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Brand Name: Retrovir
Common Name: zidovudine (ZDV) or AZT
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 Retrovir is available.
AWP: $410.5 (generic $365.04) / month
Manufacturer contact: GlaxoSmithKline,
www.treathiv.com, 1 (888) 825–5249
AIDSInfo:1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov
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| Potential side effects and toxicity: |
Most common side effects include headaches, fever, chills, muscle soreness, fatigue, nausea, and fingernail discoloration. AZT has been associated with alteration of various cells in the blood through bone marrow suppression resulting in anemia (low red blood cells) and/or neutropenia (low white blood counts), particularly in people with advanced HIV during the first three months. Potential for severe anemia requiring blood transfusion, erythropoietin injections, or hospitalization when used on its own or in combination with hydroxyurea. Prolonged use of high doses of AZT has been associated with symptomatic myopathy (muscle damage). Rare but potentially fatal toxicity with all NRTIs is pancreatitis (inflammation of the pancreas), hepatomegaly (enlarged liver) with steatosis (fat) 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 nukes for a long time; and 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, and difficulty breathing or shortness of breath; and enlarged, fatty liver. Pancreatitis can be life-threatening and may cause pain in the stomach and back, along with nausea, vomiting and blood in the urine. Risks for pancreatitis include: higher than recommended doses of NRTIs, advanced HIV, and alcohol use. The risk for pancreatitis with AZT is low compared to ddI.
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| Potential drug interactions: |
| Biaxin, Dilantin, Mycobutin, and rifampin (under various brand names) may decrease AZT blood levels. Benemid and Depakote may increase AZT blood levels and decrease AZT clearance, but no dosing adjustments are recommended. AZT and Zerit should not be used together due to evidence that one limits the other’s effectiveness. Also, bone marrow supression should be monitored with use of ganciclovir, amphotericin B, pentamidine, dapsone, flucytosine, sulfadiazine, interferon-alpha, ribavirin (Rebetol), and with other antineoplastics (anti-tumor treatment) such as hydroxyurea and doxorubicin. Ribavirin and AZT may cancel each other out, so this combination should be monitored closely. |
| Tips: |
In combination with Epivir, Retrovir is recommended as a preferred NRTI agent in U.S. HIV treatment guidelines in people on HIV therapy for the first time. The not-so-good news for people adding AZT: the fatigue and the potential anemia. You can start taking erythropoietin (Procrit or Epogen) for some anemias, but that’s adding an expensive weekly injectible. Some doctors would prefer switching out the AZT for another drug. Also, some clinicians are avoiding the “T” drugs, or thymidine analogs (AZT and Zerit) because of implication in lipoatrophy. AZT has for years been associated with “AZT butt,” a disheartening flatness that happens gradually. Taking with food may minimize upset stomach.
Also available in Combivir (with Epivir) and in a triple combination in Trizivir (with both Epivir and Ziagen), so Retrovir should not be taken with these drugs. |
| Doctor |
| Retrovir (AZT) is the oldest and most widely studied antiretroviral agent (approved 20 years ago). Until recently it was unchallenged as one of the essential first-line nucleoside backbone drugs. Since it is a thymidine analogue (like d4T), it has been linked to mitochondrial toxicity (though to a lesser extent than d4T). Many of its side effects have been well known for many years and there is a small subset of patients (less than 10%) who have significant gastrointestinal or constitutional side effects that interfere with the ability of the patient to tolerate the drug (those side effects may account for the results of studies showing superior results for tenofovir versus ZDV-based regimens). Lipoatrophy has emerged as a difficult problem to manage, so much effort needs to be made for prevention. Retrovir has been linked to lipoatrophy (usually to a lesser extent than seen with d4T), so chronic use has been diminishing in regions where alternative drugs are available (typically non-thymidine RTIs such as tenofovir or abacavir). Bone marrow suppression is often exacerbated when used with other marrow suppressing agents. It remains as a vital drug for prevention of vertical transmission of HIV in pregnancy and has well demonstrated central nervous system (CNS) penetration with proven benefit in CNS manifestations of AIDS. It is available in two fixed dose combinations (Combivir and Trizivir). There remains uncertainty in how to optimize sequencing of NRTIs. Resistance to ZDV is often linked to NRTI-related mutations which blunt the effectiveness of tenofovir, while it is less certain whether tenofovir-related mutations (such as K65R) diminish the response to ZDV.—Keith Henry, MD |
| Activist |
| AZT, the grandmother of all HIV therapy, was originally developed to treat cancer but never used for that purpose. In the ’80s, scientists re-discovered AZT as a potential treatment for AIDS—which at that time was almost certainly a death sentence. In 1987 it became the first approved antiretroviral drug and holds the title of being one of the highest priced drugs ever to hit the market (of course that title has long since been stripped away). The very early doses of this drug were unusually high and caused an alarming number of side effects in people who took it (unfortunately the horror stories of the “old AZT” still seem to haunt the HIV community, and are often the root of fears about taking meds for HIV). Once we learned how to use this drug more effectively in the ’90s, it became a backbone in standard combination therapy…and remains that way today. Although it still has potential for side effects (all drugs do), it is the one drug that we have the most experience overall with, and is one of the few medications that can cross the blood-brain barrier. AZT was the key drug involved in ACTG 076 study in the mid ’90s that showed antiretroviral therapy during pregnancy could prevent mother-to-child transmission.—Cathy Olufs |
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