Zidovudine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Zidovudine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Zidovudine

ATX code: J05AF01

Active ingredient: Zidovudine (Zidovudine)

Manufacturer: Aurobindo Pharma (India); Obolensk pharmaceutical company (Russia)

Description and photo update: 2018-11-05

Zidovudine is a drug used in the complex treatment of HIV infection.

Release form and composition

film-coated tablets: biconvex, round, almost white, engraved "D" on one side, "11" on the other (in plastic bottles of 50, 60, 100 pcs., in a cardboard box 1 bottle; in blisters 10 pcs., 10 packs in a cardboard box);
capsules: white, size # 1; the capsules contain an almost white or white powder (in blister packs of 10 pcs., in a cardboard bundle of 1, 3, 5 or 10 packs; in blister packs of 25 pcs., in a carton pack of 4 packs).

Composition of 1 tablet:

active substance: zidovudine - 300 mg;
auxiliary components: magnesium stearate - 1.05 mg; microcrystalline cellulose - 24.95 mg; sodium carboxymethyl starch - 16 mg; hypromellose - 8 mg;
shell: Opadry white (macrogol - 400 - 0.93 mg; hypromellose - 9.36 mg; titanium dioxide - 4.71 mg) - 15 mg.

Composition of 1 capsule:

active substance: zidovudine - 100 mg;
auxiliary components: magnesium stearate - 1.2 mg; microcrystalline cellulose - 34.5 mg; sodium carboxymethyl starch - 11.5 mg; corn starch - 82.8 mg;
capsule: titanium dioxide, gelatin.

Pharmacological properties

Pharmacodynamics

Zidovudine is a synthetic nucleoside analog. Inside the cell, it is phosphorylated to an active metabolite, zidovudine-5-triphosphate. Zidovudine triphosphate inhibits HIV reverse transcriptase, which occurs due to the interruption of viral DNA synthesis after inclusion in the nucleotide chain. Inhibits cellular DNA polymerases gamma and alpha slightly.

When combined with other antiviral HIV drugs, an increase in the number of CD4 cells is observed.

Pharmacokinetics

The pharmacokinetics of Zidovudine when taken orally in the dose range from 2 mg / kg every 8 hours to 10 mg / kg every 4 hours is dose-independent.

Possesses fast absorption. Food intake does not affect the pharmacokinetics of the substance. Bioavailability is 54–74%. Apparent V _d - 1–2.2 l / kg. The time required to reach C _max in plasma is from 0.5 to 1.5 hours. Plasma protein binding <38%.

Metabolized in the liver. The main metabolite is zidovudine glucuronide, the AUC of which is 3 times higher than that of zidovudine. In the urine after ingestion, there is a substance and its metabolite (14/74%, respectively). Systemic clearance varies within 1–2 l / h / kg, renal clearance - from 0.3 to 0.4 l / h / kg. The ratio of the concentration of zidovudine in plasma and cerebrospinal fluid is 1 / 0.62.

In chronic renal failure (with creatinine clearance - 16-18 ml / min) AUC 2800-3400 ng × h / ml, T _1/2 (half-life) is 1.4 hours. Zidovudine clearance in hepatic insufficiency decreases. T _1/2 - from 0.5 to 3 hours.

Indications for use

treatment of HIV infection caused by HIV-1 (in combination with other antiretroviral drugs);
prevention of transplacental HIV infection of the fetus (during pregnancy, in childbirth, in newborns born to HIV-infected mothers).

Contraindications

Absolute:

neutropenia / leukopenia (neutrophil count <0.75 × 10 ⁹ / L or 750 / μL);
anemia (hemoglobin <75 g / l or 4.65 mmol / l);
combined use with doxorubicin, stavudine and other drugs that reduce antiviral activity;
children under 3 years of age (capsules) or weighing <30 kg (tablets);
lactation period;
individual intolerance to the components of the drug.

Relative (diseases / conditions in the presence of which caution is required):

oppression of bone marrow hematopoiesis;
anemia (hemoglobin in the range of 75–90 g / l);
deficiency of folic acid or cyanocobalamin;
hepatitis or other risk factors for liver disease;
liver failure;
hepatomegaly;
obesity;
neutropenia / leukopenia (the number of neutrophils 0.75-1 × 10 ⁹ / l or 750-1000 / μl);
1-14 weeks of pregnancy;
elderly age.

Instructions for the use of Zidovudine: method and dosage

The drug is taken orally, with a sufficient amount of liquid, regardless of food intake. Do not chew the tablets.

Recommended dosing regimen (in combination with other antiretroviral drugs):

tablets: children weighing over 30 kg and adults: 600 mg per day in 2 divided doses;
capsules: children 3-12 years old - 360-480 mg / m ² per day, divided into 3-4 doses; children from 12 years old and adults - 500 or 600 mg per day, divided into 2-3 doses; the course of treatment is carried out for a long time (practically unlimited); breaks of up to 1 month are allowed.

With a decrease in the hemoglobin content by 25% of the initial indicator, the number of neutrophils - by 50%, the daily dose should be reduced by 2 times, or the drug is temporarily canceled; resumption of therapy / initial dose is possible after restoration of indicators. If the hemoglobin content is <75 g / l or the number of neutrophils is <0.75 × 10 ⁹ / l, therapy is stopped.

Prevention of transplacental transmission of HIV in women preserving pregnancy:

tablets: 2 times a day, 300 mg, starting from the 36th week of pregnancy and before the onset of labor, then every 3 hours, 300 mg until the umbilical cord is crossed;
capsules: 5 times a day, 100 mg, starting from the 14th week of pregnancy and before childbirth.

In patients with hepatic impairment, dosing regimen adjustment may be required, but existing information is insufficient to develop dosage recommendations. If it is impossible to monitor the plasma concentration of Zidovudine, it is recommended to pay attention to signs of drug intolerance. If necessary, the interval between doses should be increased.

The recommended dose of Zidovudine in patients with severe functional impairment of the kidneys (with creatinine clearance <10 ml / min) is 300 mg once a day.

Side effects

Possible adverse reactions (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

nervous system: very often - headache; often - dizziness; rarely - convulsions, drowsiness, paresthesia, insomnia, decreased thinking speed;
respiratory system: sometimes - shortness of breath; rarely - cough;
cardiovascular system: rarely - cardiomyopathy;
hematopoietic system: often - anemia, leukopenia and neutropenia (the incidence of neutropenia increases in patients who have had a decrease in the number of neutrophils, serum vitamin B ₁₂ and hemoglobin at the beginning of therapy); sometimes - pancytopenia and thrombocytopenia; rarely - erythrocyte aplasia; very rarely - aplastic anemia;
urinary system: rarely - frequent urination;
musculoskeletal system: often - myalgia; sometimes myopathy;
endocrine system: rarely - gynecomastia;
digestive system: very often - nausea; often - pain in the upper abdomen, diarrhea, vomiting; sometimes flatulence; rarely - taste disturbance, pigmentation of the oral mucosa, dyspepsia;
skin and its appendages: sometimes - itchy skin, skin rash (excluding urticaria); rarely - urticaria, skin / nail pigmentation, increased sweating;
liver and pancreas: often - an increase in the activity of liver enzymes and the level of bilirubin; rarely - severe hepatomegaly with steatosis, pancreatitis;
metabolism: often - hyperlactatemia; rarely - anorexia, lactic acidosis; accumulation / redistribution of subcutaneous adipose tissue (the appearance of the disorder depends on various factors, including the combination of antiretroviral drugs);
psyche: rarely - depression, anxiety;
others: often - malaise; sometimes asthenia, generalized pain syndrome, fever; rarely - chest pains, chills, flu-like syndrome.

Pregnant women who take the drug in accordance with the dosage regimen usually tolerate it well. In children, there is a decrease in the hemoglobin content, but blood transfusions are not required. After completion of therapy, anemia resolves after 6 weeks.

Overdose

Main symptoms: headache, feeling tired, vomiting; very rarely - changes in blood counts; with a significant overdose, there are no clinical, hematological or biochemical symptoms.

Therapy: symptomatic. Peritoneal dialysis and hemodialysis to remove zidovudine from the body are not highly effective, but they lead to increased excretion of its metabolite, glucuronide.

special instructions

During therapy, systematic monitoring of the peripheral blood picture is required: during the first 3 months of therapy - once every 2 weeks, then - once a month.

Hematological changes, as a rule, appear after 4-6 weeks from the moment the drug is started. Neutropenia and anemia more often occur against the background of high doses of Zidovudine - from 1.2 to 1.5 g per day in patients with a decrease in the content of CD4 + cells, with advanced HIV infection. With a decrease in hemoglobin by more than 25%, or a decrease in the number of neutrophils by more than 50% in comparison with the initial value, blood tests should be performed more often. Severe hepatomegaly with steatosis and lactic acidosis can be fatal, therefore, in cases of laboratory / clinical signs of these conditions, Zidovudine is canceled.

The main risk factors for lactic acidosis include obesity, female sex, long-term therapy with antiviral drugs - nucleoside analogues. When assessing the tolerance of Zidovudine, it should be taken into account that anemia, anorexia, skin rash, weakness, dizziness, headache, diarrhea, thrombocytopenia and myalgia may not be a toxic effect of the drug, but a manifestation of HIV infection itself and secondary diseases associated with it …

Zidovudine should not be prescribed with other medicines containing zidovudine.

Immunity reactivation syndrome may develop during therapy, and medical intervention may be required.

The use of the drug does not prevent the transmission of HIV through sexual contact and through infected blood.

Zidovudine can cause accumulation / redistribution of fatty tissue, in particular "buffalo hump" (accumulation of fatty tissue in the dorsocervical region), central obesity, thinning of fatty tissue in the face / limbs, "cushingoid" face, breast enlargement.

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment, you should refrain from driving.

Application during pregnancy and lactation

Zidovudine crosses the placenta. It is not recommended to prescribe therapy to women before the 14th week of pregnancy. If it is necessary to use the drug during this period, it is necessary to carefully balance the expected benefit with the potential risk.

Due to the threat of infection of the child, women should not take Zidovudine during lactation.

Pediatric use

According to the instructions, Zidovudine in the form of capsules is contraindicated for children under 3 years of age, tablets - for children weighing up to 30 kg.

With impaired renal function

In patients with severe functional impairment of the kidneys (with creatinine clearance <10 ml / min), dose adjustment is performed.

For violations of liver function

In liver failure, hepatomegaly, hepatitis, or in cases of any risk factors for liver disease, the drug should be administered with caution.

Use in the elderly

Elderly patients are prescribed Zidovudine with caution.

There are no special recommendations for correcting the dosage regimen in this group of patients. When prescribing the drug, age-related changes in peripheral blood parameters and the functional state of the kidneys should be taken into account.

Drug interactions

clarithromycin: decreased absorption of zidovudine (the recommended interval between taking these drugs is 2 hours);
inhibitors of liver microsomal enzymes, including acetylsalicylic acid, valproic acid, morphine, indomethacin, codeine, ketoprofen, naproxen, lorazepam, clofibrate, cimetidine, oxazepam, inosine pranobex: increased plasma concentration of zidovudine;
paracetamol: an increase in the incidence of neutropenia (associated with inhibition of zidovudine metabolism, since both drugs are glucuronid);
drugs with myelosuppressive and nephrotoxic effects, including interferon alfa, dapsone, pyrimethamine, co-trimoxazole, pentamidine, amphotericin B, ganciclovir, flucytosine, vincristine, vinblastine, doxorubicin: an increase in the likelihood of the toxic effect of zidovudine;
probenicid and other inhibitors of tubular secretion: prolongation of T _{1/2 of} zidovudine;
fluconazole: an increase in its plasma concentration;
radiation therapy: enhancing the myelosuppressive effect of zidovudine;
phenytoin: a change in its concentration in the blood;
stavudine: decreased effectiveness of zidovudine (combination not recommended);
other drugs used against HIV (especially lamivudine): synergistic effect on HIV replication in cell culture;
ganciclovir, interferon alfa, ribavirin, other drugs that inhibit bone marrow hematopoiesis, including cytostatics: increased hematotoxicity of zidovudine;
rifampicin: a decrease in the plasma concentration of zidovudine, which may lead to a decrease in its effectiveness (the combination is not recommended);
nucleoside analogs that lead to a violation of DNA replication, including ribavirin: a decrease in the antiviral effect of zidovudine (the combination is not recommended);
doxorubicin: mutual weakening of activity (combination not recommended).

Analogs

Analogs of Zidovudine are: Viro-Zet, Azimitem, Retrovir, Timazid, Zido-Eich, Azidothymidine.

Terms and conditions of storage

Store in a place protected from light and moisture at temperatures up to 25 ° C. Keep out of the reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Zidovudine

Zidovudine is not used as monotherapy. Potent drug combinations are currently being prescribed, which are used in high doses to suppress viral replication.

Doctors note that almost all antiretroviral therapy drugs, including zidovudine, are highly toxic. Hematological changes (anemia and neutropenia) when using the drug usually develop one month after the start of treatment.

In reviews of Zidovudine, it is often noted that the drug is usually prescribed in the first year of therapy, after which it is canceled due to the development of adverse reactions.

The price of Zidovudine in pharmacies

Approximate price for Zidovudine (depending on the dosage form):

tablets (60 pcs in a package) - 1100-1280 rubles;
capsules (pack of 100) - 1270 rubles.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!