Abacavir (Ziagen)

Summary

Abacavir is a type of antiretroviral drug called a nucleoside analogue (“nuke”). The most common side effects of abacavir can include headache, nausea, vomiting, unexpected tiredness, and loss of appetite. It is usually taken at a dose of 600 mg daily, with or without food.

Note: Up to 8% of the people who take abacavir may have a serious allergic (“hypersensitivity”) reaction to it: please see the "Warning" section.

What is abacavir?

Abacavir, sold under the brand name Ziagen, is a type of antiretroviral (anti-HIV) drug called a nucleoside analogue or “nuke.” Abacavir is used in combination with other antiretroviral drugs to treat (but not cure) HIV.

How does abacavir work?

When HIV infects a cell, it takes control of that cell. HIV then forces the cell to make many more copies of the virus. To make these copies, the cell uses proteins called enzymes. When the activity of these enzymes is reduced the production of HIV slows.

Abacavir belongs to a class of antiretrovirals called nucleoside analogues. Abacavir interferes with an enzyme called reverse transcriptase (RT), which is used by HIV-infected cells to make new viruses. Since abacavir inhibits, or reduce the activity of this enzyme, this drug causes HIV-infected cells to produce fewer viruses.

How do people with HIV use abacavir?

Abacavir is used in combination with several other antiretroviral drugs, usually including drugs from different classes, such as protease inhibitors and/or non-nukes (non-nucleoside reverse transcriptase inhibitors). Combinations such as this are called antiretroviral therapy, or ART. For more information on ART, see CATIE's Your Guide to HIV Treatment.

For many people with HIV, the use of ART has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to reduce the risk of developing a life-threatening infection. Neither abacavir nor any other antiretroviral medication is a cure for HIV. It is therefore important that you do the following:

  • see your doctor regularly so that he/she monitors your health
  • continue to practice safer sex and take other precautions so as not to pass HIV on to other people

Warnings

1. Hypersensitivity reaction

In up to 8% of people with HIV who use abacavir, an exaggerated reaction against abacavir by the immune system—abacavir hypersensitivity—can occur. This reaction is very serious and can be fatal.

Although the hypersensitivity reaction can occur at any time while a person is taking abacavir, on average it occurs within the first six weeks of use. The manufacturer, ViiV Healthcare, states that you should stop using abacavir if you have signs or symptoms from two or more of the following groups:

  1. Fever
  2. Rash
  3. Gastrointestinal symptoms (including nausea, vomiting, diarrhea or belly pain)
  4. General symptoms (including fatigue, lack of energy, achiness)
  5. Respiratory symptoms (sore throat, shortness of breath, cough, unusual findings on X-rays of the chest)

If you develop symptoms from two or more of these groups while you are taking abacavir or any drug containing abacavir, you should stop taking this medicine and contact your doctor right away. If a hypersensitivity reaction to abacavir has indeed occurred, then abacavir should never be restarted, as a fatal reaction could occur within hours. You should also never take any other drug that contains abacavir.

There is now a screening test to help predict whether you are likely to have an abacavir hypersensitivity reaction. See CATIE’s fact sheet Abacavir hypersensitivity screening.

2. Restarting treatment

Abacavir should never be restarted following a hypersensitivity reaction, as a fatal reaction could occur within hours. You should also never take any other drug that contains abacavir (this includes Kivexa and Trizivir).

This hypersensitivity reaction has even occurred among people who did not have any problems when they first took abacavir-containing drugs, but who then stopped and restarted.

3. Cardiovascular risk

There are conflicting data from some studies about a link between heart attacks and the initial use of abacavir-containing products (Ziagen and in Kivexa and Trizivir). However, a review by the U.S. Food and Drug Administration (FDA) of randomized clinical trials has not found any link between abacavir use and an increased risk of heart attack. If you or your close family members (mother, father, brother, sister) have a history of heart problems, let your doctor know. Before using abacavir-containing medicines, always speak to your doctor about getting tested for abacavir hypersensitivity.

4. Lactic acidosis and hepatic steatosis

Two related conditions, lactic acidosis (a buildup of lactic acid in the blood) and hepatic steatosis (excess fat in the liver), have occurred in some people who have used nucleoside analogues. These conditions can be serious or fatal. They have mostly been seen in women and people who are overweight or who have been on nucleosides a long time, and can cause the following symptoms:

  • unexpected tiredness or weakness
  • nausea and/or vomiting
  • persistent abdominal pain
  • painful inflammation of the pancreas (pancreatitis)

If any of these symptoms occur without apparent reason, call your nurse or doctor right away.

Lactic acidosis is rare (less than one case per year for every thousand patients). If you do develop any of these symptoms, it does not necessarily mean you have lactic acidosis, but you should still let your doctor know right away.

Side effects

1. General
Common side effects that have been reported by some abacavir users include: headache, nausea, vomiting, unexpected tiredness, diarrhea, loss of appetite, fever, and skin rash. Many people find that side effects caused by antiretrovirals improve or go away after the first several weeks of treatment.

2. Lipodystrophy syndrome
The HIV lipodystrophy syndrome is the name given to a range of symptoms that can develop over time when people use ART regimens. Some features of the lipodystrophy syndrome include:

  • loss of fat just under the skin (subcutaneous fat) in the face, arms, and legs
  • bulging veins in the arms and/or legs due to the loss of fat under the skin
  • increased waist and belly size
  • fat pads at the back of the neck (“buffalo hump”) or at the base of the neck (“horse collar”)
  • small lumps of fat in the abdomen
  • increased breast size (in women)

Together with these physical changes, lab tests of your blood may detect the following:

  • increased levels of fatty substances called triglycerides
  • increased levels of LDL-cholesterol (low-density lipoprotein), or "bad" cholesterol
  • increased levels of sugar (glucose)
  • increased levels of the hormone insulin
  • decreased sensitivity to insulin (insulin resistance)
  • decreased levels of HDL-cholesterol (high-density lipoprotein), or "good" cholesterol

The precise causes of the HIV lipodystrophy syndrome are not clear and are difficult to understand because in some PHAs there may be one or more aspects of the syndrome taking place. For instance, some people may experience fat wasting, others fat gain, and others may experience both fat gain and wasting. What is becoming increasingly clear is that unfavourable changes in the lab readings of glucose, cholesterol, and triglycerides over a period of several years increase the risk of diabetes and cardiovascular disease. So far, however, the many benefits of ART are much greater than the increased risk of cardiovascular disease or other side effects.

Maintaining a normal weight, eating a healthy diet, exercising regularly, and quitting smoking are all important in helping you to reduce your risk of diabetes, heart disease, and other complications. Regular visits to your doctor for checkups and blood tests are a vital part of staying healthy. If necessary, your doctor can prescribe lipid-lowering therapy.

Researchers are studying the lipodystrophy syndrome to try to discover ways of helping PHAs avoid or reduce this problem. To find out more about options for managing aspects of the lipdystrophy syndrome, see CATIE's Practical Guide to HIV Drug Side Effects.

Among the antiretrovirals, abacavir appears to be one of the least likely to cause or contribute to lipodystrophy.

Drug interactions

Always consult your doctor and pharmacist about taking any other prescription or non-prescription medication, including herbs, supplements, and street drugs.

Some drugs can interact with abacavir, increasing or decreasing its levels in your body. Increased drug levels can cause you to experience side effects or make pre-existing side effects worse. On the other hand, if drug levels become too low, HIV can develop resistance and your future treatment options may be reduced.

It may also be necessary to avoid drugs that do not affect abacavir drug levels, but cause similar side effects.

If you must take a drug that has the potential to interact with your existing medications, your doctor can do the following:

  • adjust your dose of either your antiretroviral drugs or other medications
  • prescribe different antiretroviral drugs for you

Drug interactions

The following drugs interact or have the potential to interact with abacavir. This list may not be exhaustive.

  • In men, the use of alcohol in combination with abacavir causes an increase of abacavir in the blood, which could cause an increase in toxic effects. This has not been studied in women.
  • Abacavir can reduce levels of methadone in the blood, which might require an adjustment to your dose of methadone.

Resistance and cross-resistance

Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes are called mutations and can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you. Combining abacavir with at least two other anti-HIV drugs delays the development of drug resistance.

To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed, or not taken as prescribed, levels of abacavir in the blood may fall too low. If this happens, resistant virus can develop. If you find you are having problems taking your medications as directed, speak to your doctor and nurse about this. They can find ways to help you.

When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future therapies might be, at some point your doctor can have a small sample of your blood analysed using resistance testing. Should HIV in your body become resistant to abacavir, your doctor, with the help of resistance testing, can help put together a new treatment regimen for you.

Dosage and formulations

Abacavir is available as 300 mg tablets and 20 mg/mL liquid. The standard adult dose of abacavir is either one tablet twice daily, or two tablets once daily, with or without food. Formulations can change, and dosages may need to be customized. All medications should always be taken as prescribed and directed.

Availability

Abacavir is licensed in Canada for the treatment of HIV infection in adults, in combination with other antiretroviral drugs. Your doctor can tell you more about the availability and coverage of abacavir in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage.

Also see CATIE’s fact sheets on Kivexa, Trizivir and abacavir hypersensitivity screening.

References

Health Canada. Drug Products Database: www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index_e.html [Accessed January 3, 2007.]

Vispo E, Barreiro P, Maida I, et al. Abacavir-containing HAART reduces the chances for sustained virological response to pegylated-interferon plus ribavirin in HIV-infected patients with chronic hepatitis C. Third International Workshop on HIV and Hepatitis Coinfection. June 7-9, 2007, Paris. Abstract 46.

Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 10 2006.

Rauch A, Nolan D, Martin A, et al. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in Western Australian HIV Cohort Study. Clinical Infectious Diseases 2006;43(1):99-102.

GlaxoSmithKline. Ziagen: Canadian Product Monograph. September 20, 2006.

Berenguer J, Padilla B, Estrada V, et al. Safety of abacavir therapy after temporary interruptions in patients without hypersensitivity reactions to the drug. AIDS 2002; 16(9):1299-1301.

Bart PA, Rizzardi PG, Gallant S, et al. Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir. Therapeutic Drug Monitoring 2001;23(5):553-555.

Clumeck N, Goebel F, Rozenbaum W, et al. Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA. AIDS 2001;15(12):1517-1526.

Fellay J, Boubaker K, Ledergerber B, et al. Prevalence of adverse events associated with potent antiretroviral treatment: Swiss HIV Cohort Study. Lancet 2001;358(9290):1322-1327.

Frissen PH, de Vries J, Weigel HM, Brinkman K. Severe anaphylactic shock after rechallenge with abacavir without preceding hypersensitivity. AIDS 2001;15(2):289-292.

Loeliger AE, Steel H, McGuirk S, et al. The abacavir hypersensitivity reaction and interruptions in therapy. AIDS 2001; 15(10):1325.

Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. Journal of Acquired Immune Deficiency Syndrome. 2012 Dec 1;61(4):441-447.

Author(s): Thaczuk D, Ziegler B

Published: 2014