approval as the first anti-HIV drug in March 1987. Originally prescribed at what we now know to be overdosed levels (400 mg every four hours), AZT was toxic. It was eventually reformulated to one 300 mg tablet taken twice a day and the lower dosage decreased toxicity and the side effects (anemia, bone marrow suppression, and neuropathy) became manageable, if not completely tolerable. Despite being the oldest (and most widely studied) drug in the arsenal of antiretrovirals, AZT remains efficacious, particularly since it is one of the few ARVs capable of penetrating the blood-brain barrier. AZT is a component of Combivir and Trizivir. -- Morris Jackson

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