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

Excipients: sodium carboxymethyl starch 35 mg, silicon colloidal dioxide 7 mg, magnesium stearate 7 mg, povidone K-30 28 mg, microcrystalline cellulose 291.6 mg.

Composition of the film shell: Opadrai II yellow 22 mg, including: hypromellose (hydroxypropylmethylcellulose) 7.48 mg, lactose monohydrate 6.16 mg, macrogol (polyethylene glycol) 2.64 mg, titanium dioxide 4.62 mg, iron oxide dye yellow 1.1 mg.

1 tablet, film-coated 600 mg, contains:

Active substance: abacavir sulfate 702.8 mg, calculated as abacavir 600 mg.

Excipients: sodium carboxymethyl starch 58 mg, silicon colloidal dioxide 11 mg, magnesium stearate 11 mg, povidone K-30 46 mg, microcrystalline cellulose 391.2 mg.

Composition of the film shell: Opadrai II yellow 38 mg, including: hypromellose (hydroxypropylmethylcellulose) 12.92 mg, lactose monohydrate 10.64 mg, macrogol (polyethylene glycol) 4.56 mg, titanium dioxide 7.98 mg, iron oxide dye yellow 1.9 mg.

Description:

Tablets are oval biconvex, with a risk, covered with a film coating of yellow color. On a cross-section - white or almost white color.

Pharmacotherapeutic group:Antiviral [HIV] agent

ATX: & nbsp

J.05.A.F.06 Abacavir

Pharmacodynamics:

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, carbovir-5'-triphosphate (carbovir-TF). According to research in vitro, the antiviral effect of the drug is due to 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 an HIV protease inhibitor, 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 iP vitro and in vivo formed slowly. For a clinically significant increase in the 50% inhibitory concentration (IC₅₀) (increase IC₅₀ 8 times the "wild" strain of the virus) requires multiple mutations. 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, 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).

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 concentration (T_m_Oh) when taking abacavir orally in the form of tablets is about 1.5 hours, and as a solution for oral administration - about 1 hour. Area under the pharmacokinetic curve "concentration-time" (AUC) for the tablet form of abacavir does not differ from that for abacavir in the form of a solution for oral administration.When taking the tablet form of abacavir orally at a dose of 300 mg 2 times a day, the maximum concentration in the blood plasma (C_m_Oh) on reaching the equilibrium state is on the average 3 μg / ml, a AUC during The 12-hour interval between doses is an average of 6.02 μg / h.

After a single admission of abacavir tablets in a dose of 600 mg C_m_Oh averages about 4.26 μg / ml, a AUC ∞ - an average of 11.95 μg / h.

According to the study, 20 HIV-infected patients abacavir at a dose of 300 mg twice a day and only one dose (300 mg) before the 24-hour sampling period for analysis, the geometric mean of the terminal half-life (T1 / 2) of intracellular carbovir-TF at equilibrium is 20.6 h a similar index for the concentration of abacavir in serum - 2.6 h). Equilibrium pharmacokinetic indices when taking abacavir 600 mg once a day were identical with those with abacavir 300 mg twice a day in a clinical study with a cross-over design 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 once daily compared with 300 mg twice a day for abacavir (an increase AUC in a state of equilibrium in 24 hours (AUC_24,_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 dose of a single dose was shown in a clinical study (CNA30021).

Eating slows the absorption of abacavir and reduces C_m_Oh, but does not affect AUC. therefore abacavir can be taken with or without food. Receiving a crushed tablet with a small amount of semi-solid food or liquid does not affect the pharmacokinetics and, therefore, the clinical effectiveness. This conclusion is based on the physicochemical and pharmacokinetic parameters of the active substance and solubility in water of abacavir tablets, it is assumed that the patient will grind and add the whole tablet to the food or liquid and take it immediately inside.

Distribution and binding to blood plasma proteins

The volume of distribution of abacavir with intravenous administration is about 0.8 l / kg, which indicates its ability to easily penetrate into tissues.

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 pharmacokinetic study of phase I it was found that 1.5 hours after taking abacavir 300 mg twice a day, its mean concentration in the CSF was 0.14 μg / ml. the use of abacavir in a dose of 600 mg twice a day, the concentration of the drug in the CSF increased from 0.13 μg / ml 0.5-1 hour after admission to 0.74 μg / ml when it was measured 3-4 hours after taking abacavir. Thus, even if the concentration of abacavir, observed in the CSF 4 hours after taking the drug at a dose of 600 mg twice a day, is not the maximum achievable with this mode of therapy, it already exceeds IFROM₅₀ (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 released by the kidneys of less than 2% of the accepted dose of the drug. In organism rights abacavir is metabolized mainly by the action of alcohol dehydrogenase to form the 5'-carboxylic acid andby conjugation with glucuronic acid to form 5'-glucuronide, which is about 66% of the total administered dose of the drug. These metabolites are excreted by the kidneys.

Excretion

On average, the half-life of abacavir is about 1.5 hours. Prolonged intake of abacavir orally at a dose of 300 mg 2 times 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 quantity is excreted through the intestine.

Special patient groups

Children

Abacavir is well and rapidly absorbed in the form of a solution for ingestion and in the form of tablets when ingested in children. Exposure of abacavir in blood plasma was the same for both forms of release at the same dosage. In children receiving abacavir in the form of a solution for oral administration in accordance with the recommended dosing regimen, the exposure of abacavir in blood plasma was similar to that of adults. In children receiving abacavir in the form of tablets in accordance with the recommended dosing regimen, the exposure of abacavir to plasma was higher than that of children receiving abacavir in the form of a solution for oral administration, due to the use of higher doses in mg / kg when taking tablets. Pharmacokinetic studies in children showed that taking the drug 1 time per day is equivalent in terms of indices AUC_0-24Reception of the same dose of the drug, divided into 2 times a day.

There is insufficient safety data to recommend - the use of abacavir in children younger than 3 months. 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 medications taken.

Patients with impaired renal function

Abacavir is metabolized primarily in the liver, less than 2% of 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 adjustment is 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 (5-6 on the Child-Pugh scale) indicate an increase AUC an average of 1.89 times and a half-life of 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 may receive 200 mg of abacavir 2 times a day for therapeutic purposes.

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

Indications:

Treatment of HIV infection in adults and children weighing more than 14 kg as part of combined antiretroviral therapy.

Contraindications:

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

- Children weighing less than 14 kg (for this dosage form);

- Hepatic insufficiency of moderate and severe degree (class 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;

- The period of breastfeeding;

- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Carefully:

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

Pregnancy and lactation:

Pregnancy

The use of abacavir during pregnancy and after childbirth was studied 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 the use of abacavir, compared with the frequency of malformations in the comparison group.However, adequate and well-controlled studies in pregnant women are not available, the safety of abacavir in women during pregnancy has not yet been established. 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 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 inpregnancy time 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 canon is taken orally, regardless of food intake. The drug should be prescribed by a doctor with experience of treatment

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.

Adults and children with a body weight of at least 25 kg

The recommended dose of Abacavir canon is 600 mg / day. The drug is given in a dose of 300 mg (1 tablet 300 mg or ½ 600 mg tablets, accurately break the risk) 2 times a day or 600 mg (2 tablets 300 mg or 1 tablet 600 mg) once a day.

Special patient groups

Children

Children with a body weight of 14 to 25 kg

-Children with a body weight of 14 to 20 kg: recommended dose of the drug Abacavir Canon - 150 mg (1/2 tablet 300 mg, break down accurately at risk) 2 times a day or 300 mg (1 tablet 300 mg) once a day;

- Children with a body weight of more than 20 kg, but less than 25 kg: the recommended dose of the drug Abacavir Canon - 150 mg (½ 300 mg tablets, break down exactly according to risk) in the morning and 300 mg (1 300 mg tablet) in the evening or 450 mg (1 ½ 300 mg tablets) once a day;

For children weighing less than 14 kg or patients unable to swallow tablets, the use of the drug as a solution for oral administration is recommended.

Patients with impaired renal function

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

Patients with impaired hepatic function

Abacavir is metabolized predominantly in the liver. The recommended dose of abacavir for patients with mild liver function disorders (5- 6 points on the Child-Pugh scale) is 200 mg 2 times a day. Considering the need to use smaller doses of abacavir in patients with mild liver function disorders, it is prescribed in an alternative dosage form - oral solution for correct dosing of the drug.There is no data on the pharmacokinetics and safety of abacavir in patients with moderate or severe liver dysfunction. Thus, the use of abacavir in patients with impaired liver function of medium and severe degree is contraindicated.

Side effects:

The nature of other adverse reactions other than MRI, but observed in patients taking Abacavir canon, is not fully understood. Whether these unwanted reactions result from the use of the drug Abacavir Canon or a wide range of other drugs concomitantly prescribed for the treatment of HIV infections or caused by the disease itself has not been established to date.

Many of the undesirable reactions associated with taking the drug Abacavir canon (nausea, vomiting, diarrhea, fever, fatigue, rash) are usually observed with the development of the hypertensive drug to abacavir. therefore, if any of these symptoms appear, a thorough examination of the patient is shown to confirm the development of the MRI. If the drug Abacavir Canon was canceled due to the appearance of the above symptoms and the decision was made to resume therapy with the drug Abacavir Canon, then this can only be done 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, 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 from> 1/100 to <1/10,

infrequently - from> 1/1000 to <1/100,

rarely from> 1/10000 to <1/1000,

very rarely - <1/10000.

Clinical Trials Data

Disorders from the metabolism and nutrition

Often: loss of appetite.

Disturbances from the nervous system

Often: headache.

Violations from the groan of the gastrointestinal tract

Often: nausea, vomiting, diarrhea.

General disorders and disorders at the site of administration

Often: fever, drowsiness, fatigue.

In controlled clinical trials, it was shown that changes in laboratory parameters in the treatment of abacavir are not infrequent, as in the control group of patients who did not receive abacavir.

Children

Safety data confirming once abacavir dosing in children in the study were obtained ARROW (COL 105677), in which 669 children infected with HIV-1, was obtained abacavir and lamivudine - 1 or 2 times a day. No additional safety signals were identified in children who took abacavir 1 or 2 times a day compared with adults.

Post-registration data

Disorders of metabolism and nutrition

Often: hyperlactatemia.

Rarely: lactic acidosis, accumulation and / or redistribution of adipose tissue. The frequency of these undesired reactions is dependent on many factors, including the antiretroviral drugs used in combination with abacavir.

Disorders from the gastrointestinal tract

Rarely: pancreatitis (a cause-and-effect relationship with the use of abacavir is not exactly established).

Disturbances from the skin and subcutaneous tissues

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

Very rare: erythema polymorph, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Lactoacidosis, sometimes fatal, has been reported, 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 diverse and these phenomena can occur many months after the initiation of therapy.

Cases of osteonecrosis have been reported,especially in patients with well-known risk factors, advanced stage of 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 (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 that occur in at least 10% of patients with MRSV are indicated in bold type. Practically 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 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

Shortness of breath, 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

Increase in biochemical parameters of liver function, hepatitis, hepatic insufficiency.

Disturbances from musculoskeletal and connective tissue

Myalgia, myolysis, arthralgia, increased activity of creatine phosphokinase.

Disorders from the kidneys and urinary tract

Increased serum creatinine, renal failure.

General disorders and disorders at the site of administration

Fever, fatigue, malaise, swelling, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions. Renewal of Abacavir canon following MRI on abacavir leads to a rapid return of symptoms within a few hours. Repeated MRI usually proceeds 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 Canon after its withdrawal caused by the appearance of just one of the main symptoms of hypersensitivity (see above) and in very rare cases this reaction occurs when the drug Abacavir canon is resumed in patients who, prior to discontinuation of the drug there were no symptoms of MRI (ie, in patients previously thought to be abacavir-tolerant).

Detailed information on the clinical management of the case of a suspected MRSV abacavir see "Special instructions".

Overdose:

Symptoms

In clinical studies, there were no undesirable reactions with the use of abacavir in single doses up to 1200 mg and diurnal up to 1800 mg. The effect of the drug in higher doses has not been studied to date.

Treatment

In case of an overdose, a 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 mediated by cytochrome P450 is unlikely.

Abacavir does not suppress metabolic reactions involving isoenzyme CYP3A4 cytochrome P450.

In studies in vitro shown, that - Abacavir does not interact with drugs that are metabolized by isoenzymes CYP3A4, CYP2C9 and CYP2D6. Clinical studies have not revealed induction of hepatic metabolism of exogenous substances under the influence of abacavir. Thus, the interaction of abacavir with HIV protease inhibitors and other drugs metabolized with the participation of the main cytochrome P450 isoenzymes 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 plasma can be slightly reduced.

Ethanol: ethanol slows the metabolism of abacavir, which leads to increase AUC on 41%.However, the clinical significance of this change is small. On the metabolism of ethanol abacavir does not affect.

Methadone: according to pharmacokinetic studies, the use of abacavir in a dose of 600 mg twice a day in combination with methadone reduces C_m_Oh abacavir in serum by 35%, increases T_m_Oh in serum for 1 h, but does not change AUC. The clinical significance of these changes is small.

The same study found that abacavir increases the systemic clearance of methadone by 22%. In most cases, these changes are also considered clinically insignificant, but in certain situations, a dose change in methadone may be required.

Retinoids: retinoids, for example, isotretinoin, are eliminated with involving alcohol dehydrogenase, so they can interact with abacavir, but to date no special studies have been conducted.

Ribavirin: due to abacavir and ribavirin have the same phosphorylation pathways, interaction between these substances is expected, which can lead to a decrease in intracellular phosphorylation of ribavirin metabolites andpotentially leading to a decrease in the likelihood of achieving a sustained virologic response in HCV coinfected HIV-infected patients taking pegylated interferon and ribavirin therapy. Controversial data have been published on the simultaneous use of abacavir and ribavirin. According to some data, it is assumed that HIV-infected patients receiving abacavir-containing drugs may have a low risk of responding to antiviral therapy with pegylated interferon and ribavirin. Care should be taken when taking these medications at the same time.

Special instructions:

The drug should be prescribed by a doctor with experience in the treatment of HIV infection.

Each patient should read the instructions for use.

Hypersensitivity

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

The following rules should be observed.

- A study should be conducted for the presence of an allele HLA-B*5701 before the beginning of therapy with the drug Abacavir Canon and also before the resumption of therapy with the drug Abacavir Canon in patients with unknown status for the allele HLA-B*5701, who had previously tolerated abacavir therapy.

- It is not recommended to use the drug Abacavir Canon in patients with an allele HLA-B*5701 or in patients who were suspected of having an MRI during the administration of any other drug containing abacavir regardless of status in relation to 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 Canon. Also, patients should be reminded that it is necessary to constantly carry a warning card attached to the drug.

- In all patients receiving Abacavir canon therapy, a clinical diagnosis of a suspected MRS should remain the basis for making a clinical decision.

- If MRI is suspected, therapy with Abacavir canon should be stopped immediately, even if there is no allele HLA- B * 5701. The delay in stopping therapy with Abacavir canon after the occurrence of MRI may lead to a life-threatening reaction.

- Patients who developed MRLT should be informed of the need to transfer the remaining tablets of the drug Abacavir Canon to the treating physician in order to avoid the resumption of abacavir.

- Resumption of use of drugs, contents abacavir, after the suspected MRI on 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 the MRI can not be ruled out, the use of the drug Abacavir Canon or any other medications containing abacavir.

- If the MRI is excluded, it is possible to resume therapy with the drug Abacavir Canon. In rare cases, patients who discontinued abacavir use for reasons other than MRS symptoms also reported the development of life-threatening reactions within a few hours after resumption of abacavir therapy (see section "Description of individual adverse reactions").

Patients should be informed of the possibility of developing an MRI with the resumption of therapy with the drug Abacavir Canon or other medications containing abacavir, should be carried out only with the availability of quick access to medical care.

Clinical picture of MRI on abacavir

MIRVs on abacavir were well studied in clinical trials and during post-registration follow-up. Symptoms usually appear within the first 6 weeks (median time of onset of this reaction is 11 days) after initiation of abacavir therapy, however these reactions can develop at any time during therapy.

Virtually all of the responses of the WGS to abacavir include fever and / or rash, as part of the syndrome. Other signs and symptoms that are noted as a manifestation of WGS on abacavir, include symptoms on the part of the respiratory and gastrointestinal tract, which can lead to incorrect diagnosis of MRI as a respiratory disease (pneumonia, bronchitis, pharyngitis) or gastroenteritis (see "Side effects", "Description of individual adverse reactions"). Patients should be closely monitored with consultations every 2 weeks, especially during the first 2 months of therapy with the drug Abacavir Canon.

If, with the emergence of symptoms associated with MRI, treatment with abacavir continues, they become more pronounced and can take a life-threatening character. In most cases, these symptoms disappear when discontinuing abacavir.

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.

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

Lactic acidosis has a high mortality in the absence of emergency treatment and can be associated with pancreatitis, hepatic or renal insufficiency. Lactic acidosis, as a rule, manifested itself several months of therapy. It is necessary to stop therapy with analogues of nucleosides in case of symptomatic manifestations of hyperlactatemia and metabolic or lactic acidosis, progression of hepatomegaly or fast increased activity of aminotransferases.

The use of Abacavir canon and other abacavir-containing drugs 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 with high risk require careful monitoring.

If clinical or laboratory signs of lactic acidosis occur with or without hepatitis (hepatomegaly and steatosis may appear even in the absence of a marked increase in aminotransferase activity), treatment with Abacavir canon should be stopped.

Mitochondrial dysfunction

Research in vitro and in vivo showed that the analogues of nucleosides and nucleotides can cause a different degree of damage to the mitochondria. Mitochondrial dysfunction was observed in HIV-negative children who received intrauterine and / or post-nucleoside analogues. The main undesirable reactions were hematologic disorders (anemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipazemia). These undesirable reactions are often transient. Some neurological disorders with late onset have been reported (increased muscle tone, convulsions, behavioral disorders).Are these neurological disorders transient or permanent in the present time is unknown. Any child, even HIV-negative, exposed to prenatal exposure to nucleoside and nucleotide analogues, must undergo a clinical and laboratory examination in order to exclude mitochondrial dysfunction in case of revealing the corresponding signs or symptoms. These data do not 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 central obesity, dorsocervical fat deposition ("buffalo buffalo"), a reduction in the subcutaneous fat layer on the face and extremities, enlargement of the mammary glands , increased serum lipid concentrations and glucose concentrations in the blood.

Although one or more of the above unwanted reactions associated with a common syndrome, which is often referred to as lipodystrophy, can cause all drugs of the HIV and NRTI classes.The data indicate the existence of differences between individual representatives of these classes of drugs in the ability to cause 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, possibly 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 concentrations and blood glucose concentrations. If the lipid metabolism is disturbed, an appropriate treatment is prescribed.

Pancreatitis

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

Therapy with three nucleoside reverse transcriptase inhibitors (NRTIs)

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

There were recorded cases of high rates of virological failure and the emergence of resistance in the early stages, when a combination of abacavir and tenofovir dezoproxil fumarate and lamivudine was used as a therapy regimen 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 Abacavir canon is contraindicated in patients with impaired liver function of medium and severe degree.

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

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 drugs.

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

Kidney Diseases

The drug Abacavir canon 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 jiroveci (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-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 flow.

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 seen in patients at a late 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 the drug Abacavir canon or other antiretroviral drugs does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the supervision of a doctor who has experience in the treatment of HIV-associated diseases.

Transmission of HIV infection

The provision of antiretroviral therapy, including the drug Abacavir Canon, 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 abacavir connection was detected within 6 months with an increased risk of myocardial infarction. According to the generalized analysis of clinical trials, there was no increase risk of myocardial infarction associated with the use of abacavir. Biological mechanisms that explain a potentially increased risk are unknown. In general, the available data from cohort observations and controlled clinical studies do not allow one to unequivocally determine the relationship between abacavir therapy and the risk of myocardial infarction.

However, 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 all modifiable risk factors (such as hypertension, dyslipidemia, diabetes and smoking).

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

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 of 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.

Form release / dosage:The film-coated tablets are 300 mg and 600 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 60, 90, 120 tablets (300 mg dosage) or 30, 60, 90 tablets (600 mg dosage) to a polymer can for polyethylene terephthalate medicines with a polypropylene cover.

By 3, 6, 9 contour cell packs or 1 bank of polymer for medicines together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C in the manufacturer's packaging.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004201

Date of registration:17.03.2017

Expiration Date:17.03.2022

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp13.04.2017

Illustrated instructions

Instructions

Abacavir Canon (Abacavir Canon)