Zidovudine

The brand name for Zidovudine is Retrovir, and it falls into the class of drugs known as reverse transcriptase inhibitors which are used to treat human immunodeficiency virus and acquired immunodeficiency virus (HIV/AIDS).

Overview:

First approved in 1987, Zidovudine, also known as azidothymidine (AZT) was the first of a family of medications that are used to treat medical conditions known as retroviruses. A retrovirus functions differently than a traditional virus. It is made from ribonucleic acid (RNA) rather than deoxyribonucleic acid (DNA). That composition allows for a specific enzyme to cause reverse transcriptase which modifies the RNA in a cell, which then enters the DNA in the cell and rewrites the code, causing abnormal cell growth and replications. It is that enzyme that Zidovudine inhibits, preventing and controlling the rewriting of the DNA.

The triphosphate derivative in Zidovudine acts as an inhibitor to the functions of the retrovirus in HIV, preventing the virus from replicating. It also can be used as a preventive measure after exposure to the AIDS retrovirus. Since the invention and application of Retrovir and other versions of Zidovudine, the prognosis and life expectancy for patients suffering from HIV/AIDS has improved significantly. However, because Zidovudine comes with so many side effects and drug interactions, in recent years, it is used more as a second line of defence or an alternative medication choice in the treatment of HIV/AIDS.

Because Zidovudine can carry with it a host of side effects, and has been shown to cause hematological toxicity, including neutropenia and severe anemia, the United States no longer recommends it for initial treatment of HIV/AIDS, although it can be used as an alternative treatment if other medications are not effective. The World Health Organization lists it as an alternative, initial treatment option. Its most common application today is in preventing the transmission of the retrovirus from mother to newborn.

Conditions treated:

  • Pregnant women infected with HIV/AIDS to prevent transmission to their fetus
  • Suppression of HIV/AIDS virus in patients who have contracted the retrovirus
  • Prevent development of HIV/AIDS

Type of Medicine:

  • Antiviral/Antiretroviral (thymidine analog)

Side effects:

As with any strong medication, Zidovudine carries the risk of side effects, some of which can be quite significant. The levels of toxicity that can be created in the blood stream of the patient, particularly after 12 months or so of use, have relegated Zidovudine to an alternative form of treatment for HIV/AIDS. It is no longer the first line of defense in suppressing the virus, other than in transmission from mother to fetus and newborn child.

Because it suppresses the replication of the virus, it also suppresses red blood cell production, sometimes at quite dangerous levels, and leads to severe anemia in some patients. This is especially true in some of the more resource poor areas where HIV/AIDS is quite prevalent, but often coexists with other viruses and infections such as malaria which also impact hemoglobin levels.

Granulocytopenia, pancytopenia with marrow hyperplasia, aplastic anemia, lymphadenopathy, hemolytic anemia, leukopenia and aplastic anemia are all hematologic effects tied to Zidovudine. It has also been linked to a condition called neutropenia, which is the suppression of the production of white blood cells. When Zidovudine is used prophylactically to prevent a pregnant mother from passing the virus on to her unborn child, one common side effect is the presence of transient anemia in the newborn. That condition can usually be treated relatively quickly after the birth. Zidovudine remains the primary medication to prevent the transmission of HIV/AIDS to a newborn from the mother.

Zidovudine can also cause a condition called lactic acidosis, which is marked by the accumulation of lactic acid or lactate in the body. This can lead to dangerously low pH levels in the bloodstream, which causes generalized weakness, nausea and vomiting, and if left untreated may cause death.

Another serious side effect can be the worsening of liver disease in HIV/AIDS patients who are also suffering from Hepatitis C (HCV), a common combination in these patients. The interaction between Zidovudine and the medications used to treat HCV can lead to further impairment of liver function, even to the point of death.

There are other, less serious side effects. Patients taking Zidovudine can experience nausea and fatigue. Almost half of patients treated with this medicine indicate some increased level of fatigue. They may also suffer from insomnia. It has been linked to increased levels of anxiety and depression as well. Skin may appear pale, and less frequently, blue or brown bands may appear on the nails. This discoloration may disappear after a few months of use or if the drug is discontinued. Zidovudine may also cause rashes or other skin sensitivities.

Another potential side effect is redistribution of total body fat. In some patients, this takes the form of increased weight in the trunk of the body, while the extremities and face actually lose total fat volume. There can be overall weight gain or weight loss in the patient as well. Zidovudine has been linked, rarely, to the development of anorexia in the patient. It has also been identified as a cause of lipoatrophy, or the localized loss of fat tissue in an area of the body. This can be a side effect of other antiviral medications as well.

There have also been rare but reported incidences of the development of congestive heart failure that can be reversed if medication is discontinued. Zidovudine has also been linked, again rarely, to the onset of vasculitis and cardiomyopathy. The drug can also affect the musculoskeletal system of the patient, often in ways similar to the disease itself. Zidovudine leads to higher levels of creatine kinase, which can lead to myopathy (muscle weakness), polymyositis (inflammatory of the muscles), tenderness, weakness in the arms and legs, as well as tremors. If polymyositis develops, it can make it difficult for the patient to breathe deeply. Patients affected by this will breathe rapidly and shallowly, and this condition can be magnified if the patient also suffers from one of the opportunistic infections that can accompany HIV/AIDS such as pneumonia or tuberculosis. A rapid breakdown of muscular tissue known as rhabdomyolysis has also been reported. About 5% of patients who take Zidovudine will experience some sort of musculoskeletal side effect, but most of those reported side effects are not dangerous.

Up to 51% of patients on Zidovudine experience some degree of nausea, while 17% actually experience severe vomiting. Constipation, dyspepsia, dysphagia, abdominal cramping and pain and other digestive symptoms have also been commonly reported among patients on this medication. Another rare side effect is mouth ulcers, which while potentially painful, are not terribly significant. More serious, but equally rare is the development of pancreatitis, which can be very dangerous in patients whose condition is already fragile.

Almost all patients will develop some form of resistance to Zidovudine over the course of treatment. Zidovudine is often used in combination with other medications to help forestall that resistance. It is not clearly understood why that resistance develops.

Dosage:

Zidovudine comes in four different forms. It can be administered orally by capsule, tablet, or in syrup form. Tablets are in 300 mg doses and capsules are 100mg. The syrup's strength is 10mg/mL per dose. The medication does not have to be taken with food, although it can be.

Levels of dosage depend on the levels of HIV/AIDS virus present in the blood of the patient. Dosages can be adjusted up or down depending on those levels and how they respond to the medication protocol. The standard adult dose is 600mg divided into two doses per day, generally in combination with other antiretroviral drugs. Pediatric dosing is typically based on patient's weight. As a child grows and his or her weight changes, it is critical to monitor the dosage to be sure it is adequately controlling virus levels in the patient.

If the patient misses a dose of Zidovudine, he or she should take it as soon as possible. If it is close to the next prescribed time, the patient should skip that dose and just take the next one. Patients should never take a double dose of Zidovudine. In the event that a patient takes too much medication, he or she should contact a health care provider immediately or local poison control for advice and/or immediate treatment. Overdosing may require a trip to the closest emergency treatment center.

Major Drug Interactions:

As with any other medication or medical conditions, advice and counsel of the health care provider is paramount to successful treatment. The chemical formula for Zidovudine interacts with many other medications and families of medication. It is critical for the patient to share all current medications, including over the counter and herbal medicines as they may interact as well. Below is a list of the medications with which Zidovudine has major interactions.

  • adalimumab
  • alpha interferon
  • alemtuzumab
  • avonex
  • bexarotene
  • certolizumab
  • clozapine
  • deferiprone
  • etanercept
  • fingolimod
  • ganciclovir
  • golimumab
  • infliximab
  • infergen
  • interferon gamma - 1b
  • interferon alfa-n3
  • interferon alfacon-1
  • ipilimumab
  • interferon beta-1b
  • leflunomide
  • lomitapide
  • mipomersen
  • natalizumab
  • peginterferon alfa-2b
  • peginterferon beta-1a
  • ribavarin
  • roferon
  • teriflunomide
  • tofacitinib
  • valganciclovir

These are major interactions and generic medications only. A comprehensive list of all the medications that Zidovudine interacts with would include over 315 drugs representing over 2100 brand and generic names. Because of the high level of interaction of this medication with others, it is critical for the patient to follow his or her doctor's directions very closely and to be very upfront about any medicines they are already taking. One issue with Zidovudine is that it is highly interactive with all forms of interferon, a medication used to treat liver disease. As hepatitis C is a condition that often coexists with HIV/AIDS, treating both conditions successfully requires a careful balance of medications with vigilant monitoring of liver function. Generally, an antiviral other than Zidovudine would be indicated for a patient with both illnesses.

Zidovudine also interacts with many medications used to treat cancer or suppress rejection in the case of organ transplants. It would not be recommended for patients that are suffering from HIV/AIDS in combination with one of those other complicated conditions.

Warnings:

Because Zidovudine affects so many of the body's systems (musculoskeletal, circulatory, cardiovascular, digestive, respiratory, genitourinary) and interacts with medications from so many different families of drugs, there are many symptoms and conditions that patients should be aware of. Patients should contact their doctor immediately if any of those symptoms become present:

  • Rash
  • Rapid breathing
  • Shortness of breath
  • Bruising easily
  • Bleeding that won't stop easily
  • Chronic tiredness
  • Pale or yellowing skin
  • Chronic low grade fever
  • Chills
  • Sore throat
  • Increased Fatigue
  • Decreased appetite or inability to keep food down
  • Upset stomach
  • Vomiting
  • Urine that is significantly darker in color
  • Yellowing of your skin or the whites of your eyes (jaundice)
  • Light-colored bowel movements
  • Muscle weakness
  • Lack of strength
  • Muscle pain
  • Pain in the stomach, particularly the upper right side

Additionally, it is critical that doctors monitor red and white blood cell counts in patients using Zidovudine to watch for the development of several forms of anemia or neutropenia. Prolonged use of Zidovudine can also create toxicity in the patient's bone marrow, or suppression of bone marrow formation, so that needs to be monitored closely as well.

Vigilant and regular monitoring of liver function is certainly indicated as well, most particularly in patients with HCV or any sort of impaired liver function. In the event that liver function shows further decline, particularly if the patient is showing signs of jaundice or elevated levels of bilirubin, discontinuing use of Zidovudine would generally be indicated.

For patients that struggle with depression, anxiety or suicidal thoughts, Zidovudine can heighten those thoughts and interacts negatively with many of the anti-psychotic drugs that may be prescribed to treat those conditions. If a regimen is prescribed that includes Zidovudine to treat HIV/AIDS, the physician must also monitor the patient's emotional and mental health as well.

Zidovudine has been shown to interact negatively alcohol. Alcohol may prevent the medication from working at full efficacy. Patients with an alcohol abuse problem need to share that with their physician so a more effective combination of medication can be prescribed.

Storage:

Zidovudine should be stored at room temperature (between 15-20 degrees Celsius). It should only be stored in the container that it came in and kept tightly sealed between doses. It should also be kept in a cool, dark place where the medication is not exposed to light.

Zidovudine does lose some of its efficacy once it has expired, so it should be properly disposed of if it has expired or its use has been discontinued for whatever reason. Any healthcare professional or health department can advise the patient on proper ways to dispose of the remaining medication. As with any medication, if the seal has been broken prior to first use, do not use it and keep it away from children.

Summary:

Zidovudine represents the first in a family of medications that changed the prognosis and life expectancy of people around the world who suffer from human immunodefiency virus and acquired immundeficiency virus. The development of antiviral and antiretroviral medication meant that a HIV/AIDS diagnosis was not an automatic death sentence. Zidovudine is a thymidine analog that acts as an inhibitor to the retrovirus that causes HIV/AIDS. While it does not actually cure the virus, by inhibiting replication of the virus in the bloodstream of the patient it essentially puts the virus into remission, thus allowing the patient to lead a relatively normal and otherwise healthy life.

However, Zidovudine comes with many unwanted side effects that can range from inconvenient to life threatening. Many patients experience uncomfortable symptoms such as stomach aches and gastrointestinal issues, while others may experience more serious and severe side effects such as severe anemia and liver failure.

Because the function of Zidovudine is to suppress replication of the virus in the bloodstream, it also suppresses other functions linked to creation of bone marrow and red and white blood cells. It also interferes with and is affected by other medications that are prescribed to treat a wide spectrum of illnesses and conditions that also have to be treated. These interactions include medications for mental and emotional conditions, muscular issues, fibromyalgia, and autoimmune disorders to diseases like cancer and liver failure.

Today, Zidovudine is generally not used as a first line of defense in the treatment of HIV/AIDS for most people. Other newer antivirals that carry fewer and less severe side effects are recommended over Zidovudine. It is, however, still a primary medication for pregnant mothers who are infected with HIV/AIDS in an effort to prevent transmission to the unborn child during birth. It is also used in newborns if the mother did not take the medication prior to giving birth. It is also still used in some cases where patients have been exposed to the AIDS virus but have not yet exhibited symptoms or have yet to have actual virus show up in their bloodstream. It can also serve as a valuable second alternative if the patient fails to respond to other antiviral combinations. Almost all patients will develop resistance to antivirals over time and so it is vital to have other options available.

While Zidovudine has been replaced over time with other medications, it represented a significant turning point in the world's ability to fight the HIV/AIDS epidemic. In 1987, when it was first approved for use in the treatment of AIDS, it was the only medication available that had shown any sort of impact against the disease. Today, it remains a powerful tool in the arsenal of HIV/AIDS treatment.

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Last Reviewed:
December 25, 2017
Last Updated:
December 22, 2017
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