Patients should be informed that treatment with antiretroviral drugs does not prevent the risk of HIV transmission to other people. During sexual intercourse, appropriate precautions should be taken.
Simultaneous use with other medicinal products
Tenofovir should not be used concurrently with drugs that contain
tenofovir or adefovir. It is not recommended simultaneous use of tenofovir and didanosine.
Osteonecrosis
Although the etiology of osteonecrosis is considered multifactorial (for example, taking glucocorticosteroids, drinking alcohol, acute immunosuppression, increased body mass index play an important role in the development of this complication),there are reports of such cases, particularly in patients with advanced HIV infection / or duration of antiretroviral therapy. Patients should seek medical advice from a physician if symptoms such as lethargy, stiffness, joint pain or difficulty with movement occur. Mitochondrial dysfunction
In conditions in vitro and in vivo the ability of nucleotide and nucleoside analogs to cause damage to mitochondria of different degrees was revealed. There have been cases mitochondrial dysfunction in HIV-negative children exposed to nucleoside analogues in utero or immediately after birth. The main manifestations of mitochondrial dysfunction, often transient, were anemia, neutropenia, hyperlactatemia and increased lipase activity in blood plasma. Lactic acidosis, vyraeyuenaya hepatomegaly with steatosis When used in HIV-infected patients, the nucleotide and nucleoside analogs, including tenofovir disoproxil fumarate in combination with other antiretroviral drugs, reported cases of lactic acidosis and a marked increase in size of the liver and its steatosis, including fatal cases.Due to the high risk of developing lactic acidosis, special care should be taken when administering tenofovir to patients (especially women with excessive body weight) with hepatomegaly and fatty liver disease, with hepatitis, and in the presence of risk factors for liver damage. Clinical or laboratory signs of lactic acidosis can be detected several months after the start of treatment, but the development of this complication is possible in a shorter time. If the patient develops clinical (from the digestive system - nausea, vomiting, abdominal pain, general malaise, loss of appetite, weight loss, respiratory failure, neurologic symptoms - impaired motor function, muscle weakness) or laboratory (lactic acid in serum blood levels above 5 mmol / l) signs of lactic acidosis, or severe hepatotoxicity, therapy with tenofovir should be suspended.
Patients with impaired renal function
The excretion of tenofovir mainly occurs through the kidneys. With the use of tenofovir in clinical practice, there have been cases of renal failure, increasing the concentration of creatinine, hypophosphatemia, as well as Fanconi syndrome.
All patients before the start of therapy and, if there is a clinical indication, during therapy with tenofovir is recommended to determine the clearance of creatinine. Correction of intervals between doses of the drug should be carried out in accordance with the recommendations presented in the section "Method of administration and dose" (subsection "Patients with impaired renal function").
In patients at risk of developing renal dysfunction, including patients who previously had renal dysfunction with adefovir, regular monitoring of creatinine clearance and serum phosphorus concentrations should be performed.
Tenofovir is not recommended to be used concomitantly with nephrotoxic drugs or after the recent use of such drugs.
The safety and effectiveness of the use of tenofovir in patients with creatinine clearance from 30 to 49 ml / min are not determined, therefore, the ratio of the potential benefit of taking the drug and the possible risk of toxic effects on the kidneys should be evaluated. If nevertheless there is a necessity of appointment of tenofovir,then correction of the intervals between doses is required. Such patients should be closely monitored for the function of the kidneys.
Undesirable reactions listed in the section "Side effect", presented above, can arise from renal tubulopathy of the proximal type: rhabdomyolysis, osteomalacia (manifested by bone pain, occasionally leads to fractures), hypokalemia, muscle weakness, myopathy, hypophosphatemia. It is believed that the cause of the development of these phenomena is not associated with therapy with tenofovir in the absence of renal tubulopathy of the proximal type.
Patients infected with both HIV and hepatitis B virus g and C The risk of hepatotoxic effect of antiretroviral drugs in patients with co-infected HIV infection and the hepatitis B or C virus is higher than in the presence of only HIV infection. Therefore, patients with chronic hepatitis B or C who simultaneously take antiretroviral drugs are at increased risk of adverse effects on the liver with possible fatal outcome. These patients should be carefully monitored, both clinically and laboratory.
In patients infected with both HIV and hepatitis B virus, severe exacerbations of hepatitis may occur after discontinuation of therapy with tenofovir. In some cases, it may be necessary to resume therapy for viral hepatitis. In patients with severe liver disease (cirrhosis), it is not recommended to discontinue treatment, since the aggravation of hepatitis that occurs after the abolition of therapy can lead to decompensation of liver function. Patients infected with HIV and hepatitis B virus should be closely monitored, both clinically and laboratory, for at least 6 months after stopping therapy with tenofovir. It is recommended that all HIV-infected patients be tested for the presence of viral hepatitis B before initiating antiretroviral therapy.
Caution should be exercised when assigning nucleotide and nucleoside analogues to patients with concomitant hepatitis C who receive interferon alfa and ribavirin in connection with the high risk of lactate-acidosis. Such patients should undergo thorough clinical and laboratory monitoring.
Diseases of the liver
Hepatotoxic reactions occur at different times against combined antiretroviral therapy. The risk of developing hepatotoxicity with combined antiretroviral therapy is higher in patients with underlying liver function impairment. For patients with liver disease receiving tenofovir in combination antiretroviral therapy, careful monitoring should be conducted; if signs of impaired liver function appear, consideration should be given to the possibility of interrupting or canceling therapy.
Triple therapy with nucleosides
A decrease in the frequency of the virologic response in the administration of triple therapy with nucleosides was reportedtenofovir in combination with abacavir and lamivudine), as well as the development of resistance at an early stage of using this combination when taking medications once a day.
Lipodystrophy
In patients receiving antiretroviral therapy, there was a redistribution / accumulation of fatty tissue, including obesity of the central type, an increase in adipose tissue in the dorso-cervical region ("buffalo buffalo"), a reduction in the volume of peripheral adipose tissue, a reduction in subcutaneous fat in the face, mammary hypertrophy and "Cushingoid appearance."The mechanism of development and the long-term effects of these effects are currently unknown, their cause-and-effect relationship with the use of certain drugs has not been established. Effect on the bone system
In animals, after administration of tenofovir, toxic effects on bone tissue were observed, including a reduction in bone mineral density. However, in the clinical study of long-term use of the drug (more than 3 years), there were no clinically significant pathological changes in bone tissue. Nevertheless, pathological changes in bone tissue (occasionally leading to fractures) can be observed with renal tubulopathy of the proximal type (see section "Side effect"). If there is a suspicion of disturbances from the bone system, an appropriate examination should be carried out.
Early virological inefficiency
In clinical studies involving HIV-infected patients, it has been shown that a number of therapeutic regimens involving only three nucleoside reverse transcriptase inhibitors are generally less effective than triple regimes involving the use of two nucleoside inhibitors reverse transcriptase in combination with either a non-nucleoside reverse-inhibitor transcriptase, or with an HIV-1 protease inhibitor. In particular, it was reported about early virological inefficiency and high incidence of mutations (by type of replacement), causing the development of resistance. On this basis, regimes involving the use of three nucleoside reverse transcriptase inhibitors should be used with caution. For patients whose treatment regimens involve the use of only three nucleoside reverse transcriptase inhibitors, careful monitoring should be conducted; in such cases, it is also recommended to consider the possibility of changing the treatment regimen.
Immunodeficiency Syndrome
In HIV-infected patients receiving combined antiretroviral therapy, the immune reconstitution syndrome was observed. In patients with severe immunodeficiency, an inflammatory response may occur in response to asymptomatic or residual opportunistic infections, which can lead to the development of serious clinical conditions or increased symptom severity.Such reactions are usually observed in the first few weeks or months of antiretroviral therapy. Examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and pneumonia caused by Pneumocystis jirovecii. Any symptomatology of an inflammatory nature requires an appropriate evaluation and, if necessary, the initiation of treatment. Patients should be under close clinical supervision of specialists with experience in the treatment of patients with HIV disease. Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) were observed against the background of restoration of immunity, but the time of primary manifestations varied, and the disease could occur many months after the initiation of therapy and have an atypical course.