Abacavir – nucleoside analog, HIV reverse transcriptase inhibitory and selectively suppresses replication of HIV-1 and HIV-2, including HIV-1 strains resistant to zidovudine, lamivudine, zalcitabine, didanosine and nevirapine. Abacavir undergoes intracellular metabolism, turning into an active form karbovir- 5′-triphosphate (carbovir-TF). According to studies in vitro, the antiviral effect of the drug due to inhibition of HIV reverse transcriptase, leading to breakage of DNA synthesis on the RNA template and stop virus replication. There was no antagonism in antiviral abacavir activity in cultured cells by combination with nucleoside reverse transcriptase inhibitors (NRTIs) didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine or zidovudine, non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine or a protease inhibitor (PI HIV) amprenavir .
We obtained in vitro HIV-1 strains resistant to abacavir, mutations were detected in several codons
reverse transcriptase gene
(RT) – M184V, K65R, L74V and Y115F. Resistance of HIV to abacavir Ip vitro and in vivo formed slowly. For clinically significant increase of 50% inhibitory concentration (IC50) (IC50 increase 8 times the “wild” strains of virus) required multiple mutations. Strains resistant to abacavir may have reduced sensitivity to lamivudine, zalcitabine and / or didanosine, but remain fully sensitive to zidovudine and stavudine. Cross-resistance to abacavir and SP HIV NNRTIs or unlikely. Inefficiency mode first line comprising abacavir, lamivudine and zidovudine, preferably associated with a single mutation – M184V, that retains the ability to select a wide second-line therapy regimes
Abacavir penetrates into cerebrospinal fluid (CSF) and reduces the HIV-1 RNA content therein. In combination with other antiretroviral drugs it may prevent the development of neurological complications of HIV infection and delay the emergence of resistant strains within the central nervous system (CNS).
Abacavir is rapidly and well absorbed when taken orally. The absolute bioavailability of abacavir when administered in adults is about 83%. The time to reach maximum concentration (Tmax) of abacavir inside a pill is about 1.5 hours, and in the form of oral solution – approximately 1 hr. The area under the concentration-time “concentration-time” curve (AUC) for the tablet form of abacavir is not different from that of abacavir as oral solution. When receiving the tablet form of abacavir oral dose of 300 mg 2 times daily maximum plasma concentration (Cmax) upon reaching the equilibrium state is an average of 3 ug / ml, and AUC for the 12-hour interval between doses doses – an average of 6, 02 mkg’ch / ml.
After a single dose of abacavir tablets of 600 mg average Cmax is about 4.26 mcg / mL and AUC ∞ – average 11.95 mkg’ch / ml
According to a study in 20 HIV infected patients, abacavir 300 mg 2 times a day, only one dose (300 mg) before a 24-hour period of sampling for analysis, the geometric mean terminal half-life (T1 / 2) intracellular carbovir-TF at equilibrium is 20.6 hrs (the figure for abacavir serum concentration – 2.6 h). Equilibrium pharmacokinetic parameters of abacavir 600 mg 1 time per day were identical with those of abacavir 300 mg 2 times a day in a clinical study with cross-over design in 27 HIV-infected patients. Intracellular carbovir-TF content in peripheral blood mononuclear cells was higher with abacavir 600 mg 1 time per day as compared with the abacavir 300 mg 2 times a day (increased AUC in equilibrium for 24 hours (AUC24, ss) 32% , daily maximum concentration at equilibrium (Cmax24, ss) is 99%), which suggests the possibility of such a dosing regime of HIV-infected patients. Efficacy and safety of abacavir subject receiving a single daily dose has been shown in a clinical study (CNA30021).
Eating slows down the absorption of abacavir and reduces the Cmax, but no effect on the AUC. Therefore ZIAGEN can be taken with food or without it. Receiving crushed tablets with a small amount of semi-solid or liquid food has no effect on the pharmacokinetics and hence on the clinical efficacy. This conclusion is based on the physicochemical and pharmacokinetic parameters of the active agent and the solubility in water of tablets abacavir, it is assumed that the patient is chop and add to the food or liquid and the entire tablet will immediately inside.
Distribution and protein binding blood plasma
The volume of distribution of abacavir intravenous administration is about 0.8 L / kg, indicating that its ability to easily penetrate tissue.
Studies with HIV-infected patients showed that abacavir is well into the CSF, wherein the AUC ratio of abacavir CSF to abacavir AUC blood plasma “is 30-44%. In the phase I pharmacokinetic study it was found that after 1.5 hours after abacavir 300 mg 2 times a day, its average concentration in CSF was 0.14 g / ml. When using abacavir 600 mg 2 times a day, the drug concentration in CSF should increase from 0.13 .mu.g / ml after 0, 5-1 h after administration to 0.74 ug / ml when measured 3-4 hours after administration of Ab Avir. Thus, even if the concentration of abacavir observed in CSF after 4 hours after administration at a dose of 600 mg 2 times daily, is not a maximum achievable in this mode of therapy, she already exceeds IC50 (0.08 ug / ml or 0 , 26 mmol / l) in 9 times.
In in vitro studies have found that in therapeutic doses abacavir moderate (about 49%) protein binds to human blood plasma. This suggests that abacavir drug interactions by displacement from their connection to plasma proteins is unlikely.
Abacavir is metabolized primarily in the liver, released in unaltered form by kidneys less than 2% of the dose preparation. In humans, abacavir metabolized mainly by the action of alcohol dehydrogenase to form a 5′-carboxylic acid by conjugation with glucuronic acid to form the 5′-glucuronide, constituting about 66% of the total administered dose. These metabolites are excreted by the kidneys.
The average half-life of abacavir is about 1.5 hours. Prolonged abacavir oral dose of 300 mg 2 times a day does not lead to significant accumulation of the drug. Excretion abacavir achieved by metabolism in the liver followed by the excretion of metabolites mainly kidneys. About 83% of the administered dose excreted by the kidneys as metabolites and abacavir unchanged, and the remainder is output through the intestine.
Special groups of patients
Abacavir is well absorbed and rapidly in the form of a solution for oral administration in the form of tablets upon ingestion in children. abacavir exposure is in the blood plasma was the same for both forms of release at the same dosage. In children receiving abacavir in the form of oral solution, in accordance with the recommended dosing regimen, abacavir exposure in plasma was similar to that in adults. In children receiving abacavir in tablet form according to the recommended dosage regimen, and plasma exposure of abacavir was higher than in children receiving abacavir in solution form for ingestion, due to the reception of higher doses in mg / kg of tablets with the reception. Pharmacokinetic studies in children have shown that taking the drug 1 time per day is equivalent in terms of AUC0-24 receive the same dose divided into 2 times a day.
There is insufficient safety data to recommend – the use of abacavir in children younger than 3 months. There is limited data showing that a dose of 2 mg / kg in the newborn must be 30 days or more provides similar performance AUC value as compared with a dose of 8 mg / kg in older children.
The pharmacokinetics of abacavir in patients older than 65 years have not been studied. In the treatment of elderly patients is necessary to consider more frequent violations of the liver, kidney and heart in this age, and comorbidities and medications taken.
Patients with impaired renal function
Abacavir is metabolized primarily in the liver, less than 2% of the excreted by the kidneys in unchanged form. Pharmacokinetics of abacavir in end-stage renal failure is about the same as with normal renal function. Therefore, in case of violation of renal function dose adjustment is not required.
Patients with impaired liver function
Abacavir is metabolized mostly in the liver. Results of the study the pharmacokinetics of abacavir in patients with impaired liver function mild (5-6 points on a scale Child-Pugh) evidence of an increase in AUC on average of 1.89 times, and half-life – 1.58 times. The indicator AUC metabolite of abacavir abnormal liver function is not affected, but the rate of their formation and removal thus decreases.
Patients with impaired mild liver function for therapeutic purposes can take abacavir 200 mg 2 times a day.
The pharmacokinetics of abacavir in patients with impaired liver function moderate and severe has not been studied, therefore, the use of abacavir is not recommended in these patient populations.
Adults are prescribed by a doctor, children on prescription
1 tablet, film-coated 600 mg contains:
Active substance: abacavir sulfate 702.8 mg, based on 600 mg of abacavir
Excipients: Sodium carboxymethyl starch 58 mg Colloidal silica 11 mg Magnesium stearate 11 mg Povidone K-30 46 mg Microcrystalline cellulose 391.2 mg
Composition of film-coating: Opadry II yellow 38mg, including: hypromellose (hydroxypropylmethylcellulose) 12.92 mg lactose monohydrate 10.64 mg macrogol (polyethylene glycol) 4.56 mg, 7.98 mg of titanium dioxide, iron oxide yellow dye 1.9 mg.
Treatment of HIV infection in adults and children weighing more than 14 kg as part of combination antiretroviral therapy.
– Hypersensitivity to abacavir or any other components that make up the drug;
– children weighing less than 14 kg (for a given dosage form);
– Liver failure secondary to severe (Class B and C of Child-Pugh), due to the lack of clinical data and the recommended dosing regimen;
– Hepatic impairment mild (Class A according to Child-Pugh), due to the inability to provide dosing regimen;
– are breast-feeding period;
– Lactose intolerance, lactase deficiency, glucose-galactose malabsorption
Patients with a possible risk of ischemic heart disease; the combined use of abacavir and ribavirin (see. “Interaction” section).
The nature of other adverse reactions, other than HSR, but observed in patients taking Abacavir Canon, is not completely clear. Are these adverse reactions resulting from the application of the drug or Abacavir Canon wide range of other drugs simultaneously prescribed for the treatment of HIV infections or they are caused by the disease has not yet been established.
Many of the following adverse reactions associated with drug intake Canon Abacavir (nausea, vomiting, diarrhea, fever, fatigue, rash) typically observed during the development of HSR to abacavir. so if you experience any of these symptoms indicated a thorough examination of the patient to confirm the development of HSR. If the drug Abacavir Canon has been canceled due to the emergence of the above symptoms and a decision to resume therapy with Abacavir Canon, then it can be done only under direct medical supervision.
It has been reported very rare cases of polymorphic erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, which can not be excluded HSR to abacavir. In such cases it is necessary to stop taking medicines containing abacavir forever.
Most of the following adverse reactions are not limitative treatment. The frequency of occurrence is defined as follows:
very often – > 1/10,
frequently – by > 1/100 to < 1/10,
infrequently – from > 1/1000 to < 1/100,
rarely – from > 1/10000 to < 1/1000,
very rarely – < 1/10000.
Data from clinical studies
Violations by the metabolism and nutrition
Often:. Loss of appetite
Disorders of the nervous system
Violations by the groans of the gastrointestinal tract
Common: nausea, vomiting, diarrhea
General disorders and administration site in
Common: fever, lethargy, fatigue
In controlled clinical studies have shown that changes in laboratory values in the treatment of abacavir is observed infrequently, as in the control group of patients who did not receive abacavir.
Safety data confirming once abacavir dosing in children, were obtained in the study ARROW (COL 105677), in which 669 children infected with HIV-1, prepared abacavir and lamivudine – 1 or 2 times per day. There were no additional safety signals in children abacavir 1 or 2 times a day compared to an adult.
These post-marketing surveillance
Metabolic disorders and nutrition
Rare: 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.
Violations by the gastrointestinal tract
Rare: pancreatitis (causal connection with the use of abacavir is not certain)
Violations of the skin and subcutaneous tissue
Often:. Rash (without systemic signs)
Very rarely. Polymorphous erythema multiforme, including Stevens-Johnson syndrome and toxic epidermal necrolysis
Cases of lactic acidosis have been reported, sometimes fatal, usually associated with severe hepatomegaly and hepatic steatosis, when using nucleoside analogues.
The use of combination antiretroviral therapy has been associated with redistribution of adipose tissue (lipodystrophy) in HIV patients, including the reduction of subcutaneous fat in the face and extremities, increased intra-abdominal and visceral fat, breast enlargement and dorsotservikalnoe fat deposition ( “buffalo hump”). < br>
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 immune deficiency at the time of the start of combination antiretroviral therapy may cause an inflammatory reaction to asymptomatic or residual opportunistic infections. Also cases of autoimmune diseases have been reported (eg, Graves’ disease), taking place in conditions of immune reactivation, however, presented as possible manifestations of the disease are more varied, and these events can occur many months after initiation of therapy.
cases of osteonecrosis, especially in patients with well-known risk factors for patients with advanced HIV infection or long-term use of combination antiretroviral therapy have been reported. The frequency of this phenomenon is unknown.
Description of individual adverse reactions
hypersensitivity reaction (HSR) to abacavir was defined as the total undesirable reaction during treatment preparations containing ABC. Signs and symptoms of HSR are listed below. These signs and symptoms were found during clinical trials or post-registration monitoring. Symptoms and signs occurring no less than 10% of patients with HSR, bold. Virtually all patients with HSR develop fever and / or rash (usually maculopapular or urticaria) as part of the syndrome, but the reaction can proceed without rash or fever. Other major symptoms include symptoms of the gastrointestinal tract, respiratory or constitutional symptoms such as lethargy or malaise.
Violations of the skin and subcutaneous tissue
Rash (usually maculopapular or urticaria).
Violations by the gastrointestinal tract
Nausea, vomiting, diarrhea, abdominal pain, ulceration of the mucous membranes of the mouth.
Violations of the respiratory system, thorax and mediastinum
Shortness of breath, cough, sore throat, adult respiratory distress syndrome, respiratory failure.
Disorders of the nervous system
Blood disorders and lymphatic system
Violations of the liver and biliary tract
Increasing the biochemical parameters of liver function, hepatitis, liver failure.
Violations by musculoskeletal and connective tissue
Myalgia, myolysis, arthralgia, increased creatine kinase activity.
Violations by the kidneys and urinary tract
Increasing the concentration of creatinine in serum, kidney failure.
General disorders and administration site in
Fever, fatigue, malaise, swelling, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis. Resumption of the drug after Canon Abacavir HSR to abacavir leads to a rapid return of symptoms within a few hours. Re HSR is usually more severe than the first, and may include life-threatening hypotension and death. In rare cases the reactions also occur when resuming therapy with Abacavir Canon after cancellation caused by the appearance of only one of the main symptoms of hypersensitivity (see. Above) and in very rare cases, this reaction occurs at the resumption of the drug Abacavir Canon patients who prior to withdrawal of the drug There has been no symptoms of HSR (ie patients previously considered transferring therapy with abacavir).
For more information on the clinical management of suspected abacavir hypersensitivity reaction, see “Cautions”.
How to accept, acceptance rate and dosage
The drug Abacavir Canon taken orally, regardless of food intake. The drug should be prescribed by a doctor with experience in treating
HIV infection. To ensure accurate dosing of the drug is recommended to swallow the tablet completely without division, but alternatively allowed division and grinding the tablets with the addition of a small amount of semi-solid food or liquid. The entire amount of the resulting mixture to be taken inside immediately.
Adults and children weighing at least 25 kg
The recommended dose of the drug Abacavir Canon – 600 mg / day. The drug is administered at a dose of 300 mg (1 tablet of 300 mg ½ tablet or 600 mg, break exactly risk), 2 times a day, or 600 mg (2 tablets of 300 mg or 600 mg 1 tablet) 1 time per day.
Special groups of patients
Children weighing 14 to 25 kg
-Kids weighing 14 to 20 kg: The recommended dose Abacavir Canon – 150 mg (300 mg tablet 1/2, break exactly risk) 2 times a day or 300 mg (1 tablet of 300 mg), 1 time per day;
-Kids weighing more than 20 kg, but less than 25 kg: The recommended dose Abacavir Canon – 150 mg (½ tablet 300 mg, break exactly risk) in the morning and 300 mg (1 tablet of 300 mg) or evening 450 mg (1 ½ 300 mg tablets) 1 times a day;
For children weighing less than 14 kg or patients unable to swallow tablets, it is recommended to use the drug in the form of oral solution.
Patients with impaired renal function
In patients with impaired renal function dose adjustment of the drug Abacavir Canon is not required.
Patients with impaired liver function
Abacavir is metabolized primarily in the liver. The recommended dose of abacavir for patients with mild impaired hepatic function (5- 6 points on Child-Pugh) 200 mg 2 times a day. Given the need for smaller doses of abacavir in patients with impaired liver function mild, for its correct dosing of the drug administered in alternative dosage form – solution for oral administration. There are no data on the pharmacokinetics and safety of abacavir in patients with impaired liver function moderate and severe. Thus, the use of abacavir in patients with impaired liver function moderate and severe contraindicated.
At temperatures above 25 ° C in the package manufacturer.
Keep out of the reach of children.
Studies in vitro and analysis of the major metabolic pathways of abacavir indicate that its interaction with other drugs, mediated by cytochrome P450, it is unlikely.
Abacavir not inhibit metabolic reactions involving CYP3A4 isoenzyme of cytochrome P450.
In in vitro studies have shown that – abacavir does not interact with drugs that are metabolised isozymes CYP3A4, CYP2C9 and CYP2D6. Clinical studies have not revealed the 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 involving major cytochrome P450 isoenzymes, it is unlikely.
Clinical studies have shown no clinically significant interactions between abacavir, zidovudine, and lamivudine. Potent inducers of enzymes, such as rifampin, phenobarbital and phenytoin when exposed to UDP-glucuronyl may slightly reduce the concentration of abacavir plasma.
Ethanol: ethanol abacavir metabolism slows down, resulting in an increase in AUC is 41%. However, the clinical significance of this change is small. Ethanol metabolism of abacavir is not affected.
Methadone: according to the pharmacokinetic studies, the use of abacavir 600 mg 2 times a day in combination with methadone reduces serum abacavir Cmax by 35% and increases Tmax serum for 1 hour, but does not alter the AUC. The clinical significance of these changes is small.
The same study found that abacavir increases systemic clearance of methadone by 22%. In most cases, these changes are also regarded as clinically non-significant, but in certain situations it may be necessary to change the dose of methadone.
Retinoids: Retinoids, such as isotretinoin, are eliminated with alcohol, so they can interact with abacavir, but to date has not been specific studies
Ribavirin: due to the fact that abacavir and ribavirin have identical path phosphorylation supposed interaction between these materials, which can lead to a decrease in intracellular phosphorylation of ribavirin metabolites and potentially leading to a decrease in the probability of achieving sustained virologic response in a co-infected with hepatitis C HIV-infected patients taking therapy with pegylated interferon and ribavirin. Published contradictory data on the simultaneous use of abacavir and ribavirin. According to some data it is assumed that HIV-infected patients receiving abakavirsoderzhaschie medications may be at risk of low frequency response to antiviral therapy with pegylated interferon and ribavirin. Care must be taken while taking these drugs.
The drug should be prescribed by a doctor with experience in treating HIV infection.
Each patient should be apprised of the application instruction.
Use of the drug Abacavir Canon associated with the risk of HSR, characterized by the appearance of fever and / or a rash and other symptoms suggestive of multiple organ lesions. HSR can be life-threatening and in rare cases when it is not assigned to the appropriate treatment, can lead to death. The risk of HSR when using the drug Abacavir Canon significantly increased in patients with a positive test result for the presence of the allele HLA-B * 5701. However, the abacavir hypersensitivity reaction were observed less frequently in patients who are not carriers of this allele.
Should adhere to the following rules.
– It is necessary to conduct a study on the presence of the allele HLA-B * 5701 before the start of therapy with abacavir Canon and also before resuming therapy with Abacavir Canon in patients with unknown status with regard to the allele HLA-B * 5701, which had previously tolerated abacavir therapy
– use of the drug is not recommended for patients Abacavir Canon allele HLA-B * 5701 or in patients who have had a suspected HSR during use any other medicament comprising abacavir regardless of the status in relation to HLA- B * 5701
– Each patient should be reminded that it is necessary to read the instructions for use, the package insert of the drug Abacavir Canon. Patients should also be reminded of the need to carry a warning card that came with the drug.
– All patients receiving therapy with Abacavir Canon, the clinical diagnosis of suspected HSR should remain the basis for clinical decision making
– If you suspect a drug Abacavir HSR therapy Canon should be discontinued immediately, even in the absence of allele HLA- B * 5701. Delay termination of therapy with abacavir Canon after the occurrence of HSR can lead to life-threatening reaction.
– Patients who develop HSR should be informed about the need to transfer the remaining tablets of the drug Abacavir Canon doctor in order to avoid the resumption of abacavir
– Re-use preparations contents abacavir, after suspected abacavir hypersensitivity reaction can lead to rapid return of symptoms within a few hours, which can include life-threatening hypotension and death
– When considering the resumption of treatment with abacavir after cessation of treatment with any medication containing abacavir for any reason should be established cause of discontinuation of therapy, regardless of the patient’s carrier allele HLA- B * 5701. If the HSR can not be ruled out, it is impossible to renew the use of the drug Abacavir canon or any other pharmaceutical preparations containing ABC.
– If HSR is not possible, perhaps the resumption of therapy with abacavir Canon. In rare cases, patients who discontinued use of abacavir for reasons other than symptoms of HSR, also noted the development of life-threatening reactions in a few hours after the resumption of treatment with abacavir (see. Section “Description of selected adverse reactions”).
Patients should be informed of the possibility of development of HSR when resuming therapy with Abacavir Canon or other medicinal products containing abacavir should be carried out only if there is quick access to medical care.
The clinical picture of HSR to abacavir
The abacavir hypersensitivity reaction have been well studied in clinical trials and post-marketing surveillance in. Symptoms usually appear within the first six weeks (median time of the beginning of the reaction – 11 days) after the start of therapy with abacavir, but these reactions can develop at any time of the therapy
Almost all the reactions to abacavir HSR and include fever or rash as part of the syndrome. Other signs and symptoms that mark as a manifestation of the abacavir hypersensitivity reaction, include symptoms of the respiratory and gastrointestinal tract, which can lead to an incorrect diagnosis of HSR as a respiratory disease (pneumonia, bronchitis, pharyngitis), or gastroenteritis (see. Sections on “Side action “,” Description of selected adverse reactions “). Patients should be monitored closely with consultations every 2 weeks, especially during the first 2 months of therapy with abacavir Canon.
If the appearance of the symptoms associated with the HSR, abacavir treatment continues, they become more pronounced and can take life-threatening. In most cases, these symptoms disappear with discontinuation of 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 nucleoside analogues, including abacavir, taken either separately or in combination. In most cases, these complications occur in women.
Symptoms that may indicate the development of lactic acidosis include general weakness, loss of appetite, rapid weight loss of unknown etiology, disorders of the gastrointestinal tract (nausea, vomiting and abdominal pain), disorders of the respiratory system (dyspnea and tachypnea) or neurological symptoms (including motor).
Lactic acidosis has a high mortality in the absence of emergency treatment and may be associated with pancreatitis, hepatic or renal insufficiency. Lactic acidosis, usually manifested after a few months of therapy. It is necessary to discontinue therapy with nucleoside analogues in the case of symptomatic hyperlactatemia and metabolic manifestations or lactic acidosis, progressive hepatomegaly, or rapid increase in transaminases.
Use of the drug Abacavir abakavirsoderzhaschih Canon and other drugs requires care to any patient (especially women with overweight) with hepatomegaly, hepatitis or other known risk factors for liver injury and hepatic steatosis (including the use of certain medications and alcohol). Patients with combined hepatitis C treated with interferon alpha and ribavirin may be a particular risk group. Patients with an increased risk require careful observation.
When a clinical or laboratory signs of lactic acidosis with or without hepatitis (hepatomegaly and can manifest steatosis even in the absence of pronounced increase of aminotransferases) treatment with Abacavir Canon necessary to suspend.
Studies in vitro and in vivo showed that the analogues of nucleosides and nucleotides can cause varying degrees of damage to mitochondria. itohondrialnoy dysfunction cases were reported in HIV-negative children treated in utero and / or after the birth of nucleoside analogues. The major adverse reactions were hematologic disturbances (anemia, neutropenia), metabolic disorders (hyperlactatemia, giperlipazemiya). These adverse reactions are often transitory. Have been reported, some neurological disorders with late onset (increased muscle tone, seizures, behavioral disorders). Are these neurological disorders transient or permanent is currently unknown. Any child, even HIV-negative, are exposed in utero effects of nucleoside analogues and nucleotides must undergo clinical and laboratory examination in order to exclude mitochondrial dysfunction in case of relevant signs or symptoms. These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Redistribution of adipose tissue
In some patients receiving combination antiretroviral therapy, there may be redistribution and / or the accumulation of subcutaneous fat, including obesity of the central type, dorsotservikalnoe fat deposition ( “buffalo hump”), a decrease in the subcutaneous fat layer on the face and extremities, breast enlargement , increased serum concentrations of lipids and blood glucose.
Although one or more of the above adverse reactions associated with a common syndrome, which is often referred to as lipodystrophy can cause all classes of HIV drugs SP and NRTIs. The data indicate that there are differences between individual representatives of these classes of drugs in the ability to cause these undesirable reactions.
It should also be noted that the lipodystrophy syndrome is a multifactorial etiology; eg, stage of HIV infection, older age and duration of antiretroviral therapy are important, possibly synergistic role.
The long-term consequences of these adverse reactions are currently unknown.
In a clinical study of patients should pay attention to the redistribution of subcutaneous fat. Laboratory evaluation should include a determination of lipid concentrations in blood serum and blood glucose concentrations. In case of violation of lipid metabolism prescribe appropriate treatment.
Cases of pancreatitis were reported although a causal relationship with the use of abacavir is not certain.
Therapy three nucleoside reverse transcriptase inhibitors (NRTIs)
In patients with high viral load (> 100,000 copies / ml) Designation of a triple combination comprising abacavir, lamivudine and zidovudine, requires special consideration
the case of high frequency of virologic failure and emergence of resistance were recorded in the early stages when, as a mode of therapy 1 time per day to use a combination of abacavir with tenofovir dezoproksil fumarate and lamivudine.
The efficacy and safety of abacavir have not been established in patients with severe concomitant diseases of the liver. The drug Abacavir Canon is contraindicated in patients with impaired liver function moderate and severe.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function during combination antiretroviral therapy and should be monitored in accordance with accepted practices. It is necessary to consider the suspension or discontinuation of treatment in case of worsening of symptoms of the disease in these patients.
Concomitant hepatitis B or C
Patients with concomitant chronic hepatitis B or C receiving combination antiretroviral therapy have an increased risk of severe and potentially lethal adverse reactions by the liver. In the case of concomitant antiviral therapy of hepatitis B or C, it should also be familiar with appropriate instructions for use of the present medicaments.
Caution should be exercised with concomitant administration of abacavir and ribavirin.
The drug Abacavir Canon should not be administered to patients with terminal chronic renal failure.
immune reconstitution syndrome
In the presence of HIV-infected patients with severe immune deficiency asymptomatic opportunistic infections or their residual effects at the time of initiation of antiretroviral therapy carrying out such therapy may lead to increased symptoms of opportunistic infections or other serious consequences. Usually these reactions occur within the first weeks or months after initiation of antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized and / or alopecia infection caused by mycobacteria and pneumonia caused by Pneumocystis jiroveci (formerly P. carinii). The appearance of any symptoms of inflammation requires immediate inspection and, if necessary, treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have 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.
Despite the fact that 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 in the late stage of HIV infection and / or long-receiving combination antiretroviral therapy. Patients should consult their doctor if they experience pain and stiffness in the joints, or difficulty in movement.
Use of the drug Abacavir Canon 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.
Antiretroviral therapy, including drug Abacavir Canon does not exclude the possibility of sexual transmission of HIV transmission or contact with infected blood, and therefore does not alter the need to observe the appropriate precautionary measures.
As a result, prospective observational epidemiological study to examine the incidence of myocardial infarction in patients receiving combination antiretroviral therapy, have found a link prior abacavir for 6 months with an increased risk of myocardial infarction. According to a generalized analysis of clinical trials no increased risk of myocardial infarction associated with abacavir. Biological mechanisms that explain the increased risk of potentially unknown. In general, the available data from observational cohort studies and controlled clinical trials did not conclusively define the relationship between abacavir treatment and the risk of myocardial infarction.
Nevertheless, caution should be given antiretroviral therapy, including medications that contain abacavir, patients with a possible risk of ischemic heart disease. It is necessary to take all measures to minimize all modifiable risk factors (such as hypertension, dyslipidemia, diabetes mellitus, and smoking).
Effects on ability to transp. Wed. and fur .:
There is no evidence of abacavir influence on the ability to engage in potentially hazardous activities that require attention. However, patients should be informed about the possible development of such adverse reactions as fatigue, during treatment with abacavir. It should encourage them to use caution when driving and management mechanisms.
In clinical studies found no adverse reactions when applying abacavir in single doses up to 1200 mg and daily to 1800 mg. Effect of the drug in higher doses has not yet been studied.
In case of overdose, the patient establish surveillance to detect poisoning symptoms and timely treatment initiation. If necessary symptomatic treatment. The efficiency of peritoneal dialysis and hemodialysis to remove abacavir is unknown.