Doctors are being warned to look out for a new symptom of lactic acidosis, neuromuscular weakness, following a warning by the European Agency for the Evaluation of Medicinal Products.
Bristol Myers Squibb has already written to doctors alerting them to the problem, although this side effect is not confined to d4T and ddI, the two nucleoside analogues manufactured by the company. Lactic acidosis has been associated with all drugs in the nucleoside analogue class (AZT, 3TC, abacavir, ddC, d4T and ddI), but is very rare.
Studies have shown that in any given year, less than 1% of patients taking nucleoside analogues will develop lactate levels high enough to cause symptoms, and even fewer could be technically described as having lactic acidosis (venous lactate >5mmol/L and plasma pH < 7.35).
Bristol Myers Squibb has already written to doctors alerting them to the problem, although this side effect is not confined to d4T and ddI, the two nucleoside analogues manufactured by the company. Nevertheless, a
report on patients who developed clinical symptoms as a result of elevated lactate found that patients taking d4T/ddI or d4T/ddI/abacavir were much more likely to present with symptoms.
Fourteen cases of rapidly ascending neuromuscular weakness mimicking Guillain-Barré Syndrome have been associated with the use of nucleoside analogues. Five of these 14 cases had a fatal outcome. In most of these cases, non-specific symptoms and signs associated with lactic acidosis preceded the development of neuromuscular problems.
Early symptoms of lactic acidosis include:
Severe lactic acidosis has a high mortality rate and may be associated with pancreatitis, liver failure, kidney failure, or paralysis.
- Nausea, vomiting, diarrhoea and abdominal pain
- Rapid and deep breathing, especially after physical activity
- Cramps, myalgia and paresthesia
- Fatigue
- Weight loss