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 (zidovudine) is available.
Most common side effects include headaches, fever, chills, muscle soreness, fatigue, nausea, and fingernail discloration. Zidovudine (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 zidovudine 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 zidovudine is low compared to ddI.
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 supression 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 healthcare 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:
In combination with Epivir, zidovudine 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 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 implication in lipoatrophy. 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, more commonly called AZT, was the first drug approved for the treatment of HIV infection, and it prolonged many lives back in the late '80's and early '90's. It got a new life in the form of Combivir after 3TC became available, experienced another resurrection as part of Trizivir, a once popular "triple-nuke" combination, and has been a cornerstone of therapy in the HAART era. However, AZT's time has finally passed. Compared to the nukes we're using now (namely tenofovir and abacavir), it's weaker, is dosed twice a day, is harder on the stomach, is more prone to resistance, and causes anemia and mitochondrial toxicity, including lipoatrophy. I still have a few patients still taking AZT because of resistance to other drugs (it becomes stronger if you have mutations that cause resistance to 3TC, FTC, abacavir, or tenofovir), but that may change as newer, safer agents become available. So long, AZT, and congratulations on a good, long run!. -- Joel Gallant, M.D.
Activist
Retrovir/AZT was the first drug developed for the treatment of HIV. In subsequent years, activists fought many battles to speed up the drug development process, but the history of AZT demonstrates that the mechanisms and ability to quickly test and approve drugs were present all along. What was lacking, except in the case of AZT, was the will to do it. AZT certainly has served a useful place in the history of treatment for HIV, but it has always come at a price. There is almost a cultural memory of the early and often severe side effects, but people don't always remember that this was primarily the result of overdosing. When dosed properly, AZT can still have side effects but they are seldom severe. Still, many people today believe it is time to reconsider the whole class of drugs that AZT comes from. Most of them have potentially significant side effects that derive from the very nature of what they are doing. It is difficult to conceive of a drug of this type that would be completely free of side effects. With so many new and relatively non-toxic drugs becoming available in recent years, it may be time to ask whether we can build fully effective regimens that don't rely on the old paradigm of "two nukes and a protease inhibitor" or "two nukes and a non-nuke." When this paradigm first became standard in 1996, it wasn't chosen because this was inherently the right or best way to treat HIV. Rather, it was simply the only kind of combination available at the time. -- Martin Delaney
