Andriol testocaps disoproxil fumarate is converted in vivo to andriol testocaps, nucleoside analog (nucleotide), adenosine monophosphate. andriol testocaps is subsequently converted to the active metabolite – andriol testocaps diphosphate.andriol testocaps – nucleotide reverse transcriptase inhibitor has a specific activity against human immunodeficiency virus (HIV-1 and HIV-2), and hepatitis B virus
andriol testocaps diphosphate inhibits the reverse transcriptase of HIV-1 and hepatitis B virus polymerase in the competitive mechanism, resulting termination of DNA synthesis circuit.
andriol testocaps diphosphate is a weak inhibitor of DNA polymerases in mammals.
in in vitro tests andriol testocaps concentrations up to 300 mmol / l had no effect on the synthesis of mitochondrial DNA and the production of lactic acid. Antiviral Activity The antiviral activity against HIV Antiviral Activity andriol testocaps and donor laboratory strains of HIV-1 was assessed on lymphoblastoid cell lines, primary monocyte / macrophages and peripheral blood lymphocytes. Indicator andriol testocaps effective concentration is in the range from 0.04 to 8.5 mol. The cell culture andriol testocaps showed antiviral activity against HIV-1 subtypes A, B, C, D, E, F, G , D (effective concentration is in range from 0.5 to 2.2 mol), and the inhibitory effect of some strains of HIV-2 (the effective concentration is in the range from 1.6 mol to 5.5 mol). When using andriol testocaps in vitro synergy observed antiviral activity of the preparations . In studies of the drug combination with HIV protease inhibitors and nucleoside analogs and non-nucleoside reverse transcriptase inhibitors, HIV-1 were observed or siner’gicheskie additive effects. Antiviral activity against HBV antiviral activity of andriol testocaps against hepatitis B virus was evaluated for cell line HepG2 2.2 .15. Performance indicators concentrations of andriol testocaps was in the range of 0.14 to 1.5 mol with an effective cytotoxic concentrations of> 100 umol. The cultures of combinations of antiviral activity of andriol testocaps study cells with nucleoside reverse transcriptase inhibitors, acting on the hepatitis B virus (emtricitabine, entecavir, telbivudine and lamivudine ) detected antagonistic activities preparations. resistance resistance to HIV-1: were obtained in vitro HIV-1 strains with reduced susceptibility kandriol testocapsu and K65R mutation in reverse transcriptase, and in some patients. The use of andriol testocaps disoproxil fumarate should be avoided in patients with strains K65R mutation previously received antiretroviral therapy.The resistance in hepatitis B: mutation of the virus of hepatitis B associated with resistance to andriol testocaps have been identified.
Pharmacokinetics Absorption Following oral administration in HIV-infected patients, andriol testocaps disoproxil fumarate is rapidly absorbed and converted to andriol testocaps. Maximal serum concentrations of andriol testocaps were observed one hour after ingestion fasting and two hours after administration with food. The bioavailability of andriol testocaps from andriol testocaps disoproxil fumarate after ingestion on an empty stomach was about 25%. As a result of andriol testocaps disoproxil fumarate with food increased bioavailability perorapnom reception, with an area under the curve “concentration-time” and the mean maximum concentration of andriol testocaps increased by approximately 40% and 14%. after the first administration of andriol testocaps disoproxil fumarate food maximum concentration in serum is from 213 to 375 mg / ml. distribution The volume of distribution at equilibrium after intravenous administration of andriol testocaps estimated approximately 800 ml / kg. At concentrations of andriol testocaps from 0.01 to 25 mg / mL of TDF binding to plasma proteins and serum in vitro was less than 0.7% and 7.2%, respectively. Metabolism In in vitro studies it was found that none of andriol testocaps disoproxil fumarate or andriol testocaps are not substrates of cytochrome P450 isoenzymes. Moreover, at concentrations significantly (about 300 times) than drug concentrations observed in vivo, andriol testocaps in vitro conditions did not inhibit metabolism which occurs with major cytochrome P450 isoenzymes human (CYP3A4, CYP2D6, CYP2C9, CYP2EI or CYP1A1 / 2). andriol testocaps disoproxil fumarate is not affected to any isozymes of cytochrome P450, except CYP1AI / 2 (mentioned small (6%) but statistically significant decrease in substrate metabolism by cytochrome CYP1A1 / 2). Derivation Derivation andriol testocaps mainly occurs via the kidneys by filtration and Systems . active tubular transport Linearity / nonlinearity pharmacokinetics of andriol testocaps did not depend on the dose andriol testocaps disoproxil fumarate (at a dose of 75 to 600 mg); Repeated taking the drug at any dose also had no effect on the pharmacokinetics of andriol testocaps. Pharmacokinetics in special populations Bounded on the pharmacokinetics of andriol testocaps data in women indicate no significant gender differences. There has been no pharmacokinetic studies involving children, adolescents under 18 years old and seniors over 65 years. Specific pharmacokinetic studies in different ethnic groups have been conducted.
Treatment of HIV-1 infection in adults in combination with other antiretroviral agents.
Treatment of chronic hepatitis B in adults with compensated liver disease, active viral replication, postoyannno increased activity in serum alaninaminotranferazy (ALT), histological evidence of active inflammation and / or fibrosis.
Hypersensitivity to any component of the drug.
Children under 18 years of age.
Patients with renal insufficiency with creatinine clearance <30 ml / min and patients who require hemodialysis.
Age older than 65 years.
Renal insufficiency with creatinine clearance greater than 30 mL / min and less than 50 ml / min.
Simultaneous treatment with ddI.
Do not rekomneduetsya accept patients with lactase deficiency, lactose intolerance, glucose-galactose mal-absorption, as the product contains lactose .
Pregnancy and lactation
Viread should be used during pregnancy only if the expected benefit of treatment to the mother outweighs the potential risk to the fetus.
In animal studies it has been shown that andriol testocaps is excreted in breast milk. It is not known whether andriol testocaps is excreted in human breast milk. It is not recommended to breast-feed mothers infected with HIV or hepatitis B who received therapy with Viread for the purpose of preventing the risk of postnatal transmission of HIV or hepatitis B.
Dosing and Administration
Adults I tablet daily by mouth during a meal or on an empty stomach. Patients with renal impairment For patients with mild renal impairment (creatinine clearance 50 – 80 ml / min) receiving Viread drug once a day is safe and effective, so there is no the need to adjust the dose in these patients is necessary to carry out continuous monitoring of creatinine clearance and serum phosphate. in patients with creatinine clearance 30 to 49 mL / min interval between doses doses should be adjusted in accordance with the guidelines given in table I.
Table 1 Dosage adjustment in patients with altered creatinine clearance
|Creatinine clearance (ml / min) 1|
|≥50||30-49||<30 (including patients
who require hemodialysis)
|The recommended interval
|Every 24 hours||Every 48 hours||The drug Viread
is not recommended.
|1 when calculating the ideal body weight were used (excluding adipose tissue)|
Patients with impaired liver function does not require dose adjustment. Antiretroviral therapy is usually lifelong. In the treatment of chronic hepatitis B:
– In HBeAg-positive patients without cirrhosis, treatment should continue for at least 6-12 months after HBe seroconversion confirm (HBeAg loss or disappearance of HBV DNA with detection of anti-HBe) or seroconversion to HBs, and the time of loss of efficiency. To detect any delayed virologic relapse after treatment is necessary to regularly measure the levels of ALT and HBV DNA in serum.
– In HBeAg-negative patients without cirrhosis, treatment should continue at least until seroconversion HBs or until loss of efficiency. With prolonged treatment for more than 2 years of age it is recommended to regularly inspect a patient in order to confirm that the selected treatment for a particular patient is adequate.
The duration of therapy with Viread is determined individually by the attending physician.
From the gastrointestinal tract: diarrhea, vomiting, nausea, flatulence, pancreatitis, increased amylase, abdominal pain, bloating. From the nervous system: dizziness, headache, depression. On the part of the immune system: allergic reactions, including angioneurotic edema. On the part of metabolism: hypophosphatemia, lactic acidosis, hypokalemia. The respiratory system: dyspnea. liver and biliary: hepatic steatosis, elevated liver enzymes (most of the ACT – aspartataminotranferaza, ALT – alanine aminotransferase, GGT . – gamma-glutamyl), hepatitis With the skin side, and subcutaneous fat: . rash From the musculoskeletal system and connective tissue disorders: rhabdomyolysis, osteomalacia (often manifested by pain in the bones, occasionally leading to fractures), muscular weakness, myopathy. With kidney side and urinary tract: renal dysfunction, including acute renal failure, acute necrosis of renal tubules, Fanconi syndrome, renal tubulopathy proximal type, interstitial nephritis (includes cases of acute nephritis), increased creatinine concentration, proteinuria, polyuria, nephrogenic diabetes insipidus. Other: fatigue, asthenia.
In case of overdose should be monitored for the condition of the patient for signs of toxicity; if necessary – to carry out standard maintenance treatment. andriol testocaps can be derived from the body by hemodialysis; Median clearance of andriol testocaps is 134 ml / min.
There is limited clinical experience with the drug receiving Viread in doses exceeding therapeutic – 300 mg. In a study of 901 patients received 8 mg of andriol testocaps disoproxil 600 fumarate for 28 days, with no severe adverse reactions were observed. Symptoms of overdose at higher doses is not known.
Interaction with other drugs
Didanosine content increase observed in the body resulting in joint use of didanosine and andriol testocaps 400 mg / day (in the form of enteric-coated tablets). For such patients should be closely monitored for the development of didanosine-related adverse events such as pancreatitis and lactic acidosis. The combined use of didanosine and andriol testocaps 400 mg per day, accompanied by a decrease in the number of CD4 + lymphocytes. In patients weighing more than 60 kg, a daily dose of didanosine should be reduced to 250 mg. To provide any recommendations to determine the dosage of the drug in patients weighing less than 60 kg are missing required data.
andriol testocaps alters the pharmacokinetics of atazanavir. andriol testocaps can be used simultaneously only with atazanavir in combination with ritonavir (atazanavir 300 mg / ritonavir 100 mg).
In studies in healthy volunteers had no clinically significant interaction with the simultaneous use of andriol testocaps with abacavir, efavirenz, emtricitabine, lamivudine, indinavir, lopinavir / ritonavir , nelfinavir, oral contraceptives, ribavirin, saquinavir / ritonavir. andriol testocaps is primarily excreted through the kidneys, the combined use of andriol testocaps with drugs that affect renal function or reduce / stop active tubular secretion may increase serum concentrations of andriol testocaps and / or increase the concentration of the drugs together, output from the kidneys.
drug should not be used simultaneously with the drugs Truvada (andriol testocaps / emtricitabine), Atripla (efavirenz / emtricitabine / andriol testocaps), or with the drug Gepsera (ADF).
Patients taking the drug Viread, precautions must be taken, or avoid driving vehicles and occupation other potentially hazardous activities that require high concentration and psychomotor speed reactions taking into account the profile of side effects. Patients should be advised that antiretroviral therapy does not prevent the risk of HIV and hepatitis transmission in others. When sexual intercourse should take the appropriate precautions. Lactic acidosis, severe hepatomegaly with steatosis When used in HIV-infected persons of nucleoside analogs, including andriol testocaps disoproxil fumarate in combination with other antiretroviral drugs, reported cases of lactic acidosis and a marked increase in the size hepatic steatosis with her, sometimes with fatal consequences. In the case of the patient’s clinical (on the part of the digestive system – nausea, vomiting, abdominal pain, malaise, loss of appetite, weight loss, respiratory failure, neurological symptoms – mobility impairments, muscle weakness) or laboratory signs (lactic acid content serum above 5 mmol / l), pointing to lactic acidosis or pronounced hepatotoxicity, therapy with Viread should be suspended. Patients with impaired kidney excretion of andriol testocaps occurs mainly via the kidneys. When using andriol testocaps in clinical practice, reported cases of renal failure detection, increasing the concentration of creatinine, hypophosphatemia, and Fanconi syndrome. In all patients prior to initiating therapy and if there is clinical evidence during therapy with Viread is recommended to calculate creatinine clearance. Interval correction between the doses should be in accordance with the recommendations presented in the section “Dosage and Administration”:. Subsection “Patients with impaired renal function” in patients at risk for renal impairment, including patients who have previously been identified renal impairment with adefovir therapy should be regular monitoring of calculated creatinine clearance and phosphorus concentration in the serum. The drug should not be used concurrently with nephrotoxic drugs, or in the case of the recent use of drugs of this type. The safety and efficacy of the drug in patients with creatinine clearance 30 to 49 mL / min are not defined, and therefore it is necessary to evaluate the ratio of the potential benefits of drug therapy and possible the risk of toxic effects on the kidneys. If you still have the need to use the drug, the correction is required intervals between doses of the drug. These patients should be closely monitored for renal function. Adverse reactions are listed in section Side effects presented above, may arise as a result of renal tubulopathy proximal type: rhabdomyolysis, osteomalacia (manifested by pain in the bones, occasionally leading to fractures), hypokalaemia, muscular weakness, myopathy, hypophosphatemia. It is believed that the cause of these phenomena is not associated with andriol testocaps therapy in the absence of proximal renal tubulopathy type. Patients with HIV and hepatitis B virus in patients infected with HIV and hepatitis B after discontinuation of therapy with Viread may experience severe exacerbations of hepatitis. For patients infected with HIV and HBV should be closely monitored, both clinical and laboratory, at least for several months after discontinuation of therapy. In some cases, may require the resumption of treatment of viral hepatitis B in patients with severe liver disease (cirrhosis) is not recommended to stop treatment because occurring after discontinuation exacerbation of hepatitis may lead to hepatic decompensation. Testing for HIV antibodies should be available for all patients infected with hepatitis B virus prior to therapy with Viread. should be used as part of an appropriate antiretroviral therapy in the treatment of patients infected with both HIV and hepatitis B. Because of the risk of development of resistance VireadLipodystrophy in patients undergoing antiretroviral therapy, there was a redistribution / accumulation of body fat tissues in the body, including the central type obesity, increased deposition of adipose tissue on the back and neck ( “buffalo hump”), a decrease of peripheral adipose tissue and subcutaneous fat in the face, breast hypertrophy and so-called “cushingoid” appearance. The mechanisms and long-term consequences of these events are still unknown, not set their causal connection with the use of certain drugs. The effect on the skeletal system in animals after administration of andriol testocaps was observed toxic effects on bone, including reduced bone mineral density. However, in clinical studies, the drug lasting (more than 3 years), there were no clinically significant abnormal changes in bone tissue. However, the pathological changes of bone tissue (sometimes resulting in fractures) may be observed in the proximal renal tubulopathy (see. “Side effects” section). If you suspect a violation on the part of the skeletal system should consult the appropriate specialist. Early virological failure in clinical trials involving HIV-infected patients have shown that a number of therapeutic regimens involving the use of only three nucleoside reverse transcriptase inhibitors, in general, less effective, than triple mode involving the use of two nucleoside reverse transcriptase inhibitors, or in combination with non-nucleoside reverse transcriptase inhibitor or inhibitor of HIV-1 protease. In particular, reports of early virologic failure and a high frequency of mutations (like replacement) that lead to the development of resistance. Accordingly, the modes involving the use of three nucleoside inhibitors should be used with caution. For patients, treatment regime which involves the use of only three nucleoside inhibitors should be closely monitored; in such cases it is also recommended to consider treatment regimen changes. immune reconstitution syndrome in HIV-infected patients receiving combination antiretroviral therapy observed the development of immune reconstitution syndrome. In patients with severe immune deficiency at the start of antiretroviral therapy, an inflammatory reaction can occur in response to asymptomatic or residual opportunistic infection that can lead to serious medical conditions or increase in severity of symptoms. Such reactions are usually in the first few weeks or months of antiretroviral therapy. Examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infections and pneumonia caused by Pneumocystis jiroveci. Any inflammatory symptoms requires appropriate evaluation and, if necessary, the start of treatment. Patients should be under close clinical supervision of specialists with experience in treating patients with HIV disease.
The effect on the ability to drive the vehicle and operate machinery
There has been no research on the effects of andriol testocaps disoproxil fumarate on the ability to drive a car and operate machinery. However, patients should be notified that during treatment of andriol testocaps disoproxil fumarate observed cases of dizziness. xtreme anabolics