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 [Epogen or Procrit], 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. Your physician will check for pancreatitis by checking for increased levels of amylase and lipase in the blood. 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.
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. Cytovene, Vitrasert and Valcyte increase AZT blood levels, and perhaps AZT-related anemia. Prescriber may need to adjust doses accordingly. 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 and may increase the risk of lactic acidosis, therefore combination use should be avoided.
Tips: AZT came to the rescue of triple nuke therapy. After the bad news that the two most potent nukes, Viread and Ziagen, failed badly in the triple-nuke combination with Epivir, came the good news that the three drugs worked well in the nuke-only regimen of Trizivir/Viread. AZT (found in Trizivir) helps fight off the drug resistance problems that plague triple nukes that don’t include it. These results are still preliminary. A nuke-only regimen should only be tried by people with low viral loads (below 50,000)—see aidsinfo.nih.gov for a full discussion. 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. Taking with food may minimize upset stomach. Studies show that AZT crosses the blood-brain barrier to a useful degree, which may be beneficial for patients at risk for neurological damage (such as dementia) from HIV. Proven to significantly reduce mother-to-infant transmission.
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 (zidovudine) was first approved by the FDA for use by HIV patients in 1987. Since then, it has remained a mainstay in many nucleoside backbones. In the past, it was most commonly used in combination with 3TC (lamivudine) in the form of Combivir. However, as more data become available about newer agents and the importance of sequencing (carefully selecting the order in which HIV drugs are used in order to allow for the maximum number of viable options later on if a regimen should fail due to resistance) has emerged, doctors have begun to make changes in the use of this drug. In some cases, it may be combined with a “less-traditional” nucleoside or “saved” to be used later in the planned sequence of regimens. Its side effects have not changed: anemia, fatigue, and nausea limit its use in some patients. It has also been implicated in lipoatrophy (fat wasting), although much less so than stavudine (Zerit). Generic AZT is now available and reduced price may encourage providers to reconsider this drug.—Chad J. Zawitz, MD
Activist
I am one of the people who are still alive from the original high dose placebo-controlled AZT study in the late ‘80s and early ‘90s. In 1993 we were shocked and depressed after finding out that high dose AZT was killing us faster. Fortunately, we later found out that a lower dose would work well in combination with other meds. AZT is now available alone or in a combo of AZT + Epivir called Combivir. There is also a new generic version available that may be lower in price (we are waiting to see). It is one of the few drugs shown to penetrate the blood-brain barrier, so it may have some protective effects on neurological complications like dementia. Too bad it can cause anemia, muscle weakness, and fatigue in some, and now we are also learning that it may cause lipoatrophy. There are also some studies suggesting that AZT may have a “protective role” in preventing a key mutation, K65R, in all nuke regimens. This mutation may render most HIV resistant to several nucleosides.—Nelson Vergel
|
