For the treatment of children and those patients who are difficult to swallow tablets, lamivudine in the form of a solution for oral administration.
During treatment with lamivudine, the condition of patients should be monitored regularly by a physician with experience in managing patients with HIV infection.
During the treatment, the peripheral blood pattern is monitored: 1 every 2 weeks for the first 3 months of therapy, then 1 time per month. Hematologic changes appear 4-6 weeks after initiation of therapy: anemia and neutropenia develop more often in patients receiving high doses, with late stage diseases (with a reduced reserve of bone marrow before the start of therapy), neutropenia, anemia, vitamin B12 deficiency. With a decrease in glycosylated hemoglobin (Hb) by more than 25% or a decrease in the number of neutrophils by more than 50 % in comparison with baseline, blood test control is performed more often.
During the treatment period it is necessary to control activity alanine aminotransferase (ALT), aspartate aminotransferase (ACT), amylase, lipase, concentration of triglycerides (TG) in blood serum. Patients with impaired renal function need to monitor the concentration of urea nitrogen, creatinine in the blood serum.
In patients on the background of therapy, opportunistic infections and other complications of HIV infection can develop, so they should remain under the supervision of doctors. In the event of discontinuation of treatment for any reason, patients should be under the supervision of a physician for at least 6 months after its withdrawal.
Antiretroviral therapy is not prevents the transmission of HIV through sexual contact and through infected blood. If resistance to lamivudine appears, zidovudine-resistant strains of the virus may again appear susceptible to zidovudine.
Osteonecrosis. Although etiology is considered multifactorial (including the use of corticosteroids, alcohol use, severe immunosuppression, increased body mass index), cases of osteonecrosis are noted especially in patients with advanced HIV disease and / or long-term combined antiretroviral therapy. When there is pain and aches in the joints, joint stiffness or difficulty of movement, patients should seek medical help.
Mitochondrial dysfunction. In conditions in vitro and in vivo the ability of nucleotide and nucleoside analogs to cause damage to mitochondria of different degrees was revealed. There have been cases of mitochondrial dysfunction in HIV-negative children exposed to nucleoside analogues in utero or immediately after birth.
Impaired renal function. In patients with impaired renal function of moderate to severe severitythe concentration of lamivudine in plasma is increased due to the decrease in clearance of the drug, therefore dose adjustment is required. In patients with impaired renal function with creatinine clearance <30 ml / min, another dosage form - oral solution (see section "Method of administration and dose") should be used.
Patients with impaired liver function. Patients with hepatic insufficiency of moderate and severe degree of dose reduction of lamivudine are not required, unless a violation of liver function is accompanied by renal insufficiency.
Pancreatitis. Several cases of pancreatitis developed in patients who received lamivudine. However, it remains unclear whether this complication is caused by lamivudine or HIV infection itself. When there is abdominal pain, nausea, vomiting, or characteristic changes in biochemical parameters in a patient receiving lamivudine, you should stop taking the drug until the diagnosis of pancreatitis is not ruled out.
Lactate acidosis / severe hepatomegaly with fatty liver dystrophy. In HIV-infected patients (predominantly in women) who took antiretroviral drugs from the nucleoside analogues group as monotherapy or in combination with lamivudine, cases of lactate acidosis,which was usually accompanied by severe hepatomegaly and fatty liver dystrophy, including fatal. Symptoms that may indicate the development of lactic acidosis include: general weakness, loss of appetite, sudden unexplained weight loss, disorders of the gastrointestinal tract and respiratory system (dyspnea).
Treatment with lamivudine always requires caution, especially if the patient has risk factors for developing liver disease. In case of clinical or laboratory signs of lactic acidosis or liver dysfunction (including hepatomegaly and fatty liver dystrophy even in the absence of a marked increase in liver transaminase activity), lamivudine should be discontinued.
Caution should be exercised when prescribing nucleoside analogues to patients with concomitant hepatitis C who receive interferon alfa and ribavirin in connection with the high risk of lactate-acidosis. Such patients should undergo thorough clinical and laboratory monitoring.
Redistribution of subcutaneous fat. In some patients, combined antiretroviral therapy may be accompanied by a redistribution / accumulation of subcutaneous fat, including a decrease in the amount of peripheral fat and increased visceral fat, thinning of the limbs and face, enlargement of the mammary glands and fat deposition on the back of the neck and back ("buffalo buffalo "), as well as an increase in the concentration of lipid glucose in blood plasma.
Although one or more of the above unwanted reactions associated with a common syndrome, often called lipodystrophy, can cause all drugs from classes of protease inhibitors and nucleoside reverse transcriptase inhibitors, the accumulated evidence suggests that there are differences between individual representatives of these classes of drugs in the ability to induce these unwanted 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 in the development of this complication.The long-term effects of these undesirable reactions are not currently established. Clinical examination of patients should include an assessment of physical signs of fat tissue redistribution. Serum lipids and glucose levels should also be measured. Disorders of lipid metabolism should be adjusted, guided by their clinical manifestations.
Syndrome of restoration of immunity. Have HIV-infected patients with severe immunodeficiency during the onset of antiretroviral therapy may exacerbate the inflammatory process caused by an asymptomatic or slow-moving opportunistic infection, which can lead to serious deterioration or worsening of symptoms. As a rule, similar reactions were observed in the first weeks or months after the onset of antiretroviral therapy. The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and pneumocystis pneumonia. Any symptoms of inflammation should be immediately identified and treatment should begin without delay.
Autoimmune diseases (such as Graves' disease, Wagner's syndrome, polymyositis, Guillain-Barre syndrome, etc.) were observed against the background of restoration of immunity, but the time of primary manifestations varied, and the disease could occur many months after the initiation of therapy and have an atypical course.
Patients infected with both HIV and hepatitis B virus. In patients infected with both HIV and hepatitis B virus, after the termination of lamivudine therapy, clinical or laboratory signs of hepatitis relapse may appear that may have severe consequences of decompensation of liver function. After the termination of lamivudine therapy in patients infected with HIV and hepatitis B virus, it is necessary to monitor biochemical parameters of liver function and markers of hepatitis B virus replication for several months.
Simultaneous use with other medicinal products. The likelihood of adverse interaction of lamivudine with other drugs is very small due to limited metabolism in the liver, a slight degree of binding to plasma proteins and almost complete excretion of lamivudine in unchanged form.
Lamivudine is predominantly excreted by the cationic transport system, therefore, it should be remembered that lamivudine can interact with drugs that have the same elimination route, for example trimethoprim. The clinically significant interaction of lamivudine with drugs that are excreted primarily through an anionic transport system or glomerular filtration is unlikely.
Do not simultaneously assign lamivudine with zalcitabine, cladribine, as well as with high doses of co-trimoxazole used to treat PCP (see "Interaction with other drugs "),
In patients who simultaneously received lamivudine and immunosuppressants (eg, ciclosporin A) in standard doses, clinically significant adverse interactions were not observed. Special studies have not been conducted.
Preventive maintenance after probable infection of a HIV. According to the international recommendations (the Center for Disease Control, June 1998), with the probable infection through the blood of an HIV-infected person (for example, through an injection needle),it is necessary urgently (within 1-2 hours from the moment of infection) to appoint combined therapy with zidovudine and lamivudine. In the case of a high risk of infection, a drug from the protease inhibitor group should be included in the antiretroviral regimen. Preventive treatment is recommended for 4 weeks. Data on the effectiveness of preventive treatment after accidental HIV infection have not been accumulated enough; controlled studies were not conducted.
Despite the rapid onset of treatment with antiretroviral drugs, seroconversion can not be ruled out.