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

Active substance:
Abacavir Sulfate	351.0 mg
in terms of abacavir base	300.0 mg
Excipients:
Microcrystalline cellulose	283.9 mg
Copovidone	35.0 mg
Sodium carboxymethyl starch	21.0 mg
Silica colloidal dioxide (Aerosil)	2_,1 mg
Magnesium stearate	7.0 mg

Composition of the film shell: Opaprai II 85F220031 yellow 21.0 mg, [polyvinyl alcohol (40.0%), macrogol 4000 (20.2%), titanium dioxide (20.2%), talc (14.8%), iron oxide (4.8%)]

Description:

Tablets are round, biconvex, covered with a film coat of brownish-yellow color, two layers are visible on a cross section. The tablet core is from almost white to light yellow or light brown in color.

Pharmacotherapeutic group:Antiviral [HIV] agent

ATX: & nbsp

J.05.A.F.06 Abacavir

Pharmacodynamics:

Mechanism of action

Abacavir is a nucleoside analogue that inhibits HIV reverse transcriptase and selectively suppresses the replication of HIV-1 and HIV-2, including HIV-1 strains resistant to zidovudine, lamivudine, zalcitabine, didanosine and nevirapine.

Abacavir undergoes intracellular metabolism, becoming an active form of carbovir-5'-triphosphate (carbovir-TF). According to research in vitro, the antiviral effect of the drug is due to the inhibition of HIV reverse transcriptase, which leads to the breakdown of DNA synthesis on the RNA template and the stopping of HIV replication. There was no antagonism in the antiviral activity of abacavir 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) amprenavir .

The obtained in vitro HIV-1 strains resistant to abacavir, mutations in several codons of the reverse transcriptase gene (RT) - M184V, K65R, L74V and Y115F. HIV resistance to abacavir in vitro and in vivo formed slowly. For a clinically significant increase in 50% inhibitory concentration (IC₅₀) (increase IC₅₀ at 8 times with respect to the "wild" strain of the virus) multiple mutations are required. Strains resistant to abacavir may have decreased sensitivity to lamivudine, zalcitabine and / or didanosine, but retain a sensitivity to zidovudine and stavudine. Cross-resistance to abacavir and HIV or NNRTI is unlikely. Inefficiency of the first-line regime, 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, it can prevent the development of neurological complications of HIV infection and slow the emergence of resistant strains within the central nervous system (CNS).

According to a study involving 20 HIV-infected patients who took abacavir in a dose of 300 mg 2 once a day and only one dose (300 mg) before the 24-hour sampling period for analysis, the geometric mean of the terminal half-life (T_1/2) intracellular carbovir-TF at an equilibrium state was 20,6 h (the same indicator for the concentration of abacavir in serum - 2.6 h). Equilibrium pharmacokinetic parameters when taking abacavir in a dose of 600 mg 1 once a day were similar to those with abacavir 300 mg twice daily in a cross-sectional clinical trial in 27 HIV-infected patients.

The intracellular content of carbovir-TF in peripheral blood mononuclear cells was higher with abacavir at a dose of 600 mg 1 once a day in comparison with the reception of abacavir in a dose of 300 mg 2 times a day (an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) in equilibrium for 24 hours (AUC₂₄_,_ss) by 32%, the maximum daily concentration in a state of equilibrium (C_max₂₄_,_ss) - by 99%), which indicates the possibility of such a regimen of taking the drug by HIV-infected patients.

The efficacy and safety of abacavir provided a single daily dose was shown in a clinical trial (CNA30021).

Pharmacokinetics:

Suction

Abacavir is quickly and well absorbed when taken orally. Absolute bioavailability of abacavir for oral administration in adults is about 83%. The time to reach the maximum concentration (T_mOh) when taking abacavir orally in the form of tablets is about 1.5 hours. When taking a tablet form of abacavir orally at a dose of 300 mg 2 times a day, the maximum concentration in the blood plasma (C_mOh) on reaching the equilibrium state is on the average 3 μg / ml, a AUC during 12hour interval between doses - on average 6,02 mcg / ml. After a single admission of abacavir tablets in a dose of 600 mg C_mOh averages about 4.26 μg / ml, a AUC_∞ - an average of 11.95 μg h / ml.

Eating slows the absorption of abacavir and reduces C_mOh, but does not affect AUC. therefore abacavir can be taken with or without food.

Receiving a crushed tablet with a small amount of softened food or liquid does not affect the pharmacokinetics and, therefore, the clinical effectiveness.This conclusion is based on the physico-chemical and pharmacokinetic parameters of the active substance and the water solubility of abacavir tablets, it being assumed that the patient will grind and add the whole tablet to the food or liquid and immediately take it inside.

Distribution and binding to blood plasma proteins

Studies involving HIV-infected patients showed that abacavir well penetrates into the CSF, and the relation AUC abacavir in CSF to AUC Abacavir in blood plasma is 30-44%. In the Phase I pharmacokinetic study, it was found that, 1.5 hours after taking abacavir 300 mg twice daily, its mean concentration in the CSF was 0.14 μg / ml. When using abacavir in a dose of 600 mg 2 once a day, the concentration of the drug in the CSF increased from 0.13 μg / ml after 0.5-1.0 hours after administration to 0.74 μg / ml when it was measured 3-4 hours after taking the drug. Thus, even if the concentration of abacavir observed in the CSF 4 hours after taking the drug at a dose of 600 mg 2 once a day, is not the maximum achieved with this mode of therapy, it already exceeds IC50 (0.08 μg / ml, or 0.26 μmol / L) 9-fold.

In studies in vitro it was found that in therapeutic doses abacavir moderately (approximately 49%) binds to human plasma proteins. This indicates that the interaction of abacavir with other drugs by their displacement from the compound with plasma proteins is unlikely.

Metabolism

Abacavir is metabolized predominantly in the liver, in unchanged form it is secreted by the kidneys (less 2% of the accepted dose of the drug). In the human body abacavir is metabolized mainly by the action of alcohol dehydrogenase with the formation of 5'-carboxylic acid and by conjugation with glucuronic acid to form 5'-glucuronide constituting about 66% of the total amount of the administered dose of the drug. These metabolites are excreted by the kidneys.

Excretion

Average T_1/2is about 1.5 hours. Prolonged intake of abacavir orally at a dose of 300 mg 2 once a day does not lead to significant cumulation of the drug. 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 is excreted by the kidneys in the form of metabolites and abacavir in unchanged form, and the remaining amount - 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 have shown that taking the drug 1 once a day is equivalent in terms of indicators AUC_0-₂₄reception of the same dose of the drug, divided by 2 once a day for existing dosage forms. This will provide slightly higher mean concentrations of the drug in children in plasma, ensuring that in most children the therapeutic concentrations will be equivalent to the dosing regimen of 300 mg twice daily for adults.

There is insufficient safety data to recommend the use of abacavir in children younger than 3 months. There are limited data showing that the dose 2 mg / kg in neonates under 30 days of age provides similar or greater values of indicators AUC in comparison with the dose 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 medications taken.

Patients with impaired renal function

Abacavir is metabolized predominantly in the liver, less 2% it is excreted by the kidneys unchanged. The pharmacokinetics of abacavir in the terminal stage of renal failure is about the same as with normal kidney function. Therefore, if the renal function is not corrected, dose adjustments are not required.

Patients with impaired hepatic function

Abacavir is metabolized mainly in the liver. The results of a study of the pharmacokinetics of abacavir in patients with mild liver function disorder (class A on the Child scale-Pugh) indicate an increase AUC an average of 1.89 times and T_1/2- in 1,58 times. On the metric AUC metabolites of abacavir, liver function is not affected, but the rate of their formation and excretion decreases.

Patients with a mild liver function disorder for therapeutic purposes can take 200 mg abacavir 2 times a day.

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

Indications:

Treatment of HIV infection in adults and children over 12 years old and weighing more than 30 kg (as part of combined antiretroviral therapy).

Contraindications:

- Hypersensitivity to abacavir or any other component included in the preparation;

- Children younger than 12 years of age and weighing less than 30 kg;

- hepatic insufficiency of moderate and severe degree (classes B and C on the Child-Pugh scale), due to the lack of clinical data and the recommended dosing regimen;

- hepatic insufficiency of mild degree (class A on the Child-Pugh scale), due to the inability to provide a dosing regimen.

Carefully:

Patients with a possible risk of coronary heart disease; joint use of abacavir and ribavirin (see section "Interaction with Other Drugs").

Pregnancy and lactation:

Pregnancy

Data available in the National Clinical Guidelines for the Use of Antiretroviral Medications in Pregnant Women,do not indicate an increase in the risk of developing major congenital malformations associated with the use of abacavir, compared with the frequency of malformations in the comparison group. However, proper and well-controlled studies involving pregnant women are not available, and the safety of using abacavir in women during pregnancy has not been established to date. 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 took NRTIs during pregnancy and childbirth. 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 causal relationship of these disorders to NRTIs in mothers during pregnancy and childbirth has not been 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:

The drug Abacavir-ABC is taken orally, regardless of food intake. The drug should appoint a doctor who has experience in the treatment of HIV infection.

Adults, adolescents and children over 12 years of age and weighing more than 30 kg

The recommended dose of the drug Abacavir-ABC is 600 mg once a day (2 tablets of 300 mg) or 300 mg twice a day (1 tablet 300 mg).

Special patient groups

Patients with impaired renal function

In patients with impaired renal function, dose adjustment of the drug Abacavir-ABC is not required.

Patients with impaired hepatic function

The use of abacavir is contraindicated (for this dosage form, due to the lack of clinical data and the recommended dosing regimen).

Side effects:

The nature of unwanted reactions other than the hypersensitivity reaction, but observed in patients taking abacavir, to the end is not clear. Whether these unwanted reactions result from the use of abacavir or a wide range of other drugs concomitantly prescribed for the treatment of HIV infection or caused by the disease itself has not been established to date. Many of the undesirable reactions associated with taking abacavir (nausea, vomiting, diarrhea, fever, fatigue, rash) are usually observed when a hypersensitivity reaction to abacavir develops. Therefore, if any of these symptoms appear, a thorough examination of the patient is shown to confirm the development of a hypersensitivity reaction.

If abacavir was canceled in connection with the appearance of the above symptoms and the decision was made to resume therapy with abacavir, then this can be done only under direct medical supervision.

Very rare cases of polymorphic exudative erythema, Stevens-Johnson syndrome, or toxic epidermal necrolysis were reported in which the hypersensitivity reaction to abacavir could not be ruled out.In such cases, you must permanently stop taking medication containing abacavir.

Most of the undesirable reactions listed below are not limiting treatment. Frequency of occurrence is defined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10,000 and < 1/1000), very rarely (<1/10 000).

Clinical Trials Data

Disorders from the metabolism and nutrition: often - loss of appetite.

Impaired nervous system: often a headache.

Disorders from the gastrointestinal tract: often - nausea, vomiting, diarrhea.

General disorders: often - fever, drowsiness, fatigue.

In controlled clinical trials, it has been shown that laboratory changes in abacavir treatment are infrequent, as in the control group of patients who do not receive the drug.

Post-registration data

Metabolic and nutritional disorders: often - hyperlactatemia; rarely - lactic acidosis, accumulation and / or redistribution of adipose tissue. The frequency of this unwanted reaction depends on many factors, including antiretroviral drugs used in combination with abacavir.

Disturbances from the gastrointestinal tract: rarely - pancreatitis (the cause-and-effect relationship with the use of abacavir is not exactly established).

Disturbances from the skin and subcutaneous tissues: often a rash (in the absence systemic manifestations); very rarely polymorphic exudative erythema, Stevens-Johnson syndrome and toxic epidermal necrolysis.

There have been reported cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and fatty liver dysfunction, using nucleoside analogues.

The use of combined antiretroviral therapy has been associated with the redistribution of adipose tissue (lipodystrophy) in patients with HIV, including a reduction in the subcutaneous fat layer on the face and extremities, an increase in intra-abdominal and visceral fat, an increase in mammary glands, and dorsocervical fat deposition (buffalo hump).

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

In HIV-infected patients with severe immunodeficiency, the onset of combined antiretroviral therapy may result in inflammatory responses to asymptomatic or residual opportunistic infections. There have also been cases of autoimmune diseases (eg, Graves' disease) occurring under conditions of immune reactivation, but the presented terms of the disease manifestation are more variable, and these phenomena can develop many months after the initiation of therapy.

Osteonecrosis has been documented, especially in patients with well-known risk factors, advanced HIV infection, or long-term use of combination antiretroviral therapy. The frequency of this phenomenon is unknown.

Description of individual adverse reactions

Hypersensitivity

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

Symptoms and signs that occur in at least 10% of patients with a hypersensitivity reaction have been identified in bold.

Practically all patients with a hypersensitivity reaction develop fever and / or a rash (usually maculopapular or urticaria) as part of the syndrome, but similar reactions can occur without a rash or fever. Other major reactions include symptoms from the gastrointestinal tract, respiratory system, or constitutional symptoms such as drowsiness or 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: dyspnoea, cough, sore throat, adult respiratory distress syndrome, respiratory failure.

Disturbances from the nervous system: headache, paresthesia.

Violations of the blood and lymphatic system: lymphopenia.

Disturbances from the liver and bile ducts: rise biochemical parameters of liver function, hepatitis, hepatic failure.

Disturbances from the musculoskeletal and connective tissue: myalgia, Myolysis, arthralgia, increased creatine kinase activity.

Disorders from the kidneys and urinary tract: rise serum creatinine concentration, renal failure.

General disorders: fever, fatigue, malaise, swelling, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis.

Renewal of Abacavir-ABC administration after reaction hypersensitivity to abacavir leads to a rapid return of symptoms within a few hours. Repeated hypersensitivity reactions usually occur more severely than the first, and may include life-threatening arterial hypotension and death. In rare cases, reactions also occur with the resumption of therapy with the drug Abacavir-ABC after its withdrawal caused by the appearance of just one of the main symptoms of the hypersensitivity reaction (see above), and in very rare cases this reaction occurs when the drug Abacavir-ABC is resumed in patients with which before the withdrawal of the drug did not show any symptoms of hypersensitivity reaction (i.e.in patients previously thought to be abacavir-treated).

For detailed information on the clinical management of suspected hypersensitivity reactions to abacavir, see the "Specific guidance" section.

Overdose:

In clinical trials, patients received single doses of abacavir up to 1200 mg and daily doses up to 1800 mg. There were no reports of unexpected adverse reactions. The effect of higher doses of abacavir is unknown.

Treatment: It is necessary to monitor the patient's condition in order to detect signs of intoxication and, if necessary, to carry out symptomatic therapy. There is no data on the possibility of excretion of abacavir by hemodialysis and peritoneal dialysis.

Interaction:

Research results in vitro and data on the main ways of metabolism of abacavir indicate a low probability of drug interactions involving abacavir. Abacavir Does not inhibit metabolism processes involving isoenzyme CYP3A4 systems of cytochrome R₄₅₀.

During the research in vitro it was found that abacavir does not interact with drugs that are metabolized by isoenzymes CYP3A4, CYP2C9 or CYP2D6.In the course of clinical studies, there was no evidence of increased hepatic metabolism under the action of the drug. Consequently, the interaction of abacavir with HIV protease inhibitors and other drugs metabolized with enzymes of the cytochrome system is unlikely R₄₅₀.

Clinical studies have not shown clinically significant interactions between abacavir, zidovudine and lamivudine.

The use of abacavir simultaneously with rifampicin, phenobarbital and fetonoid (inducers of uridine-5-diphosphate-glucuronyltransferase) can lead to a slight decrease in the concentration of abacavir in plasma.

Ethanol. Ethanol slows the metabolism of abacavir. as a result of which the abacavir AUC increases by approximately 41%. Given the safety profile of abacavir, these changes can be considered clinically insignificant. Abacavir does not affect the metabolism of ethanol.

Methadone. In a pharmacokinetic study, the simultaneous administration of abacavir at a dose of 600 mg 2 times / day and methadone led to a decrease in C_maxabacavir by 35% and an increase in the time of its attainment by 1 h. Moreover, under the curve "concentration in plasma-time" did not change.It is believed that these data have no clinical significance. In this study abacavir increased the average systemic clearance of methadone by 22%. For most patients, these changes are not clinically significant, but sometimes a further increase in the dose of methadone may be required.

Retinoids. Retinoids (for example, isotretinoin) are inactivated by the action of alcohol dehydrogenase. Interaction with abacavir is possible, but no special studies have been conducted.

Ribavirin. Special care should be taken when concomitant administration of abacavir and ribavirin, since a decrease in the concentration of phosphorylated ribavirin metabolites is possible, which in turn can lead to a decrease in the effectiveness of treatment in patients infected simultaneously with HIV and hepatitis C virus receiving pegylated interferon and ribavirin therapy.

Special instructions:

The drug should appoint a doctor who has experience in the treatment of HIV infection.

Hypersensitivity

The use of abacavir is associated with a risk of developing a hypersensitivity reaction characterized by fever and / or rash and other symptoms that indicate multiple organ failure.The reaction of hypersensitivity can be life threatening and in rare cases, when no appropriate treatment is prescribed, it can lead to death. The risk of developing a hypersensitivity reaction with abacavir is significantly increased in patients with a positive test for the presence of an allele HLA-B* 5701. However, hypersensitivity reactions to abacavir have been observed with less frequency in patients who are not carriers of this allele.

It is necessary to adhere to the following rules:

- A study should be conducted for the presence of an allele HLA-B* 5701 before initiation of abacavir therapy, and before resumption of abacavir therapy in patients with unknown status for this allele who previously tolerated abacavir therapy.

- Abacavir is not recommended for patients with an allele HLA-B* 5701 or patients who were suspected of a hypersensitivity reaction during the use of any other drug containing abacavir, regardless of the status of the allele HLA-B*5701.

- Each patient should be reminded that it is necessary to read the instructions for use, enclosed in the packaging of the drug Abacavir-ABC.

- In all patients receiving abacavir therapy, the clinical diagnosis of suspected hypersensitivity reactions should remain the basis for deciding whether to conduct a clinical trial.

- If hypersensitivity is suspected, abacavir should be discontinued immediately, even in the absence of an allele HLA-B* 5701. The delay in stopping abacavir therapy after a hypersensitivity reaction can lead to a life-threatening reaction.

- Patients who developed a hypersensitivity reaction should be informed about the need to transfer the remaining tablets of the drug Abacavir-ABC to the treating doctor in order to avoid the resumption of taking abacavir.

- Renewal of the use of drugs containing abacavir, after a suspected hypersensitivity reaction to abacavir can lead to a rapid return of symptoms within a few hours, which may include life-threatening arterial hypotension and death.

- When considering the resumption of therapy with abacavir after discontinuation of treatment with any containing abacavir the drug for any reason should be determined the reason for discontinuing therapy, regardless of the patient's carriage of the allele HLA-B*5701.

- If a hypersensitivity reaction can not be ruled out, you can not resume taking abacavir or any other medications containing abacavir.

- If a hypersensitivity reaction is excluded, it is possible to resume therapy with Abacavir-ABC. In rare cases, patients who discontinued abacavir for reasons other than hypersensitivity reactions also reported the development of life-threatening reactions within a few hours after the resumption of abacavir therapy (see "Descriptions of individual adverse reactions" subsection). Patients should be informed of the possibility of developing a hypersensitivity reaction when resuming therapy with Abacavir-ABC or other medications containing abacavir, and that the resumption of therapy with the drug Abacavir-ABC or other medications containing abacavir, should be carried out only with the availability of quick access to medical care.

The clinical picture of a hypersensitivity reaction to abacavir

The reaction of hypersensitivity to abacavir is characterized by the appearance of symptoms indicating multiorgan lesion. The most frequent symptoms are: fever and / or rash - noted in most patients. Other symptoms of hypersensitivity to abacavir are fatigue, malaise, disorders of the gastrointestinal tract, including vomiting, nausea, diarrhea and abdominal pain, impairment of the respiratory system, including shortness of breath, sore throat, cough, lung damage (mainly in the form of local infiltrative changes revealed by chest x-ray).

Symptoms of hypersensitivity may appear at any time after initiation of abacavir treatment, However, most often they occur during the first 6 weeks of application.

Patients should be closely monitored with advice every 2 weeks, especially during the first 2 months of therapy with the drug Abacavir-ABC.

If, when hypersensitivity symptoms appear, abacavir treatment continues, they become more pronounced and can take a life-threatening character. In most cases, these symptoms disappear when discontinuing abacavir.

Lactate acidosis and severe hepatomegaly with steatosis

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

Symptoms that may indicate the development of lactic acidosis include general weakness, lack of appetite, rapid weight loss of unclear etiology, gastrointestinal disturbances (nausea, vomiting and abdominal pain), respiratory system disorders (dyspnea and tachypnea) or neurologic symptoms (including motor problems).

Lactatecidosis is characterized by high mortality and can be associated with pancreatitis, hepatic or renal insufficiency. Lactate acidosis, as a rule, manifested itself after several months of therapy. It is necessary to stop therapy with nucleoside analogues in case of symptomatic manifestations of hyperlactatemia and metabolic / lactic acidosis, progression of hepatomegaly or rapid increase in aminotransferase activity.The use of Abacavir-ABC requires caution for any patient (especially overweight 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).

Patients with co-infected hepatitis C receiving interferon alfa and ribavirin therapy can be a particular risk group. Patients in the high-risk group require careful follow-up.

When clinical or laboratory signs of lactate acidosis with or without hepatitis appear (hepatomegaly and steatosis may appear even in the absence of a marked increase in aminotransferase activity) treatment with Abacavir-ABC should be stopped.

Mitochondrial dysfunction

Research in vitro and in vivo showed that the analogues of nucleosides and nucleotides can cause damage to mitochondria of different degrees. 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 (increased muscle tone, convulsions, behavioral disorders). Whether these neurological disorders are transient or permanent, is currently unknown.

Any child, even HIV-negative, who has undergone intrauterine exposure to nucleoside and nucleotide analogues, must undergo a clinical and laboratory examination to exclude mitochondrial dysfunction in the event that appropriate signs or symptoms are identified. These 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.

Redistribution of subcutaneous fat

In some patients receiving combined antiretroviral therapy, there may be a redistribution and / or accumulation of subcutaneous fat,including obesity by the central type, dorsocervical fat deposition ("buffalo buffalo"), a decrease in the subcutaneous fat layer on the face and extremities, enlargement of the mammary glands, increased serum lipid concentrations and glucose concentration in the blood.

Although one or more of the above undesirable reactions associated with the common syndrome, which is often referred to as lipodystrophy, can cause all drugs of the HIV and NRTI classes, the data of the studies indicate that there are differences between the 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, the elderly age and the duration of antiretroviral therapy play an important, perhaps synergistic role.

The long-term effects of these undesirable reactions are currently unknown.

When clinically examining patients, attention should be paid to the redistribution of subcutaneous fat. Laboratory examination should include the determination of serum lipid concentration and concentrationglucose in the blood.

If the lipid metabolism is disturbed, an appropriate treatment is prescribed.

Pancreatitis

There have been recorded cases of pancreatitis, although the causal relationship with the use of abacavir is not exactly established.

Therapy with three NRTIs

In patients with high viral load (>100 000 copies / ml) the use of a triple combination comprising abacavir, lamivudine and zidovudine, requires special consideration.

There were recorded cases of high incidence of virological failure and the emergence of resistance in the early stages, when as a regimen of therapy 1 once a day, a combination of abacavir with tenofovir, dizoproxil fumarate and lamivudine was used.

Diseases of the liver

The drug Abacavir-ABC is contraindicated in patients with impaired liver function in classes A, B and C on the Child-Pugh scale. 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.

Concomitant Hepatitis B or C

Patients with concomitant chronic hepatitis B or C who receive combination antiretroviral therapy have an increased risk of severe and potentially lethal adverse reactions from the liver. In the case of concomitant antiviral therapy for hepatitis B or C, you should also read the appropriate instructions for the use of these medicines.

Care should be taken when concurrent administration of abacavir and ribavirin.

Kidney Diseases

The drug Abacavir-ABC should not be given to patients with terminal chronic renal failure.

Immunodeficiency Syndrome

If HIV-infected patients with severe immunodeficiency have asymptomatic opportunistic infections or their residual effects at the time of initiation of antiretroviral therapy, such therapy may lead to an increase in the symptoms of opportunistic infections or other severe consequences. Typically, these reactions occur within the first weeks or months after initiation of antiretroviral therapy.

Typical examples are cytomegalovirus retinitis, generalized and / or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jirovecii (formerly 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-Barré syndrome) have also been observed on the background of immune reconstitution, but the time of the primary manifestations varied, and the disease may occur many months after initiation of therapy and have an atypical course.

Osteonecrosis

Although the etiology of this disease is multifactorial (including receiving corticosteroids, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis is most common in patients with advanced HIV infection and / or long-receiving combination antiretroviral therapy. The patient should consult a doctor if he experiences pain and stiffness in the joints or difficulty in moving.

Opportunistic infections

Use of the drug Abacavir-ABC or other antiretroviral drugs does not preclude the development of opportunistic infections and other complications of HIV infection, so patients must remain under the supervision of a physician who is experienced in the treatment of HIV-associated diseases.

Transmission of HIV infection

The provision of antiretroviral therapy, including the drug Abacavir-ABC, does not exclude the possibility of sexual transmission of HIV or in contact with infected blood and therefore does not negate the need for appropriate precautions.

Myocardial infarction

As a result of a prospective observational epidemiological study in order to study the incidence of myocardial infarction in patients receiving combined antiretroviral therapy, a previous link was found during 6 months, receiving abacavir with an increased risk of myocardial infarction. According to the generalized analysis of clinical studies, there was no increase in the risk of developing myocardial infarction associated with the use of abacavir.

Biological mechanisms that explain a potentially increased risk are unknown. Available data from observational cohort and controlled clinical trials do not allow one to unequivocally determine the relationship of abacavir therapy with the risk of developing myocardial infarction.

Nevertheless, care should be taken to prescribe antiretroviral therapy, including drugs containing abacavir, patients with a possible risk of coronary heart disease. It is necessary to take all measures to minimize risk factors (such as hypertension, dyslipidemia, diabetes and smoking).

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

Special studies of the ability to drive vehicles and control mechanisms were not carried out.

There is no evidence to support the effect of abacavir on the ability to engage in potentially hazardous activities requiring increased attention. Nevertheless, patients should be informed about the possible development of such undesirable reactions as increased fatigue, during treatment with abacavir. It should be recommended that they take care when driving and controlling machinery. In the case of the development of increased fatigue, patients should abandon such potentially dangerous occupations as driving a car and controlling the mechanisms.

Form release / dosage:Film-coated tablets, 300 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.For 60 tablets in a jar (bottle), a polymer (made of polyethylene or polypropylene) for drugs, sealed with a polymer lid (made of polyethylene or polypropylene).

Free space in the jar (vial) is filled with cotton wool with a hygroscopic or sterile cotton ball.

Each jar (bottle) or 6 contour squares, together with instructions for use, is placed in a pack of cardboard for consumer containers.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002340

Date of registration:13.01.2014 / 23.09.2016

Expiration Date:13.01.2019

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

R-PHARM, JSC Russia

Information update date: & nbsp07.02.2017

Illustrated instructions

Instructions

Abacavir-ABC (Abacavir-ABC)