Composition, form of production and packaging
The tablets covered with a cover of yellow color, capsular, biconcave, with a risk and squeezed out inscription "GX 623" on both sides of the tablet.
1 tab.
abacavir sulfate 351 mg,
which corresponds to the content of abacavir 300 mg
Auxiliary substances: cellulose microcrystalline 414.6 mg, sodium carboxymethyl starch, type A 24 mg, magnesium stearate 8 mg, silicon colloid anhydrous 2.4 mg, opadrai yellow (hypromellose 8.4 mg, titanium dioxide 3.6 mg, triacetin 1.1 mg, iron oxide yellow 0.9 mg, polysorbate 80 0.1 mg) 14 mg.
10 pieces. - blisters (6) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2013.
PHARMACHOLOGIC EFFECT
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 in vitro studies , 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 viral RNA template and the stopping of HIV replication. In vitro, abacavir acts synergistically with nevirapine and zidovudine and shows an additive effect with didanosine, zalcitabine, lamivudine, and stavudine.
Pharmacodynamics
In vitro- derived HIV strains resistant to abacavir, mutations in several codons of the reverse transcriptase (RT) gene - M184V, K65R, L74V and Y115F - were detected. The resistance of HIV to abacavir in vitro and in vivo is slow. For a clinically significant 8-fold increase in 50% inhibitory concentration (IC 50 ), multiple mutations of the viral genome are required. Strains resistant to abacavir may have reduced sensitivity to lamivudine, zalcitabine, and didanosine, but retain their sensitivity to zidovudine and stavudine. Cross-resistance to abacavir and HIV protease inhibitors or non-nucleoside reverse transcriptase inhibitors is unlikely.Inefficiency of the combination 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 CNS.
Clinical efficacy
An analysis of randomized, double-blind, comparative studies of combinations of Ziagen with lamivudine and zidovudine and indinavir with lamivudine and zidovudine, administered for 48 weeks in adult HIV-infected patients who had not previously received antiretroviral therapy, showed comparable virological efficacy of the compared combinations. However, in a subset of patients with an initial content of HIV-1 RNA in serum in excess of 100,000 copies / ml, the mode containing indinavir was more effective. With the initial content of viral RNA less than 100,000 copies / ml, the effectiveness of both regimes was the same.
In a multicentre, double-blind, controlled study (CNA30021), involving 770 HIV-infected patients who had not previously taken antiretroviral drugs, a single-dose and two-fold dosing regimen for Ziagen was compared. Patients were randomized into two groups. In the first group, the preparation Ziagen was administered in a dose of 600 mg 1 time / day, in the second - 300 mg 2 times / day; simultaneously with Ziagen, patients in both groups received lamivudine 300 mg once a day and efavirenz 600 mg once a day. Depending on the initial level of viral RNA in the serum, 2 subgroups of patients with an HIV-1 RNA level of less than 100,000 copies / ml and with an HIV-1 RNA of more than 100,000 copies / ml were isolated. The duration of treatment was at least 48 weeks. The results of the study are presented below.
The proportion of patients with serum levels of HIV-1 RNA less than 50 copies / ml at 48 weeks after initiation of treatment (ITT analysis).
Subgroups of patients with different baseline viral RNA levels Patient groups
Ziagen (1 time / day) + lamivudine + efavirenz (N = 384) Ziagen (2 times / day) + amivudine + efavirenz (N = 386)
Less than 100,000 copies / ml 141/217 (65%) 145/217 (67%)
More than 100,000 copies / ml 112/167 (67%) 116/169 (69%)
Total number of patients 253/384 (66%) 261/386 (68%)
Thus, it was shown that the dosage regimen of Ziagen does not affect the effectiveness of treatment in either the general population of patients or in subgroups with different initial levels of viral load. The frequency of adverse events was the same in both groups of patients who took Ziagen in a dose of 600 mg once a day or 300 mg 2 times / day.
In patients with virological inefficiency of therapy (HIV-1 RNA concentration more than 50 copies / ml to 48 weeks of therapy), a genotypic analysis of virus isolates was performed. The frequency of virological inefficiency was low - in 10 and 8% of patients in the groups taking Ziagen 600 mg 1 and 2 times a day, respectively.Resistance to nucleoside reverse transcriptase inhibitors was most often due to mutations in the 184th codon (M184V or M184I). The second was L74V mutation. The most common mutations were Y115F and K65R.
A comparative study of three combinations of nucleoside reverse transcriptase inhibitors (abacavir with lamivudine, abacavir with zidovudine, or lamivudine with zidovudine) taken by children in combination with nelfinavir or placebo, showed that abacavir-containing regimens significantly outperformed the combination of lamivudine and zidovudine. It was found that a decrease in HIV-1 RNA concentrations of less than 400 copies / ml at 24 weeks of therapy was observed in 73% of the group of children taking the combination of abacavir with lamivudine, 70% of children taking abacavir with zidovudine and only 44% of children, who took lamivudine with zidovudine.
The combination of abacavir with lamivudine and zidovudine in children who previously received different regimens of highly active antiretroviral therapy (HAART) was characterized by a moderate but persistent antiviral effect.
In patients previously treated with HAART, the effectiveness of Ziagen depends on the pattern and duration of previous treatment, which could lead to cross-resistance to Ziagen.
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 C max when taking abacavir orally in the form of tablets is about 1.5 hours.
The 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 abacavir is administered orally at a dose of 300 mg 2 times / day, Cmax on average reaches an average of 3 Ојg / ml, and the AUC for a 12-hour period between doses is an average of 6.02 Ојg x В· h / ml days - about 12 Ојg x h / ml). After a single administration of abacavir tablets at a dose of 600 mg Cmax averages about 4.26 Ојg / ml, and AUC - an average of 11.95 Ојg h / ml.
According to the study, in 20 HIV-infected patients who took abacavir 300 mg twice daily and only one dose (300 mg) before the 24-hour sampling period for analysis, the geometric mean of the terminal T 1/2 intracellular carbovir-TF at an equilibrium state of 20.6 hours (the same index for the concentration of abacavir in the serum - 2.6 hours). Equilibrium pharmacokinetic parameters when taking abacavir 600 mg 1 time / day were similar to those with abacavir 300 mg 2 times / 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 1 time / day compared with 300 mg of abacavir / 2 times / day (24-hour increase in AUC in 24 hours (AUC 24, ss ) by 32 %, the maximum daily concentration in the equilibrium state (C ss max ) by 99%), which indicates the possibility of such a regimen of taking the drug by HIV-infected patients. The efficacy and safety of the Ziagen preparation, provided a single daily dose was administered, was shown in a clinical study (CNA30021).
Eating slows the absorption of abacavir and reduces C max , but does not affect the AUC. Therefore, abacavir can be taken with or without food.
Receiving a crumbled 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 physico-chemical and pharmacokinetic parameters of the active substance and the water solubility of abacavir tablets, with the assumption that the patient will crush and add the whole tablet to the food or liquid and take it immediately inside.
Distribution
V d of abacavir with iv introduction is about 0.8 l / kg, which indicates its ability to easily penetrate into tissues.
In studies in HIV-infected patients, it has been shown that abacavir penetrates CSF well, with a ratio of abacavir AUC to CSF ​​and abacavir AUC in plasma of 30-44%. In the Phase I pharmacokinetic study, it was found that 1.5 h after administration of abacavir at a dose of 300 mg 2 times / day, its concentration in the CSF was 0.14 μg / ml. With the use of abacavir in a dose of 600 mg 2 times / day, the concentration of the drug in the CSF increased from 0.13 μg / ml when measured 0.5-1 hour to 0.74 μg / ml when measured 3-4 hours after taking abacavir. Thus, even if the abacavir concentration observed in the CSF 4 hours after taking the drug at a dose of 600 mg 2 times / day is not as high as possible with this treatment regimen, it already exceeds IC 50 (0.08 μg / ml or 0.26 μmol / L ) 9 times.
In vitro studies 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. Less than 2% of the accepted dose of the drug is excreted by the kidneys unchanged. In the human body, abacavir is metabolized primarily by the action of alcohol dehydrogenase to form a 5'-carboxylic acid and by 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, T 1/2 of abacavir is about 1.5 hours. Prolonged intake of abacavir orally at a dose of 300 mg 2 times / day does not result in significant cumulation of the drug. Abacavir excretion is carried out by metabolism in the liver, followed by excretion of metabolites mainly through 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.
Pharmacokinetics in special clinical cases
Abacavir is well and rapidly absorbed when ingested in children. All pharmacokinetic parameters in children are comparable to those in adults with slightly greater variability in plasma concentrations. Pharmacokinetic studies in children showed that taking the drug 1 time / day is equivalent in AUC 0-24 to the same dose of the drug divided by 2 times / day for existing dosage forms (oral solution and film-coated tablets). 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 a dosage regimen of 300 mg 2 times / day in adults.
There is insufficient safety data to recommend the use of abacavir in children younger than 3 months. There is limited evidence that a dose of 2 mg / kg in infants younger than 30 days provides similar or greater AUC values ​​than do 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, 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.
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 impaired, dose adjustment is not required.
Abacavir is metabolized mainly in the liver. Results of the study of the pharmacokinetics of abacavir in patients with mild liver function disorder (5-6 points on the Child-Pugh scale) indicate an increase in AUC by 1.89 times and T 1/2 in 1.58 times. The index of AUC metabolites of abacavir is not affected by liver dysfunction, however, the rate of their formation and excretion decreases.
Patients with a mild liver disease for therapeutic purposes can take 200 mg (10 ml solution for ingestion) of abacavir 2 times / day.
The pharmacokinetics of abacavir in patients with impaired liver function of moderate and severe degree has not been studied, thus, the use of abacavir is contraindicated in these groups of patients.
INDICATIONS
- Treatment of HIV infection in adults and children in combination antiretroviral therapy.
DOSING MODE
The drug Ziagen take inside, regardless of food intake.
Patients who swallow a tablet cause difficulties, prescribe the preparation Ziagen in the form of a solution for oral administration. However, as an alternative, the division and crumbling 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.
For adults, children and adolescents with a body weight of more than 30 kg, the recommended dose of Ziagen is 600 mg / day. The drug is prescribed in a dose of 300 mg (1 tab.) 2 times / day or 600 mg (2 tab.) 1 time / day.
For children aged 3 months and older with a body weight of 14 to 21 kg, the recommended dose of Ziagen is 0.5 tablets. (break exactly according to the risk) 2 times / day or 1 tab. 1 time / day; children with a body weight of more than 21 kg, but less than 30 kg - the recommended dose of the drug Ziagen - 0.5 table. (break accurately at risk) in the morning and 1 tablet in the evening or 1.5 tablets 1 time / day.
For children weighing less than 14 kg or patients unable to swallow tablets , the use of Ziagen in the form of a solution for oral administration is recommended.
Data on the use of Ziagen in children younger than 3 months are limited.
In patients with impaired renal function, dose adjustment of Ziagen is not required.
Abacavir is metabolized predominantly in the liver. The recommended dose of Ziagen for patients with mild liver function disorder (5-6 points on the Child-Pugh scale) is 200 mg (10 ml solution for ingestion) 2 times / day. Considering the need to use smaller doses of Ziagen in patients with mild liver function disorder, it is prescribed as a solution for oral administration in order to correctly dispense the drug. Patients with violations of liver function of moderate and severe degree oftaking Ziagen are contraindicated because the pharmacokinetics of the drug in this population of patients has not been studied.
SIDE EFFECT
Hypersensitivity
According to clinical studies conducted before the screening for the presence of the HLA-B * 5701 allele, approximately 5% of patients taking abacavir had a hypersensitivity reaction, in rare cases fatal. Hypersensitivity to abacavir is characterized by multiple organ dysfunction.
Most patients with hypersensitivity develop fever and rash (usually maculopapular or urticaria), although in some cases these manifestations are absent.
Symptoms of hypersensitivity reactions may appear at any time after initiation of abacavir treatment, but most often they occur during the first 6 weeks of treatment (median time of onset of this reaction is 11 days).
The hypersensitivity reactions are shown below. Symptoms that occur in at least 10% of patients with hypersensitivity are indicated in bold type.
From the skin and appendages of the skin: a rash (usually maculopapular or urticaria).
From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain , ulceration of the mucous membrane of the mouth.
On the part of the respiratory system : dyspnea, cough, sore throat, adult respiratory distress syndrome, respiratory failure.
From the nervous system: headache, paresthesia.
On the part of the system of hematopoiesis and lymphatic system: lymphopenia.
From the liver and pancreas: increased activity of liver enzymes, hepatic insufficiency.
From the musculoskeletal system: myalgia , rarely - rhabdomyolysis, arthralgia, increased activity of creatine phosphokinase.
From the urinary system: increase in serum creatinine, renal failure.
Other: fever, fatigue, malaise , edema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis.
Resumption Ziagen dosing patients with a history of hypersensitivity reaction results in the development in the repeated reaction for a few hours. Re hypersensitivity reaction can proceed more difficult than the first, and manifest life-threatening hypotension, until death.
The nature of adverse events other than hypersensitivity reactions, but observed in patients receiving Ziagen, is not completely clear. Are these undesirable phenomena Ziagen consequence of the drug or other drugs at the same time assigned to it, or they are caused by the disease has not yet been established.
Many of the following adverse events associated with taking the drug Ziagen (nausea, vomiting, diarrhea, fever, fatigue, rash), may be observed in the development of hypersensitivity reactions. Therefore, when any of these symptoms is shown a thorough examination of the patient to confirm or eliminate hypersensitivity reactions.
If Ziagen drug was withdrawn due to a hypersensitivity reaction is suspected, the resumption of the drug is prohibited. Resuming therapy with Ziagen after an interruption due to the advent above symptoms only after eliminating hypersensitivity reactions and under direct medical supervision.
Most of the following adverse reactions do not limit the application Ziagen preparation.
The undesirable phenomena presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: very common (1/10?), Common (1/100 and <1/10?), Infrequently, rarely (1/10 000 and (1/1, 000 and <1/100?)? <1/1 000), very rare (<1/10 000, including isolated cases). With the adverse reactions and syndromes that can occur on antiretroviral therapy, including nucleoside analogues, can be found in the section "Special instructions".
Data from clinical studies
of metabolic disorders and nutrition: often - loss of appetite.
Neurological disorders: common - headache.
Gastrointestinal disorders: common - nausea, vomiting, diarrhea.
Systemic manifestations and local reactions: often - fever, lethargy, fatigue.
In controlled clinical studies have shown that changes in laboratory values in the treatment of drug Ziagen observed as rare as in the control group of patients not receiving the drug.
These post-marketing surveillance
of metabolic disorders and nutrition: often - hyperlactatemia; rarely - lactic acidosis, accumulation / fat redistribution. The frequency of these undesired reactions is dependent on many factors, including of antiretroviral drugs used in combination with abacavir.
Violations of the gastrointestinal tract: rarely - pancreatitis (causal connection with the use of abacavir is not certain).
Violations of the skin:often - rash (in the absence of systemic manifestations); very rarely - polymorphic erythema, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
CONTRAINDICATIONS
- hypersensitivity to abacavir or any other component of the formulation;
- human liver moderate and severe;
- under the age of 3 months and weighing less than 14 kg.
PREGNANCY AND LACTATION
Safety of abacavir in women during pregnancy has not yet been studied. There are experimental data on the toxic effects of abacavir on the development of rat embryos, but these effects were not replicated in rabbits. If necessary, use Ziagen during pregnancy should weigh the anticipated benefits to the mother and the potential risk to the fetus.
There is evidence of a slight transient increase in lactic acid concentration in the serum of newborns and infants whose mothers during pregnancy and childbirth took nucleoside reverse transcriptase inhibitors. Perhaps this is due to mitochondrial disorders. The clinical significance of this phenomenon has not yet been established. Furthermore, there are very rare reports of developmental delay, epileptic seizures and other neurological disorders in infants, although a causal relationship of these disorders with taking nucleoside reverse transcriptase inhibitors mothers during pregnancy and childbirth has not been established. These data do not cancel the existing recommendations on the use of antiretroviral drugs during pregnancy to prevent vertical transmission of HIV.
Experimental studies in rats during lactation showed that abacavir and its metabolites are excreted in breast milk. It is assumed, though it has not yet been proved that abacavir and its metabolites penetrate into breast milk. Data on the safety of abacavir in children under the age of 3 months are not available. Some experts recommend that HIV-infected women in all situations to avoid breastfeeding to prevent HIV transmission to their children. Thus, women who use abacavir is not recommended to breastfeed.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function, adjustment of dosing regimen is necessary.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Abacavir is metabolized primarily in the liver. The recommended dose for the drug Ziagen patients with an impaired liver mild (5-6 points on the Child-Pugh) is 200 mg (10 ml) 2 times per day. Given the need for smaller doses Ziagen in patients with impaired liver function mild, for its correct dosing of the drug administered as an oral solution. Patients with impaired liver function moderate to severe degree of the drug Ziagen is contraindicated because the pharmacokinetics of the drug in this patient population has not been studied.
APPLICATION FOR CHILDREN
The drug is used in children older than 3 months, weighing over 14 kg.
APPLICATION IN ELDERLY PATIENTS
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.
SPECIAL INSTRUCTIONS
The drug should be prescribed by a doctor with experience in treating HIV infection.
Hypersensitivity
According to clinical studies conducted prior to the screening for the presence of the allele HLA-B * 5701, approximately 5% of patients taking abacavir, develop hypersensitivity to the drug, in rare cases, fatal.
Risk factors
In clinical studies it was shown that carriers of the allele HLA-B * 5701 is associated with a significantly increased risk of a hypersensitivity reaction to abacavir. A prospective clinical CNA106030 study (PREDICT-1) in patients with the presence of the allele HLA-B * 5701 preparations containing abacavir, not prescribed, which allowed to significantly reduce the incidence of clinically suspected hypersensitivity reaction, from 7.8% (66 patients out of 847) to 3.4% ( 27 of 803 patients) (p <0.0001), as well as the incidence of hypersensitivity reactions, skin-applicative confirmed that the sample with 2.7% (23 patients out of 842) to 0.0% (0 out of 802 patients) (p <0,0001). Thus, based on the results of this study, it was shownthat 48? 61% of patients who are carriers of the allele HLA-B * 5701 developed a hypersensitivity reaction compared with 0-4% of patients who have this allele is absent.
Physicians are advised to be screened for the carriage of allele HLA-B * 5701 in HIV-infected patients who had not previously prescribed drugs containing Abacavir. Screening is recommended prior to the reappointment of abacavir in patients of unknown HLA-B * 5701-positive status who have previously tolerated abacavir therapy.
Resumption receiving abacavir-containing regimen is not recommended in patients having allele HLA-B * 5701. In exceptional cases, where the potential benefits outweigh the risks, the appointment of abacavir-containing medicines can be discussed in these patients, and the patient should be kept under close medical supervision.
The clinical diagnosis of suspected hypersensitivity reaction must remain the basis for a decision on the use of products containing abacavir in all patients. Even in the absence of the allele HLA-B * 5701 and abacavir should be abolished not to renew his appointment in all cases where a hypersensitivity reaction can not be excluded, guided by clinical data, due to the potential risk of serious adverse effects or even death.
The clinical picture
Hypersensitivity to abacavir is characterized by the appearance of symptoms suggestive of multiple organ failure. Most patients report a fever and / or rash as part of the syndrome.
Other symptoms of hypersensitivity to abacavir are fatigue, malaise, disorders of the gastrointestinal tract, including vomiting, nausea, diarrhea, and abdominal pain; disorders of the respiratory system, including shortness of breath, sore throat, cough, lung damage (mainly in the form of local infiltrative changes detected by chest X-ray). Symptoms of hypersensitivity may occur at any time after the initiation of treatment with abacavir, but often they occur within the first six weeks.
If the development of hypersensitivity reactions, patients continue to take the drug Ziagen, the clinical manifestations are more severe and can take life-threatening. In most cases, these symptoms disappear upon discontinuance of the drug Ziagen.
Treatment
When the symptoms of hypersensitivity to abacavir, the patient, regardless of the carrier allele HLA-B * 5701, should immediately contact your doctor for advice. Diagnosis of hypersensitivity reactions to abacavir requires immediate discontinuation. The resumption of treatment Ziagen or other preparation containing abacavir (such as Epzicom, Trizivir) patients with hypersensitivity reaction history strictly contraindicated because for several hours after taking the drug may re-growth reaction in a more severe form, up to life-threatening arterial hypotension or death.
If we exclude hypersensitivity to abacavir should not be, in order to avoid late diagnosis and minimize the risk of developing life-threatening conditions ABC canceled forever, even if there is another diagnosis (eg disease of the respiratory tract and lungs, influenza-like syndrome, gastroenteritis or undesirable effect of other drugs). The resumption of treatment Ziagen or other preparation containing abacavir (such as Epzicom, Trizivir) is unacceptable, even if the re-development of the symptoms of hypersensitivity observed when resuming administration of other drugs used together with abacavir-containing drug.
The drug Ziagen packaging kit should include a warning card with information for patients about the hypersensitivity reaction to abacavir.
Specific guidance on the treatment after a break in therapy with Ziagen
Regardless of the carrier allele HLA-B * 5701, if after the abolition of the drug Ziagen is expected resumption of treatment with this drug, you must find out the cause of cancellation and to make sure that the patient was not observed symptoms of hypersensitivity. If it is impossible to exclude hypersensitivity reaction, the treatment with Ziagen or other preparation containing abacavir (such as Epzicom, Trizivir) is prohibited.
Described a few cases of hypersensitivity reaction when resuming treatment with abacavir after its cancellation in connection with the appearance of any one of the typical symptoms of hypersensitivity (rash, fever, malaise, fatigue, gastrointestinal disorders and disorders of the respiratory system). As in all such cases it is impossible, taking into account the data of the more serious it within with repeated use of abacavir, resumption of therapy with Ziagen or any other abacavir-containing drug (such as Kivexa, Trizivir) in these patients is not recommended to exclude hypersensitivity reaction. However, if in such cases the question of the re-appointment of abacavir is solved positively, the treatment it is only carried out with the direct medical supervision.
Hypersensitivity reactions occur, albeit rarely, even with the resumption of treatment abacavir-containing drug in patients who have symptoms of this reaction has not been seen before, and a break in the administration of drugs containing Abacavir has been associated with other causes. In this case, the resumption of the drug is possible, but requires the patient or the people around him quick access to medical care.
Screening for carriage of the allele HLA-B * 5701 is recommended to re-appointment of abacavir in patients of unknown HLA-B * 5701 status, previously well-tolerated therapy with abacavir. Reappointment of abacavir for patients carrying the allele HLA-B * 5701 is not recommended and can be considered only in exceptional cases under close meditsinskimkontrolem when the potential benefits of treatment with higher than all possible risks.
Required information for the patients
physician prescribers should inform the patient with the following information on the hypersensitivity reaction:
- the patient must be aware of the possibility of life-threatening hypersensitivity symptoms and the risk of death, as well as an increased risk of hypersensitivity reactions in carriers of the allele HLA-B * 5701;
- the patient must be warned that even in the absence of the allele HLA-B * 5701 may develop a hypersensitivity reaction. Thus, all patients for symptoms that may be due to hypersensitivity reactions should immediately contact your doctor ;
- Patients with known hypersensitivity to abacavir should be warned of non Ziagen resumption of the drug or other preparations containing abacavir (such as Epzicom, Trizivir), regardless of the HLA-B * 5701 status;
- in order to avoid re-use of the drug Ziagen patients undergoing hypersensitivity reaction, it is recommended to recover the remaining drug tablets or Ziagen Ziagen drug solution for oral doctor;
- patients who for any reason, an interrupted treatment with Ziagen (especially due to possible adverse reactions or treatment of complications), before resuming the drug must Referring
