Retrovir - instructions for use, dose, side effects, contraindications

Component name	Amount, mg
Active substance
Zidovudine	100
Excipients
Corn starch	82,8
Microcrystalline cellulose	34,5
Carboxymethyl starch of sodium, type A	11,5
Magnesium stearate	1,20

Composition of hard gelatin capsule:

Components	Content per 1 capsule, mg
The cap and the capsule body
Titanium dioxide E 171	1,35
Gelatin	up to 50,00
Ink (Opacode Black S-1-27794)	0.15 mg

Composition of ink (Opacode black S-1-27794):

Colour	Opacode code	Name of components	Quantity,% (m / m)
The black	Opacode	Shellac glazed-47% (esterified by 22%)	59,42
	S-1-27794	Shellac glazed-47% (esterified by 22%)
		Iron oxide black	24,65
		Propylene glycol	1,3
		H-butyl alcohol *	9,75
		Purified water*	3,25
		Industrial methylated spirit 74 *	1,08
		Isopropyl alcohol *	0,55

* substances are removed during production.

Description:

Hard gelatin capsules №3, opaque, white, with the inscription "GSYJU" on the capsule case with black ink. The capsule contains a white or almost white powder.

Pharmacotherapeutic group:An antiviral [HIV] agent.

ATX: & nbsp

J.05.A.F.01 Zidovudine

Pharmacodynamics:

Mechanism of action

Zidovudine is an antiviral drug, an analog of thymidine, in vitro Highly active against retroviruses, including the human immunodeficiency virus (HIV). Zidovudine is subjected to phosphorylation in both infected and intact cells to form monophosphate by means of cellular thymidine kinase.Subsequent phosphorylation of zidovudine monophosphate to zidovudine diphosphate, and then to zidovudine triphosphate is catalyzed by cellular thymidylate kinase and nonspecific kinases, respectively.

Zidovudine triphosphate acts as an inhibitor and substrate for viral reverse transcriptase. The formation of proviral DNA is blocked by the incorporation of zidovudine triphosphate into its chain, which leads to chain termination. The competition of zidovudine triphosphate for reverse transcriptase of HIV is approximately 100 times stronger than for cellular a-polymerase of human DNA.

Antagonism between zidovudine and other antiretroviral drugs (abacavir, didanosine, lamivudine and interferon alfa) in vitro was not observed.

The development of resistance to thymidine analogues (zidovudine - one of them) occurs as a result of gradual accumulation of specific mutations in 6 codons (41, 67, 70, 210, 215 and 219) of HIV reverse transcriptase. Viruses acquire phenotypic resistance to thymidine analogues as a result of combined mutations in codons 41 and 215 or accumulation of at least 4 of 6 mutations. These mutations do not cause cross-resistance to other nucleoside analogues,which allows further use of other reverse transcriptase inhibitors to treat HIV infection.

Two kinds of mutations lead to the development of multiple drug resistance.

In one case, mutations occur in 62, 75, 77, 116, and 151 codons of HIV reverse transcriptase, and in the second case, a T69S mutation with the insertion of 6 pairs of nitrogen bases in this position is accompanied by the appearance of phenotypic resistance to zidovudine, and also to other nucleoside reverse transcriptase inhibitors (NRTIs). Both types of these mutations significantly limit the therapeutic possibilities for HIV infection.

Decreased sensitivity to zidovudine in vitro HIV isolates were observed with long-term treatment of HIV infection with zidovudine. Available data indicate that in the early stages of HIV infection, the frequency and degree of decrease in sensitivity in vitro significantly less than in the late stages of the disease.

Currently, the relationship between sensitivity to zidovudine in vitro and the clinical effect of therapy has not been studied. Determination of sensitivity in vitro It has not been standardized, and the results may vary depending on methodological factors.

Research in vitro zidovudine in combination with lamivudine have shown that zidovudine-resistant isolates of the virus become susceptible to zidovudine while simultaneously acquiring resistance to lamivudine. Clinical studies have demonstrated that the use of zidovudine in combination with lamivudine inhibits the emergence of zidovudine-resistant strains of the virus in patients who have not previously received antiretroviral therapy (APT). Zidovudine is widely used as a component of combined APT in conjunction with other antiretroviral drugs of the same class (NRTIs) or other classes (HIV protease inhibitors (HIV PI), non-nucleoside reverse transcriptase inhibitors (NNRTIs)).

Pharmacokinetics:

Suction

Zidovudine is well absorbed after oral administration, the bioavailability is 60-70%. The mean values of the maximum concentration in the equilibrium state (C_ss _max) and the minimum concentration in the equilibrium state (C_ss _min) in blood plasma with the intake of 5 mg / kg 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, according to the area under the pharmacokinetic curve "concentration-time" (AUC), the zidovudine solution for oral administration is bioequivalent to zidovudine capsules.Absorption of zidovudine after administration in the form of a solution for oral administration occurred slightly faster than after administration in the form of capsules, while the average time to reach the maximum concentrations (C_max) in blood plasma was 0.5 and 0.8 hours, respectively. Average values of C_{ss max}after normalization at a dose of 200 mg were 5.8 μmol (or 1.55 μg / ml) and 4.5 μmol (1.2 μg / ml) for oral solution and capsules, respectively. These data were obtained using zidovudine syrup for oral administration, but may be considered equivalent to those applicable for zidovudine for oral administration.

Distribution

Binding to blood plasma proteins is relatively low, amounts to 34-38%, so it is unlikely that interactions with other drugs that affect binding to plasma proteins are unlikely.

Zidovudine penetrates into the cerebrospinal fluid, placenta, amniotic fluid, fetal blood, sperm and breast milk.

Metabolism

The 5'-glucuronide of zidovudine is the main terminal metabolite of zidovudine, determined in blood plasma and urine and is approximately 50-80% of the dose of the drug, which is excreted by the kidneys.

Excretion

The renal clearance of zidovudine greatly exceeds the creatinine clearance, which indicates the predominant excretion of zidovudine by tubular secretion.

Special patient groups

Children

In children older than 5-6 months, pharmacokinetic parameters are similar to those in adults.

Zidovudine is well absorbed from the intestine, bioavailability is 60-74% with an average of 65%. After taking zidovudine in the form of a solution for oral administration at doses of 120 mg / m and 180 mg / m² of the body surface area, the maximum equilibrium concentration was 4.45 μM (1.19 μg / ml) and 7.7 μM (2.06 μg / ml), respectively.

In children, the mean ratio of zidovudine concentration in the cerebrospinal fluid and plasma varied from 0.52 to 0.85 in terms of 0.5-4 hours after taking the drug inside.

Pharmacokinetic data suggest that zidovudine glucuronization in newborns and infants is reduced, leading to increased bioavailability. Reduced clearance and a longer half-life are recorded in newborns under 14 days, then the pharmacokinetic parameters become similar to those in adults.

Elderly patients

The pharmacokinetics of zidovudine in patients older than 65 years has not been studied.

Patients with impaired renal function

In patients with progressive impaired renal function the maximum concentration of zidovudine in the blood plasma is increased by 50% compared with that in patients with normal renal function. AUC zidovudine increases by 100%, the half-life does not change significantly. When renal dysfunction is observed, a significant cumulation of the main metabolite of 5'-glucuronide of zidovudine is observed, however, no signs of toxic effect are detected. Hemodialysis and peritoneal dialysis do not affect the excretion of zidovudine, while the excretion of 5'-glucuronide zidovudine is enhanced.

Patients with impaired hepatic function

If liver function is abnormal, zidovudine cumulation may be observed due to a reduction in glucuronization, which may require dose adjustment, but since only limited data are available, it is impossible to provide accurate recommendations.

Pregnancy

The pharmacokinetics of zidovudine has been studied in 8 women during the last trimester of pregnancy.As the gestation period increased, there were no signs of zidovudine accumulation. The pharmacokinetics of zidovudine was similar to that of non-pregnant adults. Zidovudine concentrations in blood plasma of infants at birth were similar to those in mothers plasma, which is consistent with passive zidovudine through the placenta.

Indications:

Treatment of HIV infection in combination therapy;
treatment of HIV infection in pregnant women to reduce the frequency of transplacental transmission of HIV from the mother to the fetus.

Contraindications:

Hypersensitivity to zidovudine or any other component of the drug;
neutropenia (the number of neutrophils is less than 0.75 x 10⁹/ l);
reduction in hemoglobin (less than 75 g / l or 4.65 mmol / l).

Carefully:

Patients of advanced age;
oppression of bone marrow hematopoiesis;
anemia;
severe hepatic insufficiency.

Pregnancy and lactation:

Fertility

There is no evidence of the effect of retrovir® on women's fertile function. In men, taking Retrovir® does not affect the sperm composition, morphology and motility of spermatozoa.

Pregnancy

Zidovudine penetrates the placenta.The drug Retrovir can be used earlier than 14 weeks of pregnancy only if the potential benefit to the mother exceeds the risk to the fetus. There have been reports of a slight, transient increase in serum lactate concentration, which may be due to mitochondrial dysfunction in newborns and infants exposed to NRTI for intrauterine or perinatal periods.

The clinical significance of the transient increase in serum lactate concentration is unknown. There are very rare reports of cases of developmental delay, convulsive seizures and other neurological disorders (eg, muscle tone increase). Nevertheless, the cause-and-effect relationship between these phenomena and intrauterine or perinatal exposure of NRTIs is not established. These data do not affect these recommendations for the use of APT in pregnancy to prevent vertical transmission of HIV.

Prevention of HIV transmission from mother to fetus

In the ACTG 076 study, the use of zidovudine after 14 weeks of gestation followed by administration to neonates resulted in a decrease in the vertical transmission rate of HIV (incidence of 23% in the placebo group compared to 8% in the zidovudine group).Therapy with zidovudine for oral administration began between the 14th and 34th week of pregnancy and continued until the onset of labor. During childbirth zidovudine was administered intravenously. Newborns were receiving zidovudine Inside up to 6-week-old age. Newborns unable to take the drug inside, injected zidovudine in the form of an injection. In a study of zidovudine monotherapy for oral administration in pregnant women, from the 36th week of gestation to the birth, resulted in a significant reduction in the rate of HIV transmission from the mother to the fetus (the incidence of infection was 19% in the placebo group compared to 9% in the zidovudine group). In this study, mothers did not breastfeed their infants. The long-term effects of zidovudine in children who received it in the prenatal or neonatal periods are unknown. Based on data on carcinogenicity and mutagenicity in animals, the possibility of carcinogenic effects in humans can not be completely ruled out. The significance of these data for infected and uninfected infants exposed to zidovudine is unknown. However, pregnant women who are considering zidovudine during pregnancy should consider these findings.

Breastfeeding period

Specialists do not recommend breastfeeding to HIV-infected patients to avoid HIV transmission to the child.

Because the zidovudine and HIV penetrate into breast milk, breastfeeding is contraindicated.

Dosing and Administration:

The drug Retrovir is ingested.

The appointment of Retrovir is allowed only by a specialist with experience in the treatment of HIV infection.

Adults and adolescents weighing less than less than 30 kg

The recommended dose of Retrovir in combination with other antiretroviral drugs is 300 mg twice daily. Capsules should be swallowed without chewing.

If the patient can not swallow the capsule, then it can be opened and mixed with enough drinking water or semi-solid food, the mixture should be consumed completely immediately.

Children weighing from 8 kg, but less than 14 kg

The recommended dose of Retrovir is one 100 mg capsule twice a day.

Children weighing 14 kg, but less than 21 kg

The recommended dose of Retrovir is one 100 mg capsule in the morning and two 100 mg capsules in the evening.

Children weighing 21 kg, but less than 30 kg

The recommended dose of Retrovir is two capsules of 100 mg twice a day.

Preparation Retrovir, capsules, 100 mg not applicable in children less than 3 months old or weighing less than 8 kg.

There is insufficient data to recommend the use of the drug in children weighing less than 4 kg. Children weighing from 4 to 8 kg are recommended to take the drug Retrovir in a dosage form solution for ingestion.

Elderly patients

The pharmacokinetics of zidovudine in patients over the age of 65 has not been studied. However, given the age-related decline in kidney function and possible changes in peripheral blood parameters, such patients should be especially careful when prescribing Retrovir and perform appropriate monitoring before and during treatment with Retrovir.

Patients with impaired renal function

In severe disorders of kidney function, the recommended daily dose is 300-400 mg. Depending on the response from the peripheral blood and the clinical effect, further dose adjustment may be required. Hemodialysis and peritoneal dialysis have no significant effect on the excretion of zidovudine, but accelerate the excretion of its glucuronide metabolite.

For patients in the terminal stage of renal failure who are on hemodialysis or peritoneal dialysis, the recommended dose of Retrovir is 100 mg every 6-8 hours.

Patients with impaired hepatic function

The data obtained in patients with cirrhosis of the liver indicate that in patients with hepatic insufficiency cumulation of zidovudine can occur due to a decreased glucuronization, so dose correction may be required. If monitoring of zidovudine concentrations in plasma is not possible, the physician should pay special attention to the clinical signs of drug intolerance and, if necessary, adjust the dose and / or increase the interval between dose administrations.

Correction of dose for undesirable reactions from the hematopoietic system

Adequate correction of the dosing regimen - dose reduction or withdrawal of the drug Retrovir may be required in patients with adverse reactions from the hematopoiesis system, if hemoglobin level is reduced to 75-90 g / l (4.65-5.59 mmol / l) or the number of leukocytes to 0.75-1.0 x 10⁹/ l.

Prevention of HIV transmission from mother to fetus

The efficacy of the two regimens of the Retrovir preparation, capsules:

1. Pregnant women from the 14th week of pregnancy are recommended to prescribe the drug Retrovir, capsules, at a dose of 500 mg (1 capsule 100 mg five times a day) before the onset of labor. During labor and delivery, Retrovir, an infusion solution, should be administered intravenously at a dose of 2 mg / kg body weight for an hour, followed by a prolonged intravenous infusion of 1 mg / kg / h before clamping the umbilical cord.

Further, newborns should be given Retrovir, a solution for ingestion, at a dose of 2 mg / kg of body weight every 6 hours, starting no later than 12 hours from birth and up to 6 weeks of age. For children who are unable to take oral forms, it is necessary to administer Retrovir, an infusion solution, intravenously at a dose of 1.5 mg / kg body weight for half an hour every 6 hours.

2. Pregnant women should be prescribed Retrovir, capsules, 300 mg (3 capsules 100 mg) twice a day before the onset of labor and 300 mg (3 capsules 100 mg) every 3 hours from the time of onset of labor until delivery .

Side effects:

The profile of adverse events with zidovudine is similar in adults and children.The adverse events presented below are listed according to anatomophysiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1,000 and <1/100), rarely (≥1 / 10,000 and <1/1 000), rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable phenomena

From the hematopoiesis and lymphatic system

Often: anemia (which may require blood transfusion), neutropenia and leukopenia. Anemia often occurs when taking high doses of the drug (1200-1500 mg / day) and in patients in the late stages of HIV infection, in particular at a CD4 count of less than 100 cells / μl. As a result, a dose reduction or discontinuation of therapy may be required. The incidence of neutropenia was higher in patients who had low levels of neutrophils, hemoglobin, and serum levels of vitamin B12 before treatment.

Infrequent: thrombocytopenia and pancytopenia (with bone marrow hypoplasia).

Rarely: true erythrocytic aplasia.

Very rarely: aplastic anemia.

From the side of metabolism and nutrition

Often: hyperlactatemia.

Rarely: lactic acid, anorexia. Redistribution and / or accumulation of subcutaneous fat (the development of this phenomenon depends on many factors, including the combination of antiretroviral drugs).

From the central and peripheral nervous system

Very often: headache.

Often: dizziness.

Rarely: insomnia, paresthesia, drowsiness, decreased speed of thinking, convulsions.

From the psychic sphere

Rarely: anxiety, depression.

From the side of the cardiovascular system

Rarely: cardiomyopathy.

On the part of the respiratory system, the organs of the thorax and the mediastinum

Infrequent: shortness of breath.

Rarely: cough.

From the gastrointestinal tract

Very often: nausea.

Often: vomiting, abdominal pain, diarrhea.

Infrequent: flatulence.

Rarely: pigmentation of the oral mucosa, a taste disorder, dyspepsia.

From the side of the liver, bile duct and pancreas

Often: increased levels of bilirubin and liver enzyme activity.

Rarely: liver damage, such as severe hepatomegaly with steatosis; pancreatitis.

From the skin and subcutaneous fat

Infrequent: rash, itchy skin.

Rarely: pigmentation of nails and skin, urticaria, increased sweating.

From the musculoskeletal system

Often: myalgia.

Infrequent: myopathy.

From the urinary system

Rarely: frequent urination.

From the endocrine system

Rarely: gynecomastia.

General and local reactions

Often: malaise.

Infrequently: fever, generalized pain syndrome, asthenia.

Rarely: chills, chest pain, flu-like syndrome.

Undesirable reactions arising from the use of Retrovir® to prevent the transmission of HIV from mother to fetus

Pregnant women well tolerate Retrovir® at recommended doses. Children have a decrease in hemoglobin, which, however, does not require blood transfusions. Anemia disappears 6 weeks after the completion of Retrovir® therapy.

Overdose:

Symptoms

There may be a feeling of fatigue, headache, vomiting; very rarely: changes from the blood indicators. There is one report of an overdose of an unknown amount of zidovudine, when the concentration of zidovudine in the blood exceeded 16 times the usual therapeuticconcentration, however, with no clinical, biochemical or hematological symptoms.

Treatment

Symptomatic therapy and maintenance therapy. Hemodialysis and peritoneal dialysis do not have a high efficiency for the removal of zidovudine from the body, but increase the excretion of its metabolite - 5'-glucuronide of zidovudine.

Interaction:

Zidovudine is mainly excreted as an inactive metabolite, which is a glucuronide conjugate formed in the liver. Drugs that have a similar elimination route can potentially inhibit zidovudine metabolism. Zidovudine It is used in combination APT along with other NRTIs and drugs from other groups (HIV AI, NNRTI).

The list of interactions listed below should not be considered exhaustive, but they are characteristic of drugs that require careful use with zidovudine.

Atovahon: zidovudine does not affect the pharmacokinetic parameters of the atovahona. Atovahon slows the transformation of zidovudine into a glucuronide metabolite (zidovudine AUC in the equilibrium state is increased by 33% and maximum concentrations of glucuronide are reduced by 19%).It is unlikely that the safety profile of zidovudine changes at doses of 500 or 600 mg / day when combined with atavahone for 3 weeks. If a longer combined use of these drugs is necessary, careful monitoring of the clinical condition of the patient is recommended.

Clarithromycin: reduces the absorption of zidovudine. The interval between the use of zidovudine and clarithromycin should be at least 2 hours.

Lamivudine: There is a moderate increase in zidovudine Smear by 28% with simultaneous use with lamivudine, but the total exposure (AUC) does not change. Zidovudine does not affect the pharmacokinetics of lamivudine.

Phenytoin: with the simultaneous use of Retrovir® with phenytoin, the concentration of the latter in the blood plasma decreases, and in one case an increase in the concentration of phenytoin was noted; it is necessary to monitor the concentration of phenytoin in the blood plasma when using this combination.

Probenecid: Limited data showed that probenecid reduces glucuronization and increases the mean half-life and AUC of zidovudine. Kidney excretion of glucuronide (and, possibly, zidovudine itself) decreases in the presence of probenecid.

Ribavirin: a nucleoside analogue ribavirin is an antagonist of zidovudine, and their combination should be avoided.

Rifampicin: limited data have shown that the combination of Retrovir® with rifampicin leads to a decrease in AUC for zidovudine by 48% ± 34%, but the clinical significance of this change is not known.

Stavudine: zidovudine can suppress intracellular phosphorylation of stavudine when combined. therefore stavudine it is not recommended to be used together with zidovudine.

Doxorubicin: Joint use of zidovudine and doxorubicin should be avoided, since incompatibility was demonstrated in vitro.

Valproic acid, fluconazole, methadone reduce the clearance of zidovudine, which increases its systemic exposure.

Others: acetylsalicylic acid, codeine, methadone, morphine, indomethacin, ketoprofen. naproxen, oxazepam. lorazepam, cimetidine. clofibrate, dapsone, inosine pranobex can disrupt zidovudine metabolism by competitive inhibition of glucuronization or direct suppression of microsomal metabolism in the liver. The possibility of using these drugs in combination with Retrovir®, especially with prolonged therapy, should be treated with caution.

The combination of Retrovir®, especially with emergency therapy, with potentially nephrotoxic and myelotoxic drugs (eg, pentamidine, dapsone, pyrimethamine, cotrimoxazole, amphotericin B, flucytosine, ganciclovir, interferon alpha, vincristine, vinblastine, doxorubicin) may increase the risk of developing unwanted reactions to zidovudine. It is necessary to observe the function of the kidneys and the blood formula; if necessary, reduce the dose of drugs.

Since some patients receiving zidovudine, opportunistic infections can develop, it is likely that we will have to consider the concomitant use of prophylactic antibacterial therapy. Such prophylaxis included co-trimoxazole, pentamidine in aerosol form, pyrimethamine and acyclovir. Limited data from clinical studies of zidovudine do not indicate a significantly increased risk of developing adverse reactions to zidovudine with these drugs.

Special instructions:

Patients should be informed of the risk of concomitant use of Retrovir® with other drugs,that the use of Retrovir ® does not prevent the infection of HIV by sexual transmission or through infected blood. Appropriate safety measures are required. RetroVir® does not cure HIV, and patients remain at risk for developing opportunistic infections and malignant tumors, due to immunosuppression. Although zidovudine reduces the risk of developing opportunistic infections, data on the risk of developing neoplasms, including lymphomas, against the background of the use of the drug are limited. The available data on patients who received treatment for HIV infection in advanced stages indicate that the risk of developing lymphoma corresponds to that of patients who have not received treatment. In patients with an early stage of HIV infection receiving long-term treatment, the risk of developing lymphoma is unknown.

Pregnant women considering the possibility of using zidovudine during pregnancy to prevent the transmission of HIV to their children should be informed that in some cases transmission can occur even despite treatment.

Emergency prophylaxis for possible contamination

According to international recommendations, if there is a probable contact with HIV-infected blood, for example, when a needle is pricked, it is necessary to prescribe combination therapy with zidovudine and lamivudine within 1-2 hours from the moment of infection. In the case of a high risk of infection, a drug from the HIV group of HIV should be included in the treatment regimen. Preventive treatment is recommended for 4 weeks. Data on the effectiveness of preventive treatment after accidental HIV infection have not been accumulated enough, no controlled studies have been conducted. Despite the rapid onset of treatment with antiretroviral drugs, seroconversion can not be ruled out. Undesirable reactions from the hematopoiesis system

Anemia (usually observed 6 weeks after the start of the use of Retrovir®, but sometimes it may develop earlier), neutropenia (usually occurs 4 weeks after initiation of treatment with Retrovir®, but sometimes occurs earlier), leukopenia (usually of a secondary nature due to neutropenia) may occur in patients receiving Retrovir® and having reduced bone marrow hematopoies before treatment, especially with advanced HIV infection.

During the administration of Retrovir® in patients with a developed clinical picture of HIV infection, it is necessary to monitor hematologic indices at least once every 2 weeks during the first 3 months of therapy, and then monthly. In the early stages of HIV infection (with unexhausted reserves of bone marrow hematopoiesis), undesirable reactions from the hematopoiesis system are rare. General blood tests can be performed less often, depending on the general condition of the patient (for example, 1 time in 1-3 months). If the hemoglobin content decreases to 75-90 g / l (4.65-5.59 mmol / l), or the amount of neutrophils decreases to 0.75-1.0x10⁹/ l, the daily dose of Retrovir® should be reduced to restore blood counts or Retrovir® is canceled for 2-4 weeks before recovery of blood counts. Normally, the blood picture will be normalized after 2 weeks, after which the retrovir® preparation in a reduced dose can be reassigned. Despite a reduction in the dose of Retrovir®, severe anemia may require blood transfusion.

Lactic acidosis and expressed hepatomegaly with steatosis

These complications can be fatal both with monotherapy with Retrovir® and with the use of Retrovir® as a combination therapy. The risk of these complications increases in women. Clinical signs of these complications may include gastrointestinal symptoms (nausea, vomiting and abdominal pain), general weakness, anorexia, lack of appetite, rapid unexplained weight loss, respiratory symptoms (dyspnea and tachypnea), or neurologic symptoms (including motor weakness). The use of nucleoside analogues should be discontinued if symptomatic hyperlactatemia and metabolic acidosis / lactic acidosis, progressive hepatomegaly, or a rapid increase in aminotransferase activity occur.

Caution should be exercised when prescribing Retrovir® to patients (especially women with excessive body weight), with hepatomegaly, hepatitis, or other known risk factors for liver damage and steatosis of the liver (including the use of certain medications and alcohol use).Patients with co-infection with hepatitis C and patients who are treated with interferon alfa and ribavirin may be at a particular risk group. Patients with an increased risk require special attention. RetroVir ® should be withdrawn in all cases of clinical or laboratory signs of lactic acidosis with or without hepatitis, which may include hepatomegaly with steatosis, even in the absence of an increase in transaminase activity.

Redistribution of subcutaneous fat

Redistribution and / or accumulation of subcutaneous fat, including a central type of obesity, an increase in the fat layer on the back of the neck ("buffalo buffalo"), a reduction in the subcutaneous fat layer on the face and limbs, an increase in mammary glands, an increase in serum lipids and glucose in the blood was noted both in the complex and individually in some patients who received the combined APT.

To date, all drugs from the HIV and NRTI class have been associated with one or more specific adverse events associated with a common syndrome, often called lipodystrophy.However, the data show differences in the risk of developing this syndrome between specific representatives of the therapeutic classes.

In addition, lipodystrophy syndrome has a multifactorial etiology, for example, factors such as the stage of HIV infection, old age and duration of APT, play an important, possibly synergistic role.

The long-term consequences of this phenomenon are currently unknown. Clinical examination should include a physical examination to assess the presence of redistribution of subcutaneous fat. It should be recommended to study the concentration of serum lipids and glucose in the blood. Lipid disorders should be treated according to clinical indications.

Immunodeficiency Syndrome

In HIV-infected patients with severe immunodeficiency during the onset of APT, inflammation may aggravate against an asymptomatic or residual opportunistic infection, which can lead to serious worsening or worsening of the symptoms. Typically, such reactions have been described in the first weeks or months of onset of APT.The most significant examples are cytomegalovirus retinitis, generalized and / or focal mycobacterial infection, and pneumonia caused by Pneumocystis jiroveci (R.carinii). Any symptoms of inflammation should be immediately identified and, if necessary, started treatment. Autoimmune diseases (such as Graves' disease, polymyositis and Guillain-Barre syndrome) were observed against the background of restoration of immunity, but the time of primary manifestations varied, and the disease could occur many months after the initiation of therapy and have an atypical course.

Concomitant viral hepatitis C

An increase in ribavirin-induced anemia in HIV-infected patients receiving zidovudine therapy was reported. But the exact mechanism of this phenomenon is unknown. Therefore, the combined use of ribavirin and zidovudine is not recommended. You should change the APT mode. applying a scheme that does not contain zidovudine, especially in patients with a history of zidovudine-induced anemia.

In patients infected with HIV and hepatitis C virus and receiving combined APT for HIV and interferon alfa in combination with or without ribavirin,there was a development of hepatic insufficiency (sometimes with a lethal outcome). It is necessary to ensure that patients receiving interferon alfa with or without ribavirin, and Retrovir®, in order to identify the toxic effects associated with treatment, especially the development of hepatic insufficiency, neutropenia and anemia. In such cases, discontinuation of Retrovir® should be considered. Also consider the possibility of reducing the dose or stopping the use of interferon alfa, ribavirin, or both drugs in case of increased clinical toxicity, including the development of liver failure (for example, more than 6 on the Child-Pugh scale) (see the instructions for use for interferon alfa and ribavirin) .

Myopathy and myositis

Myopathy and myositis with pathological changes characteristic of the course of HIV infection were associated with prolonged use of Retrovir®.

Joint use with zidovudine-containing drugs

Retrovir ® should not be taken with drugs containing zidovudine, as one of the components (for example, the drug Combivir (lamivudine and zidovudine) or the drug Trizivir (abacavir, lamivudine and zidovudine)).

Effect on the ability to drive transp. cf. and fur:

The effect of Retrovir® on the ability to drive a car or mechanisms has not been studied. However, an adverse effect on these abilities is unlikely, based on the pharmacokinetics of the drug. Nevertheless, when deciding whether to control a car or moving machinery, one should keep in mind the patient's condition and the possibility of developing adverse reactions (dizziness, drowsiness, blocking, convulsions).

Form release / dosage:

Capsules 100 mg.

Packaging:10 capsules in a PVC / A blisterl. For 10 blisters together with instructions for use in cardboard packs

Storage conditions:

At a temperature of no higher than 30 ° C in a dry, dark place.

Keep out of the reach of children.

Shelf life:

5 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014791 / 01

Date of registration:10.09.2008

Date of cancellation:2016-05-17

The owner of the registration certificate:VeeV Helsker United Kingdom LimitedVeeV Helsker United Kingdom Limited United Kingdom

Manufacturer: & nbsp

SmithKline Beecham, PLC United Kingdom

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp25.10.2015

Illustrated instructions

Instructions

Retrovir® (Retrovir®)