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

Excipients: cellulose microcrystalline - 414.6 mg, sodium carboxymethyl starch - 24.0 mg, magnesium stearate - 8.0 mg, silicon dioxide colloid - 2.4 mg

Film Sheath: Foul yellow YS-1-12789-A (hypromellose 59%, titanium dioxide (E171) 25.86%, triacetin 8%, iron oxide yellow (E172) 6.14%, polysorbate 80 1%) - 14.0 mg.

Description:

Oval biconvex tablets from light yellow to yellow.

Pharmacotherapeutic group:Antiviral (HIV) agent

ATX: & nbsp

J.05.A.F.06 Abacavir

Pharmacodynamics:

Mechanism of action

Abacavir is a nucleoside analogue of reverse transcriptase inhibitors. It is a potent selective inhibitor of HIV-1 and HIV-2, including strains of HIV-1 with reduced sensitivity to zidovudine, lamivudine, zalcitabine, didanosine, and nevirapine. Abacavir is subjected to intracellular metabolism, becoming the active form of carbovir-5'-triphosphate (carbovir-TF). According to research in vitro its mechanism of action against HIV is the inhibition of the HIV reverse transcriptase enzyme, which leads to chain termination and stopping the replication of the virus.

There was no antagonism in antiviral activity in cell culture when combined with nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine or zidovudine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), nevirapine or a protease inhibitor (HIV II) amprenavir.

Pharmacodynamic effects

Resistant to abacavir HIV-1 strains were obtained in vitro and are characterized by specific genotypic changes in the codons of the reverse transcriptase (RT) gene (codons M184V, K65R, L74V and Y115F). Resistance of the virus to abacavir in vitro and in vivo formed slowly. For a clinically significant increase IC50 (inhibitory concentration against 50% of strains), 8 mutations are required for 8 times the "wild" strain of the virus. Resistant to abacavir strains may also exhibit reduced sensitivity to lamivudine, zalcitabine and / or didanosine, but remain sensitive to zidovudine and stavudine. The development of cross-resistance between abacavir and HIV protease inhibitors or NNRTIs is unlikely. The ineffectiveness of first-line therapy, including abacavir, lamivudine and zidovudine, is mainly associated with a single mutation M184V, which preserves the possibility of a wide choice of regimens for second-line therapy.

Abacavir penetrates into the cerebrospinal fluid (CSF) and reduces the content of HIV-1 RNA in it. In combination with other antiretroviral drugs abacavir can play a role in the prevention of the development of neurological complications of HIV infection and slow the emergence of resistant strains within the central nervous system (CNS).

According to the study, 20 HIV-infected patients abacavir at a dose of 300 mg twice a day and only one dose of 300 mg for 24 hours before sampling for analysis, the geometric mean of the final intracellular half-life of carbovir-TF in the equilibrium state was 20.6 hours, while the geometric mean of the period the elimination half-life of abacavir from the blood plasma was 2.6 hours. Equilibrium pharmacokinetic indices with the reception of abacavir 600 mg once a day were identical with those with abacavir 300 mg twice a day in a cross-sectional clinical trial involving 27 HIV infi patients. The intracellular content of carbovir-TF in peripheral blood mononuclear cells was higher with the application of abacavir at a dose of 600 mg once a day in terms of AUC in a state of equilibrium in 24 hours (AUC₂₄,_SS, higher by 32%), the maximum daily concentration in equilibrium (C_max₂₄,ss, higher by 99%) and the residual concentration in the equilibrium state in 24 hours (C_min₂₄,ss, higher by 18%) compared with the use of abacavir 300 mg twice a day, which indicates the possibility of using the drug in HIV-infected patients at a dose of 600 mg once a day. The efficacy and safety of the drug when applied once a day was also shown in the baseline clinicalresearch (CNA30021).

Pharmacokinetics:

Suction

Abacavir is quickly and well absorbed when taken orally. Absolute bioavailability of oral abacavir in adults is about 83%. The time to reach the maximum serum concentration (t_max) when taking abacavir orally in the form of tablets is about 1.5 h.

When taking abacavir orally at a dose of 300 mg twice a day, the average maximum equilibrium concentration (C_m_Oh) was 3.00 μg / ml, and the mean AUC during the 12-hour period between doses of the drug was 6.02 μg x h / ml (daily AUC was approximately 12.0 μg x h / ml). After a single administration of abacavir tablets in a dose of 600 mg, the average C_m_Oh was about 4.26 μg / ml, and the mean AUC* was 11.95 μg x h / ml.

Eating slows the absorption of abacavir and reduces C_m_Oh, but does not affect the total concentration in the blood plasma (AUC). therefore abacavir can be taken regardless of food intake.

It is not expected that taking a crushed tablet with a small amount of semi-solid food or liquid will affect the pharmacological properties of the preparation and, consequently, its clinical effectiveness.This conclusion is based on physicochemical and pharmacokinetic parameters of the active substance and solubility in vitro Abacavir tablets in water provided that the patient grinds and adds 100% tablet to the food or liquid and takes it immediately.

Distribution

Studies involving HIV-infected patients showed that abacavir well penetrates into the cerebrospinal fluid (CSF), with the ratio AUC abacavir in CSF to AUC Abacavir in blood plasma is 30-44%. In the Phase I pharmacokinetic study, the penetration of abacavir into the CSF was studied after application at a dose of 300 mg twice daily. The average concentration of abacavir in CSF was reached after 1.5 hours after administration and was 0.14 μg / ml. In another pharmacokinetic study using abacavir at a dose of 600 mg twice daily, its concentration in the CSF increased over time from about 0.13 μg / ml 0.5-1 hour after administration to about 0.74 μg / ml through a 3- 4 hours after administration. Although the maximum concentration may not be achieved after 4 hours, the observed values are 9 times higher IC50 abacavir, which is 0.08 μg / ml or 0.26 μmol / l.

In studies of binding to blood proteins in vitro It was found that in therapeutic concentrations abacavir slightly or moderately (approximately 49%) binds to human plasma proteins. This indicates a low probability of drug interactions associated with the displacement of drugs from the association with plasma proteins.

Metabolites

Abacavir is metabolized mainly in the liver, less than 2% of the administered dose is excreted by the kidneys unchanged. In the human body abacavir is metabolized mainly under the influence of alcohol dehydrogenase to form 5'-carboxylic acid and by conjugation with glucuronic acid to form 5'-glucuronide, which is about 66% of the administered dose of the drug. These metabolites are excreted by the kidneys.

Excretion

The average half-life of abacavir is about 1.5 hours. After repeated intake of abacavir intravenously at a dose of 300 mg 2 times a day, no significant cumulation of the drug is observed. Abacavir excretion is carried out by metabolism in the liver, followed by excretion of metabolites mainly by the kidneys. About 83% of the administered dose of abacavir is excreted by the kidneys in the form of metabolites and abacavir in unchanged form, and the remaining quantity is excreted through the intestine.

Special patient groups

Children

Abacavir is well and rapidly absorbed when ingested in children. All pharmacokinetic parameters in children are comparable to those in adults with slightly greater variability in plasma concentrations. Pharmacokinetic studies in children showed that taking the drug 1 time per day is equivalent in terms of indices AUC0-24 Reception of the same dose of the drug, divided into 2 times a day.

There is insufficient safety data for recommending the use of abacavir in children less than 3 months of age. There are limited data showing that a dose of 2 mg / kg in infants younger than 30 days provides similar or greater values of indicators AUC compared with a dose of 8 mg / kg in older children.

Elderly patients

The pharmacokinetics of abacavir in patients older than 65 years have not been studied. In the treatment of elderly patients, it is necessary to take into account more frequent violations of the liver, kidney and heart function at this age, as well as concomitant diseases and other medications taken.

Patients with impaired renal function

Abacavir is metabolized mainly in the liver, about 2% of it is excreted by the kidneys unchanged. The pharmacokinetics of abacavir in patients with terminal stage of renal failure is similar to that of patients with normal renal function. Therefore, in patients with impaired renal function, dose adjustment is not required.

Patients with impaired hepatic function

Abacavir is metabolized mainly in the liver. The pharmacokinetics of abacavir was studied in patients with mild liver function disorder (5-6 on the Child-Pugh scale). The results of the study indicate an increase AUC an average of 1.89 times and a half-life of 1.58 times. The violation of liver function does not affect the value AUC metabolites of abacavir, however, the rate of their formation and excretion decreases.

To achieve an exposure corresponding to the therapeutic range when the drug is administered to patients without liver disease, patients with a mild liver function disorder should take abacavir in a dose of 200 mg twice a day.

The pharmacokinetics of abacavir in patients with impaired liver function of medium and severe degree has not been studied, thus, the use of abacavir in these patient groups is not recommended.

Indications:

Treatment of HIV infection in adults, adolescents and children weighing more than 25 kg in combination antiretroviral therapy.

Contraindications:

Hypersensitivity to abacavir or any other component in the formulation.

Children weighing less than 25 kg (for this dosage form).

Hepatic insufficiency of medium and severe degree (class B and C on the Child-Pugh scale) due to the lack of clinical data and the recommended dosing regimen, mild liver failure (class A on the Child-Pugh scale) (due to the impossibility of dose adjustment).

Pregnancy and lactation:

Pregnancy

The use of abacavir during pregnancy and after childbirth was assessed according to the Registry of the use of antiretroviral drugs during pregnancy in more than 2000 women. The data available in the Registry on the use of antiretroviral drugs during pregnancy do not indicate an increased risk of developing major congenital malformations associated with abacavir use compared to the frequency of developmental defects in the comparison group. However, adequate and well-controlled studies involving pregnant women are not available,the safety of the use of abacavir in women during pregnancy has not been established to date. There is evidence of the effects of abacavir in reproductive studies in animals. If you need to use abacavir during pregnancy, you should evaluate the ratio of expected benefits to the mother and the potential risk to the fetus.

There is evidence of a slight transient increase in lactate concentration in the blood plasma of newborns and infants whose mothers during pregnancy and childbirth were receiving nucleoside reverse transcriptase inhibitors. Perhaps this is due to mitochondrial disorders. The clinical significance of this phenomenon has not been established to date. In addition, there are extremely rare reports of developmental delay, epileptic seizures and other neurological disorders (eg, muscle tone increase) in newborns, although the cause-and-effect relationship of these abnormalities with the use of NRTIs by mothers during pregnancy and childbirth is not established. These data do not abolish existing recommendations on the use of antiretroviral drugs 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 abacavir, its metabolites and HIV penetrate into breast milk, breastfeeding is contraindicated.

Dosing and Administration:

Abacavir should be prescribed by a doctor with experience in the treatment of HIV infection. To ensure the accuracy of the dosage of the drug, the tablet is recommended to be swallowed completely without division, but as an alternative, the division and grinding of tablets with the addition of a small amount of semi-solid food or liquid is allowed. All the amount of the mixture should be taken immediately.

Abacavir is taken internally, regardless of food intake.

Adults, adolescents and children weighing not less than 25 kg

The recommended dose of the drug is 600 mg / day. The drug is prescribed in a dose of 300 mg (1 tablet) 2 times a day or 600 mg (2 tablets) once a day.

Patients with impaired renal function

In patients with impaired renal function, dose adjustment is not required.

Patients with impaired hepatic function

The use of the drug is contraindicated in patients with hepatic insufficiencyand severe (class B and C on the Child-Pugh scale) due to the lack of clinical data and the recommended dosing regimen, with mild liver failure (class A on the Child-Pugh scale) due to the inability to correct the dose.

Side effects:

For many registered adverse reactions, it remains unclear whether their development is associated with the use of abacavir or a wide range of drugs used to treat HIV infection, or are a manifestation of the underlying disease.

Many of the undesirable reactions listed below (nausea, vomiting, diarrhea, fever, fatigue, rash) often develop as manifestations of a hypersensitivity reaction (MRSA) to abacavir. Therefore, if any of these symptoms appear, a thorough examination of the patient for the presence of an MRSV is indicated. If abacavir was canceled due to the appearance of any of the above symptoms, and a decision was made to resume therapy with this drug, then treatment should be started only under direct medical supervision.

Very rare cases of polymorphic exudative erythema, Stevens-Johnson syndrome, or toxic epidermal necrolysis were reported in which it was not possible to exclude MRSA from abacavir.In such cases, it is necessary to stop taking medication containing abacavir, without the possibility of renewal.

Most of the undesirable reactions listed below are not limiting treatment. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥ / 1000 and <1/100), rarely (≥1 / 10000 and <1/1000), rarely (< 1/10000).

Disorders from the metabolism and nutrition

Often: loss of appetite, hyperlactatemia.

Rarely: lactic acidosis.

Disturbances from the nervous system

Often: headache.

Disorders from the gastrointestinal tract

Often: nausea, vomiting, diarrhea.

Rarely: pancreatitis (causal relationship with the use of abacavir is not established).

Disturbances from the skin and subcutaneous tissues

Often: rash (in the absence of systemic manifestations).

Very rarely: polymorphic exudative erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

General disorders and disorders at the site of administration

Often: fever, drowsiness, fatigue.

In controlled clinical trials, laboratory changes in the treatment of abacavir were not infrequent, as in the control group of patients who did not receive the drug.

There are reports of the development of lactic acidosis, sometimes with a fatal outcome, usually accompanied by severe hepatomegaly with steatosis, due to therapy with nucleoside analogues.

Description of individual adverse reactions

Hypersensitiveart.ь

The hypersensitivity reaction (MRI) to abacavir was defined as a general undesirable reaction in the treatment with drugs containing abacavir. The signs and symptoms of MRI are listed below. These signs and symptoms were identified during clinical trials or post-marketing follow-up.

Symptoms and signs registered not less than 10% of patients from MIRV, are in bold.

Virtually all patients with HGV develop fever and / or a rash (usually maculopapular or urticaria) as part of the syndrome, but reactions can also occur without rash or fever. Other major symptoms include symptoms from the gastrointestinal tract, respiratory system, or constitutional symptoms such as drowsiness and malaise.

Disturbances from the skin and subcutaneous tissues rash (usually maculopapular or urticarum).

Disorders from the gastrointestinal tract nausea, vomiting, diarrhea, abdominal pain, ulceration of the oral mucosa.

Disturbances from the respiratory system, chest and mediastinal organs shortness of breath, cough, sore throat, adult respiratory distress syndrome, respiratory failure.

Disorders from the nervous system / psyche headache, paresthesia.

Violations of the blood and lymphatic system lymphopenia.

Disturbances from the liver and bile ducts increase of biochemical parameters of liver function, hepatitis, hepatic insufficiency.

Disturbances from musculoskeletal and connective tissue myalgia, rarely myolysis, arthralgia, increased activity of creatine phosphokinase.

Disorders from the kidneys and urinary tract increase in creatinine concentration, renal failure.

General disorders and disorders at the site of administration fever, fatigue, malaise, edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions.

Renewal of the drug after MRI on abacavir leads to rapid re-emergence of symptoms within a few hours. Repeated MRI usually occurs in a more severe form than in the primary manifestation, and may include life-threatening arterial hypotension and death. Sometimes reactions also occurred when the drug was resumed abacavir after its withdrawal caused by the appearance of one of the main symptoms of hypersensitivity (see above), and in very rare cases, the reactions were observed with the resumption of the use of the drug by patients who had no symptoms of MRI prior to its withdrawal (ie, patients who had previously believed to tolerate abacavir therapy).

Metabolic parameters

Body weight, lipid and blood glucose concentrations may increase during antiretroviral therapy.

The use of combined antiretroviral therapy was accompanied by metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia and hyperlactatemia.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency at the onset of combined antiretroviral therapy, it is possibledevelopment of an inflammatory reaction against a background of asymptomatic opportunistic infections or their residual phenomena. Autoimmune diseases (for example, Graves' disease) were also 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.

Osteonecrosis

Osteonecrosis cases have been reported, especially in patients with recognized risk factors, advanced HIV infection or long-term combined antiretroviral therapy. The frequency of this phenomenon is unknown.

Children

Safety data confirming single dosing of abacavir in children aged 3 months to 17 years were obtained in the study ARROW (COL 105677), in which 669 children infected with HIV-1 received abacavir and lamivudine once or twice a day. There were no additional safety concerns in children who took abacavir once or twice a day, compared with adults.

For detailed information on clinical management in case of suspicion of an MRSV for abacavir, see "Special instructions".

Overdose:

Symptoms

In clinical studies, no undesirable reactions were observed when the drug was used in single doses up to 1200 mg and daily to 1800 mg. The effect of the drug in higher doses has not been studied to date.

Treatment

In case of an overdose of the drug, the patient is observed to detect symptoms of poisoning and timely treatment. If necessary, perform symptomatic treatment. The efficacy of peritoneal dialysis and hemodialysis for abacavir removal is unknown.

Interaction:

Research in vitro and analysis of the main metabolic pathways of abacavir indicate that its interaction with other drugs is unlikely.

Abacavir is characterized by a lack of ability to inhibit metabolism involving isoenzyme CYP3A4 systems of cytochrome P450. In studies in vitro It is also shown that abacavir Do not enter into interactions with drugs that are metabolized by isoenzymes CYP3A4, CYP2C9 or CYP2D6. Clinical studies have not revealed induction of metabolism in the liver. Thus, the interaction of abacavir with antiretroviral HIV protease inhibitors and other drugs,the metabolism of which occurs with the participation of the main isoenzymes of the cytochrome P450 system, is unlikely. Clinical studies have shown no clinically relevant interactions between abacavir, zidovudine and lamivudine.

Powerful inducers of enzymes, such as rifampicin, phenobarbital and phenytoin, when exposed to UDP-glucuronyl transferase, the concentration of abacavir in the blood plasma may be slightly reduced.

The effect of abacavir on the pharmacokinetics of other substances

In vitro Abacavir demonstrates the lack or weak ability to inhibit drug-carrier proteins: the transporter organic anions 1В1 (ОАТР1В1), ОАТР1В3, protein resistance of breast cancer (BCRJP) or P-glycoprotein (P-gp); and minimal inhibition of the transporter of organic cations 1 (OST1), OCT2 and the extrusion protein of drugs and toxins 2-K (MATE2-K). Thus, it is not expected that abacavir will affect the concentration in the blood plasma of drugs that are the substrates of these carrier proteins.

Abacavir is an inhibitor of the protein MATE1 in vitro, but has a weak ability to influence the concentration of MATE1 protein substrates in the blood plasma at therapeutic exposure levels of the drug (up to 600 mg).

The effect of other substances on the pharmacokinetics of abacavir

In vitro abacavir is not a substrate of OATP1B1, OATP1B3, OST1, OST2, OAT1, MATE1, MATE2-K, associated with multiple drug resistance of protein 2 (MRP2) or MRP4, so it is not expected that the drugs that affect the activity of these vectors will affect the concentration of abacavir in the blood plasma.

Although in vitro abacavir is a substrate BCRP and P-gp, Clinical studies showed no clinically significant changes in the pharmacokinetics of abacavir when used concurrently with lopinavir / ritonavir (inhibitors P-gp and BCRP).

Drug Interactions Associated with Abacavir

Ethanol

When combined ethanol has an effect on the metabolism of abacavir, leading to an increase AUC abacavir by approximately 41%. Given the safety profile of abacavir, these results are not considered clinically relevant. On the metabolism of ethanol abacavir does not affect.

Methadone

According to the pharmacokinetic study using abacavir in a dose of 600 mg twice a day, together with methadone, there was a decrease in C_m_Oh abacavir by 35% and delay t_max for 1 hour, however AUC did not change. Changes in the pharmacokinetics of abacavir are not considered clinically significant. In this study abacavir increased the average systemic clearance of methadone by 22%. This change is not considered clinically significant in most patients, however, in some cases, there may be a need for a methadone dose adjustment. As a consequence, patients receiving methadone treatment and abacavir, should be monitored in connection with the possibility of developing a withdrawal syndrome, manifested with a lower dosage.

Retinoids

Retinoid compounds, such as isotretinoin, are derived with the participation of alcohol dehydrogenase. Interaction with abacavir is possible, but has not been studied to date.

Special instructions:

Hypersensitivity

The use of abacavir is associated with the risk of developing hypersensitivity reactions (MRI) characterized by the appearance of fever and / or rash with other symptoms indicating a multiple organ failure.MRIs can threaten life and, in rare cases, lead to death in the absence of proper treatment. The risk of developing MRI with abacavir is significantly increased in patients with a positive test for the presence of an allele HLA-B* 5701. At the same time, MRI to abacavir was observed with a lower frequency in patients who are not carriers of this allele.

The following rules should be observed:

- Status with respect to the allele HLA-B* 5701 should be prescribed without fail before initiating abacavir therapy.

- Under no circumstances should you begin treatment with the drug abacavir in patients with a positive status for an allele HLA-B* 5701 or in patients with a negative status for HLA-B* 5701, who previously had been suspected of having an abnormal hypertensive abcavir during the use of an abacavir-containing drug.

- If there is a suspicion of an MIRV abacavir should be discontinued immediately even in the absence of an allele HLA-B* 5701. The delay in stopping therapy with the drug after the occurrence of an MRI may lead to the development of a life-threatening reaction.

- After cessation of treatment with abacavir because of suspicion of Mitigation under no circumstances should the use of the drug or any other medications containing abacavir.

- Renewal of the use of drugs containing abacavir, after the suspected MRI on abacavir can lead to a rapid return of symptoms within a few hours. Repeated MRI usually occurs in a more severe form than in the primary manifestation, and may include life-threatening arterial hypotension and death.

- Patients who developed MRLT should be instructed to transfer the remnants of the drug to the treating physician in order to avoid the resumption of abacavir.

Clinical picture of MRI to abacavir

MRI to abacavir was well characterized in clinical trials and during post-registration follow-up.

Symptoms usually occurred within the first 6 weeks (the median time of onset of this reaction - 11 days) after initiation of abacavir therapy, however, these reactions can develop at any time during therapy.

Virtually all WGHs for abacavir include fever and / or rash as part of the syndrome.Other signs and symptoms that have been observed with MRI to abacavir include symptoms from the respiratory and gastrointestinal tract, which can lead to erroneous diagnosis of MRI, as a respiratory disease (pneumonia, bronchitis, pharyngitis) or gastroenteritis.

With the continuation of treatment, the severity of the symptoms associated with MRIs increases, and they can take a life-threatening character. As a rule, these symptoms disappear after stopping the use of abacavir.

In rare cases, patients who stopped taking abacavir for other reasons than the symptoms of MRI also developed life-threatening reactions within a few hours after resumption of abacavir therapy. The resumption of treatment with abacavir in such patients should only be carried out with quick access to medical care.

A warning card for patients with information on hypersensitivity reactions is at the end of this manual.

Lactic acidosis and severe hepatomegaly with steatosis

There are reports of the development of lactic acidosis and severe hepatomegaly with steatosis, including fatal, due to antiretroviral therapy with nucleoside analogues, including abacavir, taken either individually or in combination.In most cases, these complications occur in women.

Clinical signs of developing lactic acidosis are general weakness, loss of appetite, rapid unexplained weight loss, gastrointestinal disorders (nausea, vomiting, abdominal pain), respiratory system disorders (dyspnea and tachypnea), or neurologic symptoms (including motor weakness).

Lactic acidosis is characterized by high mortality and can develop against a background of pancreatitis, liver failure or kidney failure.

Lactic acidosis, as a rule, developed after several months of therapy.

It is necessary to stop therapy with nucleoside analogues in case of symptomatic manifestations of hyperlactatemia and metabolic acidosis / lactic acidosis, progression of hepatomegaly or rapid increase in aminotransferase activity.

Caution should be exercised when using abacavir in 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 drugs and alcohol use).Patients with co-infection with hepatitis C virus who are treated with interferon alpha and ribavirin may be at a particular risk. Patients with high risk require careful monitoring.

At the appearance of clinical or laboratory signs of lactic acidosis with or without hepatitis (including hepatomegaly and steatosis, even in the absence of a significant increase in the activity of transaminases), treatment with the drug should be stopped.

Mitochondrial dysfunction due to intrauterine exposure

Analogues of nucleosides and nucleotides can cause a different degree of damage to mitochondria, which is most pronounced when using stavudine, didanosine and zidovudine. Mitochondrial dysfunction in HIV-negative children exposed to nucleoside analogues in utero and / or after birth was documented. The main undesirable reactions were hematologic disorders (anemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipazemia).

These undesirable reactions were often transient.Rare neurological disorders with late onset have been reported (increased muscle tone, convulsions, behavioral disorders). Whether these neurological disorders are transient or permanent, is currently unknown. The probability of mitochondrial dysfunction should be considered in any child exposed to intrauterine exposure to nucleoside and nucleotide analogues, with marked clinical symptoms of unclear etiology, in particular neurological disorders.

The presented data do not influence the current national recommendations on the use of antiretroviral therapy in pregnant women for the prevention of vertical transmission of HIV infection.

Body weight and metabolic parameters

During antiretroviral therapy, weight gain, increased serum lipid and blood glucose levels can occur. Control of the disease and lifestyle changes can also contribute to this process.

In some cases, data have been obtained that indicate a link between increased lipid concentrations and therapy, but there is no strong evidence for a relationship between weight gain and any specific therapy.The need to determine the concentration of serum lipids and blood glucose should be considered. Disorders of lipid metabolism should be adjusted in accordance with clinical manifestations.

Pancreatitis

Cases of pancreatitis have been documented, although the cause-and-effect relationship with the use of abacavir has not been accurately established.

Therapy containing three NRTIs

In patients with high viral load (> 100,000 copies / ml), the appointment of a three-component combination containing abacavir, lamivudine and zidovudine, requires special consideration.

There were reports of a high incidence of virological failure and the emergence of resistance in the early stages, when a combination of abacavir and tenofovir with dizoproxil fumarate and lamivudine was used as a regimen of therapy once a day.

Diseases of the liver

The efficacy and safety of abacavir have not been established in patients with severe concomitant liver disease. The drug is contraindicated in patients with impaired liver function of medium and severe degree.

In patients with an initially present impaired hepatic function, including an active form of chronic hepatitis,there is an increase in the incidence of abnormalities in liver function during combined antiretroviral therapy. Such patients should be monitored in accordance with standard clinical practice. It is necessary to consider the possibility of suspending or stopping treatment if there are signs of worsening liver disease in such patients.

Patients with concomitant chronic hepatitis B or C

Patients with concomitant chronic hepatitis B or C receiving combination antiretroviral therapy are at increased risk of developing severe and potentially lethal adverse reactions from the liver. In the case of concomitant antiviral therapy for hepatitis B or C, the appropriate instructions for the use of these drugs should be consulted.

Kidney disease

Abacavir should not be given to patients with terminal chronic renal failure.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency at the time of the onset of combined antiretroviral therapy, an inflammatory reaction may occur against a background of asymptomatic opportunistic infections or their residual effects,which can cause serious deterioration or worsening of symptoms. Typically, these reactions occur within the first few weeks or months after the onset of combined antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized and / or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jirovecii (R. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.

Autoimmune diseases (such as Graves' disease) were also observed against the background of restoration of immunity, but the time of primary manifestations varied, and the disease could occur many months after initiation of therapy.

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 are most often found in patients at advanced stage of HIV infection and / or long-term combined antiretroviral therapy.Patients should consult a doctor if they experience pain and stiffness in the joints or difficulty moving.

Opportunistic infections

The use of abacavir or any other antiretroviral drugs does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the strict supervision of a physician with experience in the treatment of HIV-associated diseases.

Transmission of HIV infection

Although it has been proved that effective suppression of the virus with antiretroviral therapy significantly reduces the risk of transmission of HIV to other people during sexual intercourse, it is impossible to exclude this risk completely. Appropriate precautions should be taken to prevent the transmission of HIV.

Myocardial infarction

Observational studies have demonstrated a link between the development of myocardial infarction and the use of abacavir. They were mainly attended by patients who had previously received antiretroviral therapy. Clinical trials have shown a limited number of cases of myocardial infarction and do not allow to exclude a slight increase in the risk of its occurrence.In general, the data obtained from the observed cohorts and in the randomized studies are somewhat contradictory and thus do not allow either confirming or refuting the causal relationship between abacavir therapy and the risk of myocardial infarction. To date, no biological mechanism has been established to explain the potential increase in risk. When appointing abacavir, measures should be taken to minimize all modifiable factors (eg, smoking, hypertension and hyperlipidemia).

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

Data on the effects of abacavir on the ability to drive vehicles and work with mechanisms are not available.

Form release / dosage:

Film-coated tablets, 300 mg.

Packaging:

For 15 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil. 4 contour packs with a medical instruction are placed in a pack of cardboard.

For 60 tablets in a polymer jar. The bank, together with the instruction for medical use, is placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years.

Do not take the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004539

Date of registration:14.11.2017

Expiration Date:14.11.2022

The owner of the registration certificate:IBA-groups, LLCIBA-groups, LLC Russia

Manufacturer: & nbsp

RAFARMA, JSC Russia

Information update date: & nbsp07.12.2017

Illustrated instructions

Instructions

Abacavir (Abacavir)