Patients receiving tenofovir, should be informed that treatment with antiretroviral drugs does not prevent the risk of transmission of HIV and hepatitis B to other people. During sexual intercourse, appropriate precautions should be taken.
Simultaneous use with other medicinal products.
Tenofovir is contraindicated in conjunction with other drugs containing tenofovir, didanosine, adefovir.
Triple therapy with nucleoside / nucleotide, and inhibin and tori and reverse transcriptase of HIV. A possible rapid development of virological failure and the emergence of resistance in the early stages of HIV-infected patients receiving tenofovir dizoproxil fumarate in combination with lamivudine and abacavir, as well as lamivudine and didanosine, taken once a day, has been reported. Lactate acidosis and severe hepatomegaly with steatosis.
When used in HIV-infected patients individuals
nucleoside analogs, including tenofovir, dizoproxil fumarate, in combination with other antiretroviral drugs, lactate acidosis and a pronounced increase in liver size with its fatty dystrophy, sometimes fatal, have been reported. As a rule, lactic acidosis develops after several months from the beginning of treatment.
If the patient develops clinical (on the part of the digestive system - nausea, vomiting, abdominal pain, general malaise, loss of appetite, weight loss; violation of breathing;
neurologic symptoms - impaired motor functions, muscular weakness) or laboratory signs (the content of lactic acid in the serum above 5 mmol / l), indicating lactate acidosis or pronounced hepatotoxicity, tenofovir therapy must be suspended.
Caution should be exercised when prescribing nucleoside analogues following patients: women with increased mass body, patients with hepatomegaly, hepatitis or other known risk factors for liver disease (including medicines and alcohol).
Special risk present are patients with a co-infection of HIV and hepatitis C taking alpha interferon and ribavirin.
Patients with impaired renal function.
Deprivation of tenofovir mainly occurs through the kidneys. When tenofovir was used in clinical practice, cases of detection of renal failure were reported, increasing concentration creatinine, hypophosphatemia, and Fanconi syndrome. Have all patients before the start of therapy, and if there is a clinical indication, during therapy with tenofovir, it is recommended to calculate the clearance of creatinine. Interval correction between doses of the drug should be in accordance with the recommendations (see."Method of administration and dose"). Have patients with a risk of developing a disorder kidney function, including patients who have previously been found to have impaired kidney function when treated with adefovir, should be given a regular monitoring the calculated clearance of creatinine and the concentration of phosphorus in the blood serum. The drug can not be used concomitantly with nephrotoxic drugs or in the case of recent use of drugs of this kind.
Use tenofovir in patients with creatinine clearance from 30 to 49 ml / min should be used with caution, at this adjust intervals between doses (cm. "Method of administration and dose"). Have of such patients should be conduct a thorough observation behind the kidney function.
Undesirable reactions may result from renal tubulopathy of the proximal type: rhabdomyolysis, osteomalacia (manifested by pain in the bones, can lead to fractures), hypokalemia, muscle weakness, myopathy, hypophosphatemia.
Patients infected with HIV, hepatitis B and C virus.
Patients with chronic hepatitis B or C and taking antiretroviral therapy, are at increased risk of severe and potentially fatal adverse reactions from the liver.
In the case of combined antiviral therapy for hepatitis B or C, contained in the instructions on the use of these drugs.
In patients infected with HIV and hepatitis B virus, severe withdrawal may occur after withdrawal of tenofovir therapy hepatitis A. For patients infected with HIV and hepatitis B virus who stopped using tenofovir, A close monitoring, both clinical and laboratory, should be carried out at least 6 months after discontinuation of therapy. In some cases, it may be necessary resumption of hepatitis B therapy. In patients with severe liver disease (cirrhosis), it is not recommended to discontinue treatment, because after exacerbation of therapy, exacerbation of hepatitis can lead to decompensation of liver function.
Testing for antibodies to HIV should be available to all patients, infected with hepatitis B virus before the initiation of therapy with tenofovir.
In connection with the risk of developing resistance tenofovir should use as part of the relevant antiretroviral treatment for those infected with HIV and hepatitis B.
Liver disease.
Tenofovir and disoproxil fumarate are metabolized by the liver.
Patients with existing liver dysfunction, including those with chronic active hepatitis, are more likely to have liver function abnormalities with combined antiretroviral therapy. Such patients should monitor liver function in accordance with standard practice. With the development of symptoms of worsening liver disease in this category of patients, interrupt or stop treatment.
Lipodystrophy.
Patients undergoing antiretroviral therapy, redistribution / accumulation of adipose tissue in the body, including obesity of the central type, increased deposition of adipose tissue on the back and neck ("buffalo hump"), a decrease in the volume of peripheral adipose tissue and subcutaneous fat in the face, mammary hypertrophy and the so-called "Cushingoid appearance".
Mechanisms and long-term consequences of these phenomena are still unknown, there is no causal relationship with the use of certain drugs.
Osteonecrosis.
Despite the fact that the etiology of osteonecrosis is considered multifactorial (including the use of corticosteroids, alcohol consumption, etc.), cases of osteonecrosis have been documented, especially in patients with HIV infection and / or at long antiretroviral therapy. Patients should be advised to see a doctor if they experience joint pain and difficulty moving.
Early virological inefficiency.
In clinical studies involving HIV-infected patients, it was shown that a number of regimens using nucleoside reverse are generally less effective than triple regimes involving the use of two nucleoside reverse transcriptase inhibitors in combination with non-nucleoside inhibitors reverse transcriptase or HIV-1 protease inhibitors. Early virological inefficiency and high incidence of mutations (by type of substitution), causing the development of resistance. On this basis, regimes involving the use of three nucleoside inhibitors reverse transcriptase, use with caution. For patients whose mode of use of only three nucleoside inhibitors reverse transcriptase should be carefully monitored; in such cases it is also recommended to consider the possibility of changing the scheme of therapy.
Syndrome restoration of immunity.
In HIV-infected patients, receiving a combination antiretroviral therapy there was a development of the immune reconstitution syndrome.
In patients with severe immunodeficiency at the onset of antiretroviral therapy, an inflammatory response may occur in response to asymptomatic or residual opportunistic infections, which can lead to the development of serious clinical states or increase severity of symptoms. Such reactions are observed, as a rule, in the first few weeks or months of antiretroviral
Examples can cytomegalovirus generalized and / or focal mycobacterial infection and pneumonia, called Pneumocystis jiroveci. Any symptoms of an inflammatory nature requires an appropriate assessment and, if necessary, the beginning of treatment. Patients should be under careful clinical observation specialists with experience in the treatment of patients with HIV diseases.Autoimmune diseases diseases (eg, Graves' disease) were observed on background recovery immunity, however, the time of primary sprains varied and the disease could occur many months after initiation of therapy and have an atypical course.
Mitochondrial dysfunction. Nucleoside and nucleotide analogs in conditions in vitro and in vivo demonstrated the ability of damage mitochondria.
The main adverse disorders are hematologic violations (anemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipazemia). These events are often temporary. There were are registered later neurological violations (hypertension, convulsions, behavioral disorders).