Epivir - instructions for use, dose, side effects, contraindications

Components:	Content, mg / tab.
Core tablet:
Active substance:
Lamivudine	150,0
Auxiliary substances:
Microcrystalline cellulose	138,75
Carboxymethyl-sodium starch (sodium starch glycolate)	9,00
Magnesium stearate	2,25
Tablet casing:
Opadry® YS-1-7706-G white of the following composition (in percent):	6,75-8,25
Hypromellose	59,75%
Titanium dioxide	31,25%
Macrogol 400 (polyethylene glycol 400)	8,00%
Polysorbate 80	1,0%

Description:

The film-coated tablets are of a diamond-shaped white form, engraved with the inscription "GX CJ7" on each side of the tablet and risk on each side of the tablet.

Pharmacotherapeutic group:antiviral [HIV] agent

ATX: & nbsp

J.05.A.F.05 Lamivudine

Pharmacodynamics:

Mechanism of action

Lamivudine is a potent selective inhibitor of HIV-1 and HIV-2 replication in vitro. Lamivudine is also active against HIV strains. resistant to zidovudine. Inside the cells lamivudine is metabolized to 5'-triphosphate (active form), the half-life of which from the cells is 16-19 hours.

Lamivudine-5'-triphosphate to a small extent inhibits RNA and DNA-dependent reverse transcriptase (RT) of HIV.

The main mechanism of action of lamivudine is the blocking of the synthesis of the growing DNA chain during the reverse transcription of HIV. There were no antagonistic effects in vitro with the simultaneous use of lamivudine and other antiretroviral drugs (tested substances: abacavir, didanosine. nevirapine, zalcitabine and zidovudine).

Lamivudine does not interfere with the normal cellular metabolism of DNA and does not have a significant effect on the content of nuclear and mitochondrial DNA in mammalian cells.

In studies in vitro lamivudine has a weak cytotoxic effect on peripheral blood lymphocytes, as well as on lymphocytic and monocyte-macrophage cell lines and a number of other bone marrow stem cells. In this way, in vitro lamivudine has a wide therapeutic index.

Pharmacodynamic effects

Resistance of HIV-1 to lamivudine is due to a mutation in the codon M184V, located close to the active center of viral RT. This mutation is observed both in conditions in vitro. and in HIV-1-infected patients who underwent combined therapy, including lamivudine. In case of mutation in the codon M184V significantly reduces the sensitivity to lamivudine and significantly reduces the ability of the virus to replicate according to research data in vitro. In studies in vitro it is established that zidovudine-resistant isolates of the virus can become susceptible to its action if these isolates develop resistance to lamivudine simultaneously. However, the clinical significance of such changes has not been determined to date.

Mutation M184V leads to the emergence of cross-resistance of HIV only to drugs from the group of nucleoside reverse transcriptase inhibitors (NRTIs). Zidovudine and stavudine remain active in HIV-1 strains resistant to lamivudine. Abacavir antiretroviral activity against HIV-1 strains having M184V mutation resistant to lamivudine. In strains of HIV with M184V mutations determined no more than 4-fold decrease in sensitivity to didanosine and zalcitabine: the clinical significance of these phenomena is not established.

Tests on the sensitivity of HIV to various antiretroviral drugs in vitro They were not standardized, therefore various methodological factors can influence their results.

In clinical studies, the combination of lamivudine and zidovudine resulted in a decrease in HIV-1 in the blood and an increase in the content Cd4⁺ cells. But clinical research has shown that lamivudine in combination with zidovudine or zidovudine and other drugs significantly reduces the risk of progression of HIV infection and death.

HIV strains isolated from patients who received lamivudine, there was a decrease in sensitivity to lamivudine vitro.

The results of clinical studies have shown, Thuo Combined therapy with lamivudine and zidovudine in patients who had not previously received antiretroviral therapy, delayed the emergence of resistant to zidovudine strains of HIV.

Lamivudine is widely used as a component of combination antiretroviral therapy in combination with other NRTIs or preparations from other groups (protease inhibitors, notnucleoside reverse transcriptase inhibitors).

It is shown that combined antiretroviral therapy, including lamivudine, is effective against HIV strains with mutations in the codon M184V, as well as in patients who have not previously received antiretroviral therapy.

Studies are under way to establish the relationship between the sensitivity of HIV to lamivudine in vitro and the clinical effect of therapy.

Pharmacokinetics:

Suction

Lamivudine is well absorbed from the gastrointestinal tract.

Bioavailability of lamivudine in adults after oral administration is usually 80-85%. After oral administration average time (t_max) achieve maximum concentrations (C_max) lamivudine in serum is about 1 hour. When lamivudine is administered in therapeutic doses (4 mg / kg / day in 2 divided doses with an interval of 12 hours) C_m_Ohis 1-1.9 μg / ml.

Taking lamivudine together with food causes an increase t_max and a decrease in C_m_Oh(up to 47%), but does not affect the overall absorption (calculated on the basis of AUC - area under the pharmacokinetic curve "concentration-time"). Therefore, when taking lamivudine with food, dose adjustment is not required.

Grinding tablets and taking them with a small amount of semi-solid food or liquid does not change the pharmacological properties of the drug, so do not expect a change clinical effect. These conclusions are based on the physico-chemical and pharmacokinetic characteristics of the active substance and data in vitro dissolution of lamivudine tablets in water, provided that the patient immediately will take 100% of the ground tablets.

Reception 150 mg lamivudine 2 times a day is bioequivalent to admission 300 mg once a day but values AUC_∞, C_max, t_max. In adults, taking the drug in the form of tablets and in the form of a solution for oral administration is bioequivalent to values AUC_∞ and C_max.

There were differences in absorption between adult patients and children.

Distribution and binding to blood plasma proteins

With intravenous administration of lamivudine, the volume of distribution averages 1.3 l / kg, and the half-life is an average of 5-7 hours.

Lamivudine has a linear pharmacokinetics when used in therapeutic doses and bounds boundly to plasma albumin (in studies in vitro with serum albumin bound <16-36% of the amount of the drug).

Determined that lamivudine penetrates into the central nervous system (CNS) and cerebrospinal fluid. 2-4 hours after oral administration, the ratio of the concentrations of lamivudine in the cerebrospinal fluid and serum was approximately 0.12. The true degree of penetration, as well as the connection with clinical efficacy unknown.

Metabolism and excretion

On average, the systemic clearance of lamivudine is approximately 0.32 l / kg / h. Lamivudine is excreted mainly by the kidneys (more than 70%) by active tubular secretion (the system of transport of organic cations), and also slightly by metabolism in the liver (less than 10%).

The active form of lamivudine, intracellular lamivudine triphosphate, has a longer half-life from the cells (16-19 hours) compared with the half-life of it from the blood plasma (5-7 hours). According to data from 60 adult healthy volunteers, the pharmacokinetic parameters of lamivudine when taken at a dose of 300 mg once a day in the II equilibrium state are equivalent to those when administered at a dose of 150 mg twice a day in terms of AUC₂₄and C_max for lamivudine triphosphate.

The likelihood of adverse interaction of lamivudine with other drugs is very small due to limited metabolism, a slight degree of binding to the proteins of the crock plasma and almost complete excretion of lamivudine by the kidneys in unchanged form.

Special patient groups

Children

The absolute bioavailability of lamivudine (approximately 58-66%) was lower and more variable in children under 12 years of age. Pharmacokinetic studies of lamivudine in the form of a solution for ingestion and tablets coated with a film membrane, in children showed that taking the drug 1 time per day is equivalent in terms of AUC_0-24taking the drug 2 times a day in the same total daily dose.

Data on the pharmacokinetics of the drug in children younger than 3 months is not enough. In newborns in the first week of life due to the immaturity of the excretory function of the nights and the inconsistency of the absorption parameters, the clearance of lamivudine for ingestion is lower compared to older children. Thus, to achieve the same effect in adults and children, the recommended dose for newborns is 2 mg / kg 2 times a day. Data on the use of the drug in newborns older than 1 week are absent.

At children at reception of a preparation in the form of tablets were received higher values AUFROM_∞ and C_m_Oh lamivudine in the blood plasma, but compared with the values obtained when taking the drug in the form of a solution for oral administration. In children who received lamivudine in the form of a solution for oral administration in accordance with the recommended dosing regimen, exposure to lamivudine in blood plasma was achieved, the values of which were in the range obtained in adults.

Children taking lamivudine in the form of tablets in accordance with the recommended dosing regimen, the exposure of lamivudine in blood plasma was higher than in children who received lamivudine in the form of a solution for oral administration, because in the form of tablets, patients receive higher doses in terms of mg / kg of body weight, and lamivudine in the form of tablets is characterized by a higher bioavailability.

Elderly patients

Data on the pharmacokinetics of lamivudine in patients older than 65 years are absent.

Patients with impaired renal function

In patients with impaired renal function, lamivudine concentration in the blood plasma increased, since its excretion from the body is slowed down. Patients with creatinine clearance less than 50 ml / min dose Epivir ® should be reduced.

Patients with impaired hepatic function

Data on the use of lamivudine in patients with moderate to severe hepatic impairment indicate that the dysfunction of the liver does not significantly affect the pharmacokinetics of lamivudine.

Pregnancy

The pharmacokinetics of lamivudine during pregnancy does not differ from its pharmacokinetics in not pregnant women.

Studies have shown that lamivudine passes passively through the placenta. The concentration of lamivudine in the serum of newborns at the time of birth is the same as in the mother's serum and cord blood.

Indications:

Treatment of HIV infection in combination antiretroviral therapy in adults and children.

Contraindications:Hypersensitivity to lamivudine or any other component of the drug.

Pregnancy and lactation:

Pregnancy

The effect of lamivudine was evaluated based on data from the Application Registry antiretroviral drugs in pregnant women, which were obtained from more than 11,000 women who took this drug during pregnancy and in the postpartum period. Available data from the Antiretroviral Registry of Pregnancy do not indicate an increased risk of significant birth defects when lamivudine is used compared to their background frequency of occurrence. However, adequate and strictly controlled studies involving pregnant women have not been conducted and the safety of lamivudine during pregnancy has not been established.

Studies have shown that lamivudine penetrates the placenta. Lamivudine It should be used during pregnancy only if the expected benefit for the mother exceeds the potential risk to the fetus. Although the results of animal experiments can not always be extrapolated to humans, research data on rabbits indicate a possible risk of spontaneous abortion in early pregnancy. In newborns and infants whose mothers during pregnancy and childbirth took drugs from the group of nucleoside inhibitors of HIV-OT, cases of a minor transient increase in the concentration of lactate in the blood plasma, possibly due to mitochondrial disorders.

The clinical significance of this enhancement is not currently established. In addition, there are very few reports of cases of developmental delay, convulsive seizures and other neurological disorders (eg, muscle tone increase). However, the causal relationship of these disorders with admission Nucleoside inhibitors of HIV-negative during the prenatal and postpartum periods have not been established. These data do not abolish recommendations for antiretroviral therapy during pregnancy to prevent vertical transmission of HIV.

Breastfeeding period

Specialists do not recommend breastfeeding to HIV-infected patients to avoid HIV transmission to the child. Because the lamivudine and HIV penetrate into breast milk, breastfeeding is contraindicated.

Dosing and Administration:

The drug should be prescribed by a doctor, experienced in the treatment of HIV infection. The drug Epivir^® is applied inward depending on the intake of food.

To ensure the accuracy of dosing, the tablet is recommended to be swallowed completely without grinding. For those patients who are difficult to swallow tablets, the medicinal form is intended - a solution for oral administration.

However, as an alternative, grinding tablets with the addition of a small amount of semi-solid gLook for or liquids. Weight the amount of the mixture should be taken inside immediately.

Adults, adolescents and children weighing not less than 25 kg

The recommended dose is 300 mg per day - 150 mg 2 times a day or 300 mg per day in a single dose.

Special patient groups

Children under 3 months

The available data are not enough to suggest a dosing regimen for this category of patients.

Children with body weight from 14 kg to <20 kg

Recommended total daily the dose is 150 mg. You can take ½ tablets 150 mg (75 mg) 3 times a day or 1 tablet 150 mg once a day.

Children with body weight from ≥ 20 kg to <25 kg

The recommended total daily dose is 225 mg. You can take ½ tablets 150 mg (75 mg) in the morning and 1 tablet 150 mg in the evening or 1 and ½ tablets (225 mg) once a day.

Children with a body weight of at least 25 kg

You should take the drug in a dose for adults, equal to 150 mg twice a day or 300 mg once a day.

Lamivudine is also available in dosage form solution for oral administration.

Elderly patients

Currently, data on the pharmacokinetics of lamivudine in this category of patients is not enough, but special attention should be paid to this category of patients due to the age-related decline in the excretory function of the kidneys and changes in blood counts.

Patients with impaired renal function

In patients with impaired renal function of medium and severe degree, lamivudine concentration in the blood plasma (AUC) increased due to reduced clearance of lamivudine. Therefore, when creatinine clearance is less than 50 ml / min, the dose of the drug should be reduced, as shown in the table below.

Children with impaired renal function, the same dose reduction scheme is recommended, depending on the creatinine clearance value, as in adults.

If you need a dose of less than 150 mg, you should take a solution for oral administration.

Recommendations for the selection of a dose depending on the creatinine clearance for renal dysfunction in adults, adolescents and children with a body weight of at least 25 kg

Creatinine clearance (ml / min)	The first dose	Maintenance dose
from 30 to 50	150 mg	150 mg 1 once a day
from 15 to 30	150 mg	It is necessary to use another dosage form - oral solution
from 5 to 15	150 mg	It is necessary to use another dosage form - oral solution
< 5	It is necessary to use another dosage form - oral solution

Patients with impaired hepatic function

In patients with impaired liver function of moderate and severe degree of dose reduction, Epivir^® It is not required, if only the violation of liver function is not accompanied by a violation of the function kidney.

Side effects:

The undesirable reactions described below were noted in the treatment of HIV infection with lamivudine, both as monotherapy and when combined with other antiretroviral drugs.However, for many unwanted reactions, it is unclear whether they are caused by medications or are complications of the actual HIV infection.

The following classification of undesirable reactions is used depending on the frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1 / 10 000, <1/1000), very rarely (<1/10000).

On the part of the organs of hematopoiesis

Infrequent: neutropenia, anemia, thrombocytopenia.

Very rarely: true erythrocyte aplasia.

From the side of metabolism

Often: increase in the concentration of lactic acid in the serum.

Rarely: lactic acidosis; redistribution / accumulation of subcutaneous fat; frequency development depends on many factors, including a specific combination of antiretroviral drugs.

From the nervous system

Often: headache, insomnia.

Very rarely: paresthesia; cases of development of peripheral neuropathy are described.

From the gastrointestinal tract

Often: nausea, vomiting, pain in the upper abdomen and spastic pain and abdominal pain, diarrhea.

Rarely: pancreatitis; increased serum amylase activity.

From the hepatobiliary system

Infrequently: transient increase in hepatic enzyme activity (alanine aminotransferase (ALT), aspartate aminotransferase (ACT)).

Rarely: hepatitis.

From the skin and its derivatives

Often: rash, alopecia.

Rarely: angioedema.

From the musculoskeletal system and connective tissue

Often: arthralgia, muscle disorders.

Rarely: rhabdomyolysis.

From the respiratory system and the mediastinum

Often: cough, nasal symptoms.

Other

Often: a feeling of fatigue, malaise, fever.

Osteonecrosis has been reported in patients with risk factors such as late stages of HIV infection or long-term combined antiretroviral therapy (incidence is unknown).

The use of combined APT has been associated with metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia and hyperlactatemia.

In HIV-infected patients with severe immunodeficiency during the onset of combined APT, inflammatory responses to asymptomatic or residual opportunistic infections may occur. A case of autoimmune diseases (for example, Graves' disease) was also recorded;occurring in the conditions of immune reactivation, however, the presented terms of the disease manifestation are more diverse, and these phenomena can arise many months after the initiation of therapy.

Overdose:

Symptoms

There are few data on the consequences of acute overdose of lamivudine in humans. There were no lethal outcomes, the condition of all patients was normalized. There were no specific signs or symptoms of lamivudine overdose.

Treatment

It is recommended to monitor the patient's condition and conduct standard maintenance therapy. Because the lamivudine is excreted from the body by dialysis, it is possible to use continuous hemodialysis, but no special studies have been performed.

Interaction:

Interaction studies were conducted only with the participation of adult patients.

The likelihood of metabolic interaction of lamivudine with other drugs is extremely low, since lamivudine is poorly metabolized, binds insignificantly to plasma proteins and is excreted mainly by the kidneys in unchanged form.

Lamivudine is excreted from the body mainly through active tubular secretion through the transport system of organic cations.

The possibility of lamivudine interaction with drugs having the same elimination mechanism, for example, with trimethoprim, should be considered. Other drugs (for example, ranitidine, cimetidine) are only partially excreted by this mechanism and do not interact with lamivudine. Drugs that are excreted primarily by active renal secretion through the transport system of organic anions or by glomerular filtration do not appear to enter into clinically significant interactions with lamivudine.

Zidovudine

With the simultaneous use of lamivudine and zidovudine, a moderate (by 28%) increase in C_m_Oh zidovudine in plasma, while AUC does not change significantly. Zidovudine does not affect the pharmacokinetics of lamivudine.

Trimethoprim / sulfamethoxazole

Simultaneous application trimethoprim / sulfamethoxazole at a dose of 160/800 mg (co-trimoxazole) causes an increase in lamivudine exposure by 40%, which is due to the presence of trimethoprim.However, in the absence of impaired renal function, a dose reduction of lamivudine is not required. On the pharmacokinetics of trimethoprim and sulfamethoxazole lamivudine does not affect. Joint use of lamivudine with higher doses of co-trimoxazole used to treat pneumonia (caused by Pneumocystis carinii) and toxoplasmosis, has not been studied and should be avoided.

Zalcitabine

Lamivudine can suppress intracellular phosphorylation of zalcitabine while simultaneously taking these drugs. In this regard, it is not recommended to take the drug Epivir ® in conjunction with zalcitabine.

Emtricitabine

With simultaneous application lamivudine can inhibit intracellular phosphorylation of emtricitabine. In addition, the mechanism of development of resistance to both lamivudine and emtricitabine is associated with a mutation in the same codon of the HIV-O gene (M184V), and therefore the therapeutic efficacy of these drugs in combination therapy may be limited. The use of lamivudine in combination with emtricitabine or fixed dose combinations containing emtricitabine, Not recommended.

Consideration should be given to the possibility of interactions with other drugs used simultaneously,especially if their main way of excretion is active kidney secretion through the transport system organic cations; such drugs include trimethoprim.

Other medications (for example, ranitidine, cimetidine) are only partially derived by this mechanism, and it has been shown that they do not interact with lamivudine.

Analogues of nucleosides (for example, didanosine, zidovudine) are not eliminated by this mechanism, and their interaction with lamivudine is unlikely.

In vitro lamivudine inhibits intracellular phosphorylation of cladribine, which is the cause of the potential risk of loss of cladribine efficacy in the case of such a combination in clinical practice. Some clinical data also confirm the possibility of interaction between lamivudine and cladribine.

Consequently, the simultaneous use of lamivudine and cladribine is not recommended.

Special instructions:

The use of lamivudine as a monotherapy is not recommended.

Transmission of HIV infection

Patients should be warned that treatment with antiretroviral drugs, including lamivudine, does not prevent the risk of HIV transmission to other people during sexual intercourse or blood contamination.Therefore, patients should take appropriate precautions.

Opportunistic infections

In patients receiving lamivudine or other antiretroviral drugs, opportunistic infections or other complications of HIV infection may develop, so patients should be carefully monitored by a physician with experience in treating patients with HIV-associated diseases.

Impaired renal function

In patients with impaired renal function of medium and severe degree, the concentration of lamivudine in plasma is increased due to reduced clearance of lamivudine, therefore dose adjustment is required.

Pancreatitis

In patients who took lamivudine, rare cases of development of pancreatitis are described. However, it is not established whether this complication is caused by medications or the underlying disease - HIV infection. Treatment with Epivir® should be stopped immediately if there are clinical symptoms or laboratory evidence of pancreatitis (abdominal pain, nausea, vomiting, or increased biochemical markers). It is necessary to stop taking the drug before the diagnosis of pancreatitis is excluded.

Lactic acidosis and severe hepatomegaly with steatosis

There are reports of the development of lactic acidosis, severe hepatomegaly with steatosis, including fatal outcomes due to antiretroviral therapy with nucleoside analogues in the form of individual drugs, including lamivudine or a combination thereof. Similar phenomena were observed, mainly, in women. The clinical signs of developing lactic acidosis are general weakness, anorexia, rapid unexplained weight loss, symptoms of gastrointestinal tract damage (nausea, vomiting and abdominal pain) and respiratory system (rapid and / or deep breathing), neurological symptoms (including motor weakness) ).

Treatment with nucleoside analogues should be discontinued if symptomatic hyperlactatemia and metabolic acidosis / lactic acidosis develop, progressive hepatomegaly, or a rapid increase in aminotransferase levels.

Caution should be exercised when using nucleoside analogues to treat any patient (especially obese women) with hepatomegaly, hepatitis, or other known risk factors for liver damage and liver steatosis (including the use of certain drugs and alcohol use).

Patients with co-infection with hepatitis C and patients who receive treatment with alpha interferon and ribavirin may constitute a special risk group.

Mitochondrial dysfunction

Research in vitro and in vivo showed that the analogues of nucleosides and nucleotides can cause a different degree of damage to the mitochondria. Mitochondrial dysfunction was observed in HIV-negative children who received intrauterine and / or post-nucleoside analogues.

The main undesirable reactions were hematologic disorders (anemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipazemia). These undesirable reactions are often transient. Some neurological disorders with late onset have been reported (muscle tone increase, convulsions, behavioral disorders). Whether these neurological disorders are transient or persistent is currently unknown. Any child, even HIV-negative, exposed to prenatal exposure to nucleoside and nucleotide analogues, must undergo a clinical and laboratory examination in order to exclude mitochondrial dysfunction in case of revealing the corresponding signs or symptoms.These data do not affect the current national guidelines for the use of antiretroviral therapy in pregnant women to prevent the vertical transmission of HIV infection.

Lipodystrophy

In some patients receiving a combination antiretroviral therapy can be observed redistribution and / or the accumulation of subcutaneous fat, including obesity of the central type, dorsotservikalnoe fat deposition ( "buffalo hump"), a decrease in the subcutaneous fat layer on the face and extremities, breast enlargement, increased lipid concentrations in serum and concentration of glucose in the blood, either individually or together.

Although all preparations from classes of protease inhibitors and NRTIs can cause one or more of the abovementioned unwanted reactions associated with a common syndrome, often called lipodystrophy, the accumulated evidence suggests that there are differences between individual representatives of these classes of drugs in the ability to induce these undesirable reactions.

It should also be noted that lipodystrophy syndrome has a multifactorial etiology: for example, the stage of HIV infection, old age and the duration of antiretroviral therapy play an important, possibly synergistic role in the development of this complication.

The long-term consequences of these undesirable phenomena are still unknown.

During the clinical examination, attention should be paid to the signs of redistribution of subcutaneous fat. Careful follow serum lipid concentrations and glucose concentrations in blood. If the lipid metabolism is disturbed, an appropriate treatment is prescribed.

Immunodeficiency Syndrome

In the presence of HIV-infected patients with severe immunodeficiency asymptomatic opportunistic infections or their residual effects at the time of initiation of antiretroviral therapy, such therapy may lead to increased symptoms opportunistic infections or other serious consequences. Typically, these reactions occur within the first weeks or months after initiation of antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jiroveci (R. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.

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.

Co-infection of HIV and viral hepatitis B

Clinical studies and data post-registration observation of lamivudine shows that in some patients with concomitant viral hepatitis B (HBV) Clinical or laboratory signs of hepatitis recurrence may appear after stopping lamivudine, which may have more severe consequences in patients with decompensated liver disease. After the termination of lamivudine therapy in patients with co-infection caused by HIV and hepatitis B virus, it is necessary to monitor biochemical parameters of liver function and markers of hepatitis B virus replication.

Diseases of the liver

Patients with pre-existing liver dysfunction, including active chronic hepatitis, have an increased incidence of liver dysfunction during combined antiretroviral therapy and should be monitored in accordance with accepted practice. It is necessary to consider the possibility of suspending or stopping treatment in cases of manifestations of worsening liver disease in such patients.

Osteonecrosis

Despite the fact that the etiology of this disease is multifactorial (including the intake of glucocorticosteroids, heavy drinking immunosuppression, high body mass index), cases of osteonecrosis were most commonly seen in patients at a late stage of HIV infection and / or long taking a combined antiretroviral therapy. Patients should consult a doctor if they experience pain and stiffness in the joints or difficulty moving.

Preventive maintenance after probable infection of a HIV

According to international recommendations, if a person infected with HIV is to be infected through the blood (for example, through an injection needle), a combination therapy with zidovudine and lamivudine should be prescribed urgently (within 1-2 hours from the time of infection). In the case of a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral regimen.Preventive treatment is recommended for 4 weeks. Data on effectiveness preventive treatment after accidental HIV infection is accumulated insufficiently controlled no studies have been carried out.

Despite the rapid onset of treatment with antiretroviral drugs, seroconversion can not be ruled out.

Triple Nucleoside Therapy

There were reports of a high incidence of virological failure and early-onset resistance when co-administered lamivudine in combination with tenofovir disoproxil fumarate and abacavir, and with tenofovir disoproxil fumarate and didanosine once a day.

The drug Epivir^® Do not use concomitantly with any medication containing lamivudine or emtricitabine.

Effect on the ability to drive transp. cf. and fur:

Special studies of the effects of lamivudine on the ability to drive cars / mechanisms were not conducted. However, based on the pharmacological properties of lamivudine, this effect is unlikely. Nevertheless, when evaluating a patient's ability to drive a car / machinery, his general condition should be taken into account,as well as the nature of adverse reactions of lamivudine.

Form release / dosage:

Tablets, film-coated, 150 mg.

Packaging:

60 tablets per bottle of high density polyethylene, sealed with a lid with a device that protects children from opening the bottle and controlling the first autopsy.

The bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014918 / 02

Date of registration:11.12.2008 / 14.11.2014

Expiration Date:Unlimited

The owner of the registration certificate:VeeV Helsker United Kingdom LimitedVeeV Helsker United Kingdom Limited United Kingdom

Manufacturer: & nbsp

BINNOFARM, CJSC Russia

GlaxoSmithKline Pharmaceuticals, S.A. Poland

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp07.10.2016

Illustrated instructions

Instructions

Epivir® (Epivir®)