Side-effects

ddI (didanosine, Videx / VidexEC) can have a range of side-effects, which are serious in some cases. Many of ddI’s side-effects are thought to be caused by damage to the mitochondria, the components in the cell where energy is produced.1 Common side-effects are peripheral neuropathy and diarrhoea .

Peripheral neuropathy is damage to the nerves in the hands and feet. It is a common side-effect of ddI, which can causes numbness, tingling or pain, which can be severe. It occurs more frequently when ddI is combined with d4T (stavudine, Zerit), and when it is taken by people with advanced HIV infection. It usually goes away if the drug is stopped, and treatment may be resumed at a lower dose without recurrence of the neuropathy. See Peripheral neuropathy for further information.

Pancreatitis, inflammation of the pancreas, is a less frequent but very serious side-effect of ddI.2 Symptoms include the sudden onset of abdominal pain, fever, vomiting or general worsening of health. Patients developing these symptoms should contact their doctor immediately. Bristol-Myers Squibb recommends that doctors immediately suspend treatment with ddI, d4T and hydroxycarbamide (Hydrea), if pancreatitis is suspected. Patients who have had pancreatitis while on ddI should never re-start treatment with the drug.

The risk of pancreatitis is likely to be increased in patients who drink large amounts of alcohol. If ddI-related pancreatitis does develop, alcohol should be strictly avoided. High levels of fats or lipids in the blood, may also increase the risk of pancreatitis. ddI-related pancreatitis takes about three to seven months to develop.

A rare side-effect of ddI when combined with hydroxycarbamide (Hydrea) is severe liver damage.3 It usually occurs within four months of starting the drugs, and proves fatal in around two-thirds of cases. Severe liver damage has also been reported in a small number of patients who receive treatment with ddI and d4T. Treatment guidelines now recommend that these drug combinations be avoided wherever possible. If using drugs that might lead to high ddI levels, such as tenofovir (Viread), or if liver damage is already evident, early and frequent monitoring of liver enzymes is recommended.4 Fatty or enlarged liver is also a rare side-effect of ddI and some cases of liver failure have occurred in people on ddI, particularly in patients co-infected with hepatitis C who are receiving hepatitis C treatment.5 6 However, a small number of patients with liver damage have no other risk factors besides prolonged ddI use.7 Liver enzyme levels should be monitored and treatment should be permanently stopped if they rise significantly above normal.

Noncirrhotic portal hypertension is another rare but serious potential side-effect of prolonged use of ddI.8,9 This is a very serious condition involving build up of pressure in the portal vein that restricts the flow of blood to and from the liver. This can lead to oesophageal varices – extremely dilated veins in the lower oesophagus – which can haemorrhage and cause death.

Lactic acidosis, elevated levels of lactic acid in the blood, is a rare side-effect of all the nucleoside reverse transcriptase inhibitors (NRTIs) including ddI. Lactic acidosis may be life-threatening. Early symptoms of elevated lactate levels include fatigue, feeling unwell, breathlessness and nausea. Pregnant women taking ddI and d4T may be at increased risk of lactic acidosis.

Hyperuricaemia, a high level of uric acid in the blood, is another complication that seems only to affect people taking high doses of ddI. This condition can cause gout.

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 preliminary research suggests that d4T is the NRTI most associated with this syndrome, there is evidence that the other NRTIs may also trigger it. To date, the mechanism is unknown although it may be linked to mitochondrial DNA damage caused by the NRTIs. Evidence from a clinical studies shows that the combination of d4T and ddI is associated with greater fat loss than AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir).

Less common side-effects of ddI include nausea, vomiting, chills, fever; headache, pain, rash, weakness, seizures or convulsions, pneumonia, confusion, insomnia and dry mouth. Many of these are mild and only occur in the first few weeks of treatment. There is also limited evidence that breast enlargement may be related to ddI use.10 Retinal changes and optical neuritis have been reported so regular eye exams for patients are advised.

References

  1. Chen CH et al. Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol Pharmacol 39: 625-638, 1991
  2. Seidlin M et al. Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine. AIDS 6: 831-835, 1992
  3. Lai KK et al. Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI). Ann Intern Med 115: 283-284, 1991
  4. Boxwell D et al. Fatal hepatotoxicity associated with combination hydroxyurea and nucleoside reverse transcriptase inhibitors (NRTIs): cases from the FDA adverse event reporting system (AERS). Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 617, 2001
  5. Bani-Sadr F et al. Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy. J Acquir Immune Defic Syndr 40: 47-52, 2005
  6. McGovern BH et al. Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. Clin Infect Dis 43: 365-372, 2006
  7. Maida I et al. Severe liver damage associated with prolonged exposure to antiretroviral drugs. J Acquir Immune Defic Syndr 42: 177-182, 2006
  8. Kovari H et al. Association of noncirrhotic portal hypertension in HIV-infected persons and antiretroviral therapy with didanosine: a nested case-control study. Clin Infect Dis 49: 626-35, 2009
  9. Food and Drug Administration Serious liver disorder associated with the use of Videx/Videx EC (didanosine). FDA Drug Safety Communication: January 29, 2010
  10. Mira JA et al. Gynaecomastia in HIV-infected men on highly active antiretroviral therapy: association with efavirenz and didanosine treatment. Antivir Ther 9: 511-517, 2004
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

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