Composition, form of production and packaging
The tablets covered with a cover 1 tab.
zidovudine 300 mg
10 pieces. - packings cellular planimetric (10) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
Synthetic analogue of nucleosides. Inside the cell, zidovudine is phosphorylated to the active metabolite, zidovudine-5-triphosphate. Zidovudine triphosphate inhibits reverse transcriptase of HIV by interrupting the synthesis of the virus DNA after incorporation into the nucleotide chain. Zidovudine triphosphate weakly inhibits cellular DNA polymerase alpha and gamma.
In combination with other antiviral HIV agents increases the number of CD4 cells.
PHARMACOKINETICS
Pharmacokinetics for oral administration is dose-independent in the dose range from 2 mg / kg every 8 hours to 10 mg / kg every 4 hours.
Absorption is fast, food intake does not affect the pharmacokinetics of zidovudine. Bioavailability of 54-74%. Time to reach C max in plasma is 0.5-1.5 h. Apparent V dis 1-2.2 l / kg. The binding to plasma proteins is less than 38%.
Metabolised in the liver. The main metabolite is zidovudine glucuronide, whose AUC is 3 times greater than that of zidovudine. After ingestion, 14% of zidovudine and 74% of its metabolite are found in the urine. After intravenous administration, 3'-amino-3'-deoxythymidine was also detected in the blood, the AUC of which is 5 times smaller than that of zidovudine. Systemic clearance - 1-2 l / h / kg, renal clearance - 0.3-0.4 l / h / kg. The ratio of zidovudine concentration in the cerebrospinal fluid and plasma is 0.62 / 1 (0.05-2.6 / 1).
In individuals with chronic renal insufficiency (creatinine clearance (CC) 16-18 ml / min) AUC 2800-3400 ng? h / ml, T 1/2 - 1.4 hours. With hepatic insufficiency, the zidovudine clearance decreases. T 1/2 - 0.5-Hr.
Pharmacokinetics in children up to 3 months: T 1/2 - about 13 hours, bioavailability in newborns is less than 14 days longer, and clearance and T 1/2 are slower than in children older than 14 days.
Pharmacokinetics in children from 3 months. up to 12 years: the basic pharmacokinetic parameters coincide with those in adults. The main way of metabolism is the conversion into zidovudine glucuronide. After intravenous administration, 29% is excreted by the kidneys unchanged, 45% - in the form of zidovudine glucuronide.
INDICATIONS
- Treatment of HIV infection caused by HIV-1 (as part of combination antiretroviral therapy), 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).
DOSING MODE
Inside, not liquid, with a sufficient amount of liquid, regardless of food intake.
Adults and children weighing more than 30 kg: 600 mg / day in 2 divided doses in combination with other antiretroviral drugs. When the hemoglobin content is reduced by 25% from the initial, the number of neutrophils by 50% of the initial daily dose is reduced by 2 times or temporarily canceled. After recovery of the parameters, the dose can be increased again to the original daily values.
Treatment is stopped if the hemoglobin content is less than 75 g / L or the neutrophil count is below 0.75 Г— 10 9 / L.
Prevention of transplacental transmission of HIV: 300 mg 2 times / day, from 36 weeks of pregnancy until the beginning of labor, then 300 mg every 3 hours until the separation of the child from the mother (crossing the umbilical cord).
With liver failure, there may be a need for correction of the dosing regimen, but existing data are insufficient to develop recommendations for dosing. If control of zidovudine concentration in plasma is not possible, it is recommended to pay attention to signs of drug intolerance and, if necessary, to increase the interval between doses.
With QC more than 10 ml / min, correction of dosing regimens is not required. With severe renal dysfunction (CC less than 10 ml / min), the recommended dose of zidovudine is 300 mg 1 time / day.
There are no specific recommendations for changing the dosing regimen in elderly patients ; should take into account the age-related decline in kidney function and changes in peripheral blood.
SIDE EFFECT
On the part of the hemopoietic system: myelosuppression, anemia, neutropenia, leukopenia, lymphadenopathy, thrombocytopenia, pancytopenia with bone marrow hypoplasia, aplastic or hemolytic anemia.
From the digestive system: 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 hepatic activity enzymes, pancreatitis.
On the part of the nervous system: headache, dizziness, paresthesia, insomnia, drowsiness, weakness, lethargy, decreased mental performance, tremors, convulsions, anxiety, depression, confusion, mania.
From the sense organs: macular edema, amblyopia, photophobia, vertigo, hearing loss.
From the respiratory system: shortness of breath, cough, rhinitis, sinusitis.
From the cardiovascular system: cardiomyopathy, fainting.
From the urinary system: rapid or difficult urination, hypercreatininaemia.
On the part of the endocrine system and metabolism: lactic 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.
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.
CONTRAINDICATIONS
- neutropenia / leukopenia (the number of neutrophils is less than 0.75 Г— 10 9 / l or 750 / Ојl);
- anemia (hemoglobin below 75 g / l or 4.65 mmol / l);
- simultaneous reception with stavudine, doxorubicin and other drugs that reduce antiviral activity;
- Children weighing less than 30 kg.
With caution: oppression of bone marrow hematopoiesis, deficiency of cyanocobalamin or folic acid, hepatic insufficiency, advanced age, obesity, hepatomegaly, hepatitis or any risk factors for liver disease, neutropenia / leukopenia (neutrophil count 0.75-1 Г— 10 9 / l or 750-1000 / Ојl); Anemia (hemoglobin 75-90 g / l).
PREGNANCY AND LACTATION
Zidovudine penetrates the placenta. 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. Women, regardless of HIV infection, are not allowed to breast-feed due to the threat of infection of the child.
APPLICATION FOR FUNCTIONS OF THE LIVER
With QC more than 10 ml / min, correction of dosing regimens is not required. With severe renal dysfunction (CC less than 10 ml / min), the recommended dose of zidovudine is 300 mg 1 time / day.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: hepatic insufficiency, hepatomegaly, hepatitis, or any risk factors for liver disease.
With liver failure, there may be a need for correction of the dosing regimen, but existing data are insufficient to develop recommendations for dosing. If control of zidovudine concentration in plasma is not possible, it is recommended to pay attention to signs of drug intolerance and, if necessary, to increase the interval between doses.
APPLICATION FOR CHILDREN
Contraindicated in children weighing less than 30 kg.
Children weighing more than 30 kg: 600 mg / day in 2 divided doses in combination with other antiretroviral drugs. When the hemoglobin content is reduced by 25% from the initial, the number of neutrophils by 50% of the initial daily dose is reduced by 2 times or temporarily canceled. After recovery of the parameters, the dose can be increased again to the original daily values.
Treatment is stopped if the hemoglobin content is less than 75 g / L or the neutrophil count is below 0.75 Г— 10 9 / L.
Prevention of transplacental transmission of HIV: 300 mg 2 times / day, from 36 weeks of pregnancy until the beginning of labor, then 300 mg every 3 hours until the separation of the child from the mother (crossing the umbilical cord).
APPLICATION IN ELDERLY PATIENTS
With caution in old age.
There are no specific recommendations for changing the dosing regimen in elderly patients ; should take into account the age-related decline in kidney function and changes in peripheral blood.
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 initiation 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 bone marrow before the start of therapy), cyanocobalamin deficiency, with a decrease in hemoglobin by more than 25% or a decrease in the number of neutrophils by more than 50% compared to the initial value, a blood test is performed more often. therefore, when clinical or laboratory signs of these conditions appear, zidovudine should be discarded Risk factors for lactic acidosis include female sex, obesity, long-term use of antiviral agents that are nucleoside analogues. pain, anorexia, diarrhea, myalgia, anemia, thrombocytopenia can be a manifestation of HIV infection itself and secondary diseases associated with it, rather than the toxic effect of zidovudine.
Zidovudine should not be prescribed with other drugs containing zidovudine. In patients taking zidovudine in combination antiviral therapy, there may be a reactive immunity syndrome, which may require medical intervention. Zidovudine can cause redistribution / accumulation of fatty tissue, in particular, central obesity, the accumulation of fat in the dorso-cervical region ("buffalo" hump), thinning of fat in the limbs or face, breast augmentation, "Cushingoid" face.
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.
OVERDOSE
Symptoms: increased manifestations of dose-dependent side effects.
Treatment: gastric lavage, activated angle, symptomatic therapy. Hemodialysis and peritoneal dialysis are ineffective in eliminating zidovudine, but accelerate the elimination of the glucuronic metabolite.
DRUG INTERACTION
Paracetamol increases the incidence of neutropenia due to inhibition of zidovudine metabolism (both drugs are glucuronized).
Inhibitors of microsomal liver enzymes (including acetylsalicylic acid, morphine, codeine, indomethacin, valproic acid, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, inosine pranobex) increase the concentration of zidovudine in plasma.
Drugs that have a nephrotoxic and myelosuppressive effect (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 prolong T 1/2 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 synergistic effect with other drugs used against HIV (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 violate 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.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store the drug in a dry, dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2 years. Do not use after expiry date.
