Olitid

General characteristics. Structure:

Active ingredient: 351,0 mg of an abakavir of sulfate (equivalent of 300,0 mg of an abakavir).

Excipients: hypro rod, carboxymethylstarch of sodium, silicon dioxide colloid, magnesium stearate, cellulose microcrystallic.

Structure of a film cover: ready water-soluble film cover (gipromelloza, macrogoal 6000, titanium dioxide, talc, dye ferrous oxide red, dye ferrous oxide yellow).

Antiviral drug, active concerning HIV.

Pharmacological properties:

Pharmacodynamics. Antiviral drug, nukleozidny inhibitor of the HIV return transcriptase. Selectively suppresses replication of VICh-1 and VICh-2 (including VICh-1 strains steady against a zidovudine, a lamivudin, a zaltsitabin, a didanozin and not Virapinum). Abakavir is exposed to intracellular metabolism, turning into an active form a карбовир-5-triphosphate-analog of a deoksiguanozin - 5 triphosphates. The mechanism of effect of drug is connected with inhibition of the HIV return transcriptase. what leads to break of synthesis of virus DNA and the termination of replication of HIV. Possible development of resistance is connected with changes of a genotype in a certain kodonovy area of the return transcriptase (codons of M184V, K65R. L74V and Y115F). Resistance of HIV develops rather slowly; multiple mutations are necessary for increase in the half inhibiting concentration (IC50) of drug by 8 times. Development of cross resistance is improbable. Increases quantity of CD4+ cells in blood and reduces concentration of virus RNA (including in cerebrospinal fluid).

Pharmacokinetics. Abakavir is quickly and well absorbed from a GIT. At adults absolute bioavailability of an abakavir after intake makes 83%. After intake of the tablets Cmax in blood serum it is reached in 1,5 h and makes 3 mkg/ml. The area under a pharmacokinetic curve "concentration time" (AUC) during 12 h after administration of drug makes 6 mkg/ml/h. Food slows down absorption of an abakavir and reduces Cmax, but does not influence AUC. Gets through a blood-brain barrier, concentration of an abakavir in liquor makes 30-44% of that in plasma. Communication with proteins of plasma - low. It is metabolized in a liver with participation of an atsetaldegidrogenaza and formation of glyukuronidny conjugates (5-carboxylic acid and 5 glucuronide). T1/2 is 1,5 h. It is removed by kidneys: 83% in the form of metabolites and 2% in not changed look; other part is removed through intestines. Does not kumulirut.

Special groups of patients. Children. Abakavir is well and quickly soaked up at intake at children. All pharmacokinetic parameters at children are comparable to the corresponding indicators at adults. Pharmacokinetic researches at children showed that administration of drug of 1 times a day is equivalent on AUC0-24 indicator to reception of the same dose of drug divided into 2 receptions. It will provide slightly higher average concentration of an abakavir in a blood plasma thanks to what at most of children therapeutic concentration will be equivalent to the mode of dosing of 300 mg 2 times a day at adults.

Elderly patients. The pharmacokinetics of an abakavir at patients is more senior than 65 years is not studied. At treatment of patients of advanced age it is necessary to consider more frequent abnormal liver functions, kidneys and heart at this age, and also associated diseases and the accepted medicines.

Patients with a renal failure. Abakavir is metabolized preferential in a liver, less than 2% him are removed by kidneys in not changed look. The pharmacokinetics of an abakavir at patients with an end-stage of a renal failure practically does not differ from that at patients with normal function of kidneys. At patients with renal failures the dose of an abakavir is not required to be reduced.

Patients with dysfunction. Patients with abnormal liver functions of easy degree (5-6 points on a scale of Chayld-Pyyu) AUC had an abakavira more on average by 1,89 times, and T1/2 - by 1,58 times. Abnormal liver functions of easy degree do not influence indicators of AUC of metabolites of an abakavir. however at such patients the speed of education and removal of metabolites decreases.

The pharmacokinetics of an abakavir at patients with abnormal liver functions of moderate and heavy degree is not studied.

Drug use Olitid at patients with a liver failure contraindicated.

Indications to use:

HIV infection at adults and children (as a part of the combined anti-retrovirus therapy).

Route of administration and doses:

Drug Olitid is accepted inside, irrespective of meal.

Adults, children and teenagers with body weight more than 30 kg. The recommended daily dose makes 600 mg. Drug 2 times a day or 600 mg of 1 times a day appoint in a dose 300 mg.

Children at the age of 3 years are also more senior with body weight less than 30 kg. To children with the body weight from 14 to 21 kg the recommended dose makes 150 mg 2 times a day or 300 mg of 1 times a day.

To children with body weight more than 21 kg and less than 30 kg the recommended dose makes 150 mg in the morning and 300 mg in the evening or 450 mg of 1 times a day.

Patients with a renal failure. With a renal failure of dose adjustment of drug it is not required from patients.

Patients with dysfunction. Drug use Olitid at patients with a liver failure contraindicated.

Features of use:

It is possible if the expected effect of therapy exceeds potential risk for a fruit (safety of use is not established). For the period of treatment it is necessary to stop breastfeeding.

Hypersensitivity. According to the clinical trials conducted prior to screening on existence of an allele of HLA-B*5701, approximately at 5% of the patients accepting абакавир. hypersensitivity to drug, in rare instances with a lethal outcome develops.

Risk factors. In clinical trials it was shown that HLA-B*5701 allele carriage considerably increases risk of development of reaction of hypersensitivity to an abakavir. In prospective clinical trial of CNA106030 (PREDICT-1) to patients with existence of an allele of HLA-B*5701 the drugs containing абакавир were not appointed that allowed to reduce significantly the frequency of emergence of clinically suspected reaction of hypersensitivity from 7,8% (66 patients from 847) to 3,4% (27 patients from 803) (р <0,0001), and also the frequency of development of reaction of the hypersensitivity confirmed with skin and application test from 2,7% (23 patients from 842) to 0,0% (0 patients from 802) (р <0,0001). Thus, based on results of this research, it was shown that at 48-61% of patients carriers of an allele of HLA-B*5701 reaction of a giperchuvstvitelyyusta in comparison with 0-4% of patients at whom this allele is absent develops.

Doctors are recommended to carry out screening on a carriage of an allele of HLA-B*5701 at HIV-positive patients to whom the drugs containing абакавир were not appointed earlier. Screening is recommended to be carried out prior to repeated purpose of an abakavir at patients with the unknown HLA-B*5701-status who earlier well transferred therapy abakaviry.

Use of drugs of an abakavir is not recommended at the patients having HLA-B*5701 allele and has to be considered only in exceptional cases under careful medical observation when the potentsnatny advantage exceeds the risk connected from drug use.

The clinical diagnosis of the suspected reaction of a giperchuvstvitslnost has to remain a basis for making decision on use of the drugs containing абакавир with all patients. Even in case of lack of an allele of HLA-B*5701 абакавир it is necessary to cancel and not to resume its reception in all cases when reaction of hypersensitivity cannot be excluded, being guided by clinical data, because of iotentsiashny risk of development of serious undesirable effects or even a letatny outcome.

Clinical picture. Hypersensitivity to an abakavir is characterized by emergence of the symptoms indicating multiorgan defeat. Most of patients note fever and/or rash as a part of a syndrome.

Other symptoms of a giperchuvstvitelyyusta to an abakavir are: fatigue, an indisposition, disturbances from digestive tract, including vomiting, nausea, diarrhea and an abdominal pain; disturbances from respiratory system, including an asthma, a pharyngalgia, cough, damage of lungs (generally in the form of the local infiltrative changes revealed at a thorax X-ray analysis).

Symptoms of hypersensitivity can appear after an initiation of treatment abakaviry at any time. however most often they arise within the first six weeks. If at emergence of symptoms of hypersensitivity treatment abakaviry continues, they become more expressed and can accept life-threatening character. After drug withdrawal hypersensitivity symptoms usually are exposed to involution.

Patients to whom treatment abakaviry is appointed have to be observed with special care regarding emergence of hypersensitivity within the first two months of treatment with consultations each two weeks though at the same time it is necessary to remember that such reaction can be shown later, at any time.

Treatment. At emergence of symptoms of hypersensitivity an abakavir the patient, regardless of HLA-B*5701 allele carriage, immediately has to see the attending physician behind consultation. Diagnosis of reaction of hypersensitivity to an abakavir demands immediate drug withdrawal. Treatment resuming by drug Olitid or other drug containing абакавир at patients, with reaction of hypersensitivity in the anamnesis, is strictly contraindicated as within several hours after administration of drug perhaps repeated development of reaction in more severe form, up to life-threatening arterial hypotension or a lethal outcome.

If it is impossible to exclude hypersensitivity to an abakavir, then in order to avoid late diagnosis and for minimization of risk of development of life-threatening states, абакавир cancel forever even if other diagnosis is possible (for example, a respiratory disease and lungs, a grippopodobny syndrome, a gastroenteritis or undesirable effect of other drugs). It is not necessary to resume treatment by drug Olitid or other drug containing абакавир, even in case of symptoms of a giperchuvstvitelyyusta at repeated use of alternative medicines.

Special instructions on treatment after a break in therapy abakaviry. Regardless of HLA-B*5701 allele carriage. if after cancellation of an abakavir treatment resuming is supposed this drug, it is necessary to find out the cancellation reason and to be convinced that at the patient hypersensitivity symptoms were not observed. If it is impossible to exclude reaction of a giperchuvstvitelyyusta, then treatment by any drug containing абакавир it is forbidden.

Not numerous cases of development of reaction of hypersensitivity when resuming treatment are described the abakaviry ambassador of his cancellation in connection with emergence any one of typical symptoms of hypersensitivity (rash, fever, an indisposition, fatigue, gastrointestinal disturbances and disturbances from respiratory system). As in all such cases it is impossible to exclude reaction of hypersensitivity and, in view of data on its heavier current at repeated use of an abakavir. therapy resuming by the drug containing абакавир at these patients is not recommended. However if in such cases the issue of repeated purpose of an abakavir is resolved positively, then treatment by him is carried out only at direct medical observation.

Reaction of hypersensitivity is noted, though is extremely rare, even when resuming treatment by abakavir-soderzhashy drug of patients at whom symptoms of this reaction were not observed earlier, and having rummaged in administration of drug, containing абакавир, was connected with other reasons. In that case resuming of administration of drug is possible, however demands existence from the patient or people of bystry access to medical care surrounding it.

Screening on a carriage of an allele of HLA-B*5701 is recommended to be carried out before repeated purpose of an abakavir at patients with the unknown HLA-B*5701-status. earlier well transferring therapy abakaviry. Repeated purpose of an abakavir is not recommended to patsentam-carriers of an allele HLA-B*5701 and a floor can be considered by careful medical control when the potential advantage of treatment by drug exceeds all possible risks only in exceptional cases.

Necessary information for patients. The doctor appointing drug has to inform the patient of the following information on hypersensitivity reaction:

- the patient has to be informed on a possibility of emergence of life-threatening symptoms of hypersensitivity and risk of a lethal outcome, and also on the increased risk of reaction of hypersensitivity at carriers of an allele HLA-B*5701;

- the patient needs to be warned that even in the absence of an allele of HLA-B*5701 reaction of a giperchuvstvitelyyusta can develop. Thus, all patients at emergence of symptoms which can be caused by hypersensitivity reaction have to see the attending physician immediately;

- patients with гиперчувствительностыо to an abakavir have to be warned about inadmissibility of resuming of use of drug Olitid or other drugs containing абакавир regardless of HLA-B*5701 - the status;

- in order to avoid repeated use of drug Olitid by the patients who transferred hypersensitivity reaction it is recommended to return the remained drug tablets to the doctor;

- the patients who for any reason interrupted treatment with drug Olitid (especially in connection with possible undesirable reactions or complications of treatment), before resuming of administration of drug have to see the attending physician.

Lactoacidosis, hepatomegalia and fatty dystrophy of a liver. There are messages on development of lactoacidosis, a hepatomegalia and fatty dystrophy of a liver, including with a lethal outcome, owing to antiretrovirusiy therapy by analogs of nucleosides, including абакавир. accepted as separately, and in a combination. In most cases these complications arise at women.

The symptoms indicating lactoacidosis include the general weakness, a loss of appetite, bystry weight loss of not clear etiology, disturbance from a GIT and disturbance from respiratory system (an asthma and a tachypnea).

Use of the abakavir-containing drugs for any patient demands care, especially with risk factors of damage of a liver. At emergence of clinical or laboratory signs of lactoacidosis or a hepatotoxic (it can be shown by a hepatomegalia and fatty dystrophy of a liver, even for lack of the expressed increase in activity of aminotransferases) treatment abakaviry needs to be stopped.

Redistribution of a hypodermic fatty tissue. The combined antiretrovirusiy therapy can be followed by development of one or several of the listed symptoms: obesity, redistribution of subcutaneous fat with its adjournment on a trunk, a neck ("a buffalo hump"), considerable reduction of a hypodermic fatty layer on extremities and a face, a gynecomastia, increase in concentration of lipids in serum and glucose level in blood.

All these symptoms belong to manifestations of a lipodystrophy. One or several of these symptoms can arise at treatment by any inhibitors of HIV protease and nukleozidny inhibitors of the return traiskriptaza. However the risk of these undesirable reactions depends on the used drug.

The syndrome of a lipodystrophy has a difficult etiology and can develop under the influence of different factors which can synergistically work. An important role in its development is played by HIV infection, advanced age of the patient and duration of antiretrovirusiy therapy.

At clinical inspection of patients it is necessary to pay attention to redistribution of a hypodermic fatty tissue. Laboratory inspection has to include definition of concentration of lipids in serum and glucose level in blood. At disturbance of lipidic exchange appoint the corresponding treatment.

Mitochondrial dysfunction. In the conditions of in vitro and in vivo of a vyyalen ability of nukleotidiy and nukleozidiy analogs to cause damage of mitochondrions of various degree. The HIV-negative children submitted influence of nukleozidiy analogs vnutriutrobno or right after the birth have messages on mitochondrial dysfunction. The main displays of mitochondrial dysfunction, anemia, a neutropenia, a giperlaktatemiya and increase in activity of a lipase in a blood plasma were often passing. Also later manifestations of this disturbance were noted: hyper tone of muscles, spasm, anomaly of behavior.

Immunity recovery syndrome. In the presence at HIV-positive patients with a heavy immunodeficiency of asymptomatic or oligosymptomatic opportunistic infections at the time of the beginning of antiretrovirusiy therapy (APT), performing such therapy can lead to strengthening of symptomatology of opportunistic infections or other serious consequences. Usually these reactions arise within the first weeks or months after the beginning of APT. Typical examples are the Cytomegaloviral retinitis, the generalized or focal infection caused by mycobacteria, and pneumonia, the caused Pneumocystis jiroveci (P. carinii). Emergence of any symptoms of an inflammation demands immediate inspection and, if necessary, treatment. Autoimmune diseases (such as Greyvs's disease, a polymiositis and a syndrome to Giyena-Barra) were observed against the background of immunity recovery, however time of primary manifestations varied, and the disease could arise in many months after the beginning of therapy and have an atypical current.

Opportunistic infections. Use of an abakavir or other anti-retrovirus drugs does not exclude a possibility of development of opportunistic infections or other complications of HIV infection therefore patients have to remain under observation of the doctor having experience of treatment of the HIV-associated diseases.

Dysfunction. With a renal failure of dose adjustment of an abakavir it is not required from patients.

Liver failure. Drug use Olitid at patients with a liver failure contraindicated.

Patients with chronic hepatitis B or C. Risk of a hepatotoxic action of anti-retrovirus drugs at patients with a sochetanpy infection of HIV and a virus of hepatitis B or C above, than in the presence of only HIV infection. Therefore patients with chronic hepatitis B or S. which at the same time accept anti-retrovirus drugs are in group of the increased risk of adverse influence on a liver with a possible lethal outcome. For such patients careful observation, both clinical, and laboratory has to be conducted.

Abakavir and рибавирин have identical ways of phosphorylation therefore it is necessary to consider a possibility of interaction between these drugs. At co-administration of an abakavir and ribavirin reduction of concentration of fosforilirovanpy metabolites of a ribavirin is possible that in turn can lead to decrease in efficiency of treatment at the patients infected at the same time with HIV and a virus of hepatitis C, receiving therapy by pegylated interferon and ribaviriny. It is necessary to observe extra care at co-administration of an abakavir and ribavirin.

Transfer of HIV infection. Performing antirstrovirusny therapy, including abakaviry. does not exclude a possibility of transfer of HIV sexually or at contact with the infected blood and therefore does not cancel need of observance of the appropriate measures of precaution.

Myocardial infarction. As a result of a prospective, observation, epidemiological research for the purpose of studying of frequency of developing of a myocardial infarction communication previous, within 6 months, reception of an abakavir with the increased risk of development of a myocardial infarction was found in the patients receiving the combined aptiretrovirusny therapy. According to the generalized analysis of clinical trials, increase in risk of the myocardial infarction interfaced to reception of an abakavir was not observed. The biological mechanisms explaining potentially increased risk are unknown. Generally, the available data obtained from observation of cohorts and controlled clinical trials do not allow to define unambiguously therapy communication abakaviry and risk of a myocardial infarction.

Nevertheless, with care it is necessary to appoint anti-retrovirus therapy, including the drugs containing абакавир. to patients with possible risk of developing of coronary heart disease. Acceptance of all measures is necessary for minimizing risk factors (such as arterial hypertension, dislipidemiya, diabetes mellitus and smoking).

Pancreatitis. Cases of development of pancreatitis in the patients receiving абакавир are noted, but relationship of cause and effect using drug is definitely not established. At emergence of an abdominal pain, nausea, vomiting or characteristic changes of biochemical indicators in the patient receiving абакавир it is necessary to exclude pancreatitis. It is necessary to suspend administration of drug until until the diagnosis of pancreatitis is excluded.

Osteonecrosis. Though the etiology of an osteonecrosis is considered multifactor (for example, reception of corticosteroids, alcohol intake, acute immunosuppression, the raised index of body weight play an important role in development of this complication), report about such cases, in particular, at patients with the progressing HIV infection / or for a long time receiving anti-retrovirus therapy. Patients have to see behind consultation the attending physician at emergence of such symptoms as slackness, constraint, joint pains or at emergence of difficulties at the movement.

Influence on ability to manage vehicles and mechanisms. Special researches on studying of influence of an abakavir on ability to drive the car and to work with mechanisms were not conducted.

Nevertheless, the patients accepting абакавир need to observe precautionary measures, or to avoid control of vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions as drug can cause such side effects as drowsiness, a headache.

Side effects:

Hypersensitivity. According to the clinical trials conducted prior to screening on existence of an allele of HLA-B*5701 approximately at 5% of the patients accepting абакавир hypersensitivity reaction, in rare instances from the death was noted. Hypersensitivity to an abakavir is characterized by multiorgan defeat. At most of patients with a gnperchuvstvitelnost at development of this reaction fever and rash (usually makulo-papular or urtikarny) are noted though in certain cases these manifestations are absent. Symptoms of reaction of a gipsrchuvstvitslnost can appear after an initiation of treatment abakaviry at any time. however most often they arise within the first 6 weeks of treatment (a median of time of the beginning of this reaction - 11 days). Symptoms of reaction of a giperchuvstvitelyyusta are given below.

From skin and a hypodermic fatty tissue: ≥10% - rash (usually makulo-papular or urtikarny).

From digestive tract: ≥10% - nausea, vomiting, diarrhea, an abdominal pain; are possible - an ulceration of a mucous membrane of an oral cavity.

From a liver and a pancreas: ≥10% - increase in activity of enzymes of a liver; the liver failure is possible.

From respiratory system: ≥10% - short wind, cough; are possible - a pharyngalgia, a respiratory distress syndrome of adults, respiratory insufficiency.

From a nervous system: ≥10% - a headache; paresthesias are possible.

From system of a hemopoiesis: the lymphopenia is possible.

From a musculoskeletal system: ≥10% - mialgiya; seldom - a myolysis, arthralgias. increase in activity of a kreatinfosfokinaza (KFK).

From an urinary system: are possible - increase in concentration of a kreatinip in serum, a renal failure.

Others: ≥10% - fever, feeling of fatigue, an indisposition; are possible - hypostases, a lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions. Hypersensitivity reaction can be regarded as a disease of a respiratory organs (pneumonia, bronchitis, pharyngitis, a respiratory viral infection), a gastroenteritis in the beginning or as the undesirable reactions connected with reception of other drugs. Continuation of reception of an abakavir at hypersensitivity reaction development, also as resuming of its reception after subsiding of symptoms, is fraught with grave consequences, up to death. Therefore at emergence of any of the listed symptoms careful inspection of the patient is necessary for an exception of reaction of a giperchuvstvitelyyusta. If it is impossible to exclude hypersensitivity reaction, then repeated purpose of drug Olitid or other abakavir-soderzhashy drugs strictly contraindicated.

If at hypersensitivity reaction development patients continue to accept абакавир, then clinical manifestations become more expressed, and at cancellation of an abakavir they usually are exposed to involution.

Resuming of reception of an abakavir by patients with reaction of hypersensitivity in the anamnesis leads to development of repeated reaction within several hours. Repeated reaction of a giperchuvstvitelyyusta can proceed more hard, than the first and be shown by life-threatening arterial hypotonia, up to a lethal outcome. At hypersensitivity reaction development, regardless of HLA-B*5701 allele carriage, it is necessary to refuse forever drug use Olitid and other drugs containing абакавир.

Sometimes reaction of hypersensitivity develops when resuming therapy the abakaviry ambassador of his cancellation caused by emergence of only one of the main symptoms of this reaction (rash, fever, an indisposition, fatigue, disturbances from digestive tract or respiratory system).

In rare instances this reaction arises when resuming reception of an abakavir by patients at whom before drug withdrawal no symptoms of a gipsrchuvstvitslnost were noted.

The nature of other undesirable phenomena other than hypersensitivity reaction, but observed at the patients receiving абакавир up to the end is not clear. Whether these undesirable phenomena are a consequence of use of an abakavir or other drugs which are at the same time appointed with it, or they are caused by a disease, so far is not established.

Many of the undesirable effects given below connected with reception of an abakavir (nausea, vomiting, diarrhea, fever, fatigue, rash) can be observed also at hypersensitivity reaction development. Therefore at manifestation of any of these symptoms careful inspection of the patient for confirmation or an exception of reaction of hypersensitivity is shown. If абакавир it was cancelled owing to suspicion on hypersensitivity reaction, resuming of administration of drug is forbidden. It is possible to resume therapy the abakaviry ambassador of interruption in connection with emergence of above-mentioned symptoms only after an exception of reaction of hypersensitivity and under direct medical observation. The majority of the undesirable reactions given below do not limit use of an abakavir. Determination of frequency of side reactions: very often (> 1/10), it is frequent (from 1/100 to 1/10), infrequently (from 1/1000 to 1/100), is rare (from 1/10 000 to 1/1000) and is very rare (frequency lower than 1/10 000).

From a metabolism: often - a giperlaktatemiya; seldom - lactoacidosis, accumulation/redistribution of fatty tissue, a gipertriglitseridemiya, a hypercholesterolemia, resistance to insulin, a hyperglycemia.

Frequency of these undesirable reactions depends on many factors, including on the anti-retrovirus drugs used in a combination with abakaviry.

From digestive tract: often - nausea, vomiting, diarrhea; seldom - pancreatitis (relationship of cause and effect using an abakavir is definitely not established).

From gepatobiliarny system: seldom - hepatitis, a hepatomegalia. fatty dystrophy of a liver.

From a nervous system: often - a headache.

From skin and a hypodermic fatty tissue: often - rash (in the absence of system manifestations); very seldom - a mnogoformny exudative erythema, including Stivsnsa-Johnson's syndrome and a toxic epidermal necrolysis.

Others: often - fever, drowsiness, fatigue, appetite loss. It was reported about osteonecrosis cases at patients with such risk factors as late stages of HIV infection or the long combined aitiretrovirusny therapy (frequency of occurrence is unknown).

At the patients accepting абакавир or other anti-retrovirus drugs, development of opportunistic infections or other complications of HIV infection is possible.

Interaction with other medicines:

Results of the researches in vitro and the analysis of the main ways of metabolism of an abakavir indicate that its interaction with other drugs mediated by isoenzymes of system of P450 cytochrome is improbable. Abakavir does not oppress processes of metabolism with CYP3A4 enzyme participation. In the researches in vitro it is shown what абакавир does not suppress activity of isoenzymes of CYP3A4, CYP2C9 or CYP2D6. During clinical trials induction of hepatic metabolism of exogenous substances under the influence of drug is not revealed. Thus, interaction of an abakavir with the inhibitors of HIV protease and other drugs which are metabolized with participation of the main isoenzymes of system of P450 cytochrome is improbable.

Clinical trials showed lack of clinically significant interactions between abakavirom.zidovudiny and lamivudiny.

Use of an abakavir along with rifampicin, phenobarbital and Phenytoinum (UDF-glyukuroniltransferaza's inductors) can lead to insignificant reduction of concentration of an abakavir in plasma.

Ethanol slows down metabolism of an abakavir that leads to increase in AUC of an abakavir by 41%. However the clinical importance of this change is small. Abakavir does not influence ethanol metabolism.

According to pharmacokinetic researches, use of an abakavir in a dose of 600 mg 2 times a day in a combination with metadoiy lower Cmax of an abakavir in serum by 35%, increases time of achievement of the maximum concentration in serum by 1 h, but does not change AUC. The clinical importance of these changes is small. In the same research it is established what абакавир increases total clearance of methadone for 22%. In most cases these changes are also regarded as clinically insignificant, however in certain situations change of a dose of methadone can be required. Retinoids. for example изотретиноин. are removed with alcohol dehydrogenase participation. therefore can enter interaction with abakaviry, however so far special researches were not conducted.

At co-administration of an abakavir and ribavirin reduction of concentration of fosforilirovanny metabolites of a ribavirin is possible that in turn can lead to decrease in efficiency of treatment at the patients infected at the same time with HIV and a virus of hepatitis C, receiving therapy by pegylated interferon and ribaviriny. It is necessary to observe extra care at co-administration of an abakavir and ribavirin.

Contraindications:

— hypersensitivity to an abakavir or any other component of drug,

— liver failure,

— the children's age up to 3 years and body weight is less than 14 kg (for this dosage form).

With care: pregnancy, patients with possible risk of developing of coronary heart disease.

Overdose:

Symptoms: In clinical trials patients received single doses of an abakavir to 1200 mg and daily doses to 1800 mg. Messages on side reactions were not. Action of higher doses of an abakavir is unknown.

Treatment: In case of overdose control of a condition of the patient for the purpose of identification of symptoms of intoxication and an early treatment is necessary. If necessary symptomatic therapy is appointed. There are no data on a possibility of removal of an abakavir by means of a hemodialysis and peritoneal dialysis.

Storage conditions:

To store in original packaging of the producer at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 150, 300 and 600 mg. Are located in a polymeric can with the tense cover with control of the first opening. After 1 bank together with the application instruction place in a pack from a cardboard.