Retrovir Syrup for newborn instructions for use. Preventive use of antiretroviral drugs in newborns. Special groups of patients
Indications
HIV infection in adults and children. Warning of HIV graft transplantation.
Contraindications
Hypersensitivity; Pronounced neutropenia (less than 0.75х109 / l), significantly reduced hemoglobin level (less than 75 g / l).
pharmachologic effect
Pharmacological action - antiviral. Blocks the synthesis of viral DNA due to inhibiting HIV reversion transcriptase.
Active substance
\u003e\u003e Zidovudine * (Zidovudine *)
Latin name
Retrovir.
ATH:
\u003e\u003e J05AF01 Zidovudin
Pharmacological group
\u003e\u003e HIV treatment agents
Nonological Classification (ICD-10)
\u003e\u003e B20-B24 disease caused by human immunodeficiency virus [HIV]
Composition and form of release
1 ml of a solution for receiving inside contains zidovudine 10 mg, complete with a dosing syringe, adapter, plastic lid, in the box 1 set.
1 capsule - 100 mg; In a blister 10 pcs., In a box of 10 blisters.
1 bottle with 20 ml solution for infusions - 200 mg; In a box of 5 bottles.
Pharmacokinetics
Absorbed in the intestines. Bioavailability - 60-70%. Binds with plasma proteins by 34-38%. T1 / 2 - 1.1 h, Cl - 27.1 ml / min / kg, explicit distribution volume - 1.6 l / kg. Metabolized, mainly to the 5'-glucuronide of Zidovudine (50-80% administered dose). Zidovudine penetrates the placenta and is found in the amniotic fluid and blood of the fetus.
Application in pregnancy and breastfeeding
The appointment of the drug during pregnancy (from the period of 14 weeks to childbirth) reduces the risk of HIV transplantar transmission.
Side effects
Anemia, neutropenia, leukopenia (on early stages HIV diseases manifest less often), anorexia, vomiting, abdominal pain, dyspepsia, headache, increase body temperature, insomnia, malaise, myalgia, paresthesia, rash.
Method of application and dose
Inside. Adults and children over 12 years old: 500-600 mg / day (in 2-3 receptions) when it is combined with other antiretroviral drugs. Children from 3 months to 12 years: 360-480 mg / m2 / day (for 3-4 reception) in combination.
When pregnancy from 14 weeks and before the start of childbirth: 100 mg 5 times a day.
During the birth - V / B, infusion 2 mg / kg for 1 hour, then continuously 1 mg / kg / h before pupil samples (preventing the transplacentating transmission of HIV).
Newborn: oral solution 2 mg / kg every 6 hours, the course is the first 12 hours (up to 6 weeks); V / B, infusion, 1.5 mg / kg (for at least 30 minutes) every 6 hours.
Precautions
It is recommended to conduct blood tests every 2 weeks for the first 3 months of treatment, and then - at least 1 time per month (especially in patients with impaired function bone marrow). In case of deterioration of hematological indicators, a dose refinement is required or the cessation of treatment. Do not be taken without the appointment of a doctor, especially in combination with aspirin, paracetamol, Codene.
Shelf life
5 years
Storage conditions
List B.: In the dry place protected from light, at a temperature not higher than 30 ° C.
Found in 40 or questions:
November 19, 2015 / Erik Kivexa
Hello. Not. See titles active substances. Retrovir This is Zidovudine, Zidol is a lamivudine + zidovudine - an analogue of Combivir.
I have HIV. I gave birth to a child and give prevention retrovir Every 6 hours. What will happen if I give a child at 6 am retrovir Not during, that is, I can give at 6:08, at 6:40, at 6:30. And so for 2 weeks.
Catad_pgroup antiviral with HIV
Retrovir Solution - Instructions for use
Registration number:
Trade name of the drug: Retrovir ® / Retrovir ®.
International non-specific name: Zidovudine / Zidovudine.
Dosage form:
Solution for intake.Structure
5 ml of the drug contains:
Description
Transparent light yellow solution with a characteristic strawberry smell.
Pharmacotherapeutic group
Antiviral (HIV) agent.
ATH code: J05AF01.
Pharmacological properties
Pharmacodynamics
Mechanism of action
Zidovudine - antiviral drug, analogue of thymidine, highly active against retroviruses, including human immunodeficiency virus (HIV).
Zidovudine is subject to phosphorylation in both infected and intact cells with the formation of monophosphate by cellular thymidicinase. Subsequent phosphorylation of zidovudine monophosphate to zidovudine diphosphate, and then to zidovudine trifhosphate catalyzed by cell thymidylatelates and nonspecific kinases, respectively.
Zidovudine trifhosphate acts as an inhibitor and substrate for viral reverse transcriptase. The formation of a surusive DNA is blocked by the embedding of the 5th trifosphate in its chain, which leads to a chain cliff. Competition of Zidovudine Trifosphate for reverse HIV transcriptase is approximately 100 times stronger than the cell-polymerase of human DNA.
Zidovudine acts additive or synergistically with a large number of antiretroviral drugs, such as lamivudine, didanosine,-interferon, suppressing HIV replication in cell culture.
Development of resistance to thymidine analogues (zidovudine - one of them) occurs as a result of the gradual accumulation of specific mutations in 6 codons (41, 67, 70, 210, 215 and 219) reverse HIV transcriptase. Viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in positions 41 and 215 or accumulation, at least 4 of 6 mutations. These mutations do not cause cross-resistance to other nucleoside analogues, which makes it possible to further apply for the treatment of HIV other reverse transcriptase inhibitors.
Two types of mutations lead to the development of multiple medicinal resistance.
In one case, mutations occur in 62, 75, 77, 116 and 151 positions of reverse HIV transcriptase, and in the second case we are talking about T69S mutation with inserting 6 pairs of nitrogenous bases in this position, which is accompanied by the appearance of phenotypic resistance to zidovudine, and Also to other nucleoside reverse transcriptase inhibitors. Both types of these mutations significantly limit the therapeutic capabilities in HIV infection.
Reducing the sensitivity to Zidovudine in vitro isolates of HIV was observed with long-term treatment of HIV infection with Zidovudine.
Currently, the connection between the sensitivity to the in vitro zidovudine and the clinical effect of therapy has not been studied.
Research in vitro. Zidovudine in a lamivudine combination showed that zidovudine-resistant virus isolates become sensitive to zidovudine while simultaneously acquiring resistance to lamivudine. Clinical studies have demonstrated the fact that the use of Zidovudine in a combination with lamivudine delays the emergence of a virus resistant to zidovudine in patients who have previously received antiretroviral therapy.
Pharmacokinetics
Suction
Zidovudine is well absorbed after oral administration, bioavailability is 60-70%. The average values \u200b\u200bof the maximum concentration in the equilibrium state (C SS MAX) and the minimum concentration in the equilibrium state (C SS MIN) in the plasma when receiving 5 mg / kg of zidovudine every 4 hours were 7.1 and 0.4 μmol, respectively (or 1.9 and 0.1 μg / ml).
Bioequivalence
It was shown that in terms of the area under the pharmacokinetic curve "Concentration-time" (AUC) solution of zidovudine for reception inside bioequivalenten Zidovudine capsules.
Distribution
Bonding with blood plasma proteins is relatively low, is 34-38%.
Zidovudine penetrates B. spinal fluid, placenta, amniotic fluid, fetal blood, cum and breast milk.
Metabolism
5 "Zidovudine -Glucronid is the main ultimate metabolite of zidovudine, is determined in plasma and urine and is approximately 50-80% of the dose of the drug, which is excreted by the kidneys.
Election
The kidney clearance of zidovudine is much higher than creatine clearance, which indicates the predominant removal of zidovudine with the help of the channel secretion.
Special groups Patients
Children
In children over 5-6 months, pharmacokinetic indicators are similar to those in adults.
Zidovudine is well absorbed from the intestines, bioavailability is 60-74% with an average value of 65%. After receiving the zidovudine in doses of 120 mg / m 2 and 180 mg / m 2 as a solution for receiving inside, the maximum equilibrium concentration was 4.45 μm (1.19 μg / ml) and 7.7 microns (2.06 μg / ml ) respectively.
Pharmacokinetic data suggests that Zidovudine glucooner in newborns and breast-age children is reduced, which leads to an increase in bioavailability. Reducing the clearance and a longer half-life is recorded in breast-age children under 14 days, then pharmacokinetic parameters become similar to those in adults.
Elderly patients
Pharmacokinetics of Zidovudine in patients older than 65 years have not been studied.
In patients with severe renal failure, the maximum concentration of zidovudine in the plasma rises by 50% compared with that in patients without disturbing the function of the kidneys. The systematic exposure to Zidovudine (AUC) increases by 100%, the half-life does not change significantly. With a violation of the kidney function, there is a significant cumulation of the main metabolite 5 "-Glucronida of Zidovudine, but the signs toxic action It is not detected. Hemodialysis and peritoneal dialysis do not affect the elimination of Zidovudine, at the same time removal of the 5 "-glucronida of the Zidovudine increases.
With liver failure, the Cumulation of Zidovudine may be observed due to the reduction of glucuronization, which requires a dose correction of the drug.
Pregnancy
The pharmacokinetic parameters of Zidovudine in pregnant women do not change, the signs of cumulation of Zidovudine are not marked.
The concentration of Zidovudine in plasma in children at birth is the same as their mothers during childbirth.
Indications for use
Fertility
There is no data on the influence of the drug Retrovir ® for the childbearing function of women. In men, the drug retrovir ® does not affect the composition of sperm, morphology and the mobility of spermatozoa.
Pregnancy
Zidovudine penetrates the placenta. The drug Retrovir ® can be used earlier 14 weeks of pregnancy only if the potential benefit for the mother exceeds the risk for the fetus.
Prevention of HIV Transfer from Mother Fruit
The use of drug Retrovir ® After 14 weeks of pregnancy, followed by its appointment in newborns leads to a decrease in the frequency of vertical HIV transmission.
The long-term consequences of the use of the drug Retrovir ® in children who have received it in the intrauterine or neonatal periods are unknown. It is impossible to completely exclude the possibility of carcinogenic influence. Pregnant women should be informed about it.
Pregnant women involving the use of the drug Retrovir ® during pregnancy for preventing the vertical transfer of HIV should be informed about the risk of fetal infection, despite the therapy.
Lactation
Since Zidovudine and HIV penetrate into breast milk, during the reception of the drug Retrovir ® women should not breastfeed. Method of application and dose
The drug Retrovir ® is designed to receive inside.
Adults and teenagers with a body weight of at least 30 kg
The recommended dose is 500 or 600 mg per day, divided into two receptions, as part of combined therapy. Dose 1000 mg per day, divided into several techniques, used within clinical studies. The efficiency of doses in the range is below 1000 mg / day for the treatment or prevention of neurological dysfunction associated with HIV infection.
Children
Children with body weight of at least 9 kg, but less than 30 kg
The recommended dose is 18 mg / kg per day, divided into two receptions, as part of combination therapy. The efficiency of doses in the range is below 720 mg / m 2 / day (approximately 18 mg / kg 2 times a day) for the treatment of neurological dysfunction associated with HIV infection. Maximum daily dose It should not exceed 600 mg (300 mg 2 times a day).
Children with a body weight of at least 4 kg, but less than 9 kg
The recommended dose is 24 mg / kg per day, divided into two receptions, as part of combination therapy.
Elderly patients
The pharmacokinetics of Zidovudine in patients under the age of 65 did not study. However, given the age reduction of the kidney function and possible changes in peripheral blood indicators, in such patients it is necessary to observe special care when prescribing the drug Retrovir ® and carry out appropriate observation before and during treatment.
Patients with impaired kidney function
With severe renal impairments, the recommended dose of the drug Retrovir ® is 300-400 mg per day. Depending on the reaction from the peripheral blood and clinical effect, further dose correction may be required. Hemodialysis and peritoneal dialysis do not have a significant impact on the elimination of Zidovudine, however, accelerates the removal of 5 "-Glucronida of Zidovudine.
For patients with terminal stage renal failureHemodialysis or peritoneal dialysis, the recommended dose of the drug Retrovir ® is 100 mg every 6-8 hours.
Patients with impaired liver function
The data obtained in patients with cirrhosis of the liver indicate that the patients with hepatic failure may occur the Cumulation of Zidovudine due to the reduction of glucuronization, and there may be a dose correction correction. If the monitoring of the zidovudine concentration in the plasma is impossible, then the doctor should pay special attention to clinical signs intolerance to the drug and, if necessary, conduct a dose correction and / or increase the interval between the drugs.
Dose correction with unwanted reactions from the blood formation system
Adequate correction of the dosing mode is a reduction in the dose or cancellation of the drug Retrovir ® - it may be necessary in patients with unwanted reactions from the blood formation system (in case of decrease in hemoglobin concentration to 75-90 g / l (4.65-5.59 mmol / l) or The number of leukocytes to 0.75-1.0 * 10 9 / l).
Prevention of HIV infection from the Mother Fruit
The effectiveness of the following 2 prophylaxis schemes for pregnant women was shown.
The newborn shows the purpose of the drug Retrovir ® at a dose of 2 mg / kg body weight every 6 hours, starting from the first 12 hours after birth and continuing until the age of 6 weeks. Newborn, which can not make a solution of the drug Retrovir ® inside, it is necessary to prescribe a drug Retrovir ® intravenously.
Instructions for using the dosing syringe
The attached dosing syringe and the adapter are designed to accurately dosing the drug Retrovir ®, a solution for intake.
- Remove the lid from the bottle.
- Insert the supplied adapter in the vial of the bottle, holding the bottle
- Insert the dispensing syringe into the opening of the adapter.
- Turn the bottle.
- By pulling the piston of the dosing syringe, measure the exact amount of the first portion from the full dose of the drug appointed to you.
- Turn the bottle of the ball up, remove the syringe from the adapter.
- Carefully place the syringe in the mouth, behind the cheek, swallow the drug, slowly pressed on the piston of the syringe. Do not push the piston too much, the solution can get on the rear wall of the pharynx and call the suffocation.
- Repeat procedures 3? 7 before receiving a full dose.
- Do not leave the syringe in the vial, after use thoroughly rinse the dosing syringe and the adapter with clean water.
- Tightly close the bottle with a lid.
The profile of unwanted phenomena at the reception of Zidovudine is similar in adults and children. The undesirable phenomena shown below are listed depending on the anatomical-physiological classification and frequency of occurrence. The frequency of occurrence is determined as follows: often (≥1/10), often (≥1 / 100 and<1/10), infrequently (≥1 / 1000 and<1/100), seldom (≥1 / 10000 and<1/1000), rarely (<1/10000, включая отдельные случаи). Категории частоты были сформированы на основании клинических исследований препарата и пострегистрационного наблюдения.
Frequency of occurrence of unwanted phenomena
From the side of the blood formation and lymphatic system
Often: anemia (which may require hemotransphus), neutropenia and leukopenia. The anemia more often occurs when receiving high doses of the drug (1200-1500 mg / day) and in patients in the later stages of HIV infection, in particular at the concentration of CD4 lymphocytes of less than 100 cells / μl. As a result, a dose decreased or cessation of therapy may be required. The rate of development of neutropenia was higher in patients who, before starting treatment, the number of neutrophils, hemoglobin content and whey level of vitamin B12 were low.
Infrequently: thrombocytopenia and barbecue (with bone marrow hypoplasia).
Rarely: True Erythrocyte Aplasia.
Very rarely: aplastic anemia.
From the metabolism and nutrition
Often: hyperlactatema.
Rarely: lactic acid, anorexia. Redistribution and / or accumulation of subcutaneous fluid (the development of this phenomenon depends on many factors, including from a combination of antiretroviral drugs).
From the central and peripheral nervous system
Very often: Headache.
Often: dizziness.
Rarely: insomnia, paresthesia, drowsiness, reducing the speed of thinking, convulsions.
From the mental sphere
Rarely: anxiety, depression.
From the cardiovascular system
Rarely: Cardiomyopathy.
From the respiratory system, chest and mediastinal organs
Infrequently: shortness of breath.
Rarely: cough.
From the gastrointestinal tract
Very often: nausea.
Often: vomiting, abdominal pain, diarrhea.
Infrequently: flatulence.
Rarely: Pigmentation of the mucous membrane of the oral cavity, disruption of taste, dyspepsia.
From the liver, biliary tract and pancreas
Often: raising the level of bilirubin and liver enzyme activity.
Rarely: liver damage, such as pronounced hepatomegaly with steatosis; Pancreatitis.
From the skin and subcutaneous fatty fiber
Infrequently: rash, skin itch.
Rarely: nail and skin pigmentation, urticaria, increased sweating.
From the bone-muscular system
Often: Malgy.
Infrequently: myopathy.
From the urinary system
Rarely: rapid urination.
From the endocrine system
Rarely: gynecomastia.
General and local reactions
Often: malaise.
Infrequently: fever generated by pain syndrome, asthenia.
Rarely: chills, chest pain, influenza-like syndrome.
Unwanted reactions arising from the use of a drug Retrovir ® to prevent the transfer of HIV infection from the Mother Fruit
Pregnant women are well tolerated the drug Retrovir ® in recommended doses. Children have a decrease in hemoglobin content, which, however, does not require hemotransphus. Anemia disappears after 6 weeks after the completion of therapy with a drug Retrovir ®. Overdose
Symptoms
Possible feeling of fatigue, headache, vomiting; Very rarely: changes from blood indicators. There is one report on the overdose by an unknown amount of zidovudine, when the concentration of zidovudine in the blood exceeded 16 times the usual therapeutic concentration, nevertheless, while clinical, biochemical or hematological symptoms were absent.
Treatment
Symptomatic therapy and supporting therapy. Hemodialysis and peritoneal dialysis do not have high efficiency to remove zidovudine from the body, but enhance its metabolitis - 5 "-Glucronida of Zidovudine. Interaction with other drugs
Zidovudine is primarily excreted in the form of an inactive metabolite, which is a glucuronide conjugate formed in the liver. Preparations that have a similar dismissal path can potentially inhibit the metabolism of Zidovudine.
Zidovudine is used in combined antiretroviral therapy together with other nucleoside inhibitors of reverse transcriptase and drugs from other groups (HIV protease inhibitors, non-nucleoside inhibitors of reverse transcriptase).
The list of interactions listed below should not be considered exhaustive, but it includes groups of drugs that require cautious use with Zidovudine.
Atovahon: Zidovudine does not affect the pharmacokinetic parameters of the Atovachon. The athovahon slows down the transformation of zidovudine into the glucuronide derivative (AUC of zidovudine in an equilibrium state increases by 33% and maximum glucuron concentrations decrease by 19%). It is unlikely to change the zidovudine safety profile in doses of 500 or 600 mg / day with a combined application with an athuma for three weeks for the treatment of pneumatic pneumonia. If necessary, a longer combined application of these drugs is recommended to carefully monitor the patient's clinical condition.
Clarithromycin: Reduces suction of Zidovudine. The interval between the receptions of Zidovudine and Clarithromycin should be at least 2 hours.
Lamivudine: There is a moderate increase in the maximum concentration of zidovudine (with max to 28%) while using lamivudine, however, the total exposure (AUC) does not change. Zidovudine does not affect the pharmacokinetics of Lamivudine.
Phenytoin: With the simultaneous use of the drug Retrovir ® with phenytino, the concentration of the latter in the blood plasma decreases, the concentration of phenytoin in the blood plasma should be monitored when using this combination.
Probecid: Reduces glucuronization and increases the average half-life and AUC of Zidovudine. Glucronid and Zidovudine kidney is reduced in the presence of a probelecide.
Rifampicin: The combination of the drug Retrovir ® with rifampicin leads to a decrease in AUC for zidovudine by 48% ± 34%, but the clinical significance of this change is not known.
Study: Zidovudine can suppress intracellular phosphorylation of staudine. Thus, it is not recommended to apply a staudine simultaneously with Zidovudine.
Others: Acetylsalicylic acid, codeine, morphine, methadone, indomethacin, ketoprofen, naproxen, oxaisapam, oil-beams, cimetidine, clofibrate, dapson, isoprinozin can violate zidovudine metabolism by competitive inhibition of glucuronization or direct suppression of microsomal metabolicism in the liver. To the possibility of using these drugs in combination with the drug Retrovir ®, especially for long-term therapy, it should be used with caution.
The combination of the drug Retrovir ®, especially with urgent therapy, with potentially nephrotoxic and myelotoxic preparations (for example, pentamidine, dapson, pyrimetamine, co-trimoxazole, amphotericin, fluocitosine, ganciclovir, interferon, vincristine, vinblastine, doxorubicin) increases the risk of unwanted reactions to the drug Retrovir ®. It is necessary to observe the function of the kidneys and blood formula, if necessary, reduce the dose of drugs.
Since some patients, even despite therapy with the drug Retrovir ®, opportunistic infections can develop, it is necessary to consider the appointment of preventive antimicrobial therapy. Such prevention includes co-trimoxazole, pentamidine in aerosol, pyrimetamine and acyclovir. Limited data obtained during clinical studies did not reveal a significant increase in the risk of developing unwanted reactions when the preparation of Retrovir ® with these drugs. Special instructions and precautions when applying
Treatment with a drug Retrovir ® should conduct a doctor who has experience in treating HIV-infected patients. After opening the bottle, it is not more than 28 days at a temperature not higher than 30 ° C.
Patients should be informed about the danger of the simultaneous use of the drug Retrovir ® with non-receptible vacation preparations and that the use of the drug Retrovir ® does not prevent HIV infection during sexual contact or infected blood. Appropriate security measures are needed.
Emergency prevention in probable infection
According to international recommendations (the Center for the Control and Prevention of Diseases, USA, June 1998), with probable contact with HIV-infected material (blood, other liquids), it is necessary to assign a combined therapy with drugs Retrovir ® for 1-2 hours on the moment of infection. and Epivir ®. In the event of a high risk of infection in the treatment regimen, a drug from a group of protease inhibitors should be included. Preventive treatment is recommended for 4 weeks. Despite the rapid beginning of treatment with antiretroviral drugs, seroconversion is impossible to exclude.
Symptoms that are adopted for the adverse reactions of therapy drug Retrovir ® can be a manifestation of the main disease or a reaction to the reception of other drugs used to treat HIV infection. The relationship between the developed symptoms and the action of the drug Retrovir ® is often very difficult to establish, especially with the deployed clinical picture of HIV infection. In such cases it is possible to reduce the dose of the drug or cancellation.
Retrovir ® does not cure from HIV infection, and patients retain the risk of developing opportunistic infections and malignant neoplasms, which is associated with the suppression of immunity. Retrovir ® reduces the risk of developing opportunistic infections. Data on the risk of development of lymphom on the background of the use of the drug is limited.
Unwanted reactions from the blood formation system
Anemia (is usually observed after 6 weeks from the beginning of the use of the drug Retrovir ®, but sometimes it can develop earlier), neutropenia (usually develops after 4 weeks from the beginning of treatment with Retrovir ® drug, but sometimes it occurs before), leukopenia may occur in the later stages of HIV infection. In patients receiving retrovir ®, especially in high doses (1200-1500 mg / day), and having reduced bone marking blood-forming prior to the start of treatment.
During the reception of the drug Retrovir® in patients with a detailed clinical picture of HIV infection, it is necessary to control hematological indicators at least once every 2 weeks during the first 3 months of therapy, and then monthly. In the early stages of HIV infection (with inexpressible reserves of bone marcing), unwanted reactions from the hematopoietic system are rarely developing, so general blood tests can be carried out less often, depending on the general state of the patient (once every 1-3 months).
If the hemoglobin content decreases to 75-90 g / l (4.65-5.59 mmol / l) or the number of neutrophils decreases to 0.75-1.0 * 10 9 / l, the daily dose of the drug Retrovir ® should be reduced to Recovery of blood indicators or retrovir ® is canceled 2-4 weeks before restoring blood indicators. Typically, the blood pattern is normalized after 2 weeks, after which the drug Retrovir ® in a reduced dose can be re-assigned. Despite the reduction in the dose of the drug Retrovir ®, hemotransfusion may be required under pronounced anemia.
Radiation therapy enhances the myelosuppressive action of Zidovudine.
Acidosis lactic acid and severe hepatomegaly with steatosis
These complications may have a fatal outcome of both during monotherapy with a retrovir ® and when the drug Retrovir ® is used in combination therapy. The clinical signs of these complications may be weakness, anorexia, sudden inexplicable loss in weight, symptoms from the gastrointestinal tract, respiratory symptoms (shortness of breath and tachipne).
Care should be taken when prescribing the drug to patients, especially with the risk factors of the liver disease. The risk of data development of complications increases in women. The drug Retrovir ® should be canceled in all cases the appearance of clinical or laboratory signs of acidic acid acid or hepatotoxicity, which may include hepatomegaly with steatosis even in the absence of increasing transaminase activity.
Redistribution of subcutaneous fatty fiber
Redistribution and / or accumulation of subcutaneous fiber tissue, including a central type of obesity, an increase in the fat layer on the rear surface of the neck ("buffalo hump"), a decrease in the subcutaneous fat layer on the face and limbs, an increase in the mammary glands, an increase in serum lipids and blood glucose It was noted both in the complex and separately in some patients who received combined antiretroviral therapy.
To date, all drugs from the inhibitors of protease (PI) and nucleoside inhibitors of reverse transcriptase (nita) were associated with one or more specific undesirable phenomenon associated with a common syndrome, often called lipodystrophy. However, data show the presence of differences in the risk of developing this syndrome between specific representatives of therapeutic classes.
In addition, lipodystrophy syndrome has multifactorine etiology, for example, factors such as HIV stage, an elderly age and the duration of antiretroviral therapy, play an important, perhaps a potent role.
The long-term consequences of this phenomenon are currently unknown. The clinical examination should include a physical inspection to assess the presence of the redistribution of subcutaneous fatty fiber. It should be recommended a study of the concentration of serum lipids and blood glucose. Lipid violations should be treated in accordance with clinical indications.
Immunity restoration syndrome
At HIV-infected patients with severe immunodeficiency during the start of antiretroviral therapy, an exacerbation of the inflammatory process is possible against the background of an asymptomatic or residual opportunistic infection, which may cause a serious deterioration of the state or exacerbation of symptoms. Typically, such reactions were described in the first weeks or months of the beginning of antiretroviral therapy. Most significant examples? cytomegalovirus retinit, generalized and / or focal mycobacterial infection and pneumatic pneumonia ( P. Carinii.). Any symptoms of inflammation must immediately identify and, if necessary, begin treatment.
Coinfection of HIV and viral hepatitis with
The increase in ribavirin-induced anemia in HIV-infected patients receiving simultaneously with therapy with zidovudine, but the exact mechanism of this phenomenon is unknown. Therefore, the combined use of Ribavirin and Zidovudine is not recommended. Antiretroviral therapy mode should be changed, applying a scheme that is not containing zidovudine, especially in patients with zidovudine-induced anemia. Impact on the ability to control vehicles, mechanisms
The effect of the drug Retrovir ® on the ability to control the car or mechanisms has not been studied. However, the adverse effect on these abilities is unlikely, based on the pharmacokinetics of the drug. Nevertheless, when solving the question of the possibility of driving a car or moving mechanisms, it is necessary to keep in mind the patient's condition and the possibility of developing adverse reactions (dizziness, drowsiness, inhibition, seizures). Form release
Solution for intake, 50 mg / 5 ml, 200 ml.
200 ml in a yellow glass bottle, covered with a polyethylene cap equipped with an autopsy control device. One bottle along with a plastic dosing syringe, adapter and instructions for use in a cardboard pack. Shelf life
2 years.
Do not use after the expiration date indicated on the package. Storage conditions
At a temperature not higher than 30 ° C.
Keep out of the reach of children. Conditions of vacation
On prescription. Manufacturer
"Glasosmitklein Inc." / GlaxosmithKline Ink. Canada, L5N 6L4, Ontario, Mrs., Missisoga Road North, 7333/7333, Mississauga Road North, Mississauga, Ontario, L5N 6L4, Canada The name and address of the legal entity, in the name of which the registration certificate was issued
"Viiv Healthcare UK Limited" / VIIV Healthcare UK Limited United Kingdom, TW8 9GS Middlsex, Brentford, Great West Road 980/980 Great West Road, Brentford, Middlesex Tw8 9Gs, United Kingdom For more information contact:
JSC "Glasosmitklein Trading" 121614, Moscow, ul. Krylatskaya, d. 17, Corp. 3, fl. 5, Business Park "Krylatskaya Hills"
in glass bottles of 200 ml (with a metering adapter); In the carton box 1 bottle.
in blister 10 pcs.; In a pack of cardboard 10 blisters.
in dark glass bottles of 20 ml; In a pack of cardboard 5 bottles.
Description of the dosage form
Solution for receiving inside: Transparent, pale yellow with strawberry flavor.
Capsules: Solid, gelatin opaque, white with Welcome inscription made by black ink, unicorn sign and Y9C100 code. The capsule and the capsule body are fastened with a transparent blue gelatin ribbon. Content capsules - white or almost white powder.
Solution for infusion: Transparent, colorless or light yellow sterile aqueous solution, practically does not contain mechanical impurities.
Characteristic
Antiretroviral drug.
pharmachologic effect
pharmachologic effect - antiviral.Embedded to a chain of viral DNA and blocks its education, contributing to the cliff. Competition of the drug for reverse HIV transcriptase is approximately 100 times stronger than the alpha polymerase of human cell DNA.
Pharmacodynamics
Active in relation to retroviruses, including human immunodeficiency virus. Zidovudine is phosphorylated in an affected and non-virus cells to monophosphate (MF) derivatives using cellular thymidicinase. Further phosphorylation of Zidovudine-MF to zidovudine di- and trifhosphate is catalyzed by cellular thymidicinase and nonspecific kinases, respectively.
Pharmacokinetics
When taking inside, it is well absorbed from the intestine, bioavailability is 60 -70%. In adults, the average equilibrium maximum and minimum concentration after taking into the solution of the retrovir in a dose of 5 mg / kg each 4 h is 7.1 and 0.4 μm (or 1.9 and 0.1 μg / ml), respectively; After receiving the retrovir capsules at a dose of 200 mg every 4 h - 4.5 and 0.4 μm (or 1.2 and 0.1 μg / ml), respectively; After an infusion for an hour of 2.5 mg / kg every 4 h - 4.0 and 0.4 μm (or 1.1 and 0.1 μg / ml).
The average T 1/2, the average general clearance and the volume of the distribution is 1.1 h, 27.1 ml / min / kg and 1.6 l / kg, respectively. Kidney clearance Zidovudine is much higher than creatine clearance, which indicates its preemptive excretion using the channel secretion. 5 "Glücronid Zidovudine is a major metabolite, and is determined in plasma and in the urine and is approximately 50-80% of the dose of the drug, which is derived through the kidneys. At / in the introduction of the drug, metabolite 3" amino-3 "-deoxitidimine is formed.
In children over the age of 5-6 months, pharmacokinetic indicators are similar to those in adults. When taking inside, it is well absorbed from the intestine, bioavailability is 60-74% (on average - 65%). After taking inside the solution of the retrovir in a dose of 120 mg / m 2 of the body surface and 180 mg / m 2, the level of the average equilibrium maximum concentration is 4.45 and 7.7 microns (or 1.19 and 2.06 μg / ml). After in / in infusion at a dose of 80 mg / m 2, 120 mg / m 2 and 160 mg / m 2, it is respectively 1.46, 2.26 and 2.96 μg / ml. The average T 1/2 and the overall clearance is 1.5 hours and 30.9 ml / min / kg, respectively. The main metabolite is 5 "- glucuronide. After the introduction of 29%, the dose of the drug is excreted unchanged with the urine and 45% dose - in the form of glucuronide. The newborn under 14 days has a decrease in bioavailability, a decrease in clearance and lengthening T 1/2.
2-4 hours after oral administration in adults, zidovudine glucurone, with a subsequent increase in its average ratio of the concentration of zidovudine in the spinal fluid and in the plasma is 0.5, and in children in 0.5-4 hours - 0.52-0.85 . Pregnant women are not observed signs of Cumulation of Zidovudine, and its pharmacokinetics are similar to that of non-deaths. Zidovudine passes through the placenta and is determined in the amniotic fluid and in the blood of the fetus. The concentration of Zidovudine in plasma in children at birth is the same as in mothers during childbirth. Exactly in sperm and breast milk (after one-time intake at a dose of 200 mg, the average concentration in milk corresponds to such in serum). The binding of the drug with plasma proteins is 34-38%.
In patients with severe renal failure C Max Zidovudine in the plasma increased by 50% compared with its concentration in patients without disrupting the kidney function. The system exposure of the drug (is defined as the area under the curve of the concentration-time ratio) increased by 100%; T 1/2 is significantly violated. In renal failure there is a significant cumulation of the main metabolite of glucuronide, but not observed signs of toxic. Gemo- and peritoneal dialysis do not affect the elimination of Zidovudine, at the same time removal of glucuron enhanced.
With liver failure, the Cumulation of Zidovudine may be observed due to the reduction of glucuronization (requires a dose adjustment).
Clinical pharmacology
The development of resistance to thymidine analogues (including zidovudine) occurs as a result of the gradual appearance of specific mutations in 6 codons (41, 67, 70, 210, 215 and 219) of reverse HIV transcriptase. Viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in codons 41 and 215 or accumulation, at least 4 of 6 mutations. Mutations do not cause cross-resistance to other nucleosides, which allows to use other inhibitors of reverse transcriptase to the treatment of HIV infection.
Two types of mutations lead to the development of multiple drug resistance. In one case, mutations occur in 62, 75, 77, 116 and 151 codons of reverse HIV transcriptase, in the second case we are talking about T69S mutations with insertion to the 6th pair of nitrogen bases corresponding to this position, which is accompanied by the appearance of phenotypic resistance to Zidovudine , as well as to other nucleoside inhibitors of reverse transcriptase. Both types of these mutations significantly limit the therapeutic capabilities in HIV infection. The decrease in the sensitivity to Zidovudine was observed with long-term treatment of HIV infection with retrovir. Currently, the link between sensitivity to Zidovudine has not yet been studied. in vitro. and the clinical effect of therapy. The use of Zidovudine in a combination with lamivudine delays the appearance of a virus resistant to zidovudine in the event that the patients had not previously carried out antiretroviral therapy.
Zidovudine is used in combined antiretroviral therapy together with other nucleoside inhibitors of reverse transcriptase and drugs from other groups (protease inhibitors, nucleoside reverse transcriptase inhibitors.)
Drug Indications Retrovir ®
Treatment of HIV infection in combined antiretroviral therapy in children and adults; Reducing the frequency of transplacentate transfer of HIV from the mother to the fetus.
Contraindications
Hypersensitivity to the components of the drug, neutropenia (number of neutrophils less than 0.75 · 10 9 / l); Reducing the hemoglobin (less than 75 g / l or 4.65 mmol / l), children's age (up to 3 months).
With caution: inhibition of bone marrowing, vitamin B 12 and folic acid deficiency, liver failure.
Application in pregnancy and breastfeeding
Earlier, 14 weeks of pregnancy is possible only if the expected effect of therapy exceeds the potential risk to the fetus. At the time of treatment, breastfeeding should be stopped.
Side effects
From the hematopopitation system: >1/100-<1/10 — анемия, нейтропения, лейкопения;
>1/1000-<1/100 — тромбоцитопения, панцитопения (с гипоплазией костного мозга); <1/10000 — апластическая анемия.
From the metabolism: \u003e 1 / 10000-1 / 1000 - lactic acidosis in the absence of hypoxemia and anorexia.
On the part of the central and peripheral nervous system: \u003e 1/10 - headache; \u003e 1 / 100-<1/10 — головокружение; >1/10000-<1/1000 — бессонница, парестезии, сонливость, снижение скорости мышления, судороги, тревога, депрессия.
From the side of the cardiovascular system: >1/10000-<1/1000 — кардиомиопатия.
From the respiratory system: >1/1000-<1/100 — одышка; >1/10000-<1/1000 — кашель.
From the head of the gastrointestinal authorities: \u003e 1/10 - nausea; \u003e 1 / 100-<1/10 — рвота, боли в верхних отделах живота, диарея; >1/1000-<1/100 — метеоризм; >1/10000-<1/1000 — пигментация слизистой оболочки полости рта, нарушение вкуса, диспепсия, панкреатит.
From the hepatobiliary system: >1/100-<1/10 — повышение уровня билирубина и активности ферментов печени; >1/10000-<1/1000 — выраженная гепатомегалия со стеатозом.
From the side of the skin and its appendages: >1/1000-<1/100 — кожная сыпь (кроме крапивницы), кожный зуд; >1/10000-<1/1000 — пигментация ногтей и кожи, крапивница, повышенное потоотделение.
From the musculoskeletal system: >1/100-<1/10 — миалгия; >1/100-<1/100 — миопатия.
From the urinary system: >1/10000-<1/1000 — учащенное мочеиспускание.
From the endocrine system: >1/10000-<1/1000 — гинекомастия.
Others: >1/100-<1/10 — недомогание; >1/1000-<1/100 — лихорадка, болевой синдром различной локализации, астения; >1/10000-<1/1000 — озноб, боли в грудной клетке, гриппоподобный синдром.
When in / in the introduction within 2-12 weeks, the most often arise: anemia, leukopenia, neutropenia.
When preventing the transfer of HIV infection from Mother to the fruit in children there is a decrease in the content of hemoglobin. Anemia disappears after 6 weeks after the completion of therapy.
Interaction
Lamivudine moderately increases with Max Zidovudine (by 28%), but does not change the AUC. Zidovudine does not affect the pharmacokinetics of Lamivudine. The probenecide reduces glucuronization and increases T 1/2 and AUC of Zidovudine. The renal excretion of glucuronide and zidovudine in the presence of a probebox is reduced.
Ribavirin is an antagonist of Zidovudine (their combination should be avoided).
A combination with rifampicin leads to a decrease in AUC for zidovudine by 48 ± 34% (the clinical value of this change is not known).
Zidovudine suppresses the intracellular phosphorylation of the staudine; Reduces the concentration of phenytoin in the blood (while simultaneously assigning the level of phenytoin level in plasma).
Paracetamol, aspirin, codeine, morphine, indomethacin, ketoprofen, naproxen, oxazepam, oilzapam, cimetidine, clofibrate, dapson, isoprinozin can disrupt the zidovudine metabolism (competitively inhibit glucurium or suppress microsomal metabolism in the liver). Such combinations should be approached with caution.
Retrovir combination with nephrotoxic or myelotoxic drugs (especially with emergency assistance) - pentamidine, dapson, pyrimethanic, co-trimoxazole, amphotericin, flucitosine, ganciclovir, interferon, vincristeine, vinblastine, doxorubicin - increases the risk of retrovir adverse reactions (kidney function is required, Blood indicators and reduction of doses, if necessary).
Radiation therapy enhances the myelosuppressive action of Zidovudine.
Method of application and dose
Inside (capsules, solution for intake). Adults and children over 12 years old. Recommended dose 500-600 mg / day in 2-3 receptions in combination with other antiretroviral drugs. Daily dose efficiency of less than 1000 mg for the treatment and prevention of HIV-associated complications is not established.
Children from 3 months to 12 years. Daily dose - 360-480 mg / m 2 in 3-4 receptions in combination with other antiretroviral drugs. The effectiveness of the daily dose is less than 720 mg / m 2 (180 mg / m 2 every 6 h) for the treatment and prevention of neurological complications of HIV infection is not established. The maximum dose should not exceed 200 mg every 6 hours.
Prevention of HIV transmission from mother to the fetus. Effective 2 prophylaxis schemes.
1. Pregnant women - 500 mg / day (100 mg 5 times a day), starting from 14 weeks before the start of childbirth. During childbirth - in / in, while the cord will be imposed on the clamp.
Newborn - 2 mg / kg every 6 hours, starting from the first 12 hours after birth to 6 weeks. If it is impossible to receive inside, assigned to / c.
2. Pregnant women - 300 mg 2 times a day from 36 weeks before the start of childbirth, and then every 3 hours before the end of childbirth.
With severe renal failure, a dose of 300-400 mg / day is recommended. Depending on the reaction from the peripheral blood and clinical effect, further adjustment of the dose can be carried out. For patients with a terminal stage of renal failure in hemo- or peritoneal dialysis, 100 mg every 6-8 hours.
V / B. (Solution for infusion), by slow infusion in a diluted form for 1 hour. The solution is administered only until the patients can take the drug inside.
Breeding
A solution for in / in infusion must be diluted before administration. The desired dose (see below) is added to a 5% glucose solution for B / in administration and mix with it so that the final concentration of zidovudine was 2 mg / ml or 4 mg / ml. Such solutions remain stable for 48 hours at a temperature of 5 ° C and 25 ° C.
Since the antimicrobial preservative is absent in the solution of retrovir, dilution should be carried out under conditions of complete asepsis, immediately before administration; Unused part of the solution in the bottle should be destroyed. When clouding, it should be pulled out.
Adults and children over 12 years old - 1-2 mg / kg every 4 h. This dose with / in the introduction of a retrovir provides the same exposure of the drug, as well as the dose of zidovudine 1.5 mg / kg or 3 mg / kg every 4 h ( 600 or 1200 mg / day in patients weighing a body of 70 kg) when taking inside. The efficiency of a lower dose in the treatment or prevention of HIV-associated neurological complications and malignant tumors is unknown.
Children from 3 months to 12 years. Information on the use of retrovir for in / in infusion in children is insufficient. The drug was prescribed in various doses from 80 to 160 mg / m 2 every 6 hours (320-640 mg / m 2 / day). Doses of the drug between 240-320 mg / m 2 per day in 3-4 receptions are comparable with doses of 360 mg / m 2 to 480 mg / m 2 per day in 3 4 receptions when taking inside, however, how effective they are currently not installed.
Prevention of HIV transmission from mother to the fetus. Pregnant women, starting with 14 weeks before the start of childbirth, it is recommended to prescribe a retrovir inside. During the birth, the retrovir is prescribed to / c at a dose of 2 mg / kg in the form of infusion for 1 hour, and then in the form of a continuous infusion at a dose of 1 mg / kg / h until the clip was imposed on the umbilical.
The newborn retrovir is prescribed inside, starting from the first 12 hours after birth to 6 weeks. If it is impossible to use inside, prescribed a / c at a dose of 1.5 mg / kg in the form of infusion for 30 minutes every 6 hours.
With severe renal failure, a dose of 1 mg / kg is recommended 3-4 times a day intravenously. This dose is equivalent to the daily dose of Zidovudine 300-400 mg when taking inside, recommended for this category of patients. Depending on the reaction from the peripheral blood and clinical effect, further adjustment of the dose may be required. For patients with a finite step of renal failure, which are in hemodialysis or peritoneal dialysis, a dose of zidovudine 100 mg is recommended every 6-8 h.
Overdose
Symptoms: Fatigue, headache, vomiting, changes in blood indicators (very rarely).
Treatment: Symptomatic therapy. Gemo- and peritoneal dialysis are ineffective to remove zidovudine from the body, but enhance the removal of its metabolitis - glucuronide.
Precautions
In case of liver failure, if necessary, the dose adjustment and / or increase the interval between the introductions.
When the hemoglobin level decreases to 75-90 g / l (4.65-5.59 mmol / l) or decrease the number of leukocytes to 0.75-1 · 10 9 / l change the dosage of the drug or cancel it.
Special caution should be observed in the treatment of elderly patients (the age reduction of the kidney function and changes in peripheral blood indicators should be taken into account.
special instructions
A solution for infusions cannot be entered in / m.
It is necessary to inform the patient about the danger of use simultaneously with the retrovir of the drugs of non-prescription leave and that the use of retrovir does not prevent HIV infection through sexual contact or infected blood. It is necessary to take appropriate security measures.
Retrovir does not cure from HIV infection, patients retain the risk of developing a detailed picture of the disease with the suppression of immunity and the occurrence of opportunistic infections and malignant neoplasms. In AIDS, retrovir reduces the risk of developing opportunistic infections, but does not reduce the risk of lymph.
Pregnant women who have the prevention of HIV transmission to the fetus should be informed about the risk of fetal infection despite the therapy.
Anemia (is usually observed after 6 weeks from the start of the use of Retrovir, but sometimes it can develop earlier), neutropenia (usually develops 4 weeks after the start of treatment retrovir, but sometimes it occurs before), leukopenia may occur in patients with a deployed clinical picture of HIV infection, Receiving retrovir, especially in high doses (1200-1500 mg / day), and having reduced bone marrowing before the start of treatment.
During the period of treatment, the retrovirus in patients with a deployed clinical picture of HIV infection must be controlled by blood tests at least 1 time in 2 weeks during the first 3 months of therapy, and then monthly. In the early stage of AIDS (when bone marrowing is still within normal), the side reactions from the blood are rarely developed, so blood tests are carried out less often, 1 time in 1-3 months (depending on the general condition of the patient).
If the hemoglobin content decreases to 75-90 g / l (4.65-5.59 mmol / l), the number of neutrophils decreases to 0.75-1.0 · 10 9 / l, the daily dose of retrovir should be reduced to the recovery of indicators blood or retrovir must be canceled for 2-4 weeks. Before restoring blood indicators. Usually, the picture of the blood is normalized after 2 weeks, after which the retrovir in the reduced dosage should be prescribed again. In children, hemotransfusion may be required in pronounced anemia (despite the decline in the dose of retrovir).
The lactic acidosis and pronounced hepatomegaly with steatosis may have a fatal outcome, both under mono- and for multicomponent therapy with retrovir. The risk of developing these complications increases in women. In all cases, the appearance of clinical or laboratory signs of milk acid acidosis or toxic liver damage should be canceled.
When solving the question of the possibility of driving the car, the likelihood of developing such adverse reactions as dizziness, drowsiness, inhibition, convulsions should be taken into account.
The use of the drug for the prevention of HIV transmission from mother to the fetus helps to reduce the frequency of HIV transmission from the mother to the fetus. The long-term consequences of this prevention are unknown. It is impossible to completely exclude the possibility of carcinogenic influence. It should be informed about this pregnant women.
Manufacturer
Smithklein Bechch Farmasyukalz, United Kingdom.
Conditions for the storage of the drug Retrovir ®
In a dry, light-protected place at a temperature of 15-25 ° C.Keep out of the reach of children.
The shelf life of the drug Retrovir ®
a solution for receiving inward 50 mg / 5 ml - 2 years.
capsules 100 mg - 5 years.
solution for infusion 200 mg / 20 ml - 3 years.
Do not apply after the expiration date indicated on the package.
If possible, postnatal prophylaxis should be started in the first 6 hours after birth. Zidovudine is administered orally or - in the presence of violations by the gastrointestinal tract - intravenously. In Germany, the duration of the rate of oral standard prevention has been reduced from six to two (four) weeks (VOCKS-HAUCK, 2001).
Prevention with an increased risk of perinatal HIV transmission (multiple birth, premature delivery)
With multiple birthdays, the newborn is recommended to carry out the prevention of Zidovudi-Mr for 4 weeks in the absence of additional risk factors. The premature newborn besides Zidovudine should get nevirapin: one dose if the mother received nevirapin during childbirth, or two doses, if the mother did not receive nevirapin. If less than an hour, the child should get the first dose of Neustrapin in the first 48 hours after birth (Stringer, 2003) from receiving non-virapin's mother before the child's birth. If the mother accepted non-virapin in the composition of the combined Art scheme, the dose for the newborn should be doubled to 4 mg / kg due to the possible induction of enzymes. In addition, newborns should obtain expanded prevention by Zidovudine according to the scheme for premature (see above) duration of four (Ferguson, 2008) to six (CDC, 2008a) weeks.
Prevention with extremely high risk of perinatal HIV transmission
In newborns with additional risk factors, the combined prevention of zidovudine is recommended in combination with lamivudine. The factors of very high risk are premature oral infringement, amnionitis, high viral load from the mother before childbirth, the absence of the prevention of the perinatal transmission of HIV, cutting injury to the child during the cesarean section, as well as the aspiration of the hemorrhagic amniotic fluid from the gastrointestinal tract of the child. If there are additional risk factors, it is recommended to prescribe newborn combined prevention of zidovudine and la-mivudine, as well as two doses of nevirapine. However, data on pharmacokinetics of antiretrovi-rustic drugs in newborns is extremely small.
Prevention in cases where the mother did not receive PMRD during pregnancy and in childbirth
The combined prevention of zidovudine in combination with lamivudine should be started in the first 6-12 hours after the birth of the child. In addition, perinatal neviurapin prevention is recommended. If HIV infection in mothers is diagnosed only after delivery, the combined prevention, started in the first 48 hours after birth, is much more efficient than the monoprophylaxis, started only after third days (the frequency of the vertical transmission is 9.2% compared with 18.4%; Wade , 1998). However, even later the beginning of the prevention of zidovudine is better than the complete absence of prevention (the risk of perinatal infection is 18.4% compared with 26.6%) (see Table 15.6). Even later, the beginning of postnatal prevention (\u003e 3 days) will benefit.
Further studies of the prevention of HIV infection in newborns
Review of pharmacokinetics studies in newborns is given in Table 15.7 (Ronkavilit, 2001 and 2002; Mirichnik, 2005; Blum, 2006; Chadwick, 2008; Hirt, 2008). To continuously improve the antiretroviral treatment of HIV infection in pregnant and antiretroviral prevention of the perinatal transmission, HIV must carefully register all clinical data. In the United States, there is a register of cases of admission of antiretroviral drugs during pregnancy, which helps track all possible teratogenic effects of antiretroviral media on the basis of reports on developmental deposits Table 15.7.Studies of antiretroviral prevention in newborns Reduction trade nameAverage daily doseMost frequent side effectsResearchAZT Retrovir®2 mg / kg 4 times a day 2 mg / kg 2 times a day; then 2 mg / kg 3 times a day - premature<35 недель гестации с 15-го дня; недоношенным <30 недель гестации с 29-го дняАнемия, нейтропения Митохондриопатия при применении в комбинации с ламивудином(P)ACTG 076, 316, 321, 353, 354, 358; HIVNET 012 III PACTG 331(PI)3TC Эпивир®2 мг/кг 2 раза в сутки новорожденным (в возрасте <30 дней)Нарушения со стороны ЖКТ, рвота, в комбинации с другими препаратами - токсическое повреждение митохондрий. Нельзя применять у недоношенныхPACTG 358FTC Эмтрива1 мг/кг сразу после рождения или 2 мг/кг через 12 часов после рождения; 3 мг/кг (новорожденным в возрасте <3 мес)Нарушения со стороны ЖКТ МитохондриопатияANRS12109 Исследование фармако-кинетики GileadddI Видекс®50мг/м2 2 раза в сутки, начиная с 14-го дня жизниДиарея, панкреатит, в комбинации с другими препаратами - токсическое повреждение митохондрийPACTG 239, 249; HIV-NATd4T Зерит®0,5 мг/кг 2 раза в сутки (новорожденным в возрасте <30 дней)В комбинации с другими препаратами - токсическое повреждение митохондрийPACTG 332, 356; HIV-NATABC Зиаген®2-4 мг/кг однократно (в возрасте <1 мес) и 8 мг/кг 2 раза в сутки (в возрасте >1 month) Hypersensitivity reaction, mitochondria, lactacidozpactg 321TDF Virid4 mg / kg immediately after birth, as well as in the 3rd and 5th days 13 mg / kg after delivery (as part of the study) osteopyation, nephrotoxicityNCT00120471, HPTN 057; AnRS12109NVP Viramun®2-4 mg / kg 1 time per day for 14 days or 120 mg / m2 one-time, then 3.5-4 mg / kg 2 times a day or 120 mg / m2 2 times a day (maximum dose 200 mg 2 times a day) rash, hepatotoxicity, hyperbi-lirubineypactg 316, 356, HIVNet012NFV Virasept®40-60 mg / kg 2 times a day (as part of the study), in newborns at the age<6 недельНарушения со стороны ЖКТ: в особенности диареяPACTG 353, 356 PENTA 7RTV Норвир®350-450 мг/м2 2 раза в сутки у новорожденных в возрасте <4 недель (в рамках исследования)Гипербилирубинемия, Нарушения со стороны ЖКТ, в особенности тошнотаPACTG 345, 354LPV/r Калетра®300/75 мг/м2 2 раза в сутки у новорожденных в возрасте <6 недельНарушения со стороны ЖКТ, в особенности диареяPACTG P 1030 IMPAACTG P1060 (P)ACTG - (Pediatric) AIDS Clinical Trials Group исследования в области СПИДа (у детей). HIV-NAT - HIV-Netherlands Australia Thailand R- Объединение медицинских учреждений, проводящих клинические Сотрудничество по проведению исследова-
hIV in HIV infection in the Netherlands, Australia and Thailand. Note: With the exception of Zidovudine, the remaining drugs in these doses are applied only within the framework of the research doses. If possible, drugs that are not approved for applications in newborns should be used only within the framework of clinical studies. And other deviations in newborns, whose mothers took antiretroviral drugs during pregnancy: Antiretroviral Pregnancy Registry, Research Park, 1011 Ashes Drive, Wilmington NC 28405
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Retrovir - antiviral pharmaceutical agent shown in use in HIV infection.
Instructions for use Retrovir
What is the retrovir composition and form of release?
The active ingredient in the antiviral drug retrovir is represented by Zidovudine, the amount of which is 100 milligrams in the capsule and 200 mg in the bottle. Solution excipients: hydrochloric acid and sodium hydroxide.
Retroviru includes auxiliary substances: Shellac, magnesium stearate, microcrystalline cellulose, corn starch, in addition, iron oxide black, ammonium hydroxide 28%, solution of ammonium concentrated, propylene glycol, potassium hydroxide, as well as gelatin.
The drug retrovir is available in white capsules with the "GSYJU" designation on the housing, inside which is a white powder. Comes in blisters of 10 pieces. In addition, a transparent slightly opalescent solution is made, implemented in bottles of 20 milliliters. Sale is possible only after the recipe.
What is the retrovir action?
An antiviral drug whose activity is aimed at retroviruses, the most well-known representative of the human immunodeficiency virus, called the HIV abbreviation.
The mechanism of action of the drug is the ability of its active substance to violate the activities of the viral enzyme transcriptase, involved in the process of assembling the particles of the virus. As a result, the process of formation of alien DNA is disturbed, which slows down the progression of the symptoms of the disease.
Violation in the work of viral enzymes is carried out due to the structural similarity of the active substance of the drug and thymiditriphosphate. I embed to the nucleic acid chain, the derivatives of the Zidovudine violate the further processes of the DNA of the virus.
The use of retrovir leads to partial normalization of the "formula" of the blood, which increases the patient's body resistance to various dangerous factors, including infections.
It should be noted that the action of the retrovir does not carry a completely selective nature. The active ingredient drug suppresses not only the processes of assembling viral particles, but also chains of human DNA, although in significant smaller quantities. The degree of influence on the patient transcriptase is about 300 times lower.
The drug Retrovir is partially effective with respect to other viruses: hepatitis B, Epstein-Barra virus and some others. In experiments, minor antibacterial activity was also found, the overwhelming processes of the vital activity of individual representatives of the genus Enterobacteriaceae.
Adsorption from the intestine is complete. The patient introduced into the patient's body is quickly entered into systemic blood flow. Zidovudine penetrates through most fabric barriers. Metabolization processes are associated with liver activity. Half-life about an hour. The metabolites of the active substance are derived from the body with urine.
What are the retrovir testimony for use?
Retrovir readings Such:
Treatment of HIV infection in comprehensive therapy;
Prevention of the development of HIV infection in the fetus, if the mother has HIV-positive status.
The use of medication is possible only after laboratory confirmation of the diagnosis. In addition, during the use of a drug, a periodic assessment of the effectiveness of the activities carried out is required.
What are the retrovir contraindications to use?
Using the Drug Retrovir Instructions for use does not allow in the following cases:
A sharp decrease in neutrophil content in peripheral blood;
Reduced hemoglobin content;
Individual intolerance.
Relative contraindications Retrovir: an elderly patient age, renal failure, as well as a sharp depression of blood-forming processes, in addition, severe anemics.
What are the retrovir use and dosage?
Dosage Retrovir is selected individually, taking into account the activity of the blood formation system, body weight and other factors. Capsules can be used regardless of food in an amount of from 500 to 600 milligrams per day. Multiplicity of reception from 2 to 5 times.
The parenteral form of the drug Retrovir is used intravenously in an amount of from 1 to 2 milligrams per kilogram of the patient's body weight every 4 hours. The duration of therapeutic measures is determined by the attending physician, taking into account the effectiveness of the treatment.
Which retrovir side effects?
The use of drug retrovir both inward and intravenously, can lead to the appearance of the following side effects: anemic states, hepatitis, meteorism (increased gas formation), pigmentation of skin, vomiting, diarrhea, violations of the act of swallowing, anorexia, abdominal pain, headache, Sleep disorders, depressive conditions, weakness, lethargy, drowsiness. More Side Effects Retrovir Such: inflammatory changes in respiratory tract, urine delay, heart pain, skin allergic rash, anaphylactic reactions, metabolic disorders.
How to replace retrovir, what analogs are used?
Analogs Retrovir include Zido-Eich, Viro-Zeta, Timazid, Retrovir Aziti, Zidovirin, Zidovudin-Fereyn, Zidovudine, Azidothimidine.
Conclusion
Treatment of HIV infection must be integrated. The patient should adhere to all the recommendations of the specialist: the reception of drugs, full nutrition, therapeutic and security regime, the course reception of polyvitamins and multiminerals, regular observation in the medical institution.
