Side-effects

The commonest side-effects of zidovudine are nausea, vomiting, headache, dizziness, fatigue, weakness and muscle pain. These often occur in the early weeks of treatment. Medicines to control nausea and headache can be prescribed before starting zidovudine. Nausea and vomiting may also be reduced by making the following adjustments to diet:

• Taking zidovudine before meals.
• Eating many small meals during the day rather than three large ones.
• Avoiding spicy food, fried foods and sweets.
• Consuming more cool foods and drinks.
• Drinking plenty of water, apple juice, flat ginger ale or cola.
• Eating dry foods such as crackers.

Other side-effects occasionally reported from zidovudine include rashes, severe muscle pain and inflammation, nausea, insomnia, nail discoloration, and kidney disorders. These toxicities are more severe and more common in people with damaged immune systems.

When first prescribed, zidovudine was given in high doses, which commonly caused severe side-effects. Recommended doses are now much lower, and as a result, side-effects have lessened.

Zidovudine may damage the bone marrow, the substance in the body that produces blood cells. People with more advanced HIV infection are more likely to suffer blood deficiencies such as anaemia (low levels of red blood cells) or neutropenia (low levels of neutrophils, a type of white blood cell).¹ In combination with other risk factors for anaemia, such as other medications and opportunistic infections, taking zidovudine may result in more severe side-effects.

A recent meta-analysis of 54 trials of zidovudine, funded by GlaxoSmithKline, concluded that severe anaemia is rare, occurring in less than 2% of patients. Overall, zidovudine doubled the risk of anaemia, but this was also increased by higher viral loads and lower haemoglobin levels before starting therapy. The analysis also found that taking zidovudine in Combivir or Trizivir almost doubled the risk of anaemia, but the reasons for this are unknown.²

Patients starting zidovudine treatment should have their blood tested every two weeks for the first few months, for changes in levels of red or white blood cells. See Anaemia for more information on the treatment of anaemia.

There is a small risk of muscle damage (myopathy) after prolonged treatment with zidovudine, with some pain, wasting and weakness usually in the muscles around the hips, thighs and buttocks.³ Blood tests for muscle enzymes can detect this wasting early on if it is suspected.

Rare adverse reactions to zidovudine include developing an enlarged fatty liver and raised levels of lactic acid.⁴ These complications appear to be more common in obese women and people with risk factors for liver disease. People with pre-existing liver or kidney problems may need additional monitoring to ensure that AZT does not worsen these conditions. Halving the zidovudine dose may be recommended in these patients.

The nucleoside reverse transcriptase inhibitors (NRTIs) as a class have been linked to body fat loss and metabolic changes seen among people on antiretroviral therapy. Although research suggests that stavudine (d4T, Zerit) is the NRTI most closely associated with this syndrome, there is evidence that zidovudine may also trigger it. To date, the mechanism is unknown although it is probably linked to mitochondrial DNA damage caused by these drugs.^{5 6} Consequently, treatment guidelines are currently recommending that patients avoid zidovudine in favour of other NRTIs such as abacavir (Ziagen) or the nucleotide reverse transcriptase inhibitor (NtRTI) tenofovir (Viread) to reduce the risks of fat loss.

A study in rats has also suggested that zidovudine may contribute to endothelial dysfunction, a loss of elasticity in the blood vessels that is an early sign of cardiovascular disease.⁷

There has also been speculation that long-term use of zidovudine may cause cancer. This view is based on laboratory studies and tests in rats and mice. However, there is no evidence to date that long-term use of zidovudine causes cancer in humans.

Anecdotal reports of changes in skin pigmentation in people of African origin are frequently heard by community organisations, but data have not been systematically collected to demonstrate how common this problem is.

Patients taking zidovudine should inform their doctor if they experience severe abdominal pain, shortness of breath, unusual tiredness or weakness, unusual bleeding or bruising, sore throat, fever or an injury that does not heal.