The frequency of adverse reactions was determined in accordance with the WHO classification (World Health Organization): very often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10000 and <1/1000), very rarely (<1/10000), the frequency is unknown (the frequency can not be estimated from available data, including individual messages).
Violations of the side of the blood and lymphatic system: rarely - anemia, very rarely - neutropenia, thrombocytopenia.
Endocrine disorders: infrequently - gynecomastia.
Metabolic and nutritional disorders: often - lipoatrophy, lipodystrophy, asymptomatic hyperlactatemia, infrequently - lactic acidosis, anorexia, rarely - hyperglycemia, very rarely - diabetes mellitus.
Mental disorders: often - depression, infrequently - anxiety, emotional lability.
Impaired nervous system: often - peripheral neuropathy, paresthesia, peripheral neuritis, dizziness, abnormal dreams, headache, insomnia, drowsiness, frequency is unknown - pathological thinking.
Disorders from the gastrointestinal tract: often - diarrhea, abdominal pain, nausea, dyspepsia, infrequently - pancreatitis, vomiting, frequency unknown - dry mouth.
Disorders from the hepatobiliary system: infrequently - hepatitis, jaundice,
a violation of liver function, rarely - steatosis of the liver, very rarely - liver failure, the frequency is unknown increase in the activity of "liver" transaminases, hyperbilirubinemia.
Disturbances from the skin and subcutaneous tissues: often - a rash, itching, infrequently -hives.
Disturbances from the musculoskeletal system and connective tissue: infrequently - arthralgia, myalgiaI.
General disorders: often - fatigue, infrequently - asthenia, frequency unknown - chills, fever, increased lipase activity.
When used in combination with other drugs with similar toxicity, the risk of side effects increases.
Combined antiretroviral therapy has been associated with metabolic disorders, such as hypertriglyceridemia, hypercholesterolemia, insulin resistance. hyperglycemia and hyperlactatemia.
Peripheral Neuropathy is an severe and dose-dependent side effect of the drug. The risk of developing this effect increases with osimultaneous application with didanosine. Peripheral neuropathy is usually accompanied by a bilateral symmetrical sense of numbness in the limbs: tingling and pain in the soles of the feet and less in the hands. In clinical trials, the frequency of these reactions depended on the dose and / or stage of the disease. In the early stages of the disease, these phenomena are less frequent. Pancreatitis varying degrees of severity, including death, can develop in the patient at different stages of treatment and does not depend on whether the drug is administered as monotherapy or in combination with other drugs, or on the degree of immunosuppression. When using the drug in combination with didanosine or other drugs that have a toxic effect on the pancreas, the risk of developing pancreatitis increases.
Steatosis. Severe forms of steatosis with hepatomegaly, including death, are noted when nucleoside analogues are used in monotherapy or in combination with other antiviral drugs, including stavudine. With the use of stavudine in combination with didanosine, the risk of liver dysfunction significantly increases. Nausea, vomiting, pain in the abdominal region, rapid breathing or shortness of breath, or muscle weakness may indicate the development of lactic acidosis.
Redistribution of fatty tissue. In patients receiving antiretroviral therapy, there were cases of redistribution / accumulation of fatty tissue (lipodystrophy / lipoatrophy), which manifested itself as obese by the central type,an increase in the amount of fat in the dorsocervical zone, a decrease in the amount of fatty tissue in the limbs and face, an increase in the breast, and a "cushingoid face." In randomized comparative clinical trials, it was found that in patients who had not previouslyrimretroviral therapy, lipodystrophy / lipoatrophy are more common in stavudine than with other nucleoside analogues (tenofovir or abacavir).
Muscle weakness. In rare cases, the treatment with stavudine develops muscle weakness. Its symptoms may be similar to the clinical signs of Guillain-Barre syndrome (including respiratory failure). Symptoms may persist or worsen after discontinuation of therapy.
Osteonecrosis. Cases of osteonecrosis were noted in patients taking stavudine, especially with prolonged treatment with antiretroviral drugs. An important role in the etiology of osteonecrosis is played by such factors as treatment with glucocorticosteroids, alcohol abuse, severe immunosuppression, obesity.
Children. In clinical trials, the side effects of the drug in children and adults patients did not differ. The development of peripheral neuropathy in children was less common than in adults. However, the symptoms of peripheral neuropathy in children were more difficult to identify.
In conditions in vitro and in vivo the ability of nucleotide and nucleoside analogues to cause damage to mitochondria is revealed. Mitochondrial dysfunction was reported in HIV-negative children exposed to nucleoside analogues during the antenatal period or immediately after birth. The main manifestations of mitochondrial dysfunction, often transient, were anemia, neutropenia, hyperlactatemia and hyperlipazemia.
There were also later manifestations of this disorder: hypertonus of the muscles, convulsions, anomalies of behavior.
Immunodeficiency Syndrome
In HIV-infected patients with severe immunodeficiency after onset combination antiretroviral therapy may occur asymptomatic opportunistic infections or their residual manifestations. Also reported were autoimmune disorders, such as Graves' disease, polymyositis, and Guillain-Barre syndrome. The time of occurrence is very variable and may be several months fromtreatment.