Patients should be informed that zidovudine does not prevent the transmission of HIV to other people during sexual intercourse or blood transfusion. Therefore, patients should take appropriate precautions.
Zidovudine can not completely cure HIV infection or acquired immunodeficiency syndrome (AIDS). In patients receiving zidovudine or other antiretroviral drugs, opportunistic infections or other complications of HIV infection can continue to develop.
Pregnant women considering the possibility of using zidovudine during pregnancy to prevent the transmission of HIV to their children should be informed that in some cases transmission can occur even despite treatment.
FROM ribavirin, stavudine, doxorubicin antagonism in the antiviral action of zidovudine has been established. Joint use of zidovudine and stavudine, ribavirin or doxorubicin should be avoided.
Joint use of zidovudine should be avoided. rifampicin.
Violations of the blood and lymphatic system. In patients receiving zidovudine, it is possible to expect the development of anemia (most often 6 weeks after the start of zidovudine therapy, exceptions are possible), neutropenia (most often 4 weeks after the start of zidovudine therapy, exceptions are possible) and leukopenia (usually secondary, associated with neutropenia).These unwanted reactions often develop at high doses (1200-1500 mg / day) and in patients with decreased bone marrow function prior to initiation of therapy (usually in later stages of HIV infection).
It is necessary to carefully monitor blood counts. In the late stages of HIV infection, in the presence of symptoms, during the first 3 months of therapy it is recommended that the blood test be performed at least once every 2 weeks, then every month. Depending on the general condition of the patient, blood counts can be controlled less often (for example, every 1-3 months).
When the hemoglobin content is reduced to 75-90 g / l (4.65-5.59 mmol / l) and the neutrophil count to 0.75 x 109/ l and 1.0 x 109/ l daily dose of zidovudine can be reduced, taking a reduced dose can continue until the recovery of blood values. An alternative option to restore blood counts is a short-term withdrawal of the drug (for 2-4 weeks). Recovery of blood counts usually occurs after 2 weeks, after which the therapy with zidovudine (in a smaller dose) can be resumed. With severe anemia, dose adjustment does not always avoid blood transfusion.
Lactic acidosis. Lactic acidosis, observed with the use of nucleoside analogs, is usually associated with hepatomegaly and hepatic steatosis. Early symptoms of lactic acidosis include dyspeptic manifestations (nausea, vomiting and abdominal pain), a feeling of malaise, decreased appetite, weight loss, respiratory symptoms (rapid and / or deep breathing) or neurological symptoms (including muscle weakness). Lactic acidosis is a condition with high mortality and can be associated with pancreatitis, hepatic or renal insufficiency. Lactic acidosis is usually observed after several months of taking the drug.
Hyperlactatemia is accompanied by symptoms: metabolic lactic acidosis, progressive hepatomegaly, rapid increase in transaminase activity. Hyperlactatemia is an indication for the cancellation of nucleoside analogues.
Caution should be exercised when assigning nucleoside analogs to patients with hepatomegaly (especially women who are obese), hepatitis or other known risk factors for liver disease and steatosis of the liver (including a number of medications and alcohol abuse).Patients infected with the hepatitis C virus and taking interferon-alpha and ribavirin, have a particularly high risk.
Patients with a high risk of lactic acidosis should be monitored more carefully.
Mitochondrial toxicity. Analogues of nucleosides and nucleotides can cause mitochondrial toxicity of varying severity. Mitochondrial dysfunction is observed in HIV-negative neonates exposed to nucleoside analogs in the prenatal and / or postnatal period. The main undesirable phenomena include hematologic (anemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipazemia); they are often transient. There are also reports of delayed reactions from the nervous system (hypertonic muscle, seizures, pathological behavior), the degree of reversibility of which is unknown. Every child who has been exposed to nucleoside analogues in the prenatal period needs to monitor clinical and laboratory indicators regardless of HIV status.When the corresponding symptoms appear, a complete examination is shown to exclude possible mitochondrial dysfunction. Data on mitochondrial dysfunction do not affect current recommendations on the use of antiretroviral therapy in pregnant women (prevention of the vertical pathway of HIV transmission).
Lipodystrophy. Combined antiretroviral therapy in HIV-infected patients is often accompanied by a redistribution of adipose tissue (lipodystrophy). The long-term consequences of this phenomenon are currently unclear, the data on the mechanism of its occurrence are limited. It is assumed that the reception of protease inhibitors is associated with visceral lipomatosis, and the reception of nucleoside reverse transcriptase inhibitors with lipoatrophy. The factors that increase the risk of lipoatrophy are elderly age (individual factor), as well as long-term antiretroviral therapy and associated metabolic changes (drug factors). At physical examination it is necessary to pay attention to signs of redistribution of adipose tissue. It is also necessary to monitor the concentration of lipids and glucose in the blood (fasting).Therapy of lipid metabolism disorders is carried out in accordance with the clinical picture.
Myopathy. Myopathy and myositis with pathological changes characteristic of the course of HIV infection were associated with prolonged use of zidovudine.
Diseases of the liverneither. The data obtained in patients with cirrhosis of the liver suggest that, with hepatic insufficiency, zidovudine accumulation associated with suppression of glucuronization can be observed. It may be necessary to adjust the dose of the drug, however, the exposure of zidovudine in liver failure of varying degrees (from mild to severe) varies considerably, and therefore it is difficult to provide specific recommendations for dose changes. If it is not possible to control the concentration of zidovudine in plasma, clinical signs of drug intolerance should be followed (for example, severe adverse reactions from the blood system: anemia, leukopenia, neutropenia). If necessary, reduce the dose of zidovudine and / or increase the interval between doses of the drug.
Patients,suffering from chronic hepatitis B or C and receiving combination antiretroviral therapy, have an increased risk of severe unwanted liver reactions, which can also lead to death. When appointing patients with hepatitis B or C, combined antiretroviral therapy, you should carefully read information about all the medications that the patient will receive.
Presence of previous liver diseases (including chronic active hepatitis) increases the risk of liver dysfunction during combined antiretroviral therapy, the condition of such patients should be monitored in accordance with clinical practice standards. In case of aggravation of liver disease, it is necessary to reduce the dose of the drug or interrupt its reception.
Syndrome of restoration of immunity. In HIV-infected patients with severe immunodeficiency, the onset of HAART can be accompanied by an inflammatory response to asymptomatic or residual opportunistic pathogens. This reaction can lead to the development of severe clinical manifestations or aggravate existing symptoms.Usually, similar reactions are observed during the first weeks or months after the onset of HAART. Examples include cytomegalovirus retinitis, generalized and / or local mycobacterial infections and pneumocystis pneumonia. It is necessary to control the symptoms of inflammation and, if necessary, prescribe appropriate therapy. There may be autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) on the background of restoration of immunity, but the time of primary manifestations varies, and the disease can occur many months after the initiation of therapy and have an atypical course.
Osteonecrosis. Although the etiology of bone necrosis is considered multifactorial (including the use of corticosteroids, alcohol abuse, severe immunosuppression, high body mass index), cases of osteonecrosis are mainly observed in the late stages of HIV infection and / or with prolonged use of HAART. Patients should be warned that discomfort and pain in the joints, a feeling of stiffness and difficulty of movement require a doctor's advice.
Co-infection with the hepatitis C virus. Joint reception of ribavirin and zidovudine is not recommended in connection with an increased risk of anemia. Patients should be warned that taking any other medications without prescribing a doctor is undesirable.
In patients infected with HIV and hepatitis C virus and receiving combined antiretroviral therapy for HIV and interferon alfa in combination with ribavirin or without it, hepatic insufficiency (sometimes with lethal outcome) was observed. It is necessary to ensure that patients receiving interferon alfa with or without ribavirin, and zidovudine, in order to identify the toxic effects associated with treatment, especially the development of hepatic insufficiency, neutropenia and anemia. In such cases, discontinuation of zidovudine should be considered. It should also consider a dose reduction or discontinuation of interferon alpha, ribavirin, or both drugs in the event the clinical signs of toxicity, including hepatic failure (e.g., more than 6 points according to Child-Pugh classification) (see.instructions for the use of interferon alfa and ribavirin).
It is necessary to change the regimen of antiretroviral therapy, using a scheme that does not contain zidovudine, especially in patients with a history of zidovudine-induced anemia.
Simultaneous reception with other drugs containing zidovudine. Zidovudine should not be prescribed with other medications containing zidovudine.
In patients receiving zidovudine as part of combined antiviral therapy, there may be a syndrome of immune reconstitution, which may require medical intervention.
Estimating the tolerability of the drug, it should be borne in mind that skin rash, dizziness, weakness, headache, anorexia, diarrhea, myalgia, anemia, thrombocytopenia can be a manifestation of HIV infection itself and secondary diseases associated with it, rather than the toxic effect of zidovudine.