Composition, form of production and packaging
The tablets covered with a film shell of white color, capsular, with engraving "H" and risk from one side and "2" on the other; the core is white or almost white in cross section.
1 tab.
lamivudine 150 mg
zidovudine 300 mg
Excipients: microcrystalline cellulose - 258.75 mg, silicon colloidal dioxide - 3.75 mg, magnesium stearate - 7.5 mg, sodium carboxymethyl starch - 30 mg.
The composition of the film shell: Folded white YS-1-7003 - 15 mg, including hypromellose 2910 (E 464) - 59.75%, titanium dioxide (E 171) - 31.25%, macrogol 400 - 8%, polysorbate 80 (E 433) - 1%.
60 pcs. - polyethylene bottles (1) - cardboard packs.
The tablets covered with a film shell of white color, capsular, with engraving "H" and risk from one side and "2" on the other; the core is white or almost white in cross section.
1 tab.
lamivudine 150 mg
zidovudine 300 mg
Excipients: microcrystalline cellulose - 258.75 mg, silicon colloidal dioxide - 3.75 mg, magnesium stearate - 7.5 mg, sodium carboxymethyl starch - 30 mg.
The composition of the film shell: Folded white YS-1-7003 - 15 mg, including hypromellose 2910 (E 464) - 59.75%, titanium dioxide (E 171) - 31.25%, macrogol 400 - 8%, polysorbate 80 (E 433) - 1%.
60 pcs. - polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Mechanism of action
Lamivudine and zidovudine are highly effective selective inhibitors of HIV-1 and HIV-2 reverse transcriptase. Lamivudine is a synergist of zidovudine against the suppression of HIV replication in cell culture. Both drugs are sequentially metabolized by intracellular kinases to 5'-triphosphate (TF). Lamivudine-TF and zidovudine-TF are substrates for HIV reverse transcriptase and competitive inhibitors of this enzyme. However, the antiviral activity of the preparations is mainly due to the inclusion of their monophosphate form in the viral DNA chain, resulting in a chain break. Triphosphates of lamivudine and zidovudine have significantly less affinity for the DNA-sub-dimerases of human cells.
In vitro, lamivudine demonstrates low cytotoxicity to lymphocytic and monocyte-macrophage colonies and to a number of red bone marrow progenitor cells. Thus, lamivudine has a wide therapeutic index.
Resistance of HIV-1 to lamivudine is due to a mutation in the 184 codon (M184V) next to the active center of HIV reverse transcriptase. These variants of the virus arise both in vitro and in HIV-1-infected patients receiving antiretroviral regimens including lamivudine. The strains of the virus with the M184V mutation show a significant decrease in sensitivity to lamivudine and show less replicative activity in vitro .
Studies conducted in vitro have shown that zidovudine-resistant virus isolates can develop sensitivity to zidovudiyu if they acquire resistance to lamivudine. The clinical significance of this phenomenon is unclear.
Mutations in the M184V site lead to cross-resistance of HIV only to drugs from the group of nucleoside HIV reverse transcriptase inhibitors (NRTIs). Zidovudine and stavudine remain active against lamivudine-resistant strains of HIV-1. Abacavir preserves antiretroviral activity against lamivudine-resistant strains of HIV-1, which have only the M184V mutation. In strains of HIV with mutations M184V, no more than a 4-fold decrease in the sensitivity to didanosine and zalcitabine is determined; the clinical significance of this phenomenon is not established.
Resistance to thymidine analogues (such as zidovudine) is well studied and occurs as a result of gradual accumulation of specific mutations in 6 codons (41, 67, 70, 210, 215 and 219) of HIV reverse transcriptase. The viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in codons 41 and 215 or by the accumulation of at least four or six mutations. These mutations of resistance to thymidine analogs do not in themselves cause high cross-resistance to other nucleoside analogs, which subsequently allows the use of other approved reverse transcriptase inhibitors. Two types of mutations lead to the development of multiple drug resistance. In one case, mutations occur at 62, 75, 77, 116 and 151 positions of HIV reverse transcriptase, and in the second case, T69S mutations with insertion of 6 pairs of nitrogen bases in this position, which is accompanied by the appearance of phenotypic resistance to zidovudine, as well as other nucleoside reverse transcriptase inhibitors. Both types of these mutations significantly limit the therapeutic possibilities for HIV infection.
In clinical trials, the combination of lamivudine and zidovudine reduced HIV-1 load and increased CD4 + cell count. Clinical evidence suggests that the use of a combination of lamivudine and zidovudine or a combination of lamivudine and zidovudine-containing regimens leads to a significant reduction in the risk of disease progression and mortality.
Separately, monotherapy with lamivudine or zidovudine led to the appearance of HIV isolates with reduced sensitivity to these drugs in vitro . Clinical evidence suggests that combination therapy with lamivudine and zidovudine delays the emergence of zidovudine-resistant strains in patients who have not previously received antiretroviral therapy (APT).
Tests for the sensitivity of HIV to drugs in vitro have not been standardized, so the results can be influenced by various methodological factors. At present, the association between the sensitivity to lamivudine and / or zidovudine in vitro and the clinical effect of therapy has not been studied.
Lamivudine and zidovudine are widely used as components of combination therapy with other antiretroviral drugs of the same class (NRTIs) or other classes (HIV protease inhibitors [IP], non-nucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors and fusion inhibitors). Combined regimens of antiretroviral therapy, including lamivudine, are effective in treating patients who have not previously received antiretroviral drugs and patients who have strains of HIV with the M184V mutation.
Prevention of infection: International guidelines recommend the use of a combination of lamivudine and zidovudine within 1-2 hours after exposure to HIV-infected blood (for example, after a needle prick). 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 should be given within 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.
PHARMACOKINETICS
Suction
Lamivudine and zidovudine are well absorbed from the intestine. In adults after oral administration, the bioavailability of lamivudine is 80-85%, and of zidovudine 60-70%. After taking the drug Zidolam inside Cmax lamivudine and zidovudine were observed through 0.75 (0.50-2.00) h and 0.50 (0.25-2.00) h and amounted to 1.5 (1.3-1 , 8) Ојg / ml and 1.8 (1.5-2.2) Ојg / ml, respectively.
The degree of absorption of lamivudine and zidovudine (based on the AUC value under the pharmacokinetic concentration-time curve) and T 1/2 after administration with food were similar to those after fasting, although the rate of absorption was somewhat slowed.
Distribution
Lamivudine has a linear pharmacokinetics when used in therapeutic doses and is bound to bound to albumin of blood plasma (less than 36% of serum albumin in vitro). Zidovudine binds to plasma proteins by 34-38%. Thus, the interaction of lamivudine and zidovudine with other drugs through their replacement at binding sites on proteins is unlikely. It was established that lamivudine and zidovudine penetrate into the central nervous system and spinal fluid. 2-4 hours after oral administration, the ratio between the concentration of lamivudine and zidovudine in the cerebrospinal fluid and in serum is on average 0.12 and 0.5, respectively.
Metabolism
Lamivudine is excreted from the body mainly by the kidneys in unchanged form. Metabolic interactions of lamivudine are unlikely because of a slight metabolism in the liver (from 5 to 10%) and low binding to plasma proteins.
Zidovudine 5'-glucuronide is the main metabolite in plasma and urine, with approximately 50-80% of the administered dose of zidovudine excreted by renal excretion.
Excretion
T 1/2 of lamivudine is 5-7 hours. The systemic clearance of lamivudine is approximately 0.32 l / h / kg, with a kidney clearance of more than 70% involving a cationic transport system. The renal clearance of zidovudine is 0.34 l / h / kg by glomerular filtration and active tubular secretion in the kidneys.
Special patient groups
Patients of advanced age . The pharmacokinetics of lamivudine and zidovudine has not been studied in patients older than 65 years.
Patients of childhood. In general, the pharmacokinetics of lamivudine in children is similar to the pharmacokinetics in adult patients. However, absolute bioavailability (approximately 55-65%) was reduced in children younger than 12 years. Systemic clearance in children is higher than in adults, and is prone to decrease as it grows up, reaching indicators as in adults, by 12 years. Recent data indicate that exposure in children aged 2 to 6 years can be reduced by 30% compared with other age groups.
Impaired renal function. Due to reduced renal clearance, excretion of lamivudine is impaired in patients with renal insufficiency. Reduction of the dose of lamivudine is recommended in patients with creatinine clearance less than 50 ml / min. The concentration of zidovudine in plasma also increases in patients with severe renal failure.
Violation of the function of the liver. Decreased glucuronidation in patients with impaired hepatic function due to liver cirrhosis may lead to cumulation of zidovudine.Correction of doses is required in patients with severe hepatic insufficiency.
Pregnancy . Pregnancy does not affect the pharmacokinetics of lamivudine and zidovudine. Lamivudine and zidovudine are found in the serum of the baby at birth in the same concentrations as in the mother's serum and cord blood during labor, which confirms the theory of passive penetration through the hematoplacental barrier.
INDICATIONS
- Treatment of HIV infection in adults and children weighing not less than 14 kg with progressive immunodeficiency (CD4 + cell count less than 500 in 1 mm 3 ).
DOSING MODE
The drug Zidolam is taken inside, regardless of the intake of food.
Treatment Zidolam should be carried out by doctors with experience in HIV therapy. To ensure the accuracy of dosing, the tablets must be swallowed whole. For those patients who have difficulty in swallowing, it is recommended to divide and crumble the tablets with the addition of a small amount of semi-solid food or liquid. All the amount of the mixture should be taken immediately.
Adults and adolescents with a body weight of at least 30 kg:
The recommended dose of Zidolam is 1 tablet 2 times a day.
Children with body weight from 21 to 30 kg:
The recommended dose of Zidolam is 1/2 tablet in the morning plus 1 tablet in the evening.
Children with a body weight of 14 to 21 kg:
The recommended dose of Zidolam is 1/2 tablet 2 times a day.
In cases where you need to reduce the dose of Zidolam, reduce the dose or cancel one of its components (lamivudine or zidovudine), you can use separate drugs lamivudine and zidovudine.
Elderly patients
Specific data on the use of Zidolam in the elderly are not. However, in the treatment of elderly patients, special care should be taken, taking into account age-related changes, for example changes in hematologic indices and impaired renal function.
Patients with impaired renal function
Since patients with impaired renal function (creatinine clearance less than 50 ml / min) should individually choose a dose of lamivudine and zidovudine, it is recommended to assign them individual drugs lamivudine and zidovudine.
Patients with impaired hepatic function
In patients with a severe degree of impaired liver function, it is recommended to use separate preparations of lamivudine and zidovudine. Patients with mild to moderate liver function abnormalities should be treated with Zidolam with caution.
Patients with hematologic side effects
If the hemoglobin content is less than 9 g / dl (5.59 mmol / L) or neutropenia (the number of neutrophils is less than 1.0 * 10 9 / L), a dose adjustment of zidovudine may be required. When using the drug Zidolam it is impossible to individually select the dose of lamivudine and zidovudine, it is recommended to use separate preparations of lamivudine and zidovudine.
SIDE EFFECT
Treatment of HIV infection with lamivudine and zidovudine in the form of monotherapy or as a combination of these drugs can cause side effects. For many side effects, it is not known whether they are caused by lamivudine, zidovudine, a wide range of other drugs used to treat HIV infection, or are a consequence of the underlying disease. The drug Zidolam includes lamivudine and zidovudine, and therefore it can cause side effects, characteristic of each of these ingredients.
At present, there is no evidence that the combination of lamivudine and zidovudine has additive toxicity.
Combined antiretroviral therapy was associated with the development of metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia.
Frequency of occurrence is defined as follows: very often (? 1/10); often (? 1/100 and <1/10); infrequently (? 1/1000 and <1/100); rarely (? 1/10000 and <1/1000); very rarely (<1/10000, including individual cases).
Lamivudine
From the hematopoietic and lymphatic system:
Infrequent: neutropenia, anemia, thrombocytopenia.
Very rarely: true erythrocyte aplasia.
From the side of metabolism and nutrition:
Often: hyperlactatemia.
Rarely: lactic acidosis.
Redistribution / accumulation of adipose tissue: the frequency of this side effect depends on many factors, including a specific combination of antiretroviral drugs.
From the nervous system:
Often: headache, insomnia.
Very rarely: paresthesia, there are reports of peripheral neuropathy, but its association with lamivudine therapy is not known.
From the respiratory system, chest and mediastinum:
Often: cough, nasal symptoms.
From the digestive tract:
Often: nausea, vomiting, epigastric pain, diarrhea.
Rarely: pancreatitis, whose association with lamivudine treatment is not established. Increased activity of serum amylase.
On the part of the liver and gum-excreting tracts:
Infrequently: a transient increase in hepatic enzyme activity (aspartate aminotransferase (ACT), alanine aminotransferase (ALT)).
Rarely: hepatitis.
From the side of the skin and PZK:
Often: rash, alopecia.
Rare: Quincke's Edema.
From the osteomuscular system and connective tissue:
Often: arthralgia, muscle disorders.
Rarely: rhabdomyolysis.
General and local reactions:
Often: fatigue, general malaise, fever.
Zidovudine
From the hematopoietic and lymphatic system:
Often: anemia (blood transfusion may be required), neutropenia and leukopenia. These side effects often occur with high doses of zidovudine (1200-1500 mg per day), in patients with advanced HIV infection (especially with a reduced bone marrow reserve before treatment) and in particular in patients with CD4 + cell counts less 100 in 1 mm 3 . In some patients it is necessary to reduce the dose of zidovudine up to cancellation. Neutropenia occurs more often in those patients whose neutrophil count, hemoglobin content and vitamin B 12 serum levels are lower at the time of zidovudine treatment.
Infrequent: thrombocytopenia and pancytopenia (with bone marrow hypoplasia).
Rarely: true erythrocytic aplasia.
Very rarely: aplastic anemia.
From the side of metabolism and nutrition:
Often: hyperlactatemia.
Rarely: lactate-acidosis in the absence of hypoxemia, anorexia.
Redistribution / accumulation of adipose tissue: the frequency of this side effect depends on many factors, including a specific combination of antiretroviral drugs.
From the side of the psyche:
Rarely: anxiety and depression.
From the nervous system:
Very often: headache.
Often: dizziness.
Rarely: insomnia, paresthesia, drowsiness, decreased mental activity, convulsions, confusion.
From the cardiovascular system:
Rarely: cardiomyopathy.
From the respiratory system, chest and mediastinum:
Infrequent: shortness of breath.
Rarely: cough, rhinitis, sinusitis, flu-like syndrome.
From the digestive tract:
Very often: nausea.
Often: vomiting, abdominal pain and diarrhea.
Infrequent: flatulence.
Rarely: pigmentation of the oral mucosa, taste distortion, anorexia, dyspepsia, pancreatitis.
From the liver and bile ducts:
Often: increased activity of hepatic enzymes and bilirubin.
Rarely: liver damage such as severe hepatomegaly with steatosis.
From the side of the skin and PZK:
Infrequent: rash and itching.
Rarely: pigmentation of nails and skin, hives and sweating.
From the osteomuscular system and connective tissue:
Often: myalgia.
Infrequent: myopathy.
From the side of the kidneys and urinary tract:
Rarely: frequent urination.
On the part of the reproductive system and mammary glands:
Rarely: gynecomastia.
General and local reactions:
Often: general malaise.
Uncommon: fever, generalized pain and asthenia, angioneurotic edema, anaphylactic reactions.
Rare: chills, chest pain, and flu-like symptoms.
CONTRAINDICATIONS
- hypersensitivity to lamivudine, zidovudine or to any other component of the drug;
- neutropenia (? 0.75 less than 10 9 / l), anemia (hemoglobin of less than 7.5 g / dl or 4.65 mmol / l);
- children weighing less than 14 kg;
- lactation;
- renal function when creatinine clearance less than 50 mL / min (for a given dosage form);
- severe degree of impairment of liver function (for a given dosage form).
Carefully:
Hepatomegaly, hepatitis, liver cirrhosis, the risk factors that predispose to liver damage, mild to moderate liver dysfunction, obesity, pancreatitis (including history), peripheral neuropathy (including history), advanced age, inhibition of bone marrow hematopoiesis deficiency or folic acid, cyanocobalamin, neutropenia / leukopenia (neutrophil count 0.75 x 10 9 / l or 750-1000 / l), anemia (hemoglobin 7.5 g / dl).
PREGNANCY AND LACTATION
Fertility
Data on the effect of lamivudine and zidovudine on fertility in the absence of women. Zidovudine has no effect on the number, morphology and motility in men.
Pregnancy
Not recommended for use Zidolam in the first 3 months of pregnancy unless the expected benefit to the mother is less than the likely risk to the fetus. It is shown that treatment with zidovudine for pregnant women and subsequent administration of the drug decreases newborn HIV transmission frequency from mother to fetus. Lamivudine with respect to such data no. Consequently, Zidolam can be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.
In newborns and infants, who are in pregnancy or childbirth exposed to nucleoside reverse transcriptase inhibitors. There was a slight transient increase of serum lactate. There are also rare reports of developmental delay, seizures and other neurological disorders.
Causation appearance of these pathological conditions with taking nucleoside reverse transcriptase inhibitors are not installed during pregnancy.
In general, children whose mothers during pregnancy taking nucleoside reverse transcriptase inhibitors, the benefits of reducing the risk of HIV infection obviously exceeds the danger associated with the side effects of these drugs.
Lactation
HIV-infected mothers not breast-feeding is recommended for the purpose of vertical HIV transmission. Since lamivudine, zidovudine and HIV into breast milk, breast-feeding is prohibited.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in patients with impaired renal function when creatinine clearance less than 50 mL / min (for a given dosage form).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in patients with severe liver function abnormalities (for a given dosage form).
APPLICATION FOR CHILDREN
The drug is contraindicated in children weighing less than 14 kg.
SPECIAL INSTRUCTIONS
If necessary, the individual dose adjustment is recommended to use separate preparations of lamivudine and zidovudine. Physicians should follow the information on the use of these drugs. Patients should be warned of the possible consequences related to the joint use of other drugs without a doctor's prescription.
Patients should be informed that treatment with antiretroviral drugs, such as drug Zidolam, does not prevent the risk of transmission of HIV to others through sexual contact or blood contamination, so patients need to comply with the relevant safety precautions.
Despite the drug Zidolam or any other antiretroviral drugs, patients may develop opportunistic infections and other complications of HIV infection. Therefore, patients should be kept under the supervision of physicians experienced in the treatment of patients with HIV-related illnesses.
Hematologic disorders
Perhaps the development of anemia, neutropenia and leucopenia (usually secondary due to neutropenia) in patients receiving zidovudine. These effects are more frequently observed in the appointment of high doses of zidovudine (1200-1500 mg / day) in patients with advanced HIV disease with decreased bone marrow reserve prior to treatment. Therefore, in patients receiving the drug Zidolam, necessary to carry out careful monitoring of haematological parameters. These haematological changes usually appear not earlier than 4-6 weeks after initiation of therapy. In patients with extensive clinical HIV blood counts is recommended to control at least once every 2 weeks during the first three months of therapy, and then - at least once a month. Patients in the early stages of HIV infection side effects of the blood system are rare.In this situation, a common blood test can be done less often, focusing on the general condition of patients, for example, once in 1 - 3 months.
May require special selection of zidovudine dose in the case of severe anemia or myelosuppression during Zidolam drug treatment, and in patients with prior bone marrow suppression, such as hemoglobin less than 9 g / dL (5.59 mmol / L) or less than an amount neutrophils 1,0h10 9 / l. As the dose is individually choose Zidolama impossible, it is recommended to use separate preparations of lamivudine and zidovudine.
Pancreatitis
In patients treated with lamivudine and zidovudine, are described rare cases of pancreatitis. However it is not established whether this complication drugs or main disease caused - HIV infection. Treatment with Zidolam must be stopped immediately with the appearance of clinical symptoms or laboratory evidence of pancreatitis development (abdominal pain, nausea, vomiting or elevated levels of biochemical markers). Should stop taking the drug Zidolam to exclude pancreatitis diagnosis.
Lactic acidosis and severe hepatomegaly with steatosis
In patients treated with antiretroviral drugs - nucleoside analogs alone or in combination, including lamivudine and zidovudine, are described rare but with possible fatal cases of lactic acidosis in the absence of severe hypoxia and hepatomegaly with steatosis. The majority of cases were registered in women. Clinical symptoms of lactic acidosis include general weakness, loss of appetite and rapid unexplained weight loss, gastrointestinal and respiratory disorders (dyspnea and tachypnea). Zidolam drug should be used with caution in patients with risk factors for liver disease. The drug should priostanavit patients with clinical and laboratory symptoms of lactic acidosis or hepatotoxicity (including hepatomegaly and steatosis even in the absence of increased transaminase activity).
Mitochondrial dysfunction
Nucleoside and nucleotide analogs have demonstrated HIV reverse transcriptase in vitro and in vivo varying degrees of mitochondrial damage. The main adverse events are of hematologic disturbances (anemia, neutropenia), metabolic disorders (hyperlactatemia, giperlipazemiya). These conditions are temporary. With more late-onset neurological disorders have been reported (hypertension, convulsions, behavioral disorders), neurological disorders whether temporary or permanent data currently unknown.
Subcutaneous fat Redistribution
In some patients receiving combination antiretroviral therapy, there is a redistribution and / or accumulation of adipose tissue, including the central type of obesity, dorsotservikalnoe fat deposition ( "buffalo hump"), a decrease in the subcutaneous fat layer on the face and extremities, breast enlargement, elevated levels of serum lipids and blood glucose. These symptoms may occur in patients with or separately. Although one or more of the above side effects associated with obshim syndrome, which is often referred to as lipodystrophy can cause all classes of drugs HIV protease inhibitors (PIs) and nukleozidpyh traiskriptazy HIV reverse inhibitors (NRTIs),data indicate that there are differences between individual representatives of these classes of drugs in the ability to cause these side effects. lipodystrophy syndrome has a multifactorial etiology, eg, stage of HIV infection, older age and duration of antiretroviral therapy are important, possibly synergistic role.
The long-term consequences of these adverse events are currently unknown. Clinical examination should include an assessment of physical signs of redistribution of adipose tissue. It is necessary to determine the levels of serum lipids and blood glucose. Lipid disorders should be treated, guided by their
clinical manifestations.
Immune reconstitution syndrome
At the beginning of antiretroviral agents of HIV-infected patients with severe immune deficiency may increase the inflammatory process in the background asymptomatic opportunistic infection or residual effects that can cause serious deterioration or worsening of symptoms. Typically, such reactions are observed within the first weeks or months after the start of antiretroviral therapy. For example: cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and Pneumocystis (P.Carinii). Any inflammatory symptoms should be immediately identified and begin treatment if necessary.
autoimmune diseases(such as Graves' disease, polymyositis, and Guillain-BarrГ© syndrome) have been observed on the background of immune reconstitution, but the time of the primary manifestations varied, and the disease may occur many months after initiation of therapy and have an atypical course.
Liver disease
The safety and efficacy of zidovudine has not been established in patients with severe liver disease.
Co-infection with HIV and hepatitis B
Results of clinical trials and postmarketing data suggest that some patients with chronic hepatitis B cases Zidolam drug having clinical and laboratory signs of acute hepatitis, which can have serious consequences for patients with decompensated liver function. In case of cancellation Zidolam drug in patients co-infected with hepatitis B should periodically monitor both the liver function and hepatitis B markers of viral replication (within 4 months).
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased risk of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, it is necessary to consider the suspension or discontinuation of treatment.
Co-infection with HIV and hepatitis C
Worsening anemia was observed in the combination of ribavirin and zidovudine, although the mechanism of this phenomenon remains unclear. Thus, without the simultaneous application of ribavirin n zidovudine, particularly in patients with AZT-induced anemia in history. In these cases it is advisable to consider the possibility of changing antiretroviral treatment regime with a view to abolishing zidovudine.
Osteonecrosis
The etiology of osteonecrosis is considered multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported in patients with advanced HIV infection and / or long-term use of combination antiretroviral therapy (APBT). Patients should be advised to seek medical advice if they experience joint pain, joint stiffness or difficulty in movement.
Zidolam not be taken with any other medicinal products containing lamivudine or medicinal products containing emtricitabine.
Impact on the ability to drive vehicles and manage mechanisms
Not conducted a special study of the effect of lamivudine and zidovudine on ability to drive and operate machinery. Pharmacological properties of these drugs show a low probability of such an impact. It should take into account the clinical condition of the patient, as well as the nature of the adverse effects of lamivudine and zidovudine.
OVERDOSE
Symptoms:
Data on cases of drug overdose Zidolam not. There are no specific symptoms are observed in acute overdose of lamivudine and zidovudine, other than those listed in the "Side Effects".
Treatment:
In case of overdose it is recommended to monitor the patient for signs of intoxication timely detection and conduct standard maintenance therapy. Since lamivudine output by dialysis, can be used in overdose continuous hemodialysis, but the corresponding clinical experience unavailable. Apparently, hemodialysis and peritoneal dialysis are ineffective when excretion of zidovudine, but these methods accelerate the elimination of its metabolite (glucuronide). Further details are contained in the instructions for use of lamivudine and zidovudine.
DRUG INTERACTION
Since Zidolam comprises lamivudine and zidovudine, he can enter into any interactions specific to each of its components. The likelihood of metabolic interactions with lamivudine is low, since only a small part of the administered drug is metabolized and binds to plasma proteins, and the drug is almost completely excreted by the kidneys unchanged.
Zidovudine is also a small extent bound to plasma proteins, but advantageously eliminated by hepatic metabolism to inactive glucuronide. Formulations with primary hepatic metabolism, especially by glucuronidation could potentially inhibit the metabolism of AZT.
Listed below are some medicines that represent a class of drugs that should be used with caution during therapy with the drug Zidolam.
Interactions involving Lamivudine:
Lamivudine preferably derived using a cationic transport system, respectively, be aware of the possibility of drug interactions Zidolam with those drugs having the same route of elimination.
Trimethoprim: simultaneous reception of lamivudine and combinations sulfometoksazola and trimethoprim (160 mg + 800 mg, co-trimoxazole) leads to an increase in the plasma concentration of lamivudine to 40% when taking this n
