Hypersensitivity
Application of the drug Abacavir is associated with a risk of MRI development characterized by fever and / or rash and other symptoms that indicate multiple organ failure. The MRI may be life threatening and in rare cases, when no appropriate treatment is prescribed, it can lead to a legal outcome. The risk of developing MRI with the use of the drug Abacavir significantly increased in patients with a positive test for the presence of an allele HLA-B*5701. However, abacavir were observed with a lower frequency in patients who are not carriers of this allele.
The following rules should be observed.
- A study should be conducted for the presence of an allele HLA-B*5701 before starting therapy with the drug Abacavir and also before resumption of therapy with the drug Abacavir in patients with unknown status with respect to the allele HLA-B*5701, who had previously tolerated abacavir therapy.
- It is not recommended to use the drug Abacavir in patients with an allele HLA-B*5701 or in patients who have been suspected of having an MRI during the administration of any other drug containing abacavir (for example, preparations Ziagen®, Kivex, Trizivir®) regardless of status in relation to HLA-B*5701.
- Each patient should be reminded that it is necessary to read the instructions for use, enclosed in the packaging of the drug Abacavir. Also, patients should be reminded that it is necessary to constantly carry a warning card attached to the drug.
- In all patients receiving drug therapy Abacavir, the clinical diagnosis of a suspected MRI should remain the basis for making a clinical decision.
- If there is a suspicion of MRI with drug therapy Abacavir should be immediately discontinued even in the absence of an allele HLA- B * 5701. Delayed discontinuation of drug therapy Abacavir After the emergence of the MRI, it can lead to a life-threatening reaction.
- Patients who developed MRIs should be informed about need to transfer the remaining tablets of the drug Abacavir To the attending physician in order to avoid the resumption of taking abacavir.
- Renewal of the use of drugs containing abacavir, after the suspected MRI on abacavir can lead to a rapid return of symptoms within a few hours, which may include life-threatening arterial hypotension and death.
- When considering the resumption of therapy with abacavir after discontinuation of treatment with any containing abacavir the drug for any reason should be determined the reason for discontinuing therapy, regardless of the patient's carriage of the allele HLA-B*5701. If the MRI can not be ruled out, the use of the drug can not be resumed Abacavir or any other medications containing abacavir (for example, Ziagen®, Kivexa, Trizivir®).
- If the MRI is excluded, it is possible to resume therapy with the drug Abacavir. In rare cases, patients who discontinued application of abacavir but for reasons other than the symptoms of MRIs, the development of life-threatening reactions within several hours after resumption of abacavir therapy has also been noted (see section "Description of individual adverse reactions").
Patients should be informed of the possibility of developing an MRI with the resumption of therapy with the drug Abacavir or other medicinal preparations containing abacavir (for example, with preparations of Ziagen®, Kivex, Trizivir®), and that resumption of drug therapy Abacavir or other medicinal products containing abacavir (eg, drugs Ziagen®, Kivex, Trizivir®) should only be carried out with quick access to medical care.
Clinical picture of MRI on abacavir
MIRVs on abacavir were well studied in clinical trials and during post-registration follow-up. Symptoms usually appear within the first 6 weeks (median time of onset of this reaction is 11 days) after initiation of abacavir therapy, however these reactions can develop at any time during therapy.
Virtually all of the responses of the WGS to abacavir include fever and / or rash, as part of the syndrome.
Other signs and symptoms that are noted as a manifestation of WGS on abacavir, include symptoms on the part of the respiratory and gastrointestinal tract, which can lead to incorrect diagnosis of MRI as a respiratory disease (pneumonia, bronchitis, pharyngitis) or gastroenteritis (see "Side effects", "Description of individual adverse reactions"). Patients should be closely monitored with advice every 2 weeks, especially during the first 2 months of therapy with the drug Abacavir.
If there are any symptoms associated with MIRV, treatment with abacavir continues, they become more pronounced and can take a life-threatening character. In most cases, these symptoms disappear when discontinuing abacavir.
Lactic acidosis and severe hepatomegaly with steatosis
There are reports of the development of lactic acidosis and severe hepatomegaly with steatosis, including fatal, due to antiretroviral therapy with nucleoside analogues, including abacavir, taken either individually or in combination.In most cases, these complications occur in women.
Symptoms that may indicate the development of lactic acidosis include general weakness, lack of appetite, rapid weight loss of unclear etiology, gastrointestinal disturbances (nausea, vomiting and abdominal pain), respiratory system disorders (dyspnea and tachypnea), or neurologic symptoms (including movement). Lactic acidosis has a high mortality and can be associated with pancreatitis, hepatic or renal insufficiency. Lactic acidosis, as a rule, manifested itself after several months of therapy. It is necessary to stop therapy with nucleoside analogues in case of symptomatic manifestations of hyperlactatemia and metabolic / lactic acidosis, progression of hepatomegaly or rapid increase in aminotransferase activity.
Application of the drug Abacavir requires caution for any patient (especially overweight women) with hepatomegaly, hepatitis, or other known risk factors for liver damage and steatosis of the liver (including the use of certain drugs and alcohol).Patients with co-infected hepatitis C receiving interferon alfa and ribavirin therapy can be a particular risk group. Patients with high risk require careful monitoring.
At the appearance of clinical or laboratory signs of lactic acidosis with or without hepatitis (hepatomegaly and steatosis may appear even in the absence of a pronounced increase in aminotransferase activity), drug treatment Abacavir is necessary to suspend.
Mitochondrial dysfunction
Research in vitro and in vivo showed that the analogues of nucleosides and nucleotides can cause a different degree of damage to the mitochondria. Mitochondrial dysfunction was observed in HIV-negative children who received intrauterine and / or post-nucleoside analogues. The main undesirable reactions were hematologic disorders (anemia, neutropenia), metabolic disorders (hyperlactatemia, hyperlipazemia). These undesirable reactions are often transient. Some neurological disorders with late onset have been reported (increased muscle tone, convulsions, behavioral disorders).Whether these neurological disorders are transient or persistent is currently unknown. Any child, even HIV-negative, exposed to prenatal exposure to nucleoside and nucleotide analogues, must undergo a clinical and laboratory examination in order to exclude mitochondrial dysfunction in case of revealing the corresponding signs or symptoms. These data do not affect current national guidelines but use of antiretroviral therapy in pregnant women to prevent vertical transmission of HIV infection.
Redistribution of subcutaneous fat
In some patients receiving combined antiretroviral therapy, there may be a redistribution and / or accumulation of subcutaneous fat, including central obesity, dorsocervical fat deposition ("buffalo buffalo"), a reduction in the subcutaneous fat layer on the face and extremities, enlargement of the mammary glands , increased serum lipid concentrations and glucose concentrations in the blood.
Although one or more of the above unwanted reactions associated with a general syndrome,which is often referred to as lipodystrophy, can cause all drugs of HIV and NRTI classes, the data suggest that there are differences between individual representatives of these classes of drugs in the ability to induce these undesirable reactions.
It should also be noted that lipodystrophy syndrome has a multifactorial etiology; for example, the stage of HIV infection, the elderly age and the duration of antiretroviral therapy play an important, possibly synergistic role.
The long-term effects of these undesirable reactions are currently unknown.
Clinical examination of patients should pay attention to redistribution of subcutaneous fat. Laboratory examination should include the determination of serum lipid concentrations and blood glucose concentrations. If the lipid metabolism is disturbed, an appropriate treatment is prescribed.
Pancreatitis
Cases of pancreatitis have been documented, although the cause-and-effect relationship with the use of abacavir has not been accurately established.
Therapy containing three NRTIs
In patients with high viral load (> 100,000 copies / ml), the appointment of a triple combination containing abacavir, lamivudine and zidovudine, requires special consideration.
There were recorded cases of high rates of virological failure and the emergence of resistance in the early stages, when a combination of abacavir with tenofovir, dizoproxil fumarate and lamivudine was used as a regimen of therapy once a day.
Diseases of the liver
Efficacy and safety of the drug Abacavir They were not established in patients with severe concomitant liver diseases. A drug Abacavir contraindicated in patients with impaired liver function of moderate and severe degree. Patients with pre-existing liver dysfunction, including active chronic hepatitis, have an increased incidence of liver dysfunction during combined antiretroviral therapy, and should be monitored in accordance with accepted practice. It is necessary to consider the possibility of suspension or termination of treatment, in the case of manifestations of worsening liver disease in such patients.
Concomitant Hepatitis B or C
Patients with concomitant chronic hepatitis B or C who receive combination antiretroviral therapy have an increased risk of severe and potentially lethal adverse reactions from the liver.In the case of concomitant antiviral therapy for hepatitis B or C, you should also read the appropriate instructions for the use of these drugs. Care should be taken when concurrent administration of abacavir and ribavirin.
Kidney Diseases
A drug Abacavir should not be given to patients with terminal chronic renal failure.
Immunodeficiency Syndrome
If HIV-infected patients with severe immunodeficiency have asymptomatic opportunistic infections or their residual effects at the time of initiation of antiretroviral therapy, such therapy may lead to an increase in the symptoms of opportunistic infections or other severe consequences. Typically, these reactions occur within the first weeks or months after initiation of antiretroviral therapy. Typical examples are cytomegalovirus retinitis, generalized and / or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jiroveci (formerly R. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.
Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome), also were observed against the background of restoration of immunity, however, the time of primary manifestations varied, and the disease could occur many months after initiation of therapy and have an atypical course.
Osteonecrosis
Although the etiology of this disease is multifactorial (including the intake of glucocorticosteroids, alcohol use, severe immunosuppression, high body mass index), cases of osteonecrosis were most commonly seen in patients at a late stage of HIV infection and / or long-term combined antiretroviral therapy. Patients should consult a doctor if they experience pain and stiffness in the joints or difficulty moving.
Opportunistic infections
Application of the drug Abacavir or other antiretroviral drugs 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 with experience in the treatment of HIV-associated diseases.
Transmission of HIV infection
Antiretroviral therapy, including the drug Abacavir, does not exclude the possibility of sexual transmission of HIV or in contact with infected blood, and therefore does not negate the need for appropriate precautions.
Myocardial infarction
As a result of a prospective observational epidemiological study to study the incidence of myocardial infarction in patients receiving combined antiretroviral therapy, a connection was found between the previous administration of abacavir for 6 months with an increased risk of myocardial infarction. According to the generalized analysis of clinical studies, there was no increase in the risk of developing myocardial infarction associated with the use of abacavir. Biological mechanisms that explain a potentially increased risk are unknown. In general, the available data from cohort observations and controlled clinical studies do not allow one to unequivocally determine the relationship between abacavir therapy and the risk of myocardial infarction.
Nevertheless, with caution follows prescribe antiretroviral therapy, including drugs containing abacavir, patients with a possible risk of coronary heart disease. It is necessary to take all measures to minimize all modifiable risk factors (such as hypertension, hyperlipidemia, diabetes and smoking). A warning card with information for patients about the hypersensitivity reaction is in the package.
Patient Warning Card
Attention!
Abacavir coated tablets, 300 mg
Always wear with this card
Because the drug Abacavir contains abacavir, in some patients taking the drug Abacavir, a hypersensitivity reaction may develop (a serious allergic reaction), often life-threatening, if not abolish the drug. IMMEDIATELY PLEASE CONTACT YOURSELF TO THE DOCTOR FOR THE DOCTOR further drug administration Abacavir, if:
- the You appeared cutaneous rash OR
- You have appeared one or more symptoms, but at least of the TWO of the groups listed below:
- fever;
- shortness of breath, sore throat, or cough;
- nausea or vomiting or diarrhea or abdominal pain;
- increased fatigue or pain or general malaise.
If you stop taking the drug Abacavir as a result of the reaction hypersensitivity. MORE NEVER DO NOT take the drug Abacavir or any other preparation containing abacavir (Ziagen®, Trizivir®, Kivexa), since Within a few hours the ego can lead to a life-threatening fall blood pressure or death.