Solution for infusions from colorless to light yellow, transparent or slightly opalescent, without visible mechanical inclusions.
1 ml
zidovudine 10 mg
Auxiliary substances: water d / and up to 1 ml, sodium hydroxide qs, hydrochloric acid * - qs or sodium hydroxide * - qs
* Used if necessary to adjust the pH value from 4.0 to 7.0 solution of the drug in the process.
20 ml - bottles of dark glass (5) - packs of cardboard.
20 ml - bottles of dark glass (20) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
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 undergoes phosphorylation in both infected and intact cells with the formation of 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 the cellular? -polymerase of human DNA.
Antagonism between zidovudine and other antiretroviral drugs (abacavir, didanosine, lamivudine and interferon alfa) was not observed in vitro.
The development of resistance to thymidine analogues (zidovudine is 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. The 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 analogs, which allows further inhibitors of reverse transcriptase to be used in the treatment of HIV infection. Two kinds of mutations lead to the development of multiple drug resistance.
In one case, the mutations take place in the HIV reverse transcriptase codons 62, 75, 77, 116 and 151, in the second case it is a T69S mutation with insertion of 6 pairs of nitrogenous bases in this position, which is accompanied by the appearance of phenotypic resistance to zidovudine, as well as to other nucleoside reverse transcriptase inhibitors (NRTIs). Both these types of mutations significantly limit the therapeutic possibilities for HIV infection.
A decrease in the sensitivity to zidovudine in vitro of HIV isolates was observed with long-term treatment of HIV infection with zidovudine. The available data indicate that in the early stages of HIV infection the frequency and degree of in vitro sensitivity decrease is significantly lower than in the late stages of the disease.
At present, the relationship between sensitivity to zidovudine in vitro and the clinical effect of therapy has not been studied. In vitro sensitivity testing has not been standardized, and the results may vary depending on methodological factors.
In vitro studies of 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 preparations of other classes (HIV protease inhibitors HIV-IP HIV), non-nucleoside reverse transcriptase inhibitors (NNRTIs).
PHARMACOKINETICS
Adults
Suction
In patients who received Zidovudine infusion in a dose of 1-5 mg / kg 3-6 times / day for 1 hour, the pharmacokinetics of zidovudine was dose-dependent. The mean equilibrium maximum (C ssmax ) and minimum (C ssmin ) concentration of zidovudine in plasma in adults after infusion for 1 hour at 2.5 mg / kg every 4 hours were 4.0 and 0.4 Ојmol respectively (or 1.1 and 0.1 Ојg / ml respectively).
Distribution
According to the research, with IV administration of zidovudine, the mean terminal T 1/2 from the plasma was 1.1 hours, the average overall clearance was 27.1 ml / min / kg, and the apparent V d was 1.6 l / kg.
In adults, the average ratio of zidovudine concentration in the cerebrospinal fluid and plasma in 2-4 hours after the dose was approximately 0.5. The data show that zidovudine penetrates the placenta and is found in amniotic fluid and fetal blood. Zidovudine has also been found in semen and breast milk. Binding to plasma proteins is relatively low, is 34-38%, so it is unlikely that interaction with other drugs affecting the binding of zidovudine to plasma proteins is improbable.
Metabolism
Zidovudine is metabolized in the liver. The main metabolite is zidovudine 5'-glucuronide, which is determined in both plasma and urine and is approximately 50-80% of the administered dose of the drug that is excreted by the kidneys.
3'amino-3'-deoxythymidine is a metabolite of zidovudine, which is formed when the drug is injected intravenously.
Excretion
The renal clearance of zidovudine is much higher than QC, indicating a significant 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. After intravenous administration of zidovudine at a dose of 80 mg / m 2, 120 mg / m and 160 mg / m body surface area, the C ssmax values are 1.46 Ојg / ml, 2.26 Ојg / ml and 2.96 Ојg / ml, respectively. In children, the average ratio of the ratio of zidovudine concentration in the cerebrospinal fluid and plasma varied from 0.52 to 0.85 0.5 to 4 hours after ingestion and was 0.87 1-5 h after one hour intravenous infusion. During intravenous infusion the average ratio of drug concentration in plasma and cerebrospinal fluid in the equilibrium state is approximately 0.24. With IV introduction, the mean T 1/2 and total clearance is 1.5 h and 30.9 ml / min / kg, respectively. The main metabolite is 5'-glucuronide of zidovudine. After intravenous administration, 29% of the drug is excreted through the kidneys unchanged, 45% of the dose - in the form of glucuronide.
The renal clearance of zidovudine is much higher than QC, indicating significant tubular secretion.
Pharmacokinetic data suggest that zidovudine glucuronization in newborns and infants is reduced, leading to increased bioavailability. A decrease in clearance and a longer T 1/2 are recorded in newborns under 14 days, then the pharmacokinetic parameters become similar to those of adults.
Patients with a disorder of the function of packets
In patients with severe renal insufficiency, C max zidovudine in plasma is increased by 50% compared to that in patients without renal dysfunction. The system exposure of zidovudine (defined as AUC) is increased by 100%; T 1/2 of the drug does not change significantly. If there is a violation of kidney function, there is a significant cumulation of the main metabolite of zidovudine - 5-glucuronide, but there is no evidence of toxic effect.
Hemodialysis and peritoneal dialysis do not affect the excretion of zidovudine, while the removal of glucuronide is enhanced.
Patients with impaired hepatic function
With hepatic insufficiency, cumulation of zidovudine may be observed due to a decrease in glucuronization, which requires adjustment of the dose of the drug.
Elderly patients
The pharmacokinetics of zidovudine in patients older than 65 years has not been studied.
Pregnant women
Pharmacokinetic parameters of zidovudine in pregnant women do not change in comparison with the parameters in non-pregnant women, there are no signs of cumulation of zidovudine.
Zidovudine concentrations in the blood plasma of infants at birth were similar to plasma concentrations in mothers, consistent with passive zidovudine through the placenta.
INDICATIONS
- treatment of HIV-1 infection in combination with other antiretroviral drugs;
- prevention of HIV-1 transmission from mother to fetus.
DOSING MODE
Treatment with Zidovudine-AZT solution for infusion should be performed by a doctor who has experience in the treatment of HIV infection.
Zidovudine-AZT solution for infusions should be administered in diluted form by slow intravenous infusion for 1 hour.
The drug can not be administered in / m.
The drug Zidovudine-AZT solution for infusions should be used only until then. until patients can not take dosage forms for oral administration (capsules, tablets, oral solution).
Breeding
The preparation Zidovudine-AZT solution for infusions must be diluted before administration. The required dose of zidovudine solution is added in a 5% dextrose solution for intravenous administration so that the final concentration of zidovudine is 2 mg / ml or 4 mg / ml. The resulting solution is stirred. The solution remains chemically and physically stable for 48 hours at a temperature of 5 to 25 В° C.
Since there is no antimicrobial preservative in Zidovudine-AZT solution, the dilution should be carried out under full asepsis, immediately before administration, and the unused portion of the solution in the vial should be destroyed. If the solution is clouded before, during or after the dilution, it should be destroyed.
Adults and adolescents with a body weight of at least 30 kg
Zidovudine is given at a dose of 1 mg / kg or 2 mg / kg every 4 hours. This dose for IV administration of zidovudine provides the same AUC of the drug as when taking Zidovudine-AZT inside at a dose of 1.5 mg / kg or 3 mg / kg every 4 hours (600 or 1200 mg / day in a patient with a body weight of 70 kg).
Special patient groups
Children aged 3 months to 12 years
Information on the use of the drug Zidovudine-AZT solution for infusion of IV in children is not enough. The recommended dose range is from 80 to 160 mg / m 2every 6 hours (320-640 mg / m 2 / day). The daily dose of zidovudine, 240-320 mg / m 2 / day for 3-4 injections, is comparable to the recommended dose of 360 mg / m 2 to 480 mg / m 2 / day in 3-4 oral administration. However, at present, there is no evidence of the effectiveness of Zidovudine-AZT for intravenous administration at such low doses.
Children under 3 months
The available data do not allow us to formulate clear recommendations on the dosage regimen of the drug.
Prevention of HIV transmission from mother to fetus
The effectiveness of two dosage regimens of Zidovudine-AZT is proved:
1. Pregnant women, starting from 14 weeks, are recommended to prescribe Zidovudine-AZT in the form of capsules in a dose of 500 mg (1 capsule 100 mg 5 times / day) before the onset of labor. During labor and delivery, Zidovudine-AZT solution for infusion is administered iv at a dose of 2 mg / kg for 1 hour, followed by a continuous intravenous infusion at a dose of 1 mg / kg / h before clamping the umbilical cord.
Next, the newborn Zidovudine-AZT solution for oral administration is administered at a dose of 2 mg / kg every 6 hours, starting no later than 12 hours from birth to 6 weeks of age. For children who are unable to take oral forms, Zidovudine-AZT solution for infusion is administered iv at a dose of 1.5 mg / kg body weight for 30 minutes every 6 hours.
2. Pregnant women should be prescribed Zidovudine AZT capsules 300 mg (3 capsules 100 mg) 2 times / day before the onset of labor and 300 mg (3 capsules to 100 mg) every 3 weeks after pregnancy h from the time of onset of labor until delivery.
Patients with impaired renal function
With a severe degree of renal failure, the recommended dose of Zidovudine-AZT solution for infusions is 1 mg / kg 3-4 times / day, which corresponds to the recommended daily dose of 300-400 mg when ingested for patients of this group. 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 the glucuronide metabolite.
For patients in the terminal stage of renal failure who are on hemodialysis or peritoneal dialysis, the recommended dose of Zidovudine-AZT is 100 mg every 6-8 hours.
Patients with impaired hepatic function
Data obtained from patients with liver cirrhosis indicate that patients with hepatic insufficiency may experience cumulation of zidovudia due to reduced pukuronization, which may require dose adjustment, but the available data are limited and recommendations can not be given. If monitoring of zidovudia concentration 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 drug administration.
Correction of dose for undesirable reactions from the hematopoietic system
Adequate correction of the dosing regimen-dose reduction or zidovudia-cancellation-may be necessary in case of development of undesirable reactions from the hemopoietic system, if the hemoglobin level is reduced to 75-90 g / l (4.65-5.59 mmol / l) or the neutrophil count to 0.75-1.0 ? 10 9 / liter.
Elderly patients
The pharmacokinetics of zidovudia in patients over the age of 65 years 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 zidovudia and perform appropriate follow-up before and during treatment with zidovudine.
SIDE EFFECT
Undesirable reactions that occur with zidovudine treatment are the same in children and adults.
The frequency of undesirable adverse reactions is estimated according to the MedDRA classification: very often (> 1/10), often (> 1/100, <1/10) infrequently (> 1/1000. <1/100), rarely (> 1/10 000, <1/1000), very rarely (<1/10 000).
On the part of the blood and lymphatic system: often anemia (which may require blood transfusions), neutropenia and leukopenia developed with high doses of zidovudia (for example, 1200-1500 mg / day in clinical trials) and in patients with HIV infection in the far-gone stage (especially in patients with a reduced reserve of bone marrow before treatment), mainly with a decrease in the number of CD4-lymphocytes below 100 cells / mm 3 . In these cases, it may be necessary to reduce the dose of zidovudine or its withdrawal. The frequency of neutropenia develops in patients who experienced a decrease in the number of neutrophils, hemoglobin and vitamin B 12 in the serum at the beginning of the treatment; infrequently - thrombocytopenia and pancytopenia (with bone marrow hypoplasia); rarely erythrocyte aplasia; very rarely - aplastic anemia.
From the side of metabolism and nutrition: often - hyperlactatemia; rarely - lactic acidosis, anorexia, redistribution / accumulation of subcutaneous adipose tissue (the development of this phenomenon depends on many factors, including the combination of antiretroviral drugs).
Disorders of the psyche: rarely - anxiety, depression.
From the nervous system: very often - headache; often - dizziness; rarely - insomnia, paresthesia, drowsiness, decreased speed of thinking, convulsions.
From the heart: rarely - cardiomyopathy.
From the respiratory system, chest and mediastinum: infrequently - shortness of breath; rarely - a cough.
From the digestive tract: very often - nausea; often - vomiting, pain in the upper abdomen, diarrhea; infrequently - flatulence; rarely - pigmentation of the oral mucosa, a taste disorder, dyspepsia; pancreatitis.
On the part of the liver and biliary tract: often - an increase in the level of bilirubin and the activity of liver enzymes; rare - severe hepatomegaly with steatosis.
From the skin and subcutaneous tissues: infrequently - skin rash (except urticaria), itching; rarely - pigmentation of nails and skin, urticaria, increased sweating.
From the musculoskeletal and connective takna: often - myalgia; infrequently - myopathy.
From the side of the kidneys and urinary tract: rarely - frequent urination.
From the genitals and the breast: rarely - gynecomastia.
Other: often - malaise; infrequently - fever, generalized pain syndrome, asthenia; rarely - chills, chest pain, flu-like syndrome.
There is experience in prescribing zidovudine solution for iv administration more than 2 weeks up to 12 weeks. The most frequent undesirable effects were anemia, leukopenia, neutropenia; infrequent - local reactions. Undesirable reactions that occur when zidovudine is used to prevent the transmission of HIV from the mother to the fetus: pregnant women tolerate zidovudine well at the recommended doses. Children have a decrease in hemoglobin, which, however, does not require blood transfusions. Anemia disappears after 6 weeks, after the end of zidovudine therapy.
CONTRAINDICATIONS
- hypersensitivity to zidovudine or any other component of the drug.
- neutropenia (the number of neutrophils is less than 0.75-10 9; / l);
- reduction of hemoglobin (less than 75 g / l or 4.65 mmol / l);
- the period of breastfeeding.
Carefully
- patients of advanced age;
- with hepatic insufficiency;
- with oppression of bone marrow hematopoiesis.
PREGNANCY AND LACTATION
Pregnancy
Zidovudine penetrates the placenta. Earlier, the 14 th week of pregnancy, zidovudine can be used only if the potential benefit to the mother outweighs the risk to the fetus.
There are reports of a slight, transient increase in the concentration of lactate in the blood serum, which can be caused by mitochondrial dysfunction in neonates and infants exposed to NRTIs in utero or perinatal period. The clinical relevance of transient increase in serum lactate is unknown. There are very rare reports of cases of developmental delay, seizures and other neurological disorders, such as muscle spasticity. However, a causal relationship between these events and intrauterine or perinatal exposure NRTIs has not been established. These findings do not affect current recommendations but the use of antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Prevention of HIV transmission from mother to fetus
While the application of zidovudine after 14 weeks of pregnancy and then assign it to newborns, resulting in decreased transmission of HIV from mother to fetus frequency (frequency of infection with placebo - 23% compared to the frequency when using zidovudine - 8%). Zidovudine therapy for oral administration began during the period between the 14th and 34th week of pregnancy and continued until the onset of labor. During labor, ZDV was administered in / in. Newborns received zidovudine inwardly to 6 weeks of age. Newborns are not capable of taking medication by mouth, AZT was administered by injection.
The long-term consequences of the use of zidovudine in children who received it during the prenatal or neonatal period are unknown. You can not completely exclude the possibility of carcinogenic influence. Pregnant women should be informed about it.
Breastfeeding period
In order to avoid transmission of HIV baby breastfeeding HIV-infected patients is not recommended. Because zidovudine and HIV into breast milk, breastfeeding is contraindicated.
Fertility
No data on the effect of AZT on the reproductive function of women. In men zidovudine has no effect on the composition of the sperm morphology and motility.
APPLICATION FOR FUNCTIONS OF THE LIVER
In severe renal insufficiency recommended dose AZT Zidovudine-infusion solution is 1 mg / kg, 3-4 times / day, which corresponds to the recommended daily dose of 300-400 mg when administered to patients in this group. Depending on the response from the peripheral blood and clinical effect may require a further dose adjustments.
For patients in end stage renal disease who are na hemodialysis or peritoneal dialysis, the recommended dose of the drug Zidovudine, AZT is 100 mg every 6-8 hours.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Precautions apply to patients with liver failure.
APPLICATION FOR CHILDREN
Children under the age of 3 months
available data do not allow us to formulate clear recommendations on the dosage regimen of the drug.
Children aged 3 months to 12 years of
information about the use of the drug zidovudine, AZT solution for infusion / in children is not enough. The recommended dosage range is from 80 to 160 mg / m 2every 6 hours (320-640 mg / m 2 / day). The daily dose of zidovudine constituting 240-320 mg / m 2 / day for 3-4 administration is comparable to the recommended dose for use of 360 mg / m 2 to 480 mg / m 2 / day in 3-4 ingestion. Currently, however, no data on the efficacy of the drug AZT Zidovudine-for / in the introduction in such low doses.
APPLICATION IN ELDERLY PATIENTS
Be wary of drug elderly patients.
SPECIAL INSTRUCTIONS
Patients should be informed about the danger of simultaneous use of zidovudine with other drugs, and that the use of zidovudine did not prevent HIV infection through sexual contact or through infected blood. Appropriate security measures.
Zidovudine is not a cure for HIV infection and patients remain at risk of opportunistic infections and malignancies, which is associated with immunosuppression. Although zidovudine reduces the risk of opportunistic infections, data on the risk of tumor progression, including lymphomas during treatment with the drug is limited. Available data on patients treated for HIV infection in the later stages, suggest that the risk of developing lymphoma corresponds to that in patients not receiving treatment. In patients with early-stage HIV infection who are receiving long-term treatment, the risk of development of lymphoma is unknown.
Pregnant women who are considering the use of zidovudine during pregnancy to prevent HIV transmission to their children, should be informed that in some cases, transmission may occur despite treatment. Avoid the simultaneous use of zidovudine and ribavirin with doksorubitsnnom. Simultaneous treatment with stavudine is not recommended.
Emergency prevention probable infection with
According to international guidelines, when the probability of contact with HIV infected material (blood, other fluids) is an urgent need, within 1-2 h after infection, assign a combination therapy with zidovudine and lamivudine. In the case of a high risk of exposure to the treatment regimen must be enabled preparation of the HIV group SP. Prophylactic treatment is recommended for 4 weeks. Data on the effectiveness of preventive treatment after accidental HIV infection does not get controlled studies have been conducted.
Despite the rapid initiation of treatment with antiretroviral drugs can not exclude the development of seroconversion.
Adverse reactions from the hematopoietic system
Anemia (usually occurs within 6 weeks from the start of the use of zidovudine, but sometimes it can develop earlier), neytropepiya (usually occurs after 4 weeks means the treatment of zidovudine, but sometimes occurs earlier), leucopenia (usually secondary character due neytropsnii) may occur in the Nazis with extensive clinical HIV infection receiving zidovudine, particularly at high doses (1200-1500 mg / day), and having reduced hematopoiesis bone marrow before treatment, especially at the late stage of HIV infection.
At the time of zidovudine in patients with full-blown HIV haematological parameters necessary to control the NA at least 1 time per week for the first 3 months of treatment and then monthly. In the early stages of AIDS (when bone marrow hemopoiesis still within normal limits) adverse reactions on the part of the blood are rare, so blood tests are performed less frequently, depending on the general state of the patient, 1 every 1-3 months.
If the hemoglobin content is reduced to 75-90 g / L (4.65-5.59 mmol / l). neutrophil count drops to 0.75-1.0-10% daily zidovudine dose should be reduced to restore blood counts or zidovudine should be discontinued for 2-4 weeks prior to recovery of blood parameters. Generally, the blood picture normalized after 2 weeks, after which zidovudine reduced dose may be reappointed. Data I / zidovudine for periods exceeding 2 weeks, limited.
Despite the reduction in the dose of zidovudine, blood transfusion may be required in severe anemia.
Lactic acidosis and severe hepatomegaly with steatosis
These complications can be fatal as in the AZT monotherapy and during use of zidovudine in combination therapy. The risk of developing these complications increases in women.
Clinical signs of these complications may be symptoms of gastrointestinal (nausea, vomiting and abdominal pain), weakness, anorexia, loss of appetite, rapid unexplained weight loss, respiratory symptoms (dyspnea and tachypnea) or neurological symptoms (including motor weakness).
The use of nucleoside analogues should be discontinued in case of appearance of symptomatic hyperlactatemia and metabolic acidosis / lactic acidosis, progressive hepatomegaly, or with the rapid increase of aminotransferases.
Care must be taken when assigning zidovudine patients (especially women with excessive body weight) with hepatomegaly, hepatitis or other known risk factors for liver injury and hepatic steatosis (including the use of certain drugs and alcohol use). Patients coinfected with hepatitis C patients who receive treatment with interferon alpha and ribavirin, may constitute a special risk group. Patients with an increased risk require special attention. Zidovudine should cancel in all cases the appearance of clinical or laboratory signs of lactic acidosis with or without hepatitis, which may include hepatomegaly with steatosis even in the absence of increasing transaminase activity.
Redistribution of subcutaneous fat
Redistribution and / or accumulation of subcutaneous fat, including central type obesity, increased fat layer on the back of the neck ( "buffalo hump"), reducing the subcutaneous fat layer on the face and limbs, breast enlargement, elevated serum lipids, and blood glucose was noted as a package, or separately in some patients receiving combination APT. To date, all of the classes of drugs SP HIV nucleoside analogs and associated with one or more specific adverse events associated with a common syndrome is often called lipodystrophy. However, the data indicate the existence of differences in the risk of developing this syndrome among specific members of therapeutic classes.
In addition, the lipodystrophy syndrome has a multifactorial etiology, for example, such factors as the stage of HIV infection, older age and duration of antiretroviral therapy, play an important, possibly synergistic role. Long-term consequences of this phenomenon are currently unknown. Clinical examination should include physical examination to assess the presence pereraenredeleniya subcutaneous fat. It should be encouraged to study concentrations of serum lipids and blood glucose. Lipid disorders should be treated in accordance with clinical indications.
Immune reconstitution syndrome
In HIV-infected patients with severe immune deficiency at the time of the beginning of the APT may increase inflammation in the background asymptomatic or residual opportunistic infections that can cause serious deterioration or worsening of symptoms. Typically, such reactions have been described in the first months or APT pedal action starts.
The most significant examples - cytomegalovirus retinitis, generalized and / or focal mycobacterial infection and pneumonia caused by Pneumocystis jirovecii (P. carinii). Any inflammatory symptoms should be immediately identified and begin treatment if necessary.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barrs syndrome) were observed pas background of immune reconstitution, but the time of the primary manifestations varied, and the disease may occur many months after initiation of therapy and have an atypical course.
Co-infection with HIV and hepatitis C
have been reported to increase of ribavirin-induced anemia in HIV-infected patients, but the exact mechanism is unknown receiving concomitant therapy with zidovudine. Therefore it is not recommended to combine the use of ribavirin and zidovudine. APT should change mode, applying circuit, not containing zidovudine, particularly in patients with AZT-induced anemia in history.
In patients infected with HIV and hepatitis C and treated with combination APT for HIV and interferon alfa with or without ribavirin, has observed the development of hepatic failure (sometimes fatal). It is necessary to provide monitoring of the patients receiving interferon alpha with ribavirin or without drug and AZT Zidovudine, in order to identify the toxic effect associated with the treatment, especially the development of hepatic insufficiency, neutropenia, and anemia. In such cases, you should consider discontinuing use of the drug zidovudine, AZT. It should also consider a dose reduction or discontinuation of interferon alpha, ribavirin, or both drugs in the event the clinical toxicity, including hepatic failure (e.g., more than 6 points according to Child-Pugh).
Myopathy and myositis
Myopathy and myositis with pathological changes characteristic of HIV infection have been associated with prolonged use of zidovudine.
Combined use with zidovudine containing drugs and
drug Zidovudine, AZT should not be taken together with preparations containing AZT as one of the components (e.g. lamivudine + zidovudine or abacavir + lamivudine + zidovudine).
Allergy to latex
rubber stopper of the vial containing the drug Zidovudine, AZT solution for intravenous infusion may contain dry natural rubber latex which may cause allergic reactions in patients sensitive to latex.
Impact on the ability to drive vehicles and mechanisms
Effect of AZT on ability to drive and use machinery has not been studied. However, an adverse effect on these abilities is unlikely, based on the pharmacokinetics of the drug. However, when deciding on the possibility of driving vehicles and mechanisms should take into account the patient's condition and the possibility of adverse reactions (dizziness, drowsiness, lethargy, convulsions) with zidovudine.
OVERDOSE
Symptoms
There may be fatigue, headache, vomiting; very rarely - changes in the blood parameters. There is one report of an overdose of an unknown quantity of zidovudine, AZT when the concentration in the blood up to 16 times higher than the usual therapeutic concentrations. However, the clinical, biochemical or hematological symptoms while absent.
When used in clinical trials maximal doses (7.5 mg / kg body weight by infusion every 4 hours for 2 weeks) in 1 out of 5 patients showed anxiety, in the remaining 4 patients did not develop any undesirable reactions.
Treatment
Symptomatic therapy. Hemodialysis and peritoneal dialysis are not highly efficient for the removal of AZT from the body, but it increases the excretion of the metabolite glucuronide.
DRUG INTERACTION
Zidovudine mainly excreted as inactive metabolite constituting the glucuronide conjugate, produced in the liver. Preparations having similar clearance path can potentially inhibit the metabolism of AZT.
Zidovudine is used in combination therapy with other drugs and other nucleoside analogs groups (SP HIV NNRTIs).
The list of interactions listed below should not be deemed
