Composition, form of production and packaging
Tablets covered with a film coat of white color, capsular, biconvex, with a risk on one side; on the bend - white or almost white.
1 tab.
zidovudine 300 mg
lamivudine 150 mg
nevirapine 200 mg
Excipients: microcrystalline cellulose 184 mg, corn starch 66 mg, croscarmellose sodium 18 mg, povidone 16 mg, magnesium stearate 15 mg, silicon dioxide colloid 8 mg, crospovidone 18 mg.
The composition of the film shell: shell 20 mg (hypromellose 62.5%, titanium dioxide 31.25%, macrogol-400 6.25%).
60 pcs. - polymer cans (1) - packs of cardboard.
Tablets covered with a film coat of white color, capsular, biconvex, with a risk on one side; on the bend - white or almost white.
1 tab.
zidovudine 300 mg
lamivudine 150 mg
nevirapine 200 mg
Excipients: microcrystalline cellulose 184 mg, corn starch 66 mg, croscarmellose sodium 18 mg, povidone 16 mg, magnesium stearate 15 mg, silicon dioxide colloid 8 mg, crospovidone 18 mg.
The composition of the film shell: shell 20 mg (hypromellose 62.5%, titanium dioxide 31.25%, macrogol-400 6.25%).
60 pcs. - polymer cans (1) - packs of cardboard.
Tablets covered with a film coat of white color, capsular, biconvex, with a risk on one side; on the bend - white or almost white.
1 tab.
zidovudine 300 mg
lamivudine 150 mg
nevirapine 200 mg
Excipients: microcrystalline cellulose 184 mg, corn starch 66 mg, croscarmellose sodium 18 mg, povidone 16 mg, magnesium stearate 15 mg, silicon dioxide colloid 8 mg, crospovidone 18 mg.
The composition of the film shell: shell 20 mg (hypromellose 62.5%, titanium dioxide 31.25%, macrogol-400 6.25%).
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 2013.
PHARMACHOLOGIC EFFECT
Zidolam-H is a combined drug that includes lamivudine, zidovudine and nevirapine - reverse transcriptase inhibitors used in combination therapy for HIV infection.
Lamivudine and zidovudine are highly effective selective inhibitors of reverse, HIV-1 and HIV-2 transcriptase. In addition, lamivudine is active against hepatitis B virus. Zidovudine is active against hepatitis B virus and Epstein-Barr virus in vitro; However, in vivo (in monotherapy) the replication of the hepatitis B virus suppresses insignificantly. Lamivudine is a synergist of zidovudine against the suppression of HIV replication in cell culture. The combined use of lamivudine with zidovudine leads to a significant reduction in the risk of progression of the disease.
Lamivudine and zidovudine belong to the group of nucleoside reverse transcriptase inhibitors (NRTIs), lamivudine is an analog of cytidine, zidovudine is an analogue of thymidine. Both preparations are sequentially phosphorylated with the participation of intracellular kinases (thymidine kinase, thymidylate kinase, nonspecific kinase) to 5-triphosphates (TF). Lamivudine TF and zidovudine TF are a substrate and a competitive inhibitor of HIV reverse transcriptase. Antiviral activity is mainly due to the inclusion of their monophosphate form in the viral chain
DNA, resulting in a break in the chain. Triphosphates of lamivudine and zidovudine have a much lower affinity for DNA polymerases of cells.
Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase (NNRTI). Combining with reverse transcriptase directly, blocks the activity of RNA-dependent and DNA-dependent polymerase, causing destruction of the catalytic site of the enzyme. Does not compete with matrix or nucleoside triphosphates. Does not inhibit the reverse transcriptase of HIV-2 and alpha, beta, gamma or sigma-DNA polymerase. In combination with zidovudine reduces viremia and increases the number of CD4 + cells.
Resistance
The resistant to lamivudine strains of the virus appear after 12 weeks of monotherapy; resistance. is due to the replacement in 184 of the position of the reverse transcriptase of isoleucine on valine. Mutation 184V / 1 provides high level resistance to lamivudine, increases the sensitivity of the virus to zidovudine, stavudine and tenofovir, reduces the sensitivity of the virus to didanosine and abacavir, reduces the likelihood of a mutation of resistance to thymidine analogs (MPAT). In the presence of MPAT, an increase in sensitivity to zidovudine and the like is less pronounced. If the virus has only a mutation of 184V / I, a decrease in sensitivity to didanosine, etc. does not lead to clinically significant consequences. Mutations of 65R, 44D and 1181 cause moderate resistance to lamivudine, while lamivudine does not contribute to the selection of strains with these mutations: MPAT infrequently combine with a mutation of 65R.
With zidovudine monotherapy, the stability of viruses is fast and almost always developed. MPAT, which reduce the sensitivity of the virus to all NRTIs - 41L, 67N, 70R, 210W, 215Y / F, 219Q / E, of which the most common 41L, 210W and 215Y they most significantly reduce the sensitivity of the virus to NRTI. Mutations of 67N, 70R and 219Q / E also reduce the sensitivity of the virus to NRTI, but to a lesser extent. Mutations of 44D and 1181 in the presence of MPAT increase the resistance to NRTI.
Combined therapy with lamivudine and zidovudine delayed the occurrence of zidovudine-resistant strains in patients who had not previously received antiretroviral therapy and was effective in treating patients who had not previously received antiretroviral therapy and in patients who had strains of HIV with an M184V mutation.
Mutations affecting the sensitivity to nevirapine: 1001, 103N, 106A / M, 1081, 181 C / 1, 188C / L / H, 190A. In the treatment of nevirapines (not in combination with zidovudine), a mutation of 181C usually appears; In the treatment of zidovudine and nevirapine, the most common mutation is 103N. Mutations of 103N, 106M, 188L / C provide high level of resistance. The 188H mutation causes low level resistance.
PHARMACOKINETICS
Absorption from the gastrointestinal tract of all active components of Zidolam-H is high, bioavailability of lamivudine is 80-85%, zidovudine - 60-70%, nevirapine -> 90%.
Pharmacokinetic parameters after a single oral intake of Zidolam-H by healthy volunteers are shown in the table.
Parameter Lamivudine Zidovudine Nevirapine
AUC 0-t (? G? H / ml) 5065 (В± 1539) 2387 (В± 608) 156 783 (В± 45 908)
Cmax (g / ml) 1182 (В± 453) 1773 (В± 635) 1995 (В± 492)
T max (h) 1.65 (В± 1.24) 0.55 (В± 0.28) 5.02 (В± 4.76)
The presence of food in the stomach slows the absorption of lamivudine and zidovudine, its value decreases, but it has no significant effect on bioavailability - AUC and T 1/2 practically do not change. Food intake, antacids or preparations containing an alkaline buffer (eg, didanosine), the magnitude and extent of absorption of nevirapine is not affected.
The half-life of lamivudine is 5-7 hours, zidovudine - from cells - 3,3 hours, from serum in adults - about 1 hour (0,8-1,2 hours), with renal insufficiency (creatinine clearance (CK) less than 30 ml / min) - 1,4-2,9 h, with cirrhosis of the liver varies depending on the severity of liver failure; on the average - 2,4 hours; in newborns whose mothers received zidovudine -13 hours. T 1/2 lamivudine TF from the cells is 22 hours, zidovudine TF - about 7 hours. After a single oral intake of nevirapine.T 1/2 is 45 hours after repeated administration in a dose of 200-400 mg / day-25-30 hours.
Lamivudine increases the duration of zidovudine by 13%, C max by 28%, while the AUC does not change; zidovudine does not affect the pharmacokinetics of lamivudine.
The connection with plasma proteins: lamivudine 35%, zidovudine 34-38%, nevirapine about 60%, indicating a low probability of Zidolam-H interaction with other drugs due to the displacement of plasma from the bond with proteins.
The volume distribution of lamivudine is 1.3 l / kg, zidovudine - 1.6 l / kg, nevirapine -2.1 l / kg. All three active components of Zidolam-N overcome the BBB.Lamivudine is found in cerebrospinal fluid (CSF) 2-4 hours after oral administration; the concentration of zidovudine in the CSF is 15 - 64% of the concentration in the plasma, the concentration of nevirapine is 45%.
Zidovudine penetrates most tissues and body fluids; accumulates in the seminal fluid, where its concentrations exceed those in serum by 1.3-20.4 times, but does not affect the release of HIV with seminal fluid and therefore can not prevent sexual transmission of HIV.
All three active components of Zidolam-H actively penetrate the placental barrier and into breast milk. The concentrations of lamivudine and zidovudine in the serum of infants are identical to those in the serum of maternal blood and umbilical cord blood.
Lamivudine, zidovudine and nevirapine are metabolized in the liver.
Lamivudine is metabolized to an insignificant degree (5 - 10%), with the formation of an inactive transulfoxide metabolite.
Zidovudine is conjugated with glucuronic acid to inactive glucuronides. The main metabolite is 5'-glucuronide, to which 50 to 80% of zidovudine administered inside is metabolized. With intravenous administration of zidovudine, its metabolite, 3'-amino-3'-deoxythymidine, was found.
Nevirapine is extensively metabolized with the participation of cytochrome isoenzymes CYP3A, CYP2B6. More than 80% of the ingested dose of nevirapine undergoes hydroxylation and conjugation to glucuronides. Being an inducer of the isoenzymes of the P450 system, nevirapine induces its own metabolism; with a maximum drop of T 1/2 observed in the first 2-4 weeks of admission.
Lamnududine, zidovudine and nevirapine are excreted mainly through the kidneys.
The systemic clearance of lamivudine is 0.32 l / h / kg; with a kidney clearance of 70%, excretion of lamivudine occurs with the participation of a cationic transport system.
The systemic clearance of zidovudine is 1.6 l / h / kg; renal clearance 0.34 l / h / kg, excretion occurs through glomerular filtration and active tubular secretion 14-18% zidovudine is excreted by the kidneys unchanged, 60-74% in the form of glucuronides (main - 5'-glucuronide).
Nevirapine is excreted from the body mainly in the form of metabolites; in unchanged form in urine is detected less than 3% of the dose taken internally. About 10% of nevirapine is excreted through the intestine.
Patients of advanced age. There are no data on the pharmacokinetics peculiarities in this group of patients.
Patients with impaired hepatic function. Correction of the dosing regimen is required for severe hepatic insufficiency and / or cirrhosis of the liver, since zidovudine is cumulated due to a decrease in glucuronidation.
Patients with impaired renal function. Correction of the dosing regimen is required when QC is less than 50 ml / min (for lamivudine). The concentration of zidovudine in plasma increases with severe renal failure, nevirapine - in the terminal stage of CRF. Pregnant. Features of pharmacokinetics of active components of Zidolam-H were not noted.
Sex, age, race. There were no significant differences in nevirapine plasma concentrations, depending on gender. The pharmacokinetics of nevirapine in HIV-1-infected adult patients does not change with age (range 18-68 years) or race (Negroid, Latin American or Europoid race). There is no data for lamivudine and zidovudine.
INDICATIONS
- HIV infection in adults and adolescents over 16 years of age (body weight not less than 50 kg).
Zidolam-H, as a fixed combination, can be administered with known adequate, tolerable active components - lamivudine, zidovudine, nevirapine. Tolerability is assessed after a course of combined antiretroviral therapy, at which a maintenance dose of nevirapine 200 mg twice a day was achieved and applied for at least 6-8 weeks (a maintenance dose is prescribed only after 14 days of intake at an initial dose of 200 mg once daily).
DOSING MODE
Treatment Zidolam-H should be conducted by a doctor with experience management of HIV-infected patients.
Adults and adolescents over 16 years of age (body weight not less than 50 kg)
Inside, regardless of food intake, 1 tablet 2 times a day.
A prerequisite for the prescription of Zidolam-H is the previous combination therapy with mono-drugs - lamivudine, zidovudine, nevirapine, in which nevirapine was used in a maintenance dose of 200 mg twice a day for at least 6-8 weeks. In a maintenance dose, nevirapine is administered only after 14 days
reception in an initial dose of 200 mg once a day.
Elderly patients (over 65 years of age)
With preservation of the excretory function of the kidneys and normal hematological parameters, correction of the dosing regimen is not necessary. Recommended use with caution, adequate monitoring of kidney function and periodic monitoring of blood picture.
General recommendations on the dosage regimen in special clinical cases
For conditions requiring dose reduction of Zidolam-H, the patient should be transferred to mono drugs, following recommendations for correcting the dosing regimen for lamivudine, zidovudine, and nevirapine.
Dose reduction is required for renal dysfunction (KK less than 50 ml / min), moderate hepatic insufficiency, hemoglobin level less than 9 g / dL or 5.59 mmol / l, neutropenia below 1 thousand / ОјL. With hepatic failure to moderate degree of dose reduction is not required. In severe hepatic insufficiency, Zidolam-N, like nevirapine-containing remedy, is contraindicated. If, for any reason, Zidolam-N treatment was interrupted for more than 7 days, the therapy should be resumed by prescribing lamivudine, zidovudine and nevirapine separately. Nevirapine should be given 200 mg once a day for 14 days *, then - in the absence of hypersensitivity reactions and severe gastrointestinal reactions - 200 mg twice a day for 6-8 weeks. Then you can resume taking Zidolam-N. It should also be borne in mind that the maximum daily dose of lamivudine for patients with renal insufficiency (KC less than 50 ml / min) is 150 mg.
* If a rash occurs during the 14-day initial period, the dose should be increased after the rash disappears
Drug withdrawal / interruption in therapy
Indications for withdrawal of the drug / suspension of Zidolam-H treatment are severe skin reactions, impaired liver function, increased activity of "hepatic" enzymes (with the exception of gamma-glutamyltranspeptidase).
Important. Irregular intake of the drug leads to the development of resistance to the virus and reduce the effectiveness of treatment. If you miss a dose, you should take a pill as soon as possible, without waiting for the next time. Do this while not doubling.
SIDE EFFECT
Side effect of Zidolam-H is identical with the aggregate of adverse reactions of lamivudine, zidovudine, nevirapine. Additivism of undesirable reactions, as well as competitive interaction, between active components of Zidolam-N is not present. The incidence of adverse reactions is given in accordance with WHO recommendations: very often -> 10%; often -> 1% and <10%; infrequently -> 0.1% and <1%; rarely -> 0.01% and <0.1%; very rarely - <0.01%.
When Zidolam-H is taken in more than 10% of cases, rash, headache, nausea, diarrhea, abdominal pain and myalgia are noted. Of serious adverse reactions, anemia, neutropenia, leukopenia, hypersensitivity reactions and hepatotoxic reactions also develop.
From the nervous system: very often - headache; often - dizziness, insomnia; rarely - paresthesia (sensation of tingling, burning, numbness and pain in the hands, hands, feet or feet), peripheral neuropathy, drowsiness, convulsions, fatigue with mental stress, anxiety, depression; frequency is not known - tremor, confusion, mania.
From the sense organs: the frequency is not known - macular edema, amblyopia, photophobia, vertigo, hearing loss.
From the cardiovascular system: rarely - cardiomyopathy; frequency is not known-fainting.
On the part of the organs of hematopoiesis: often - anemia, neutropenia, leukopenia; infrequently, thrombocytopenia, pancytopenia; rarely - true erythrocyte aplasia;very rarely - aplastic or hemolytic anemia.
From the respiratory system: infrequently - shortness of breath; rarely - cough; frequency not known - rhinitis, sinusitis.
From the side of the digestive system: very often - nausea; often - vomiting, abdominal pain, diarrhea, hepatitis, increased activity of "liver" enzymes, gyerbilirubinemia; infrequently - flatulence, jaundice; rarely - dyspepsia, the appearance of pigmentation of the oral mucosa, a violation of taste sensations, pancreatitis, including necrotic fatal outcome, fulminant (fulminant) liver failure, severe hepatomegaly with steatosis; frequency is not known - dysphagia, ulceration of the oral mucosa, decompensation of liver diseases in patients with HIV-1 and hepatitis C.
From the side of metabolism: rarely - lactic acidosis; frequency is not known - hyperglycemia, hyperlactatemia, insulin resistance, hypercholesterolemia, redistribution of adipose tissue.
From the urinary system: rarely - frequent urination; frequency is not known - labored urination.
From the side of the reproductive system: rarely - gynecomastia.
On the part of the skin: often - a rash, incl. generalized, hair loss; rarely - pigmentation of the skin and nails, increased sweating.
From the musculoskeletal system: often - myalgia; infrequently - myopathy, osteonecrosis; rarely - arthralgia; frequency is not known - muscle spasm, myositis, rhabdomyolysis, increased activity of creatinine phosphokinase, lactate dehydrogenase.
Allergic reactions: infrequent - skin rash, itching, hives, malignant exudative erythema (Stevens-Johnson syndrome); rarely - angioedema, toxic epidermal necrolysis (Lyell's syndrome), anaphylaxis; frequency is not known - vasculitis.
Other: often - weakness, fatigue; infrequently - asthenia, fever, generalized pain; rarely - chest pain, chills, flu-like symptoms; the frequency is not known - the reactivation syndrome immunity, malaise, back pain, secondary infection, fat redistribution.
In assessing tolerability Zidolama-H, it should be considered that skin rash, dizziness, weakness, headache, anorexia, diarrhea, myalgia, anemia, thrombocytopenia may be a manifestation of HIV infection itself and secondary diseases connected with it, rather than a toxic effect within the the composition of the active components of the preparation.
CONTRAINDICATIONS
- hypersensitivity to any of the active and / or auxiliary components of the formulation;
- neutropenia / leukopenia (neutrophil count below 0.75 10? 9 / L or 750 / L);
- anemia (hemoglobin less than 7.5 g / dl or 4.65 mmol / l);
- severe liver failure - (class C Child-Pugh or transaminase (ALT activity or ACT) is more than 5 times the upper limit of the norm);
- severe skin reaction history, generalized rash and / or hepatotoxicity in nevirapine history;
- Children and teens under 16 years old.
Do not apply Zidolam-H simultaneously with rifampicin, Hypericum preparations, stavudine, doxorubicin, and other drugs which reduce the antiviral activity of zidovudine.
Carefully:
Inhibition of bone marrow hematopoiesis, neutropenia / leukopenia (neutrophil 0.75 10? 9 / L-10 0,10? 9 / l or 750-1000 / l); anemia (hemoglobin of 7.5-9.0 g / dL or 4,65-5,59 mmol / l); deficiency or folic acid, cyanocobalamin, hepatic failure, advanced age (over 65 years), obesity, hepatomegaly, hepatitis or any of the known risk factors for liver disease, pancreatitis, including a history of peripheral neuropathy.
PREGNANCY AND LACTATION
Use during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus.
In the case of use of the drug during lactation should stop breastfeeding.
HIV-infected women should be instructed to exclude breast-feeding because of the extremely high probability of transmission through breast milk.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Is contraindicated in liver failure - (class C Child-Pugh or transaminase activity (ALT or ACT) is more than 5 times the upper limit of the norm)
APPLICATION FOR CHILDREN
Contraindicated for persons under 16 years of age.
APPLICATION IN ELDERLY PATIENTS
Application with caution to persons over 65 years.
SPECIAL INSTRUCTIONS
Zidolamom-N must be treated by a doctor with experience in management of HIV-infected patients.
If necessary, the reduction (reduction) should be replaced with a fixed dose combination, in this case Zidolam-N monotherapy, in its composition by combining them in prescribed doses.
It is necessary to inform the patient about the dangers of the use of in conjunction with N-Zidolamom other medicines, including those without a prescription without first consulting with your doctor.
With the development of opportunistic infections and other complications of HIV treatment should be continued in the hospital.
The patient should be informed that antiretroviral therapy, in particular therapy Zidolamom-H, does not prevent or reduce the risk of transmission immunodeficiency virus to healthy people through blood and sexual contact. All HIV-infected patients before the start of antiretroviral therapy is recommended to test for the presence of chronic hepatitis B.
The drug is not intended for the prevention of transmission of HIV, in fact, there are cases of serious adverse events with the use of nevirapine vneodobrennyh indications (off-label).
Before starting therapy with Zidolam-H all patients need to spend .laboratornye study to assess the likelihood of potentially harmful side effects. Patients previously treated with antiretroviral therapy should be performed genotypic analysis of the virus.
The most dangerous side effects
Liver disorders
Severe life-threatening liver disease, including fulminant hepatic failure, is a reaction of hypersensitivity to nevirapine. Immune-mediated hepatic reactions may be combined with skin reactions (rash, etc.) Or general effects, such as fever, arthralgia, myalgia, malaise. The most dangerous are the first 6 weeks of therapy with nevirapine, then little danger persists until the 18th week. Risk factors are female sex, higher baseline CD4 cell count and alanine aminotransferase, co-infection with hepatitis C virus, alcohol abuse. For example, in women, in which the number of CD4> 250 cells / mm 3 , compared with women who have CD4 <250 cells / mm 3, The risk of hepatotoxic reactions above 12 times. In men, when the number of CD4> 400 cells / mm 3, the risk of hepatotoxic reactions above 5 times. Start treatment with nevirapine
women with the number of CD4> 250 cells / mm 3 and men with the number of CD4> 400 cells / mm 3 should not be, unless the expected benefit is not significantly greater than the potential risk.
Active monitoring of liver function tests should be performed in patients who have previously had a complaint on dyspepsia, anorexia, nausea, discolored, stool, pain in the liver, marked jaundice, bilirubinuria, hepatomegaly.
Any signs of hypersensitivity reactions, as well as hepatotoxic reactions are an indication for discontinuation and immediate treatment measures.
When you see these complaints as nausea, vomiting, pain in the right upper quadrant, jaundice of the skin, dark urine and discolored stools should consult a doctor immediately.
Special supervision is required during HIV co-infection with hepatitis B or C.
It will be appreciated that lamivudine cases (and correspondingly lamivudine-containing Zidolama-H) may increase hepatitis. Use caution is recommended with decompensated cirrhosis caused by chronic hepatitis B. A periodic monitoring of liver function and hepatitis B markers of viral replication; patients with a hepatitis B liver function should be monitored and after stopping Zidolama-H, for 4 months.
hypersensitivity reactions
In patients treated with nevirapine, observed serious and life-threatening dermatological reactions, including fatal - malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), hypersensitivity syndrome - a combination of rash are common phenomena and internal organ involvement. The most dangerous in relation to the likelihood of rash development are the first 6 weeks of therapy with nevirapine, to a lesser extent - to the 18th week. Even in the case of an isolated rash requires careful monitoring.
In the case of generalized rash or a rash in combination with common phenomena, such as malaise, fever, lesions of the oral mucosa (swelling, redness, tenderness, bubbles), conjunctivitis, swelling of the face, the formation of blisters on the skin, pains in the joints and muscles - the drug should be discontinued immediately and
consult a doctor.
Compliance receiving circuit nevirapine (see sections "Indication", "dosage regimen.") Prior to receiving a fixed combination - Zidolama-H minimizes the likelihood of developing a rash.
Prednisone and antihistamines are ineffective; according to some sources, with the appointment of preventive prednisone simultaneously with nevirapine during the first 14 days of treatment even increased the frequency of rash.
Reappointment after severe hypersensitivity reactions is not allowed.
Lactic acidosis / hepatomegaly with steatosis
When the use of nucleoside analogs, including lamnvudin and zidovudine, may develop lactic acidosis, a marked increase in liver with steatosis, including fatal. Risk factors are obesity, prolonged use of nucleoside female. The clinical manifestations are not specific -odyshka hyperlactatemia and tachypnea, fatigue, nausea and vomiting, weight loss, abdominal pain; also possible asymptomatic hyperlactatemia. When the patient's clinical or laboratory signs of acidosis or hepatotoxicity even in the absence of pronounced increase in transaminase levels should stop taking the drug.
Lactic acid level> 5 mmol / liter is an indication for canceling NRTIs; level> 10 mmol / L - is critical, required urgent remedial measures.
Pancreatitis
There are rare reports of pancreatitis develop in patients treated with lamivudine / zidovudine. It is not identified pancreatitis, incidental, reaction products or as a complication of HIV infection. And yet, the appearance
of clinical or laboratory signs indicating the development of pancreatitis (vzhivote pain, nausea and vomiting, increased biochemical markers), the drug should be stopped.
Other side effects
Hematologic disorders
Perhaps the development of anemia, neutropenia and leukopenia (usually is secondary to neutropenia) in patients receiving zidovudine-containing combination. Risk group is patients with advanced HIV infection, with initial myelodepression, deficiency of vitamin B 12 . Serious hematologic response characteristic of high doses of AZT (1200 - 1500 mg / day), and it would be incorrect to approximate the data at a fixed combination. Since the peak of hematological disorders are usually observed after 4-6 weeks of therapy, it is recommended to carry out blood tests at the following intervals:
in patients with advanced HIV infection: at least 1 time in 2 weeks for the first three months of treatment, then - at least 1 time in the month;
in patients early on in asymptomatic: 1 times in 1-3 month, the patient's general condition.
With the development of severe anemia and / or myelosuppression required dose reduction of AZT, respectively, the patient should be transferred to the reception monotherapies.
mitochondrial toxicity
Examination children exposed NRTI-utero and / or postnatalyyum period revealed the following disorders: hematologic (anemia, neutropenia), metabolic (hyperlactatemia giperlipazemiya ,.); in most cases transient. Several cases of long-term side effects in the nervous system: hypertension, seizures, abnormal behavior. It is not known whether these transient disturbances; Nevertheless, children exposed to NRTIs in need of supervision. These data on mitochondrial toxicity are not grounds for amending the guidelines for the prevention of vertical transmission of HIV.
Fat redistribution.
In patients receiving antiretroviral therapy, observed a redistribution of the accumulation of body fat, including abdominal obesity, dorsotservikalnoe fat deposition ( "buffalo hump"), lipoatrophy at limbs and face, breast enlargement, and "cushingoid" type of obesity. Risk factors are metabolic disorders,
duration of antiretroviral therapy, patients of advanced age. The mechanism of occurrence and long-term effects are not known. A causal relationship with receiving ARVs has not been proved.
It recommended periodic monitoring of the level of glucose and lipids in the blood; if necessary - adequate pharmacological correction.
Reactivation of the immune syndrome
Reported reactivation syndrome immunity in patients receiving combination antiretroviral therapy. Reactivation immunity syndrome manifested exacerbation indolent and opportunistic infections, activation of pathogenic flora; observed in the initial phase of treatment in HIV-infected patients, the initial severe immunosuppression.
Effect on bone tissue
may decrease the level of the initial density of bone, osteonecrosis cases are known. The etiology of multifactorial: concomitant use of corticosteroids, alcohol consumption, severe immunosuppression, higher body mass index; the risk is higher in patients with advanced HIV infection, and increases in direct proportion to the duration of therapy.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: nausea, vomiting, weakness / fatigue, fever, headache, dizziness, insomnia, rashes, swelling, erythema -uzlovataya, pulmonary infiltrates, increase in transaminases and weight loss.
Treatment: standard maintenance therapy, continuous hemodialysis. Specific antidote to any of the active ingredients of the drug there.
Data on cases of overdose combination of lamivudine / zidovudine / nevirapine no.
Acute overdose with zidovudine or lamivudine specific symptoms is no different, only observed side effects.
A case nevirapine overdose (800 - 6000 mg for 15 days), the symptoms listed above.
Deaths in any case there was no condition of all patients on a background of standard maintenance therapy normalized.
DRUG INTERACTION
Interaction caused by the presence of lamivudine
Probability lamivudine adverse interaction with other drugs is extremely low due to its slight degree of binding to proteins limited biotransformation, and excretion primarily by the kidneys in unchanged form. Lamivudine is excreted mainly by the cationic transport system, which should be considered when assigning other drugs having the same route of elimination.
Since Lamivudine may inhibit the intracellular phosphorylation of zalcitabine, it is not recommended to combine these drugs.
The simultaneous use of trimethoprim / sulfamethoxazole (160 mg / 800 mg) increases the concentration of lamivudine in the plasma by about 40%. With well-preserved kidney function need to reduce the dose not, in patients with renal insufficiency - use caution. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole. About features interaction of lamivudine with high doses of trimethoprim / sulfamethoxazole applied at toxoplasmosis and pneumocystis pneumonia, unknown.
Simultaneous reception didaiozina, pentamidine, sulfonamides and ethanol increases the risk of developing pancreatitis.
Dapsone, didanosine, isoniazid and stavudine increase the risk of peripheral neuropathy.
Pharmacokinetic interaction of lamivudine in combination with interferon alpha and immunode
