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

Components	Amount, mg
Active substance:
Lamivudine	10,00
Excipients:
Sucrose	200,00
Propylene glycol	20,00
Methylparahydroxybenzoate	1,50
Propyl parahydroxybenzoate	0,18
Aromatic Strawberry	0,80
Aromatic Banana	0,60
Sodium citrate	11,00
Lemon acid	1,00
Hydrochloric acid	to pH 6.0
A solution of sodium hydroxide	to pH 6.0
Purified water	up to 1.0 ml

Note: the amount of lamivudine substance can be adjusted depending on the purity to provide 10 mg of lamivudine in 1 ml.

Description:

Transparent solution from colorless to light yellow with a faint fruity odor.

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 in insignificantly inhibits RNA- and DNA-dependent inverse transcriptase (RT) of HIV.

The main mechanism of action lamivudine-blocking the synthesis of the growing value of DNA in the process of 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 OT. This mutation is observed both in conditions in vitro. and in HIV-1-infected patients, combined therapy, including lamivudine. In case of mutation in the codon M184V the sensitivity to lamivudine is significantly reduced and the ability virus to replicate but research data in vitro. In studies in vitro It was established that zidovudine-resistant isolates of the virus can become susceptible to its action if of these isolates at the same time, resistance to lamivudine will develop. However, the clinical significance of such changes to the present time is not definitively determined. Mutation M184V leads to the emergence of cross-resistance of HIV only to drugs from the group of nucleoside inhibitors reverse transcriptase (NRTI). Zidovudine and stevu din retain their activity against HIV-1 strains. resistant to lamivudine.

Abacavir retains 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. According to clinical studies, it is established that lamivudine in combination with zidovudine or with zidovudine and other drugs significantly reduces the risk progression of HIV infection and death.

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

Results of clinical trials showed that combined therapy with lamivudine and zidovudine in patients who have not previously received antiretroviral therapy, delays the emergence of resistant to zidovudine strains of HIV. Lamivudine received wide distribution as a component combination antiretroviral therapy in combination with other NRTI or drugs from other groups (protease inhibitors, non-nucleoside 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 clinical affect 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 blood is about 1 hour. When lamivudine is administered at therapeutic doses (4 mg / kg / day in 2 divided doses at intervals of 12 hours) C_max is 1-1.9 μg / ml.

Taking lamivudine together with food causes an increase T_max and decrease FROM_ma_x(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.

Distribution and binding to blood plasma proteins

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

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

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 the clinical efficiency are unknown.

Metabolism and excretion

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

The active form of lamivudine, intracellular lamivudine triphosphate, has a longer half-life of the cells (16-19 hours) compared with the half-life of it from the plasma blood (5-7 hours). According to data from 60 adult healthy volunteers, pharmacokinetic parameters lamivudine when administered at a dose of 300 mg once a day in an equilibrium state is equivalent to that when administered at a dose of 150 mg twice a day in terms of AUC24 and C_m_Oh for lamivudine triphosphate. The probability of an unfavorable interaction of lamivudine with other drugs is very small due to limited metabolism, a slight degree of binding to plasma proteins blood and almost complete excretion of lamivudine in unchanged form.

Special patient groups

Children

Absolute bioavailability lamivudine (approximately 58-66%) was lower and more variable in children younger than 12 years. In connection with these differences, the recommended dose of lamivudine for children (over 3 months and body weight less than 30 kg) is 4 mg / kg 2 times a day. Pharmacokinetic studies 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 AUC₀-24 taking the drug 2 times per 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 kidneys 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 AUC ∞ and C_max lamivudine in the blood plasma 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 according to recommended dosing regimen, exposure of lamivudine in blood plasma was higher than in children receiving 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, the concentration of lamivudine in plasma blood 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 degree of hepatic impairment suggest 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 nonpregnant.

Studies have shown that lamivudine passively penetrates 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 for adults and children.

Contraindications:

- Hypersensitivity to lamivudine or any other component of the drug.

- An age younger than 3 months due to the fact that data on the use of the drug in this age group is limited.

Carefully:

Use with caution in patients with renal insufficiency; pancreatitis (including in the anamnesis); peripheral neuropathy; during pregnancy and lactation.

Pregnancy and lactation:

Pregnancy

Studies have shown that lamivudine penetrates the placenta. Lamivudine should be used during pregnancy only if the expected benefit to 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 FROM HIV, cases of insignificant transient increase in concentration lactate in the blood plasma, possibly due to mitochondrial violations. Clinical Significance of this increase in present time not installed. Besides, there are separate reports on rare cases of delayed development, convulsive seizures and other neurological disorders (for example, an increase in muscle tone). However, the causal relationship of these violations with the reception of nucleoside inhibitors FROM HIV during intrauterine and postpartum periods is not established.These data do not abolish the recommendations for antiretroviral therapy during pregnancy to prevent vertical transmission 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 inside regardless of the meal.

For those patients who are difficult to swallow tablets, the medicinal form is intended - a solution for oral administration.

- Adults, adolescents and children weighing at least 25 kg

The recommended daily dose of lamivudine is 300 mg (30 mL). which can be divided into 2 150mg (15ml) or 300mg (30ml) at one time.

Special patient groups

- Children under 3 months

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

- Children aged 3 months with a body weight of less than 25 kg

The recommended dose is 4 mg / kg 2 times a day or 8 mg / kg 1 time per day. The maximum daily dose is 300 mg.

- Patients of advanced age

Currently, data on the pharmacokinetics of lamivudine in this category of patients is not enough, however, 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. In 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

Clearance creatinine (ml / min)	The first dose	Maintenance dose
from 30 to 50	150 mg	150 mg (15 ml)
	(15 ml)	1 time per day
from 15 to 30	150 mg	100 mg (10 ml)
	(15 ml)	1 time per day
from 5 to 15	150 mg	50 mg (5 ml)
	(15 ml)	1 time per day
< 5	50 mg	25 mg (2.5 ml)
	(5 ml)	1 time per day

Recommendations for the selection of a dose for children aged 3 months and with a body weight of less than 25 kg

Clearance creatinine (ml / min)	The first dose	Supportive dose
30 - less than 50	4 mg / kg	4 mg / kg once a day
15 - less than 30	4 mg / kg	2.6 mg / kg once a day
5 - less than 15	4 mg / kg	1.3 mg / kg 1 once a day
less than 5	1.3 mg / kg	0,7 mg / kg once a day

- Patients with impaired hepatic function

In patients with impaired liver function of moderate and severe degree of dose reduction, Epivir®It is not required, unless a violation of the liver function is accompanied 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 undesirable 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: Often (> 1/10), often (> 1/100, < 1/10), infrequently (>1/1000, <1/100), rarely (>1/10 000, < 1/1000), 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; the frequency of development depends on many factors, including the 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 in the abdomen, 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).

Application of combined Apt was associated with metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia and hyperlactatemia.

Have HIV-infected patients with severe immunodeficiency during the onset of combined APT there may be inflammatory responses to asymptomatic or residual opportunistic infections. Cases have also been reported autoimmune diseases (eg, Graves' disease) occurring under conditions of immune reactivation, however, the presented terms for the manifestation of the disease are more diverse, and these phenomena can occur many months after 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 carry out, if necessary, 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.

Probability of metabolic interaction of lamivudine with other drugs is extremely low, since lamivudine poorly metabolized, to an insignificant degree binds to plasma proteins blood and displayed mainly kidneys in unchanged form.

Lamivudine is excreted from the organism mainly through active tubular secretion through the system of transport 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 mainly through active renal secretion through the transport system of organic anions or by glomerular filtration, apparently do not enter clinically significant interactions with lamivudine.

Zidovudine

With simultaneous application lamivudine and zidovudine is moderate 28 %) increase in C_m_Ohzidovudine in plasma, while AUC does not change significantly. Zidovudine does not affect the pharmacokinetics of lamivudine.

Trimethoprim / sulfamethoxazole

Simultaneous application trimethoprim / sulfamethoxazole in a dose 160/800 mg (co-trimoxazole) increases the exposure of lamivudine on 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 with simultaneous administration of these drugs. AT Due to this, it is not recommended to take Epivir ® in combination with zalcitabine.

Emtricitabine

With simultaneous application lamivudine may slow down intracellular phosphorylation 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 pathway is active kidney secretion through the system of organic cation transport; 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 cladribine, which is the cause of the potential risk of loss of cladribine efficacy in the case of using this 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 doctor who has 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 clinical symptoms or laboratory evidence of pancreatitis develops (abdominal pain, nausea, vomiting, or an increase meanings 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 his combination. Similar phenomena were observed, mainly, in women.

Clinical features developing lactic acidosis are general weakness, anorexia, rapid unexplained loss body weight, 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 analogues of nucleosides should be discontinued in case of development of symptomatic hyperlactatemia and metabolic acidosis / lactic acidosis, progressive hepatomegaly, or a rapid increase in aminotransferase levels.

Caution should be exercised when using nucleoside analogs to treat any patient (especially obese women) with hepatomegaly, hepatitis, or other known risk factors for liver damage and steatosis of the liver (including the use of certain medicinal 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. Cases were recorded mitochondrial dysfunction in HIV-negative children who received in utero and / or after birth analogues of nucleosides. The main undesirable reactions were hematologic disorders (anemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipazemia). These undesirable reactions are often transient. There were some neurological disorders with late onset (increased muscle tone, convulsions, behavioral disorders). Are these neurological disorders transient or standing at the present time is unknown. Any child, even HIV-negative, exposed intrauterine effect analogs of nucleosides and nucleotides, should undergo a clinical and laboratory examination in order to exclude the mitochondrial dysfunction in the event of the identification of the relevant 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 combination antiretroviral therapy, may be observed redistribution and / or accumulation of subcutaneous fat, including obesity by the central type, dorsocervical fat deposition ("buffalo buffalo"), reduction of the subcutaneous fat layer on the face and extremities, enlargement of the mammary glands, increased serum lipid concentrations and blood glucose concentrations , both individually and jointly.

Although all preparations from classes of protease inhibitors and NRTIs can induce one or several of the above undesirable reactions associated with a general syndrome, often called lipodystrophy, the accumulated evidence suggests a difference between individual representatives of these classes of drugs in the ability to cause these unwanted reactions.

It should also be noted that lipodystrophy syndrome has a multifactorial etiology: for example, the stage of HIV infection, the elderly 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 yet unknown.During the clinical examination should pay attention to on signs of redistribution of subcutaneous fat. Careful follow the serum lipid concentration and blood glucose concentration. When lipid metabolism is disturbed prescribe appropriate treatment.

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 of opportunistic infections or other serious consequences. Usually these reactions arise during 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). Appearance 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 post-registration data observation on the use of lamivudine suggest that in some patients with concomitant viral hepatitis B (HBV) there may be clinical or laboratory signs recidivism hepatitis after discontinuation of lamivudine, which may have more severe consequences in patients with decompensated defeat liver. 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 an 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 suspension or cessation of treatment in the case of manifestations of deterioration of liver disease in such patients.

Diabetes

When appointing a solution for oral administration to patients with concomitant diabetes, it must be remembered that the recommended adult dose (150 mg = 15 ml) contains 3 g of sucrose.

Osteonecrosis

Although the etiology of this disease is multifactorial (including the intake of glucocorticosteroids, alcohol consumption, severe immunosuppression, high body mass index), cases of osteonecrosis were most often encountered in patients at a late stage of HIV infection and / or who took long-term combined antiretroviral therapy. Patients should consult a doctor if they experience pain and stiffness in the joints or difficulty moving.

Preventive maintenance after probable HIV infection

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 of 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 the effectiveness of preventive treatment after accidental HIV infection have not been accumulated enough, no controlled studies have been conducted.

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® should not be used concomitantly with any medicinal product 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, such an effect is unlikely.However, when evaluating the ability to drive a car / machinery, the general condition of the patient, as well as the nature of the adverse reactions of lamivudine, should be taken into account.

Form release / dosage:

Solution for oral administration, 10 mg / ml.

Packaging:

For 240 ml of the drug in a bottle of high-density polyethylene with a screw cap, equipped with protection from opening by children. One bottle together with the adapter, a dispensing syringe and instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years

After opening the vial: 30 days at a temperature not exceeding 25 ° С.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N 015941/01

Date of registration:22.07.2009 / 23.11.2012

Expiration Date:Unlimited

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

Manufacturer: & nbsp

GlaxoSmithKline, Inc. Canada

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp13.09.2016

Illustrated instructions

Instructions

Epivir® (Epivir®)