Are common
Dablovir® is a combination drug with a fixed dose of tenofovir, dizoproxil fumarate and emtricitabine. Therefore, this drug should not be administered concomitantly with drugs that contain tenofovir, emtricitabine or with drugs that contain lamivudine (due to its similarity to emtricitabine) or adefovir (due to its similarity to tenofovir). These are drugs such as Viread (tenofovir), Emtreeva (emtricitabine), Atripla (efavirenz / emtricitabine / tenofovir), Combivir (lamivudine / zidovudine), Epivir (lamivudine), Epivir-HBV (lamivudine), Epicom (abacavir / lamivudine), Trizivir (abacavir / lamivudine / zidovudine), Gepsera (adefovir), and Evipler (emtricitabine / rilpivirin / tenofovir).
It is not recommended to use Dablovir® as a component of a three-component nucleoside regimen.
To avoid complications, dablovir® apply under the supervision of a doctor with experience in managing HIV-infected patients.
Patients should be warned that they should not simultaneously use other drugs themselves.
Irregular intake of the drug may lead to the development of resistance to the virus and reduce the effectiveness of treatment.
Patients should be informed that therapy with Dablovir® does not reduce the risk of transmission of HIV to others during sexual intercourse or blood transfusion, and therefore does not negate the need for appropriate precautions.
Lactatacidosis / severe hepatomegaly with fatty dystrophy
When used in HIV-infected individuals, nucleotide and nucleoside analogs in combination with other antiretroviral drugs reported the development of lactic acidosis and a pronounced increase in the liver with its fatty dystrophy, including fatal cases.
Clinical and laboratory signs of lactic acidosis are usually detected a few months after the start of treatment, but the development of this complication can occur in shorter periods. It often develops in patients with liver disease and in obese patients, especially in women.
Due to the high risk of lactic acidosis, caution should be exercised when administering Dablovir® to patients (especially overweight women) with hepatomegaly, hepatitis, or other known risk factors for liver disease and fatty liver disease (including certain drugs and alcohol).
A special risk group may be patients with co-infection with the hepatitis C virus who are receiving interferon alfa and ribavirin therapy.
Reception of nucleoside or nucleotide analogues should be discontinued in patients with symptoms of hyperlactatemia, metabolic lactic acidosis, progressive hepatomegaly, or a rapid increase in aminotransferase activity.
When the patient experiences clinical symptoms (nausea, vomiting, abdominal pain, general malaise, loss of appetite, weight loss, respiratory failure, neurologic symptoms - impaired motor function, muscle weakness) or laboratory signs of lactic acidosis (lactate in the serum above 5 mmol / l), or overt hepatotoxicity (which may include liver enlargement and steatosis, even if there is no marked increase in transaminase activity), treatment with Dablovir® should be discontinued.
Patients who are simultaneously infected with HIV and hepatitis B or C virus
The risk of hepatotoxic action of antiretroviral drugs in patients with co-infection with HIV and the hepatitis 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.
All HIV-infected patients should be tested for chronic hepatitis B or C. before starting antiretroviral therapy.
The efficacy and safety of Dablovir® in the treatment of chronic hepatitis B has not been established. Emtricitabine, tenofovir and their combination demonstrated their activity against hepatitis B virus in studies of pharmacodynamics. The limited experience of application allows to assume that emtricitabine and tenofovir They have activity against hepatitis B virus when used as part of combined antiretroviral therapy for HIV infection.
In patients infected with HIV and hepatitis B virus, severe discontinuities of hepatitis can occur after discontinuation of therapy with Dablovir®. In patients infected with HIV and hepatitis B virus who have stopped using Dablovir®, liver function should be monitored by clinical and laboratory methods for at least 6 months. In some cases, it may be necessary to resume therapy for chronic hepatitis B. In patients with severe liver disease (cirrhosis), it is not recommended to discontinue treatment, since the exacerbation of hepatitis that occurs after the abolition of therapy can lead to decompensation of liver function.
Caution should be exercised when assigning nucleotide and nucleoside analogs to patients with concomitant hepatitis C receiving interferon alfa and ribavirin therapy because of the high risk of developing lactic acidosis. Such patients should be carefully monitored, monitored by laboratory indicators.
Patients with impaired renal function
Emtricitabine and tenofovir disoproxil fumarate are excreted mainly by the kidneys.
When tenofovir was used in clinical practice, cases of detection of renal failure, acute renal failure, increased creatinine concentration, hypophosphatemia, proximal tubulopathy of the proximal tubulopathy (including Fanconi syndrome) were reported.
All patients are recommended to determine the clearance of creatinine before starting treatment, as well as during therapy with the drug Dablovir ® according to clinical indications. In patients at risk of developing renal dysfunction, including patients who previously had renal dysfunction, including adefovir therapy, it is necessary to constantly monitor creatinine clearance and serum phosphorus concentration.
The potential benefit of taking Dablovir ® should be assessed in comparison with the potential risk of toxic effects on the kidneys.
Do not prescribe the drug Dablovir® at the same time or after the recent use of nephrotoxic drugs.
Effect on the bone system
A clinical study showed a decrease in bone mineral density in the bones of the lumbar region and femurs during treatment with a combined preparation containing a fixed dose of tenofovir, dizoproxil fumarate and emtricitabine.Most cases of reduction in bone mineral density were observed during the first 24-48 weeks and persisted for 144 weeks of study.
It is necessary to observe the condition of the bone tissue of HIV-infected patients with pathological bone fractures in the history and risk of osteopenia. If an anomaly is suspected from the bony system, an appropriate examination should be carried out.
Lipodystrophy
In patients receiving antiretroviral therapy, redistribution of fat accumulation was observed, including obesity in the abdomen, dorsocervical fat deposition ("buffalo hump"), loss of adipose tissue on the limbs, fat loss on the face, breast enlargement and "Cushingoid appearance." The mechanism of development and the long-term effects of these changes are unknown. Causal link is not established.
Immunodeficiency Syndrome
Immunodeficiency syndrome was reported in HIV-infected patients receiving combination antiretroviral therapy. In the initial phase of combined antiretroviral treatment in patients with severe immunodeficiency, the development of exacerbation of asymptomatic or residual opportunistic infections (infections caused by Mycobacterium avium, cytomegalovirus infection, pneumonia caused by Pneumocystis jirovecii (PCP), or tuberculosis), which may require further examination and treatment.
Such reactions are usually observed in the first few weeks or months of antiretroviral therapy, patients should be carefully monitored by specialists with experience in treating patients with HIV-associated diseases.
Against the background of the immune reconstitution syndrome, it is also possible to form autoimmune diseases (diffuse toxic goiter (Graves' disease), polymyositis, Guillain-Barre syndrome). The time of primary manifestations varies, and the disease can occur many months after the initiation of therapy and have an atypical course.
Triple therapy of nucleosomes (t) with reverse transcriptase inhibitors
Clinical studies in HIV-infected patients have shown that regimens containing three nucleoside reverse transcriptase inhibitors (NRTIs) are generally less effective than a triple therapy regimen containing two NRTIs in combination with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an inhibitor HIV-1 proteases.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 in combination with lamivudine and didanosine), as well as the development of resistance at an early stage of the use of these combinations when taking medications 1 time per day.
Therefore, triple NRTI regimens should be used with caution. In patients taking the triple regimen only from NRTIs, a thorough examination should be conducted and the issue of modifying therapy should be considered.
Osteonecrosis
Although the etiology of osteonecrosis is considered multifactorial (including taking glucocorticosteroids, drinking alcohol, severe immunosuppression, increased body mass index), there are reports of such cases, especially in patients with progressive HIV infection and / or long-term 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
Analogues of nucleotides and nucleosides show the ability to cause mitochondrial damage in vitro and in vivo. There are data on the development of mitochondrial dysfunctions in HIV-negative children exposed to nucleoside analogues during fetal and / or postnatal development. The main manifestations of mitochondrial dysfunction, often transient, were anemia, neutropenia, hyperlactatemia and increased lipase activity. Some deferred neurological disorders have been reported (hypertension, seizures, behavioral disorders). At present, it is not known whether these neurological disorders were transient or permanent. Children exposed to nucleoside analogues during the fetal development period, including HIV-negative, having described or similar symptoms, should be under clinical and laboratory observation for the detection of mitochondrial dysfunction.
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 withinitial impairment of liver function. For patients with liver disease receiving Dablovir® 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.
Use in special patient groups
Elderly age
Caution is necessary to select a dose for elderly patients, given the high frequency of violations of the liver, kidney or heart, as well as concomitant diseases or other medications.
Impaired renal function
It is recommended to increase the interval between doses of the drug in patients with creatinine clearance less than 50 ml / min. The drug should not be given to patients with creatinine clearance less than 30 ml / min or with terminal stage of renal failure requiring dialysis (see section "Dosage adjustment").