Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
АТХ:J.05.A.F.01 Zidovudine
Pharmacodynamics:HIV is an RNA-containing virus, so for the life cycle it needs to transcribe viral RNA into DNA using reverse transcriptase. Zidovudine in the cell is phosphorylated into the active 5'-triphosphate metabolite, zidovudine triphosphate, which due to structural similarity is built into the synthesized DNA chain, disrupts the addition of new nucleotides and stops its further synthesis.
Zidovudine has a 100-fold less inhibitory effect on the DNA polymerase of human cells.
Resistance to zidovudine is due to the appearance in the reverse transcriptase of the ability to discriminate the active metabolite of zidovudine from natural nucleotides.
Side effects of zidovudine are due to its interaction with gamma gamma roller polymerase, which leads to a disruption of the mitosis of the mitochondrial DNA.
Pharmacokinetics:Pharmacokinetics
When administered zadovudin quickly absorbed, the peak concentration in the plasma is noted after 0.5-1.5 hours. Bioavailability at ingestion is 64% and does not depend on food intake. The value of AUC does not depend on the dosage form (tablets, syrup, capsules). Apparent volume of distribution reaches 1.6 l / kg. About 38% of zidovudine binds to blood proteins. The ratio of CSF / plasma reaches 0.6. More than 60% of zidovudine is glucuronized.Systemic clearance is 1.6 l / h / kg, renal - 0.34 l / h / kg. The half-elimation period (T1 / 2) is within 0.5-3 hours.
Indications:Treatment of HIV infection caused by HIV-1 (as part of highly active antiretroviral therapy; HAART), in adults and children weighing more than 30 kg;
Prevention of transplacental HIV infection of the fetus (during pregnancy, in childbirth, in newborns born from HIV-infected mothers).
I.B20-B24 Disease caused by the human immunodeficiency virus [HIV]
Contraindications:Life-threatening allergic reactions (anaphylaxis, Stephen-Jones syndrome) on zidovudine or any components of dosage forms.
Carefully:Assigned with caution to patients with oppression of the braincase (number of granulocytes <1000 cells / mm3 or hemoglobin <9.5 g / dL), myopathy or myositis, lactic acidosis, severe hepatomegaly with steatosis, marked violation of liver function. Risk factors include obesity and long-term use of drugs for HIV treatment.
Pregnancy and lactation:FDA Action Category - C
It is not recommended to appoint women until 14 weeks of pregnancy.If you need to use the drug before the 14th week of pregnancy, you should carefully correlate the intended benefit to the mother and the potential risk to the fetus.
Dosing and Administration:To treat HIV infection caused by HIV-1, adult patients are recommended oral administration at a dose of 600 mg / day, for 2-3 doses as part of combined anti-HIV therapy. Children zidovudina dose can be calculated depending on the weight or body surface. The recommended dose of zidovudine 480 mg / m2 / day is divided into 2-3 doses.
For the prevention of transplacental transmission of HIV: 100 mg 5 times a day before the onset of labor. During the delivery, intravenous administration of zidovudine is given at a dose of 2 mg / kg for 1 hour, then 1 mg / kg / hour until the umbilical cord intersects. Newborn zidovudine administered 12 hours after birth to 6 weeks at a dose of 8 mg / kg / day orally or 6 mg / kg day intravenously.
Side effects:From the cardiovascular system: cardiomyopathy
From the nervous system: headache, dizziness, paresthesia, insomnia, drowsiness, weakness, lethargy, decreased mental performance, tremor, convulsions, anxiety, depression, confusion.
From the sense organs: macular edema, amblyopia, photophobia, vertigo, hearing loss.
From the hemopoietic system: bone marrow depression, anemia, neutropenia, leukopenia, lymphadenopathy, thrombocytopenia, pancytopenia with bone marrow hypoplasia, aplastic or hemolytic anemia.
From the gastrointestinal tract: nausea, vomiting, dyspepsia, dysphagia, anorexia, taste distortion, abdominal pain, diarrhea, flatulence, bloating, pigmentation or ulceration of the oral mucosa, hepatitis, hepatomegaly with steatosis, jaundice, hyperbilirubinemia, increased activity of hepatic enzymes , pancreatitis.
From the respiratory system: shortness of breath, cough, rhinitis, sinusitis.
From the urinary system: rapid or difficult urination, hypercreatininaemia.
From the endocrine system and metabolism: lactate acidosis, gynecomastia.
From the musculoskeletal system: myalgia, myopathy, muscle spasm, myositis, rhabdomyolysis, increased activity of CK, LDH.
On the part of the skin: pigmentation of nails and skin, increased sweating, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Allergic reactions: skin rash, itching, hives, angioedema, vasculitis, anaphylactic reactions.
Zidovudine can cause redistribution of adipose tissue, in particular, "central" obesity.
Other: malaise, back and chest pain, fever, flu-like syndrome, pain syndrome of different localization, chills, increased serum amylase activity, development of secondary infection, redistribution of adipose tissue.
Overdose:Overdose
Specific symptoms of overdose are absent, note the typical for zidovudine adverse reactions: weakness, headache, vomiting, hematologic disorders. Hemodialysis and peritoneal dialysis slightly affect the excretion of zidovudine, but increase the excretion of the metabolite of zidovudine glukuronata.
Interaction:Paracetamol increases the incidence of neutropenia due to inhibition of zidovudine metabolism (both drugs are glucuronized).
Inhibitors of microsomal liver enzymes (incl. acetylsalicylic acid, morphine, codeine, indomethacin, valproic acid, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, inosine pranobex) increase the concentration of zidovudine in plasma, since zidovudine is a substrate of microsomal liver enzymes.
Drugs that are nephrotoxic and myelosuppressive (dapsone, pentamidine, pyrimethamine, amphotericin B, flucytosine, ganciclovir, vincristine, vinblastine, interferon alfa, doxorubicin, cotrimoxazole), increase the risk of toxic effects of zidovudine.
Probenicid and other tubular secretion inhibitors extend T1 / 2 zidovudine.
When combined with phenytoin, it is possible to change the concentration of the latter in the blood.
Zidovudine increases the concentration of fluconazole in plasma.
There is synergy with other drugs used to treat HIV infection (especially lamivudine), with respect to HIV replication in cell culture. Stavudine reduces the effectiveness of zidovudine in vitro, so their simultaneous use is not recommended.
Rifampicin reduces the concentration of zidovudine in the plasma, which can lead to a decrease in the effectiveness of the latter (not recommended at the same time).
Absorption of zidovudine decreases with simultaneous administration with clarithromycin; in this regard, it is recommended to take these drugs with an interval of 2 hours.
Radiation therapy enhances the myelosuppressive effect of zidovudine.
Nucleoside analogues that disrupt DNA replication, such as ribavirin, can in vitro reduce the antiviral activity of zidovudine. Simultaneous use of such drugs with zidovudine is not recommended.
Simultaneous use of zidovudine and doxorubicin is not recommended due to mutual weakening of activity of each of the drugs in vitro.
Simultaneous application with ganciclovir, interferon alfa, ribavirin, other drugs that inhibit bone marrow hematopoiesis, incl. cytostatic agents may increase the hematotoxicity of zidovudine.
Special instructions:During treatment it is necessary to carry out a systematic control of the picture of peripheral blood: 1 every 2 weeks for the first 3 months of therapy, then - once a month.
Hematologic changes usually appear 4-6 weeks after the start of therapy (anemia and neutropenia develop more frequently against a background of high doses of zidovudine (1.2-1.5 g / day) in patients with a decrease in CD4 + cells, with HIV infection (with a reduced reserve of bone brain before the start of therapy), a deficiency of cyanocobalamin.With a decrease in hemoglobin by more than 25% or a decrease in the number of neutrophils by more than 50% compared to the baseline, a blood test is performed more often. Lactate acidosis and severe hepatomegaly with steatosis can be fatal, so when clinical or laboratory signs of these conditions appear zidovudine should be canceled. Risk factors for lactatacidosis are gender (female sex), obesity, long-term use of antiviral agents that are nucleoside analogues.
Antiretroviral therapy does not prevent the transmission of HIV through sexual contact and through infected blood.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment, patients should avoid driving motor vehicles and other activities that require a high concentration of attention and speed of psychomotor reactions.