Treatment with lamivudine should be carried out by a doctor who has experience in managing patients with HIV infection.
Children under 3 years of age are not recommended the use of tablet dosage forms, therefore, for the treatment of children, another dosage form should be used - oral solution (see the "Method of administration and dose" section).
The use of lamivudine as a monotherapy is not recommended.
Patients should be warned that treatment with antiretroviral drugs, including lamivudine, does not prevent the risk of HIV transmission to other people during sexual intercourse or blood transfusion. Therefore, patients should take appropriate precautions.
In patients receiving lamivudine or other antiretroviral drugs, opportunistic infections or other complications may develop, so they should be carefully monitored by a physician with experience in HIV treatment.
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.
Triple therapy with nucleosides.
There have been reports of no virologic response and no resistance toearly stage in the appointment of triple therapy with nucleosides (a combination of lamivudine with tenofovir, dizoproxil fumarate and abacavir, and lamivudine with tenofovir, dizoproxil fumarate and didanosine) with the medication once a day.
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 medium and severe degree, the 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 "Dosage and Administration") should be used.
Patients with impaired hepatic 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, pancreatitis should be excluded. It is necessary to suspend the drug until the diagnosis of pancreatitis is not ruled out.
Lactate acidosis / severe hepatomegaly with fatty liver dystrophy.
In HIV-infected patients (predominantly women) who were taking anti-retroviral drugs from the group of nucleoside analogues alone or in combination with lamivudine, cases of lactic acidosis described, which is usually accompanied by severe hepatomegaly and steatosis, 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 the respiratory system (shortness of breath).
Treatment with lamivudine always requires caution, and 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 accompanied by redistribution / accumulation of subcutaneous fat, incl. decrease in the amount of peripheral fat and increase visceral fat, weight loss of limbs and face, breast enlargement and fat deposition on the back of the neck and back ("buffalo buffalo"), as well as an increase in the concentration of blood glucose lipids.
Although one or more of the above unwanted reactions associated with a general syndrome,which is 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 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 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. It is also necessary to measure the concentration of glucose lipids in the blood plasma. Disorders of lipid metabolism should be adjusted, guided by their clinical manifestations.
Syndrome of restoration of immunity.
In HIV-infected patients with severe immunodeficiency during the onset of antiretroviral therapy, the inflammation may worsen,caused by an asymptomatic or sluggish opportunistic infection, which can cause serious deterioration or worsening of the 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 recurrence may appear, which can have serious consequences in decompensating 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 mainly excreted by means of a cationic transport system, therefore, it should be remembered that lamivudine can interact with drugs having the same elimination route, for example, with 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 pneumocystis pneumonia (cf.section "Interaction with other medicinal products"),
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.
There was no adverse pharmacokinetic interaction between lamivudine and interferon alpha.
Preventive maintenance after probable infection of a HIV.
According to the international recommendations (the Center for Disease Control, June 1998), if a person infected with HIV is likely to be infected through the blood (for example, through an injection needle), it is urgent (within 1-2 hours after the infection) to prescribe combination 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.