Catalog of medicines. Interaction with other drugs
Pharmacological action
Reverse transcriptase inhibitor from the group of nucleoside analogues. Has selective antiviral effect in relation to human immunodeficiency virus types 1 and 2 (HIV-1 And HIV-2), including HIV-1 strains resistant to zidovudine, lamivudine, zalcitabine, didanosine or nevirapine. In vitro studies have shown that the mechanism of action of abacavir is inhibition of reverse transcriptase HIV, which leads to the termination of the RNA chain and the cessation of viral replication. In vitro, a synergistic effect was detected when combining abacavir with nevirapine and zidovudine. Abacavir has an additive effect in combination with didanosine, zalcitabine, lamivudine and stavudine. Strains were isolated in vitro HIV-1 resistant to abacavir. The development of resistance is associated with genotypic changes in a specific codon region of reverse transcriptase (codons M184V, K65R, L74V and Y115F). HIV resistance to abacavir in vitro and in vivo develops relatively slowly; multiple mutations are required to increase the IC 50 concentration by 8 times compared to the wild strain of the virus, which may be clinically significant. In strains resistant to abacavir, sensitivity to lamivudine, zalcitabine and/or didanosine may be reduced, but sensitivity to zidovudine and stavudine remains. The development of cross-resistance between abacavir and protease inhibitors or non-nucleoside reverse transcriptase inhibitors is unlikely.
IN clinical studies demonstrated that treatment with Ziagen in combination with zidovudine and lamivudine was accompanied by a significant and sustained decrease in viral concentrations and a corresponding increase in the number of CD4+ cells in adults and children.
In patients who have not previously received antiretroviral drugs, Ziagen in combination with other drugs allows for highly effective initial therapy.
According to the limited data available in patients who have previously received antiretroviral therapy, the addition of Ziagen to nucleoside reverse transcriptase inhibitors leads to an additional decrease in viral concentrations and increases the number of CD4+ cells. In such cases, the effectiveness of Ziagen depends on the nature and duration of previous therapy, which may lead to the formation of HIV strains that are cross-resistant to abacavir.
Abacavir crosses the BBB and reduces HIV-1 RNA levels in cerebrospinal fluid. In combination with others antiretroviral drugs Ziagen may slow the development of resistance and may also have some value in preventing neurological complications associated with HIV infection.
Indications
Treatment of HIV infection in adults and children (as part of combination antiretroviral therapy).
Dosage regimen
Ziagen can be taken with or without food.
Ziagen should be prescribed by specialists with experience in treating HIV infection.
Adults and teenagers over 12 years old
the drug is prescribed at 300 mg 2 times a day.
Children aged 3 months to 12 years
the dose is calculated based on 8 mg/kg body weight, but not more than 600 mg/day. Frequency rate 2 times/day.
There are currently no data on the use of Ziagen in children under 3 months of age.
Currently, there is no necessary clinical data on the use of the drug in patients with liver dysfunction. Due to the fact that abacavir is metabolized primarily in the liver, a study is currently being conducted to examine the impact of liver dysfunction varying degrees severity on the pharmacokinetics of abacavir in order to develop recommendations for dosage regimens in this category of patients.
Patients with impaired renal function
special selection no dose required.
When prescribing the drug elderly people should take into account the higher incidence of decreased liver, kidney and heart function, the presence concomitant diseases and taking other medications.
Side effect
Hypersensitivity reaction
In clinical studies, a hypersensitivity reaction occurred in approximately 4% of patients taking abacavir, and in in rare cases led to fatal outcome. The hypersensitivity reaction was manifested by symptoms that were indicative of multiple organ/systemic involvement. In most cases, one of the manifestations of the hypersensitivity syndrome is fever and/or rash (usually maculopapular or urticarial), but a hypersensitivity reaction may not be accompanied by these symptoms. Symptoms usually develop during the first 6 weeks of treatment with the drug (on average 11 days after starting treatment).
Dermatological reactions:
>=10% - rash (maculopapular or urticarial).
>=10% - nausea, vomiting, diarrhea, abdominal pain, increased liver function tests; rarely - ulceration of the oral mucosa, impaired liver function.
From the outside respiratory system:
rarely - shortness of breath, sore throat.
From the central nervous system and peripheral nervous system:
>=10% - headache; rarely - paresthesia.
From the hematopoietic system:
rarely - lymphopenia.
From the outside musculoskeletal system:
>=10% - myalgia; rarely - myolysis, arthralgia, increased CPK levels.
From the urinary system:
increased creatinine levels, impaired renal function.
Other:
>=10% - fever, fatigue, general malaise; rarely - edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions.
In some patients, the hypersensitivity reaction was initially diagnosed as respiratory disease (pneumonia, bronchitis, pharyngitis), influenza-like illness, gastroenteritis, or a reaction to other drugs.
Other side effects
For many other side effects, it is not clear whether they are caused by abacavir or other medicines or are complications of HIV infection itself.
From the outside digestive system:
nausea, vomiting, diarrhea, loss of appetite. There are reports of the development of pancreatitis, but the connection with taking abacavir has not been established.
Other:
fever, headache, drowsiness, fatigue, rash (not accompanied systemic manifestations). In clinical studies, changes in laboratory parameters were rarely observed; not noted significant differences in the frequency of changes in laboratory parameters between patients of the main and control groups.
Contraindications
Hypersensitivity to the components of the drug.
Pregnancy and lactation
If it is necessary to prescribe the drug during pregnancy, the expected benefit to the mother and the potential risk to the fetus should be carefully assessed. When prescribing the drug during lactation, breastfeeding should be stopped.
At present, the safety of using abacavir during pregnancy has not been established.
IN experimental studies laboratory animals have shown that abacavir and/or its metabolites can cross the placental barrier. Abacavir provided toxic effect on the development of the embryo and fetus only in rats at doses toxic to pregnant females (500 mg/kg body weight or more). These doses are 32-35 times higher than therapeutic doses for a person. The abnormalities identified included edema and fetal abnormalities, resorption, decreased fetal weight, and an increase in the number of stillborn fetuses. Dose that has no effect adverse influence for pre- and postnatal development, was 160 mg/kg body weight per day. This dose is approximately 10 times the human dose. These changes were not found in rabbits.
A study in rats showed that abacavir at doses up to 500 mg/kg had no effect on fertility in males or females. The results of studies in animals are not always predictive for humans.
Abacavir and its metabolites are excreted into the milk of lactating rats. It can be assumed that they also penetrate into the breast milk of lactating women, but there is currently no evidence of this. There are no data on the safety of using abacavir in children under 3 months of age. Experts recommend that HIV-infected women abstain from breastfeeding to prevent the child from becoming infected with HIV.
If symptoms of hypersensitivity occur, the patient should consult a doctor immediately. If the diagnosis of a hypersensitivity reaction is confirmed, Ziagen should be discontinued immediately. It is necessary to ask the patient to return all unused tablets/syrup to the doctor in order to avoid accidental use of the drug in the future. With continued treatment, the symptoms intensify, which can threaten the patient's life. When Ziagen was discontinued, hypersensitivity symptoms generally resolved. If a hypersensitivity reaction to abacavir develops, Ziagen or another drug containing abacavir should never be prescribed subsequently, because most severe symptoms(including life-threatening hypotension), resume within a few minutes and can be fatal.
For timely diagnosis hypersensitivity reactions and to minimize the risk of developing life-threatening hypotension, Ziagen should be discontinued if hypersensitivity reactions are suspected, even in cases where the possibility of another diagnosis cannot be excluded (for example, respiratory diseases, influenza-like illnesses, gastroenteritis or reactions to other drugs) . Ziagen therapy should not be restarted even if symptoms reappear while taking other medications.
If Ziagen therapy has been suspended and a decision is made to continue it, the reasons for discontinuation of the drug must be carefully analyzed to exclude the possibility of hypersensitivity symptoms. Unless symptoms of hypersensitivity have been excluded, Ziagen therapy should not be resumed.
There are isolated reports of the development of a hypersensitivity reaction after resumption of Ziagen, when temporary discontinuation of the drug was preceded by only one main symptom (for example, rash, fever or gastrointestinal disturbances). In cases where the diagnosis of hypersensitivity is not confirmed in patients who have temporarily stopped taking Ziagen (one symptom is present), it is recommended to: consider the possibility that discontinuation of the drug was preceded by a hypersensitivity reaction; assess the balance between risk and possibility therapeutic effect resumption of Ziagen therapy; If a decision is made to restart Ziagen therapy, it should be done in an appropriate medical facility.
Very rarely, a hypersensitivity reaction has been reported following resumption of Ziagen therapy in patients without obvious previous symptoms of hypersensitivity. In a number of cases, documentary evidence was clearly insufficient. The clinical significance of these reports has not been established. If a decision is made to restart Ziagen therapy, the patient should be able to obtain prompt medical attention.
The patient should be informed about possible reactions hypersensitivity to abacavir, which may result in life-threatening or fatal symptoms, and the patient should be aware of the need immediate appeal See your doctor if you experience fever, nausea, vomiting, diarrhea or abdominal pain, or respiratory problems (shortness of breath, cough, sore throat). A special patient card containing information about hypersensitivity reactions is included in the Ziagen pack and patients should be reminded to keep it with them at all times.
In HIV-infected patients (mainly women) who took antiretroviral drugs from the group of nucleoside analogues as monotherapy or as part of complex therapy, including abacavir, rare cases of lactic acidosis and severe hepatomegaly with fatty liver degeneration (including death) have been described. Caution should be exercised when treating Ziagen, especially if patients have risk factors for liver disease. If clinical or laboratory signs If lactic acidosis or liver dysfunction occurs, Ziagen should be discontinued.
Despite taking Ziagen or other antiretroviral drugs, patients may develop infections caused by opportunistic microorganisms, and other complications of HIV infection. Therefore, patients should be under constant monitoring doctors with experience in treating HIV infection. Patients should be informed that treatment with antiretroviral drugs (including abacavir) does not prevent the risk of transmitting HIV to others through sexual contact or blood transfusions, so patients should take appropriate precautions.
The oral solution contains sorbitol, which may cause abdominal pain and diarrhea. During metabolism, sorbitol is converted to fructose, therefore Ziagen in the form of an oral solution is not indicated for patients with congenital fructose intolerance.
Impact on the ability to drive vehicles and operate machinery
There is no data to support the effect of abacavir on the ability to potentially exercise dangerous species activities that require increased attention.
Overdose
In clinical studies, patients received single doses of abacavir up to 1200 mg and daily doses of up to 1800 mg. There were no unexpected adverse reactions reported. Action more high doses abacavir is unknown.
Treatment:
It is necessary to monitor the patient's condition in order to identify signs of intoxication and, if necessary, provide maintenance therapy. There is no data on the possibility of removing abacavir using hemodialysis and peritoneal dialysis.
Drug interactions
In vitro studies and data on the main metabolic pathways of abacavir indicate a low likelihood drug interactions with the participation of abacavir. Abacavir does not inhibit metabolic processes involving the CYP3A4 enzyme of the cytochrome P 450 system. In vitro studies have shown that abacavir does not interact with drugs that are metabolized by CYP3A4, CYP2C9 or CYP2D6. Clinical studies did not reveal an increase in hepatic metabolism under the influence of the drug. Therefore, interaction of abacavir with antiretroviral protease inhibitors and other drugs metabolized by enzymes of the cytochrome P 450 system is unlikely.
Clinical studies have not revealed clinically significant interactions between abacavir, zidovudine and lamivudine.
Ethanol alters the metabolism of abacavir, causing the AUC of abacavir to increase by approximately 41%. Given the safety profile of abacavir, these changes can be considered clinically insignificant. Abacavir does not affect the metabolism of ethyl alcohol.
In a pharmacokinetic study, co-administration of abacavir at a dose of 600 mg 2 times a day and methadone led to a decrease in Cmax by 35% and an increase in the time to reach it by 1 hour. However, the AUC value did not change. It is believed that these data do not have clinical significance. In this study, abacavir increased the mean systemic clearance of methadone by 22%. For most patients, these changes are not clinically significant, but sometimes a further increase in the dose of methadone may be necessary.
Retinoids (such as isotretinoin) are inactivated by alcohol dehydrogenase. Interaction with abacavir is possible, however special research was not carried out.
Storage conditions and periods
The drug should be stored at a temperature not exceeding 30°C. Shelf life - 2 years.
Conditions for dispensing from pharmacies
Ziagen is available by prescription.
Abacavir
Composition and release form of the drug
Tablets, coated film-coated light yellow color, round, biconvex.
Excipients: microcrystalline cellulose - 395.2 mg, sodium carboxymethyl starch - 48 mg, K25 - 36 mg, magnesium stearate - 12 mg, colloidal silicon dioxide - 6 mg.
Film shell composition: Opadry II 85F220118 yellow - 30 mg, including: polyvinyl alcohol - 12 mg, titanium dioxide - 7.392 mg, macrogol-3350 - 6.06 mg, talc - 4.44 mg, iron dye yellow oxide - 0.108 mg.
10 pcs. - contour cellular packaging (1) - cardboard packs.
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Pharmacological action
The drug is a synthetic carbocyclic analogue of nucleosides. Inside the cell, abacavir is converted with the participation of cellular enzymes into the active metabolite carbovir triphosphate. Carbovir triphosphate is an analogue of deoxyguanosine-5"-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase, which is due to competition with the natural substrate dGTP and disruption of its incorporation into viral DNA. The loss of the 3"-OH group in the built-in nucleoside analog prevents formation of 5"- and 3"-phosphoroester bonds necessary for elongation of the DNA chain. As a result, the growth of viral DNA stops.
Pharmacokinetics
After oral administration, absorption is high, bioavailability is 83%. Cmax - 3 mcg/ml, Tmax - 1-1.5 hours. AUC (within 12 hours after administration) - 6 mcg/ml/hour. Food slows the absorption of abacavir and reduces Cmax, but does not affect AUC. Penetrates through the BBB, the concentration of abacavir in the cerebrospinal fluid is 30-44% of that in. Plasma protein binding is low. Metabolized in the liver with the participation of acetal dehydrogenase and the formation of glucuronide conjugates (5"-carboxylic acid and 5"-glucuronide). T 1/2 - 1.5 hours. Excreted by the kidneys - 83% in the form of metabolites and 2% unchanged; the rest is excreted through the intestines. Does not accumulate.
Indications
Treatment of HIV infection (includes combination therapy).
Contraindications
Moderate to severe liver dysfunction; childhood younger than 3 months and body weight less than 14 kg; hypersensitivity to abacavir.
Dosage
In combination with others antiviral agents orally for adults 300 mg 2 times a day, children aged 3 months to 16 years - 8 mg/kg 2 times a day.
Side effects
For the skin and skin appendages: rash (usually maculopapular or urticarial); very rarely - multiform exudative erythema, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the digestive system: loss of appetite, nausea, vomiting, diarrhea, ulceration of the oral mucosa, increased activity of liver enzymes, liver failure.
From the respiratory system: shortness of breath, cough, sore throat, respiratory distress syndrome adults, respiratory failure.
From the nervous system: headache, paresthesia, drowsiness.
From the hematopoietic and lymphatic systems: lymphopenia.
on the side of the urinary system: increased serum creatinine concentration, renal failure.
From the musculoskeletal system: often – hyperlactatemia; rarely - lactic acidosis, accumulation/redistribution of adipose tissue, myalgia, rhabdomyolysis, arthralgia, increased CPK activity.
Other: fever, feeling tired, malaise, edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions.
Drug interactions
According to pharmacokinetic studies, the use of abacavir at a dose of 600 mg 2 times a day in combination with methadone reduces the Cmax of abacavir in serum by 35%, increases the time to reach Cmax in serum by 1 hour, but does not change the AUC. Clinical relevance these changes are small. The same study found that abacavir increased the systemic clearance of methadone by 22%. In most cases, these changes are also regarded as clinically insignificant, but in certain situations The dose of methadone may need to be adjusted.
Retinoids, such as isotretinoin, are eliminated by alcohol dehydrogenase and may therefore interact with abacavir, but no specific studies have been conducted at this time.
Special instructions
Symptoms of hypersensitivity may appear at any time after starting treatment with abacavir, but most often occur during the first 6 weeks.
If patients continue to take abacavir when a hypersensitivity reaction develops, then clinical manifestations become more pronounced and can take life-threatening character. In most cases, symptoms disappear when you stop taking abacavir.
There are reports of the development of lactic acidosis, hepatomegaly and fatty liver degeneration, incl. fatalities due to antiretroviral therapy with nucleoside analogues, including abacavir, and zidovudine, taken alone or in combination. In most cases, these complications occur in women.
Symptoms suggestive of lactic acidosis include general weakness, loss of appetite, rapid weight loss unknown etiology, disorders of the gastrointestinal tract and disorders of the respiratory system (shortness of breath and tachypnea).
The use of abacavir in any patient requires caution, especially in the presence of risk factors for liver damage. If clinical or laboratory signs of lactic acidosis or hepatotoxicity (may manifest as hepatomegaly and fatty liver disease even in the absence of a marked increase in aminotransferase activity) appear, treatment with abacavir should be discontinued.
Combination antiretroviral therapy may be accompanied by the development of lipodystrophy syndrome. At clinical examination During treatment, patients should pay attention to the redistribution of subcutaneous fat. Laboratory examination should include determination of serum lipid concentrations and blood concentrations. If lipid metabolism is disrupted, appropriate treatment is prescribed.
If HIV-infected patients with severe immunodeficiency have asymptomatic or minimally symptomatic opportunistic infections at the time of initiation of antiretroviral therapy (ART), such therapy may lead to increased symptoms of opportunistic infections or other severe consequences. These reactions usually occur within the first weeks or months after starting ART. Common examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jiroveci (formerly P. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.
The use of abacavir does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the supervision of a physician experienced in treating these diseases.
Antiretroviral therapy, including drugs containing abacavir, should be prescribed with caution to patients with possible risk occurrence of ischemic heart disease. Every effort must be made to minimize all modifiable risk factors (such as arterial hypertension, dyslipidemia, diabetes mellitus and smoking).
Pregnancy and lactation
Adequate and well-controlled clinical studies of the safety of abacavir during pregnancy and lactation have not been conducted.
If use during pregnancy is necessary, the expected benefits of therapy for the mother should be weighed against the potential risk to the fetus.
It is unknown whether abacavir is secreted from breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.
Use in childhood
Children aged 3 months to 16 years - 8 mg/kg 2 times/day.
Description of the active component
Pharmacological action
Antiviral agent, synthetic carbocyclic analogue of nucleosides. Inside the cell, abacavir is converted with the participation of cellular enzymes into the active metabolite carbovir triphosphate. Carbovir triphosphate is an analogue of deoxyguanosine-5"-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase, which is due to competition with the natural substrate dGTP and disruption of its incorporation into viral DNA. The loss of the 3"-OH group in the built-in nucleoside analog prevents formation of 5"- and 3"-phosphoroester bonds necessary for elongation of the DNA chain. As a result, the growth of viral DNA stops.
Indications
Treatment of HIV infection (as part of combination therapy).
Dosage regimen
In combination with other antiviral drugs, adults 300 mg 2 times a day, children aged 3 months to 16 years - 8 mg/kg 2 times a day.
Side effect
For the skin and skin appendages: rash (usually maculopapular or urticarial); very rarely - exudative erythema multiforme, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
From the digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, ulceration of the oral mucosa, increased activity of liver enzymes, liver failure.
From the respiratory system: shortness of breath, cough, sore throat, adult respiratory distress syndrome, respiratory failure.
From the nervous system: headache, paresthesia, drowsiness.
From the hematopoietic and lymphatic systems: lymphopenia.
From the liver and pancreas:
From the musculoskeletal system: myalgia, rarely - rhabdomyolysis, arthralgia, increased CPK activity.
From the urinary system: increased serum creatinine concentration, renal failure.
From the musculoskeletal system: often – hyperlactatemia; rarely – lactic acidosis, accumulation/redistribution of adipose tissue. The frequency of these adverse reactions depends on many factors, including from antiretroviral drugs used in combination with abacavir.
Other: fever, feeling tired, malaise, edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions.
Contraindications
Moderate to severe liver dysfunction; children under 3 months of age and body weight less than 14 kg; hypersensitivity to abacavir.
Pregnancy and lactation
Adequate and well-controlled clinical studies of the safety of abacavir during pregnancy and lactation have not been conducted.
If use during pregnancy is necessary, the expected benefits of therapy for the mother should be weighed against the potential risk to the fetus.
It is not known whether abacavir is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.
Application for children
Children aged 3 months to 16 years - 8 mg/kg 2 times/day.
Special instructions
Symptoms of hypersensitivity may appear at any time after starting treatment with abacavir, but most often occur during the first 6 weeks.
If, when a hypersensitivity reaction develops, patients continue to take abacavir, the clinical manifestations become more pronounced and can become life-threatening. In most cases, symptoms disappear when you stop taking abacavir.
There have been reports of lactic acidosis, hepatomegaly and fatty liver disease, including death, due to antiretroviral therapy with nucleoside analogues, including abacavir, lamivudine and zidovudine, taken alone or in combination. In most cases, these complications occur in women.
Symptoms indicating lactic acidosis include general weakness, loss of appetite, rapid weight loss of unknown etiology, gastrointestinal tract and disorders of the respiratory system (shortness of breath and tachypnea).
The use of abacavir in any patient requires caution, especially in the presence of risk factors for liver damage. If clinical or laboratory signs of lactic acidosis or hepatotoxicity (may manifest as hepatomegaly and fatty liver disease even in the absence of a marked increase in aminotransferase activity) appear, treatment with abacavir should be discontinued.
Combination antiretroviral therapy may be accompanied by the development of lipodystrophy syndrome. When clinically examining patients during treatment, it is necessary to pay attention to the redistribution of subcutaneous fat. Laboratory testing should include determination of serum lipid concentrations and blood glucose concentrations. If lipid metabolism is disrupted, appropriate treatment is prescribed.
If HIV-infected patients with severe immunodeficiency have asymptomatic or minimally symptomatic opportunistic infections at the time of initiation of antiretroviral therapy (ART), such therapy may lead to increased symptoms of opportunistic infections or other serious consequences. These reactions usually occur within the first weeks or months after starting ART. Common examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jiroveci (formerly P. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.
The use of abacavir does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the supervision of a physician experienced in treating these diseases.
Antiretroviral therapy, including drugs containing abacavir, should be prescribed with caution to patients at possible risk of coronary artery disease. Every effort must be made to minimize all modifiable risk factors (such as hypertension, dyslipidemia, diabetes mellitus and smoking).
Pharmacological group: Reverse transcriptase inhibitors from the group of nucleoside analogues.
Pharmacological action: Has a selective antiviral effect against human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), including strains of HIV-1 resistant to Zidovudine, Zalcitabine, Didanosine or Nevirapine. In vitro studies have shown that the mechanism of action of Abacavir is the inhibition of HIV reverse transcriptase, which leads to RNA chain termination and cessation of viral replication.
Systematic (IUPAC) name: ((1S,4R)-4-cyclopent-2-en-1-yl)methanol
Trade names: Ziagen
Legal status: Available by prescription only
Application: orally (solution or tablets)
Bioavailability: 83%
Metabolism: liver
Half-life: 1.54 ± 0.63 h
Excretion: renal (1.2% Abacavir, 30% 5"-carboxylic acid metabolite, 36% 5" glucuronide metabolite, 15% unknown minor metabolites). Fecal (16%)
Formula: C 14 H 18 N 6 O
Mol. mass: 286.332 g/mol
Melting point: 165°C (329°F)
Abacavir is a nucleoside analogue reverse transcriptase inhibitor used to treat HIV and AIDS. It is available under trade name Ziagen (ViiV Healthcare) and contains combination drugs Trizivir (Abacavir, Zidovudine and ) and Kivexa/Epzicom (Abacavir and ). The drug is well tolerated: the main side effect is a hypersensitivity that can be very serious and in rare cases can be fatal. Genetic testing can be used to determine whether a person will have increased sensitivity; Abacavir is safe for more than 90% of patients. However, in a separate study the drug was shown to increase the risk heart attack almost 90%. Viral strains that are resistant to Zidovudine or are usually sensitive to Abacavir, but there are a number of exceptions.
Clinical indications
Abacavir tablets and oral solution, in combination with other antiretroviral drugs, are prescribed to treat HIV-1 infection. Abacavir should always be used in combination with other antiretroviral drugs. Abacavir should not be used as monotherapy when changing antiretroviral regimens due to loss of virological response.
Side effects of Abacavir (Ziagen)
General adverse reactions include nausea headache, fatigue, vomiting, hypersensitivity reactions, diarrhea, fever/chills, depression, rash, anxiety, increased levels of URI, aspartate aminotransferase, alanine aminotransferase, hypertriglyceridemia and lipodystrophy. Serious adverse reactions include hypersensitivity reactions, severe anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, myocardial infarction, lactic acidosis, hepatomegaly/steatosis, pancreatitis, immune reconstitution syndrome, and autoimmune disorders.
Warnings
Patients with liver disease should exercise caution when using Abacavir as it may worsen the patient's condition. The use of nucleoside drugs such as Abacavir can in very rare cases cause lactic acidosis. Resistance to Abacavir develops in laboratory versions of HIV that are also resistant to other HIV-specific antiretroviral drugs such as didanosine and zalcitabine. HIV strains resistant to protease inhibitors are not likely to be resistant to Abacavir. In people taking antiviral drugs medicines, lipodystrophy (redistribution or accumulation of fat) may develop, leading to central obesity, wasting of the face, arms, legs and/or buttocks, breast enlargement and fat accumulation at the base of the neck (“bull hump”). Abacavir is contraindicated for use in children under 3 months of age.
Overdose
Little is known about the effects of an overdose of Abacavir. Overdose victims must be taken to a hospital emergency room for treatment.
Abacavir hypersensitivity syndrome
Increased sensitivity to Abacavir is associated with a single nucleotide polymorphism in the human leukocyte antigen B*5701 locus. There is a relationship between the prevalence of HLA-B*5701 and heredity. The prevalence of this allele is estimated to average 3.4 to 5.8% in populations of European ancestry, 17.6% in American Indians, 3.0% in Hispanic Americans, and 1.2% in Chinese Americans. There is significant variability in the prevalence of HLA-B*5701 among African population. Among African Americans, prevalence is estimated to average 1.0%, 0% in the Yoruba of Nigeria, 3.3% in the Luhya of Kenya, and 13.6% in the Maasai of Kenya, although averages are inferred from highly variable frequencies across sample groups . Common symptoms of Abacavir hypersensitivity syndrome include fever, malaise, nausea and diarrhea, and some patients may also experience skin rash. Symptoms of Abacavir hypersensitivity syndrome usually appear within six weeks of treatment with Abacavir, although they may be confused with symptoms of HIV syndrome immune restoration, hypersensitivity syndrome associated with other drugs, or infections. On July 24, 2008, the FDA issued a warning regarding Abacavir and drugs containing Abacavir. Before starting treatment, it is recommended to screen for the HLA-B*5701 allele and use alternative methods treatment. Before starting or re-starting treatment with Abacavir or Abacavir-containing drugs, genetic testing of the HLA-B*5701 allele is recommended. A transdermal patch test may be used to determine whether a person will experience hypersensitivity reactions to Abacavir, although some patients susceptible to hypersensitivity may not respond to the patch test. If hypersensitivity reactions to Abacavir are suspected, Abacavir should be immediately discontinued in all patients, including patients who do not have the HLA-B*5701 allele. On March 1, 2011, the FDA informed the public of its ongoing review of the safety of Abacavir and possible increase risk of heart attack associated with this drug.
Immunopathogenesis
The mechanism underlying Abacavir hypersensitivity syndrome is associated with changes in HLA-B*5701 protein product. Abacavir binds with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen-binding cleft. This leads to a change in immunological tolerance and subsequent activation of Abacavir-specific cytotoxic T cells, which produce systemic reaction, known as “Abacavir hypersensitivity syndrome.”
Mechanism of action of Abacavir
ABC is a guanosine (purine) analogue. Its target is the viral reverse transcriptase enzyme.
Pharmacokinetics
Abacavir is taken orally and has high bioavailability (83%). It is metabolized primarily by alcohol dehydrogenase or glucuronyl transferase. Abacavir can cross the blood-brain barrier.
Story
On December 18, 1998, Abacavir was approved by the US FDA and is thus the fifteenth approved antiretroviral drug in the United States. Its patent expired in the US on December 26, 2009.
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Manufacturers: GlaxoSmithKline C.A. (Venezuela)
Active ingredients
Abacavir
Dihydrotachysterol
Disease class
Not specified. See instructionsClinical and pharmacological group
Not specified. See instructionsPharmacological action
Not specified. See instructionsPharmacological group
Medicines for the treatment of HIV infectionAbacavir oral tablets
Instructions for medical use drugContent
Description pharmacological action
Indications for use
Release form
Pharmacodynamics of the drug
Pharmacokinetics of the drug
Use during pregnancy
Use for renal impairment
Contraindications for use
Side effects
Directions for use and doses
Overdose
Interactions with other drugs
Precautions for use
Special instructions for use
Storage conditions
Best before date
Description of pharmacological action
Inhibits HIV-1 and HIV-2 reverse transcriptase. Causes RNA chain termination and stops virus replication. It is quickly and completely absorbed after oral administration. Absolute bioavailability - 83%. Cmax is reached after 1–1.5 hours and is about 3 μg/ml. Eating slows down absorption.
In the blood it binds to proteins, easily passes through histohematic barriers (except for the BBB) and penetrates into tissues, the volume of distribution is 0.8 l/kg. Metabolized in the liver with the participation of alcohol dehydrogenase and glucuronyl transferase. About 66% of the dose is excreted in the form of glucuronide conjugates (only 2% unchanged) mainly by the kidneys (over 80%), partially with feces; T1/2 - 1.5 hours. Does not accumulate.
As part of combination therapy (combination with Azidotimidine and Epivir), it slows the progression of HIV infection, reduces the frequency and severity of AIDS-associated diseases, and improves the function of the immune system.
Indications for use
Treatment of HIV infection (as part of combination therapy.
Release form
film-coated tablets 300 mg;
Pharmacodynamics
An antiviral agent from the group of nucleoside analogues. It has a selective effect on HIV-1 and HIV-2 (including HIV-1 strains resistant to zidovudine, lamivudine, zalcitabine, didanosine and nevirapine). By inhibiting reverse transcriptase, it leads to RNA chain termination and cessation of virus replication. Possible development resistance is associated with genotypic changes in a specific codon region of reverse transcriptase (codons M184V, K65R, L74V and Y115F). HIV resistance develops relatively slowly; multiple mutations are required to increase the IC50 concentration by 8-fold. The development of cross-resistance is unlikely. Increases the number of CD4 cells in the blood and reduces the concentration of viral RNA (including in the cerebrospinal fluid).
Pharmacokinetics
Absorption is high, bioavailability is 83%. Cmax - 3 mcg/ml, time to reach Cmax - 1–1.5 hours (after ingestion of the solution and tablets, respectively). AUC (within 12 hours after administration) - 6 mcg/h/ml. Food slows the absorption of abacavir and reduces Cmax, but does not affect AUC. Penetrates the BBB, the AUC ratio in the cerebrospinal fluid and plasma is 30–44%. Protein binding is low. Metabolized in the liver with the participation of alcohol dehydrogenase and the formation of glucuronide conjugates (5"-carboxylic acid and 5"-glucuronide). T1/2 - 1.5 hours. Excretion by the kidneys - 83% (in the form of metabolites) and 2% (unchanged), the rest is excreted through the intestines.
Use during pregnancy
Adequate and well-controlled clinical studies of the safety of abacavir during pregnancy and lactation have not been conducted.
If use during pregnancy is necessary, the expected benefits of therapy for the mother should be weighed against the potential risk to the fetus.
It is not known whether abacavir is excreted in breast milk. If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.
Use for renal impairment
Side effects: rarely - renal failure.
Contraindications for use
Hypersensitivity; children's age (up to 3 months).
With caution - pregnancy, lactation period.
Side effects
Allergic reactions, fever, drowsiness, fatigue, nausea, vomiting, diarrhea, abdominal pain; myalgia, arthralgia, shortness of breath, headache, paresthesia; lymphadenopathy, conjunctivitis, ulceration of the oral mucosa; increased activity of “liver” transaminases, increased CPK activity, hypercreatininemia; lactic acidosis, hepatomegaly, fatty degeneration liver (mainly in women).
Special instructions. During the treatment period, infections caused by opportunistic microorganisms may develop. Patients should be informed that treatment with antiretroviral drugs does not prevent the risk of transmitting HIV to others through sexual contact or blood transfusions, and patients should take appropriate precautions.
Directions for use and doses
Orally, adults and children over 12 years old - 300 mg 2 times a day. Children from 3 months to 12 years - 8 mg/kg 2 times a day; maximum dose- 600 mg/day.
Overdose
In clinical studies, patients received single doses of abacavir up to 1200 mg and daily doses of up to 1800 mg. There were no unexpected adverse reactions reported. The effect of higher doses of abacavir is unknown.
Treatment: It is necessary to monitor the patient's condition in order to identify signs of intoxication and, if necessary, provide maintenance therapy. There is no data on the possibility of removing abacavir using hemodialysis and peritoneal dialysis.
Interactions with other drugs
Does not inhibit metabolic processes involving the isoenzymes CYP3A4, CYP2C9 and CYP2D6. Additive effect in combination with didanosine, zalcitabine, lamivudine and stavudine. Ethanol increases AUC by 41%.
Precautions for use
Monotherapy is not allowed. Only a specialist with experience in treating HIV infection can prescribe the drug. Before starting active antiretroviral therapy, a complete clinical and laboratory examination of the patient is carried out, incl. The level of viral load in the plasma and the number of CD4+ T-lymphocytes are determined. During treatment, regular (every 3–6 months) assessment of the level of the replication process, viral load in the plasma (bDNA and RT-PCR determination) and the level of CD4+ cells is indicated.
If clinical symptoms of HIV infection are present, it is necessary to start therapy without taking into account the number of CD4+ cells and the level of viral load in the plasma. The appearance of any signs of a hypersensitivity reaction (usually occurring in the first 6 weeks of treatment) due to their potential danger for life requires discontinuation of use (and further use of the drug is unacceptable). The patient should be warned that treatment does not reduce the risk of transmitting HIV to others.
