The relationship between HIV sensitivity to didanosine in vitro and no clinical response to treatment has been established. The results of determining the sensitivity in vitro vary over a wide range. Positive correlation is established in vivo between the results of measurements of viral activity (for example, determination by the method of polymerase chain reaction of HIV RNA) and clinical progression of the disease. With the simultaneous use of the drug with drugs with toxic effects on the peripheral nervous system or pancreas The risk of these toxic effects increases significantly.
With the simultaneous use of pentamidine intravenously or drugs that increase the activity of didanosine (hydroxycarbamide, allopurinol), didanosine therapy is recommended to be suspended.
It is necessary to periodically check the vision and note any of its violations, such as changing the perception of color or a vague vision of objects. Children and adults should conduct an examination of the retina every 6 months or if there is any change in vision. Have HIV-infected patients with severe immunodeficiency during combined antiretroviral therapy, there may be signs of an inflammatory response to asymptomatic or residual opportunistic infections. This syndrome can be observed during the first few weeks or months after the onset of antiretroviral therapy. There may be signs of cytomegalovirus retinitis, generalized or focal mycobacterial infections and pneumonia caused by Pneumocystis jiroveci. Pancreatitis is a severe toxic effect of the drug. Pancreatitis of varying severity, often fatal, can develop in patients at different stages of treatment and not depend on whether the drug is administered as monotherapy or in combination with other drugs, or on the degree of immunosuppression. Pancreatitis is a dose-related complication. Patients receiving didanosine in combination with stavudine, hydroxycarbamide, are at a higher risk of developing this side effect. The risk of developing pancreatitis increases in elderly patients, in patients with pancreatitis in the anamnesis,with impaired renal function in the absence of appropriate correction of the dose of the drug, as well as in patients with progressive HIV infection.
When symptoms appear pancreatitis treatment should be discontinued. With clinically significant excess of biochemical markers, even in the absence of symptoms of pancreatitis, treatment should also be stopped.
Lactic Acidosis / severe steatosis with hepatomegaly, including fatal cases, are observed when nucleoside reverse transcriptase inhibitors are used in monotherapy or in combination with other antiretroviral drugs, including didanosine. In general, this side effect is observed in women. Obesity and long-term administration of nucleoside reverse transcriptase inhibitors may be a risk factor for this side effect. In pregnant women, the risk of developing lactic acidosis with a fatal outcome increases with the intake of didanosine in combination with stavudine or other antiretroviral drugs. In this regard, the combination of these drugs in pregnant women can be used with extreme caution.When clinically confirmed symptoms of hepatotoxicity or lactic acidosis (which may include hepatomegaly and steatosis, even if there are no clear signs of an increase in the activity of "liver" transaminases), treatment with the drug should be suspended. With a significant increase in the activity of "liver enzymes" and bilirubin (an increase of 3-4 degrees: 5 times higher than normal for "liver" transaminases and alkaline phosphatase, 2 times higher than normal for lipase, 2.6 times higher than normal for bilirubin) should be discontinued. In post-marketing studies, cases were noted portal hypertension, not associated with cirrhosis of the liver, including cases leading to liver transplantation, as well as to fatal outcomes. Non-cirrhotic portal hypertension caused by didanosine was confirmed in patients with unconfirmed viral hepatitis. Common signs of development of portal hypertension included: increased activity of liver enzymes, varicose veins of the esophagus, bloody vomiting, ascites, splenomegaly.
Patients receiving didanosine, should be regularly monitored for early signs of portal hypertension (eg, thrombocytopenia and splenomegaly) during scheduled visits to the doctor. Appropriate laboratory studies involving the study of liver enzyme activity, bilirubin concentration, albumin in blood plasma, an expanded blood test, an international normalized ratio (MHO) and ultrasonography, should be prescribed to such patients.
The drug should be discontinued if there is a sign of portal hypertension in patients not related to cirrhosis of the liver. Peripheral Neuropathy usually accompanied by a bilateral symmetrical sense of numbness of the limbs: tingling and pain in the feet and, less often, in the hands. In the early stages of the disease, these phenomena are less common. There is information that the course of peripheral neuropathy can be aggravated by the joint administration of antiretroviral drugs, including didanosine, stavudine, and hydroxycarbamide. When signs of peripheral neuropathy appear, doanosine therapy should be suspended until they disappear. After the disappearance of these symptoms, the patient may take a reduced dose of the drug.
Didanosine is rapidly destroyed in the acidic contents of the stomach. Didanosine in the form of granules is found in capsules coated with enteric coating, so that the absorption of didanosine in the intestine is increased.