Abavir: instructions for using the medicine, structure, Contraindications

Vladimir Andreevich Didenko

822 14 minutes read

Abavir - instructions for use of the drug, structure, Contraindications

Abavir is a direct acting antiviral drug..

Active substance – Abacavir.

Abavir: composition and form of release

Abavir is a tablet, Film-coated, yellow color, capsule-shaped, lenticular, with an inscription: "H" on one side and "139" – with another, numbers 13 and 9 separated by a line.

By 60 tablets in a block, by 1 block in a carton.

1 the tablet contains abavir sulfate, which corresponds to Abavir 300 mg.

Additional substances:

microcrystalline cellulose,
sodium starch glycolate,
silicon dioxide colloidal,
magnesium stearate,
dye "Opadray yellow 13K 52177" (gipromelloza (E 464),
Titanium dioxide (E 171),
triacetine,
iron oxide yellow (E172),
polysorbate 80 (E 433).

Storage conditions

Store in original packaging at temperatures not exceeding 25 ° C out of the reach of children.

Abavir: general information

Sales form:
on prescription
Current in-about:
Abacavir
Manufacturer:
Hetero Drags Limited, India
Farm. Group:
Antiviral drugs

Abavir: pharmachologic effect

Abavir belongs to the subcategory of nucleotide reverse transcriptase inhibitors., enzymes, catalyzing DNA synthesis, and is a potent inhibitor of HIV-1 and HIV-2 viruses, also considering HIV-1 isolates with reduced sensitivity to the antiviral drugs zidovudine, lamivudine, zalcitabine, didanosine or nevirapine. In the cell, Abavir is transformed into the active substance carbovir triphosphate., whose main function is to stop the production of HIV reverse transcriptase enzymes, the end result of which is the disruption of the desired connection in the viral DNA chain, and slows down its replication..

Absorption by the body of Abavir: absorbed from the gastrointestinal tract in a short time, and its oral bioavailability in patients is 83%. The maximum level of the substance in the blood serum is reached after 1,5 hours after taking a dose of tablets. When taking this drug normally 600 mg per day, the maximum concentration is about 3 g / ml, and the indicators "concentration-time" (AUC) at intervals of about 12 hours – 6 g / no / ml. The use of Abavir during a meal delays the achievement of the maximum level of its concentration in the blood., but does not affect the overall level in the body. Therefore, Abavir can be prescribed regardless of food intake..

Distribution Abavir easily reaches various body tissues. In patients with HIV, Abavir penetrates well into the cerebrospinal fluid. The average ratio of the concentration of the drug in the cerebrospinal substance and blood is approximately 30-44%. When used at the rate prescribed by the therapist, the level of protein binding is about 49%.

Metabolism Abavir is partially broken down, passing through the liver, less 2% from the norm in the body is excreted in its original form through the kidneys. The main degradation products of Abavir are 5′-carboxylic acid and 5′-glucuronide, transformation of which occurs with the participation of alcohol dehydrogenase or by conjugation of substances with glucuronic acid (glucuronization).

Eventually, the average period of partial elimination of Abavir is 1,5 o'clock. Significant accumulation after systematic use of Abavir at the standard rate 300 mg 2 does not happen once a day. The main part of the metabolites and Abavir in the original state at a concentration of approximately 83% from the accepted norm excreted by the kidneys, rest – with faeces.

The likelihood of carcinogenic formations after taking the drug in patients has not been studied. But research confirms, that the therapeutic potential of the drug Abavir significantly exceeds the carcinogenic risk in the patient.

Abavir: indications and dosage

The main indications for the use of Abavir are:

Combined Therapeutic Treatment of HIV Infection in Adults and Children.

This drug should only be treated by a doctor., having the necessary qualifications for the treatment of patients with HIV infection.

The drug can be taken regardless of the distribution of meals. In order to ensure the acceptance of a standard dose of the drug, it is recommended to swallow the tablet whole, without dividing it into parts. For the treatment of patients, who have trouble swallowing a whole tablet, you can use the drug Abavir, after dissolving it in a liquid and taking the solution orally. Alternatively, the tablet can be broken up and added to a small meal or liquid., taken in one go.

Adults and adolescents, that weigh no less 30 kg:

The standard dose of Abavir – 600 mg per day (1 tablet – 2 once a day, 2 tablets – 1 once a day).

Children weighing less 30 kg:

The standard dose of Abavir – ½ tablet in the morning, and 1 tablet in the evening or 1,5 tablets – 1 once a day.

Children with low body weight (14-21 kg):

The recommended dose of Abavir is 0,5 tablets 2 times a day, or 1 tablet 1 once a day.

Children weighing no more 14 kg:

Abavir should be taken before, dissolvable for oral administration.

Patients with renal insufficiency:Dose adjustment is not needed in this category of patients..

Patients with hepatic insufficiency:

Abavir is metabolized in the liver zone. Recommended Dosage of Abavir in Patients with Early Hepatic Insufficiency (Child-Pugh medical index 5-6) It is 200 mg 2 once a day. For this dose reduction, Abavir should be used as a liquid oral solution.. For the treatment of patients with moderate, as well as a severe stage of liver failure Abavir is prohibited for use.

Newborns:

Recorded data on the safety of the use of this drug in infants up to 3 no months. The drug in the form of tablets is used for the therapeutic treatment of children weighing more than 14 kg. Children who weigh less 14 kg Abavir should be taken as a solution by mouth.

Abavir: overdose

These studies indicate that, that after taking a dose of Abavir before 1200 mg and daily allowance up to 1800 mg no adverse reactions detected. The result of taking very large doses is not fixed. In case of an overdose, the patient should immediately consult a doctor to diagnose the symptoms of intoxication. (More in the section "Adverse reactions"), if an overdose is detected, standard maintenance therapy is carried out. Is Abavir amenable to hemodialysis unknown.

Abavir: side effects

The main side effect is the appearance of hypersensitivity in the patient.

In 3,4% patients with a seronegative category for the HLA B allele * 5701, taking Abavir, developed a hypersensitivity reaction. When taking Abavir at a dose 600 mg 1 once a day, the degree of hypersensitivity was kept within the degree of hypersensitivity when taking Abavir as the norm 300 mg 2 once a day.

Some cases of hypersensitivity have ended in death, despite therapy. In such cases, symptoms of systemic lesions of internal organs appeared..

The most common rash in patients with hypersensitivity (maculopapular or urticaria-like) and/or high fever, but there were also asymptomatic cases. The main symptoms of an allergy to the drug:

Skin reactions: maculopapular rash, or hives.

Reactions of the digestive tract: nausea, vomiting, diarrhea, abdominal pain, appearance of mouth ulcers.

Reaction the respiratory system: breathlessness, cough, sore throat, distress syndrome in adult patients, hyperventilation.

Other reactions: fever, lethargy, weakness in the body, swelling, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic shock.

Reactions of the nervous system: headache, convulsions.

Blood reactions: lymphopenia.

Reactions of the digestive system: increased response of liver function tests, gepatitы, hepatic failure.

Reactions of the musculoskeletal system: myalgia, very rarely myolysis, arthralgia, elevated levels of CPK.

Reactions of the urinary system: elevated creatinine, decreased kidney function.Adverse reactions of children to the drug: rash (81%), gastrointestinal manifestations (70%).

Partially, hypersensitivity reactions may be perceived at first as symptoms of gastroenteritis or a disease of the respiratory system. (pneumonia, pneumonia, bronchitis, faringitы), as well as flu-like conditions. The consequence of a late visit to a doctor with a diagnosis of hypersensitivity was that, that the patients continued the course of Abavir or started it again, which caused a sharp exacerbation of allergy symptoms and even led to death. Therefore, it is necessary to consult a doctor if the above symptoms appear..

Symptoms may appear at any stage of the course of Abavir., however, most often they appeared during the first 1,5 months from start of admission (on average they appear within 11 days). During the first 2 months of the course, constant monitoring by the attending physician and his consultation every 2 of the week.

Pauses in therapy threaten the risk of developing sensitivity, and then clinically significant adverse hypersensitivity reactions. Therefore, regular intake of Abavir is necessary..

Restarting Abavir after the onset of hypersensitivity may result in a rapid return of some symptoms within a few hours.. Such a sharp recurrence of an adverse hypersensitivity reaction may have a more severe form of severity., compared to the first one, and pose a threat to life, due to the risk of arterial hypotension and even death. Regardless of the presence of the HLA B allele * 5701 sick, who have hypersensitivity, you should stop taking Abavir and not resume it in the future, as for analogues.

In order to reduce the risk of developing a life-threatening reaction, therapy with Abavir should be stopped., if it is impossible to prevent the occurrence of a hypersensitivity reaction, even when another diagnosis is the cause of this condition. For Example, respiratory diseases, flu-like illnesses, gastroenteritis or a side effect of other medicines.

Rapid onset hypersensitivity reaction, including her life threatening, appeared in patients after the resumption of therapy with this drug, if they had one of the main symptoms of hypersensitivity (rash on the skin, fever, gastrointestinal ailments, respiratory or general manifestations, such as lethargy or weakness) before the end of treatment with Abavir. Rash was the most common individual symptom of hypersensitivity.. Also, in some cases, hypersensitivity during the restoration of treatment with Abavir developed in patients, who had no signs of allergic reactions before. In each of the cases described, if there is a need to restart treatment with Abavir, this must be done under medical supervision.

Each patient should be warned about the listed hypersensitivity reactions during treatment with Abavir..

In many cases, the nature of the manifestation of allergic reactions remained unclear and they are not clearly related to Abavir., other drugs or HIV infection itself.

Most of the above reactions (nausea, vomiting, diarrhea, fever, weakness, rash) appear as a separate part of the hypersensitivity itself. Therefore, patients with each of these signs should be carefully diagnosed at the onset of their hypersensitivity reactions.. If Abavir is discontinued due to these symptoms, when resuming treatment with the drug, containing abacavir, this must be done under the supervision of doctors. There are also cases of erythema multiforme, the appearance of Stevens-Johnson syndrome and the development of toxic epidermal necrolysis in patients, in which the influence of hypersensitivity to abacavir is possible. In this case, drug treatment, containing abacavir, should be canceled. Most of the side effects, given in the instructions, do not limit treatment. The frequency of occurrence of adverse reactions has its own classification, which is composed as follows: Often (> 1/10), often (> 1/100, 1/1000, <1/100), rarely (> 1/10 000, <1/1000), rarely (<1/10 000).

Metabolic reactions: often - the appearance of anorexia.

Reactions of the nervous system: often - headache.

Reaction digestive tract: often - the appearance of nausea, vomiting, diarrhea, rarely - the development of pancreatitis.

Reactions of the skin and subcutaneous tissues: often - the appearance of a rash (no systemic symptoms); rarely – erythema multiforme, development of Stevens-Johnson syndrome and toxic epidermal necrolysis.

Common reactions: often – fever, lethargy, body weakness.

When taking nucleoside medical analogues, cases of developing lactic acidosis have been recorded., with rare cases of death, associated with severe hepatomegaly and hepatic steatosis.

The use of antiretroviral treatment in HIV-infected patients is associated with a change in the distribution of body fat (lipodystrophy), including reduction of body fat in the area of the limbs and face, increased intra-abdominal and visceral fat deposits, hypertrophy in women of the mammary glands and the appearance of dorsocervical fat deposits or the so-called "buffalo hump".

Combination antiterovirus treatment is associated with metabolic defects, such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia and hyperlactataemia.

In HIV-infected patients with advanced severe immunodeficiency, at the time of initiation of treatment with antiretroviral drugs, inflammation may appear in response to asymptomatic or residual opportunistic infectious diseases in the body. Cases of osteonecrosis have been recorded., in most patients with standard risk factors, advanced stage of HIV disease, as well as during long-term combination antiretroviral treatment. The number of these cases is unknown..

Learn more about adverse reactions:

One of the duties of the attending physician is to provide all existing information to the patient about the side effects and allergic reactions to this drug..

The patient may develop the following adverse reactions while taking Abavir:

Abavir: hypersensitivity

Patients may develop hypersensitivity during treatment, which can also lead to death. Besides, the risk of developing hypersensitivity increases in patients with HLA B * 5701 allele.

Therefore, at the first signs of hypersensitivity, the patient should seek advice from the attending physician.. Carriers of the HLA B allele * 5701 it is necessary to warn in advance about the impossibility of taking a course of the drug Abavir or other medicines containing abacavir.

For patients with hypersensitivity, to prevent the resumption of the course of Abavir, it is recommended to destroy the remaining tablets of the drug..

Lactic acidosis while taking abavir

At therapy with the use of nucleoside analogues of the drug, cases of development of lactic acidosis were recorded (lactic acidemia, lactic acid coma, hyperlactatacidemia, molernkisly acidosis), which is closely associated with hepatomegaly (excessive enlargement of the liver) and hepatic steatosis (accumulation of fat in liver cells).Lactoacidosis This is an extremely rare and very dangerous complication., which can lead to the death of the patient and cause side diseases of the gastrointestinal tract, such as: pancreatitis (Pancreatic inflammation), hepatic failure (liver tissue damage, which leads to dysfunction), renal failure (acute (OHN) and chronic (CRF)).

The first symptoms of this disease are:

nausea and vomiting;
stomach ache;
uncaused weakness;
poor appetite;
sudden weight loss;
fast and deep breathing.

Lactic acidosis may occur after several months of Abavir course duration..

At the first signs of the following diseases, the course of the drug must be stopped.:

metabolic lactic acidosis;
symptomatic hyperlactatemia (increased levels of lactate in venous blood, which is permanent or intermittent);
progressive hepatomegaly;
increased levels of aminotransferases.

Carefully it is necessary to prescribe the drug for the treatment of female patients with the problem of obesity and the development of the following diseases:

gepatomegaliya;
hepatitis (A, B, C, D, IS; This is especially true for patients with hepatitis C., who have been prescribed alpha-interferon and Ribavirin);
liver disease:
hepatic steatosis.

Other risks must also be taken into account., such as alcohol or concomitant use of other medicines while prescribing Abavir. Such patients need constant medical supervision when taking this drug..

Abavir: mitochondrial dysfunction

The recognized fact is that, that nucleoside and nucleotide preparations can cause malfunctions of mitochondria of various degrees. As already said, cases of mitochondrial dysfunction have been reported in newborns with HIV-negative status, whose mothers took nucleosides during pregnancy and lactation.

The main side effects of mitochondrial failure are:

anemia (syndrome of low hemoglobin concentration in the blood, the decline in the number of red blood cells);
neutropenia (abnormally low neutrophil count);
hyperlactataemia;
hyperlipidemia (abnormally elevated levels of lipids and/or lipoproteins in a person's blood).

The features described are transitional.. There is also evidence of a number of late symptoms in children.:

hypertension;
convulsions;
behavioral disorders.

Regarding neurological conditions, it remains unclear whether they were permanent or recurrent.. Therefore, every child, who, to one degree or another, was affected by nucleoside and nucleotide preparations, including Abavir, must undergo a series of laboratory tests for the presence of mitochondrial failures in the presence of the listed symptoms. The data provided do not affect recommendations for the use of antiretrovirals in HIV-positive pregnant women..

Abavir: lipodystrophy

Antiretroviral therapy may be accompanied by changes in body fat distribution (lipodystrophy) in HIV patients. How this phenomenon affects the health of the patient remains unexplored.. An association between the following diseases and protease inhibitors is tentative:

visceral lipomatosis (the appearance of numerous lipomas in the subcutaneous tissue, having a connective tissue capsule or passing into the area of normal adipose tissue without a clear boundary);
lipoatrophy (reduction of adipose tissue in certain areas).

The increased risk of these diseases is caused by a number of factors.:

advanced age;
taking certain additional medications (antiretroviral drugs);
metabolic disorders.

Therefore, during a routine examination, an analysis of the signs of the redistribution of adipose tissue should be carried out.. This analysis includes measurement of serum lipids and fasting blood glucose.. If lipid disorders are detected, the doctor should adjust the lipid balance taking into account the clinical condition..

Abavir: pancreatitis

There were also data on the occurrence of pancreatitis in patients taking Abavir., but a direct relationship with the drug has not been determined.

Abavir: triple nucleoside therapy

Patients with high viral load (better, than 100000 copies / ml) initiation of triple therapy with a combination of drugs such as Abavir, lamivudine and zidovudine require a separate consultation with a doctor. Virologic failure data and emergence of resistance effect have been published (resistance) during the first time of taking Abavir with other drugs (tenofovir disoproxil fumarate and lamivudine) when receiving 1 once a day.

Abavir: liver disease

How safe it is to take Abavir in patients with liver problems has not been studied. Therefore, taking this drug is not recommended for patients with severe forms of liver disease and insufficiency.. You can read more about this in the "Contraindications" section.. Chronically ill with hepatitis B and C, who are on antiretroviral therapy are at high risk of fatal hepatic adverse reactions. In the case of a combination of drugs for hepatitis B and C and antiviral drugs, it is required to act strictly according to the instructions.

Patients, who have the following diseases must be constantly under medical supervision:

chronic forms of hepatitis;
active hepatitis.

In the case of the first signs of an increase in the disease, it is necessary to suspend or stop taking Abavir..

Clinical studies have been conducted on the effect of the drug with mild hepatic insufficiency. But on the issues of dosage and its reduction, no specific recommendations can be made., since there is a very large variability in the action of the drug among such patients.

clinical data, available to experts on the safety of the drug Abavir for patients with liver dysfunction is not enough. Therefore, such patients need special medical supervision.. Besides, there is evidence that, that abacavir concentrations are significantly higher in patients with mild to severe hepatic impairment. Therefore, if necessary, patients with a mild degree of insufficiency can take this drug only under the strict supervision of doctors.

Abavir: kidney disease

The use of the drug for the treatment of patients with renal insufficiency at the thermal stage is not recommended..

Abavir: immune recovery syndrome

In HIV-positive patients with severe immunodeficiency at the time of initiation of therapy (first few weeks or months) inflammatory responses to these types of infections may occur:

asymptomatic infection;
residual opportunistic infection.

This type of inflammation can lead to worsening of ongoing symptoms or other complex clinical conditions.. An example of such diseases is:

retinitis (inflammation of the retina), which may be caused by cytomegalovirus;

generalized or focal infection (caused by mycobacteria or Pneumocystis jiroveci (P. the sarins) 2).

Any inflammation should be examined and treated at the initial stage..

Also, the patient may experience the following autoimmune disorders:

Graves' disease;
poliomyositis;
Guillain Barre syndrome.

Although the listed diseases may manifest themselves some time after treatment and manifest themselves in an atypical form.

Abavir: osteonecrosis

Origin of osteonecrosis (necrosis of the bone, caused by circulatory disorders) considered a multifactorial phenomenon. It includes factors such as:

corticosteroids;
alcohol;
severe immunosuppression;
weight gain.

Also one of the factors, according to, long-term use of combination antiretroviral therapy in HIV-infected patients.

In order to prevent cases of osteonecrosis, it is necessary to warn the patient about the following possible symptoms::

joint pain;
rigidity (calcification) joints;
difficulty of movements.

If these symptoms appear, you should immediately consult a doctor.

Abavir: opportunistic infections

HIV-infected patients, who take Abavir are at risk of opportunistic infections, i.e. diseases, that do not develop with a normal level of immunity, but dangerous with low immune protection. Therefore, it is important for a doctor to have experience specifically with diseases of HIV origin..

Abavir: myocardial infarction

The relationship between the occurrence of myocardial infarction and the drug Abavir. The reasons for the increase in the risk of a heart attack have not yet been clarified.. Therefore, during the course of Abavir, it is necessary to reduce all other potential risks to a minimum., such as:

nicotine use;
hypertension;
hyperlipidemia (Hyperlipoproteinemia, dyslipidaemia).

Abavir: Contraindications

Allergic reaction to abacavir or any other component of the drug. Mild or advanced liver failure.

Abavir: interactions with other drugs and alcohol

The possibility of metabolic combined action of Abavir with other types of drugs is minimal.. Abavir has no effect on the metabolic process, via the CYP3A4 enzyme of the cytochrome P450 system, this medicine does not interact with other medicines, which are cleaved by CYP3A4 enzymes, CYP2C9 or CYP2D6. An increase in the rate of synthesis of hepatic metabolism was not recorded, therefore, the potential for concurrent action with other types of antiretroviral protease inhibitors and other types of drugs, in the cleavage of which most of the P450 enzymes are involved are quite small. Research has proven, that there is no significant clinical interaction between abacavir and the active substances zidovudine and lamivudine.

Interaction with ethanol: the process of splitting abacavir is changed under the influence of ethanol – increases the concentration – time" approximately 41%. Considering the safety profile of the drug, this indicator has no clinical significance. Abacavir itself has no effect on the metabolism of ethanol compounds..

Interaction with metadonom: abacavir increases the mean systemic clearance rate of methadone by approximately 22%. Most patients are not affected., however, in rare cases it may be necessary to change the methadone rate.

Interaction with pethinoids: retinoid composition, such as isotretinoid, eliminated by alcohol dehydrogenase. Combined action with abacavir possible, but it has not been studied.

Interaction with ribavirin: because of that, that abacavir and ribavirin share the same phosphorylation pathway, experts believe, that there is a small proportion of intracellular interaction between these drugs, which can cause a decrease in phosphorylated ribavirin metabolites inside the cell and, Consequently, reduce the chances of a sustained virological response in patients, with viral hepatitis C, when treated with a combination of pegylated interferon with ribavirin. Some data suggest, that HIV-infected patients with viral hepatitis C, who are taking Abavir, are at risk of reduced response to pegylated interferon/ribavirin therapy. Therefore, caution should be exercised when combining these drugs..

Abavir: precautions for taking

Use during pregnancy or lactation.

The safety of Abavir during pregnancy has not been studied.. Therefore, Abavir is prescribed during pregnancy only then, when the expected effect of therapy is greater than the possible risks for the child.

A slight increase in the concentration of lactate in the blood serum was recorded., which is probably the result of a malfunction of mitochondria in the baby's body. The cause of the failure may be the influence of nucleoside reverse transcriptase inhibitors while taking the drug during pregnancy..

The clinical impact of elevated blood lactate levels remains unclear.. There have also been cases of other adverse reactions in newborns.:

retardation;
convulsions;
neurological diseases.

However, did nucleoside reverse transcriptase inhibitors affect, as in the case of lactate, remains unclear.

These data do not affect recommendations for the use of antiretroviral drugs in pregnancy to prevent vertical transmission of HIV..

Also, Abavir and its degradation products were found in the milk of animals during lactation in clinical studies.. The results shown may apply to humans as well., however, there are no definitive data.

For HIV-positive mothers, there is a recommendation not to breastfeed their children in order to, so that the immunodeficiency virus is not transmitted to a newborn baby. Therefore, Abavir therapy is not carried out during breastfeeding..

Influence on the reaction rate when driving vehicles and other heavy mechanisms.

Based on the collected data, the experts came to the conclusion, that Abavir does not affect the driver's condition while driving vehicles or other heavy machinery.

Abavir: HIV transmission

Abavir therapy does not prevent the transmission of HIV infection to others through sexual intercourse or through blood! Therefore, all recommended precautions must be followed..

Before a new course of Abavir for patients, who completed the course ahead of schedule for any reason, as well as patients with side effects, you should consult with your doctor.

All patients must read the instructions before using the medicine., included in the drug box. And also during the course of therapy, always carry a special “Warning Card” with you., which is included in the Abavir kit.

Vladimir Andreevich Didenko

822 14 minutes read