Zidovudine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ZIDOVUDINE (ZIDOVUDINE)

Composition:

Active substance: zidovudine;

1 ml of solution contains zidovudine 10 mg;

Excipients: maltitol, glycerol, citric acid anhydrous, sodium benzoate (E 211), sodium saccharin, strawberry flavor, raspberry flavor, purified water.

Pharmaceutical form. Oral solution.

Main physicochemical characteristics: clear, colorless or pale yellow liquid with a characteristic strawberry odor.

Pharmacotherapeutic group. Direct-acting antiviral agents. Nucleoside and nucleotide reverse transcriptase inhibitors. Zidovudine.

ATC code J05AF01.

Pharmacological properties.

Pharmacodynamics.

Zidovudine is an antiviral agent with high activity against retroviruses, including human immunodeficiency virus (HIV). It competitively inhibits reverse transcriptase, selectively suppressing viral DNA replication.

Once inside the cell (both infected and uninfected), zidovudine is phosphorylated by cellular kinases to form mono-, di-, and triphosphate derivatives. Zidovudine triphosphate acts as both an inhibitor and a substrate for viral reverse transcriptase. Viral DNA synthesis is also blocked by incorporation of zidovudine monophosphate into the growing DNA chain, leading to chain termination. The competitive interaction of zidovudine triphosphate with HIV reverse transcriptase is approximately 100 times stronger than with human α-polymerase.

The combination of zidovudine and lamivudine reduces HIV viral load and increases CD4 cell count. Recent clinical data indicate that zidovudine, in combination with lamivudine or in other treatment regimens containing lamivudine, significantly reduces the risk of disease progression and mortality.

Zidovudine is widely used as a component of antiretroviral therapy in combination with other antiretroviral agents of the same class (nucleoside reverse transcriptase inhibitors) or of different classes (protease inhibitors, non-nucleoside reverse transcriptase inhibitors).

In vitro studies show that triple combinations of nucleoside analogues or dual nucleoside analogues combined with a protease inhibitor are more effective in suppressing HIV-induced cytopathic effects than monotherapy or dual-drug regimens.

Pharmacokinetics.

Zidovudine is rapidly and almost completely absorbed from the gastrointestinal tract; its bioavailability is 60–70%. Maximum serum concentration of zidovudine is reached within 30 minutes and, after oral administration at a dose of 5 mg/kg body weight every 4 hours, amounts to 7.1 µM (1.9 µg/mL). Plasma protein binding ranges from 34% to 38%.

Zidovudine crosses the blood-brain and placental barriers. Concentrations in cerebrospinal fluid are approximately 50% of plasma levels. The drug is detectable in semen, breast milk, amniotic fluid, and fetal blood. Zidovudine does not accumulate. Drug concentration in neonatal plasma at birth is similar to that in maternal plasma during delivery.

Zidovudine is metabolized in the liver via conjugation with glucuronic acid. The main metabolite, 5-glucuronylazidothymidine, is excreted by the kidneys and lacks antiviral activity. Approximately 30% of the administered dose is excreted unchanged in urine.

In renal insufficiency, metabolite accumulation may occur, increasing the risk of toxicity. In hepatic insufficiency and in patients with liver cirrhosis, drug accumulation is possible due to reduced conjugation with glucuronic acid. Hemodialysis and peritoneal dialysis do not significantly affect zidovudine elimination.

In children aged 5–6 months and older, the pharmacokinetic profile of zidovudine is similar to that in adults.

Clinical characteristics.

Indications.

Use in combination with other antiretroviral medicinal products for the treatment of HIV infection in children and adults.

Prevention of transplacental fetal infection and primary prevention of HIV infection in newborns.

Contraindications.

Hypersensitivity to zidovudine or to any of the excipients of the medicinal product.

Neutropenia (neutrophil count less than 0.75 × 10⁹/L) or hemoglobin levels below 7.5 g/dL (or 4.65 mmol/L) (see section "Special warnings and precautions for use").

Zidovudine is contraindicated in newborns with hyperbilirubinemia requiring treatment other than phototherapy, and in newborns with transaminase levels exceeding the normal range by more than 5 times.

Interaction with other medicinal products and other forms of interaction.

Zidovudine is primarily eliminated by hepatic conjugation to an inactive glucuronide metabolite. Active substances that are also eliminated via hepatic metabolism, particularly through glucuronidation, may potentially inhibit zidovudine metabolism. The interactions described below are not exhaustive but highlight medicinal products that require caution when co-administered.

Atovaquone. There is no information on the effect of zidovudine on atovaquone pharmacokinetics. However, according to pharmacokinetic data, atovaquone reduces the metabolism of zidovudine to its glucuronide metabolite (AUC of zidovudine increases by 33%, and peak plasma concentration of the glucuronide metabolite decreases by 19%). When dosing at 500 or 600 mg/day for 3 weeks of atovaquone treatment for Pneumocystis carinii pneumonia, in rare cases, the frequency of adverse effects associated with higher plasma levels of zidovudine may increase. Close monitoring is required during prolonged atovaquone therapy.

Clarithromycin. Clarithromycin tablets reduce the absorption of zidovudine; therefore, a two-hour interval should be maintained between administration of these agents.

Lamivudine. A moderate increase in Cmax (28%) of zidovudine is observed when administered concurrently with lamivudine, although the overall exposure (AUC) does not change significantly. Zidovudine does not affect the pharmacokinetics of lamivudine.

Phenytoin. There have been reports of low plasma phenytoin levels in some patients receiving zidovudine, although one patient had elevated levels. These data suggest that phenytoin levels should be closely monitored when both drugs are used concomitantly.

Valproic acid, fluconazole, or methadone. It has been shown that co-administration with zidovudine increases the AUC of zidovudine with a corresponding decrease in its clearance. As data are limited, the clinical significance of this phenomenon is unknown. Patients should be closely monitored for signs of zidovudine toxicity.

Probenecid. Limited data indicate that probenecid increases the mean elimination half-life and the area under the concentration-time curve (AUC) of zidovudine by reducing glucuronidation. Renal excretion of the glucuronide metabolite (and possibly zidovudine itself) is reduced in the presence of probenecid. Patients receiving both agents should be monitored for signs of hematological toxicity.

Ribavirin. Worsening anemia associated with ribavirin use has been observed in patients receiving zidovudine as part of combination HIV therapy, although the exact mechanism remains unclear. Therefore, concomitant use of ribavirin and zidovudine is not recommended. The physician should replace zidovudine with another agent in the combination antiretroviral regimen if already prescribed. This is particularly important for patients with a history of zidovudine-induced anemia.

Rifampicin. Limited data show that co-administration of zidovudine and rifampicin reduces the AUC of zidovudine by 48±34%. This may result in partial or complete loss of zidovudine efficacy. Concomitant use of zidovudine and rifampicin should be avoided (see section "Special warnings and precautions for use"), although the clinical significance of this interaction is not fully known.

Stavudine. Zidovudine may inhibit intracellular phosphorylation of stavudine when both medicinal products are administered simultaneously. Therefore, stavudine is not recommended to be combined with zidovudine.

Other interactions. Other active substances, including acetylsalicylic acid, codeine, morphine, methadone, indomethacin, ketoprofen, naproxen, oxazepam, lorazepam, cimetidine, clofibrate, dapsone, and isoprinosine (this list is not exhaustive) may affect zidovudine metabolism by competitively inhibiting glucuronidation or directly inhibiting hepatic microsomal metabolism. Therefore, potential interactions should be considered when prescribing these medicinal products, especially for long-term treatment in combination with zidovudine.

Concomitant use, mostly in acute situations, with potentially nephrotoxic or myelosuppressive agents (e.g., systemic pentamidine, dapsone, pyrimethamine, co-trimoxazole, amphotericin B, flucytosine, ganciclovir, interferon, vincristine, vinblastine, and doxorubicin) may also increase the risk of zidovudine adverse effects. When co-administration of these medicinal products is necessary, renal function and hematological parameters should be closely monitored, and dosage reduction of one or more agents should be considered if needed.

Since some patients receiving zidovudine may be at risk of opportunistic infections, prophylactic administration of antimicrobial agents may be appropriate. Such prophylaxis may include co-trimoxazole, aerosolized pentamidine, pyrimethamine, and acyclovir. Limited clinical study data suggest that concomitant use with these agents does not increase the frequency of adverse reactions to zidovudine.

Special precautions for use.

Patients should be warned against the concurrent self-administration of other medications (see section "Interaction with other medicinal products and other forms of interaction").

Patients must be informed that treatment cannot prevent HIV transmission to other individuals through sexual contact or contact with infected blood. Therefore, appropriate safety measures should be taken.

The medication does not cure HIV infection, and patients remain at risk of developing illnesses associated with immunosuppression, including opportunistic infections and malignancies. Although a reduced risk of opportunistic infections has been established, data regarding the development of tumors, including lymphomas, are insufficient. In patients with advanced HIV disease treated with zidovudine, the risk of developing lymphoma is similar to that in patients not treated with zidovudine. For patients with early-stage HIV disease receiving long-term zidovudine treatment, the risk of developing lymphoma is unknown.

Pregnant women who decide to use zidovudine to prevent HIV transmission to the child should be aware that, in some cases, HIV transmission may still occur despite treatment.

Hematological adverse reactions. In patients with advanced HIV disease, anemia (usually not occurring earlier than 6 weeks after initiation of treatment, but occasionally earlier), neutropenia (usually not earlier than 4 weeks after initiation of treatment, but sometimes earlier), and leukopenia (secondary to neutropenia) may occur during zidovudine treatment. These effects are more common with high doses (1200–1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, especially in advanced stages of HIV disease.

Hematological parameters should be closely monitored. In patients with advanced HIV disease, blood tests are recommended at least once every 2 weeks during the first 3 months of treatment and at least once a month thereafter. Hematological adverse effects occur infrequently in patients with early stages of HIV disease (when bone marrow reserve is still adequate). Depending on the patient's clinical condition, blood tests may be performed less frequently, e.g., every 1–3 months.

If hemoglobin levels decrease from 7.5 g/dL (4.65 mmol/L) to 9 g/dL (5.59 mmol/L), or if neutrophil count decreases from 0.75 × 10⁹/L to 1.0 × 10⁹/L, dose reduction may be necessary until signs of bone marrow recovery appear; alternatively, a short (2–4 week) interruption of zidovudine treatment may accelerate recovery. Bone marrow recovery usually occurs within 2 weeks, after which zidovudine therapy may be resumed at reduced doses. In cases of severe anemia, reducing the zidovudine dose does not eliminate the need for blood transfusions (see section "Contraindications").

Lactic acidosis. Cases of lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, have been reported during nucleoside analogue treatment. Early symptoms (symptomatic hyperlactatemia) include benign gastrointestinal symptoms (nausea, vomiting, and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/or deep breathing), or neurological symptoms (including motor weakness).

Lactic acidosis has high mortality and may be associated with pancreatitis, hepatic or renal failure.

Lactic acidosis typically develops after several months or more of treatment.

If symptomatic hyperlactatemia, progressive metabolic lactic acidosis, progressive hepatomegaly, or rapidly increasing aminotransferase levels occur, treatment with nucleoside analogues should be discontinued.

Nucleoside analogues should be used with caution in any patients (especially obese women) with hepatomegaly, hepatitis, or other known risk factors for liver disease and hepatic steatosis (including certain medications and alcohol). Patients co-infected with hepatitis C and receiving alpha-interferon and ribavirin are at particular risk.

Patients at increased risk require ongoing monitoring.

Mitochondrial function disorders

Nucleoside and nucleotide analogues may cause mitochondrial dysfunction of varying severity, particularly when used concomitantly with stavudine, didanosine, and zidovudine. Cases of mitochondrial dysfunction have been reported in HIV-negative infants exposed to nucleoside inhibitors during the intrauterine and/or postnatal period, primarily in regimens including zidovudine. The main adverse reactions reported were hematological disorders (anemia, neutropenia) and metabolic disturbances (hyperlactatemia, hyperlipasemia). These events were often transient. Rarely, delayed-onset neurological disorders (hypertonia, seizures, behavioral disturbances) have been reported. Whether such neurological disorders are transient or permanent is currently unknown. The possibility of such disorders should be considered in any child exposed to nucleoside and nucleotide analogues in utero who presents with severe clinical disorders of unknown etiology, particularly neurological disorders. These data do not affect current recommendations for the use of antiretroviral drugs in pregnant women to prevent vertical HIV transmission.

Lipoatrophy

Zidovudine treatment is associated with loss of subcutaneous fat, linked to mitochondrial toxicity. The frequency and severity of lipoatrophy are related to cumulative exposure. This loss of fat deposits, most evident in the face, limbs, and buttocks, may be irreversible even after switching to a zidovudine-free treatment regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine and zidovudine-containing products (Combivir and Trizivir). If lipoatrophy is suspected, patients should be switched to an alternative treatment regimen.

Body weight and metabolic parameters

Body weight, serum lipid levels, and blood glucose levels may increase during antiretroviral therapy. Contributing factors may also include disease control and lifestyle changes. There is evidence that treatment may influence increased lipid levels in some cases, while evidence for treatment-related weight gain is lacking. Monitoring of serum lipid and blood glucose levels should be performed according to established HIV treatment protocols. Management of disorders related to lipid level changes should be based on clinical indications.

Liver disease. Zidovudine clearance in patients with mild hepatic impairment without cirrhosis (Child–Pugh score 5–6) is similar to that observed in healthy volunteers; therefore, zidovudine dosage adjustment is not required. For patients with moderate to severe hepatic impairment (Child–Pugh score 7–15), specific dosing recommendations cannot be made due to the wide variability in zidovudine exposure observed; thus, zidovudine is not recommended in this patient group.

Patients with chronic hepatitis B or C receiving combined antiretroviral therapy have an increased risk of severe and potentially fatal hepatic adverse effects. When used concomitantly with other antiviral agents for hepatitis B or C treatment, refer to the respective product information for these medications.

Patients with pre-existing liver function impairment, including chronic active hepatitis, are at increased risk of liver function deterioration during combined antiretroviral therapy and should be under medical supervision. If signs of worsening liver disease occur in such patients, consideration should be given to interrupting or discontinuing treatment (see section "Dosage and administration").

Immune Reconstitution Syndrome. In HIV-infected patients with severe immunodeficiency at the start of antiretroviral therapy, inflammatory reactions to asymptomatic or residual opportunistic infections may occur, potentially causing severe clinical conditions or symptom exacerbation. Such reactions typically occur within the first weeks or months of antiretroviral treatment. Examples include cytomegalovirus retinitis, generalized or focal infections caused by mycobacteria, or Pneumocystis jiroveci (P. Carinii) pneumonia. Any inflammatory conditions should be promptly investigated and treated if necessary. Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain–Barré syndrome) have also been reported during immune reconstitution, although their onset is more variable and may occur months after starting treatment, sometimes presenting with atypical features.

Patients with rare hereditary fructose intolerance should avoid using the oral solution.

Osteonecrosis. Although the etiology of osteonecrosis is considered multifactorial (including corticosteroid use, alcohol abuse, severe immunosuppression, high body mass index), cases of osteonecrosis have been reported primarily in patients with advanced disease and/or long-term use of combined antiretroviral therapy. Patients should be advised to seek medical attention if they experience joint pain, stiffness, or movement disorders.

Patients co-infected with hepatitis C virus. Worsening anemia associated with ribavirin use has been observed in patients receiving zidovudine as part of a combined HIV treatment regimen, although the exact mechanism remains unclear. Therefore, combining ribavirin and zidovudine is not recommended. Physicians should replace zidovudine with an alternative agent in combined antiretroviral therapy if such therapy is already prescribed. This is particularly important for patients with a history of zidovudine-induced anemia.

Use during pregnancy or breastfeeding.

Pregnancy.

When deciding on the use of antiretroviral agents for treating HIV infection in pregnant women and for reducing the risk of vertical HIV transmission to the newborn, data from animal studies and clinical experience in pregnant women are generally considered.

In this case, zidovudine use by pregnant women followed by treatment of the newborn reduces the frequency of mother-to-fetus HIV transmission.
A large amount of data from pregnant women (over 3000 outcomes in the first trimester and over 3000 outcomes in the second and third trimesters) indicates no teratogenic toxicity. Zidovudine may be used during pregnancy if clinically justified. The risk of congenital malformations in humans is unlikely, based on the large amount of data mentioned.

Animal studies with zidovudine indicate reproductive toxicity. The active components of the drug may inhibit DNA cell replication, and zidovudine demonstrated transplacental carcinogenic properties in one animal study. The clinical significance of these findings is unknown. Transplacental penetration of zidovudine in humans has been established.

Mitochondrial dysfunction: nucleotide and nucleoside analogues cause mitochondrial damage in vitro and in vivo. Reports have been made of mitochondrial dysfunction in HIV-negative infants whose mothers used nucleoside analogues during pregnancy and/or postnatally (see section "Special precautions for use").

Fertility

Zidovudine did not reduce male or female fertility in rats administered doses up to 450 mg/kg/day. There are no data on the effect of zidovudine on female fertility. In men, zidovudine does not affect sperm count, morphology, or motility.

Lactation

After a single 200 mg dose of zidovudine administered to HIV-infected women, average zidovudine concentrations in breast milk were similar to those in blood serum. HIV-infected women are advised to avoid breastfeeding under all circumstances to prevent transmission of HIV infection to infants.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of zidovudine on reaction speed when driving or operating machinery have not been conducted. Based on pharmacological data of the active substance, no harmful effect on the ability to drive or operate machinery is expected. Nevertheless, the patient's overall condition and the drug's adverse effect profile should always be considered when determining the ability to perform such activities.

Method of Administration and Dosage

Zidovudine therapy should be initiated by a physician experienced in the management of HIV infection.

Use in the treatment of adults and children weighing at least 30 kg: the recommended dose of zidovudine in combination with other antiretroviral agents is 250 or 300 mg twice daily.

Children

Children weighing from 9 kg to 30 kg: the recommended dose of zidovudine is 9 mg/kg body weight twice daily in combination with other antiretroviral agents.

The maximum dose should not exceed 300 mg twice daily.

Children weighing from 4 kg to 9 kg: the recommended dose of zidovudine is 12 mg/kg twice daily in combination with other antiretroviral agents.

Children weighing less than 4 kg: available data do not allow recommendations for specific dosing in this pediatric group.

Prevention of mother-to-fetus transmission

The following zidovudine dosing regimens have been shown to be effective:

Recommended dosage for pregnant women (pregnancy beyond 14 weeks): 500 mg orally per day (100 mg 5 times daily) until the onset of labor. During labor, zidovudine should be administered intravenously at a dose of 2 mg/kg body weight over 1 hour, followed by continuous intravenous infusion of 1 mg/kg/hour until cord clamping.

Newborns should receive zidovudine at a dose of 2 mg/kg body weight orally every 6 hours, starting within the first 12 hours after birth and continuing until 6 weeks of age. To ensure accurate dosing in infants, a syringe of appropriate size should be used. For neonates unable to receive the drug orally, zidovudine should be administered intravenously at a dose of 1.5 mg/kg body weight over 30 minutes every 6 hours.

Thailand HIV/AIDS surveillance study: the recommended dose of zidovudine for pregnant women after 36 weeks of gestation is 300 mg twice daily until the onset of labor, followed by 300 mg every 3 hours from the onset of labor until delivery.

Due to the small volume of oral solution required, dosing for newborns must be calculated carefully.

In cases of planned cesarean section, intravenous infusion should be initiated 4 hours before the start of surgery. In cases of false labor, intravenous infusion should be discontinued and oral administration resumed.

Renal impairment

For patients with severe renal impairment (creatinine clearance < 10 mL/min), administer 300–400 mg daily. Further dose adjustment may be necessary based on hematological parameters (see below).

Hemodialysis and peritoneal dialysis do not significantly affect zidovudine elimination, but they increase the elimination of zidovudine glucuronide. For patients with end-stage renal disease on hemodialysis or peritoneal dialysis, the recommended dose is 100 mg every 6 or 8 hours (see section "Pharmacological properties").

Hepatic impairment

Zidovudine accumulation has been observed in patients with liver cirrhosis due to reduced glucuronidation. Dose adjustment may be necessary; however, due to insufficient data, clear recommendations cannot be provided. In the absence of plasma zidovudine level monitoring, signs of intolerance should be monitored and the dose adjusted or the dosing interval extended accordingly.

Dose adjustment in patients with hematological adverse reactions

In patients whose hemoglobin levels decrease to between 7.5 g/dL (4.65 mmol/L) and 9 g/dL (5.59 mmol/L), or whose neutrophil count falls between 0.75 × 10⁹/L and 1.0 × 10⁹/L, dose reduction or temporary interruption of zidovudine therapy may be necessary (see sections "Contraindications" and "Special warnings and precautions for use").

Elderly patients

The pharmacokinetics of zidovudine in patients aged 65 years and older have not been studied, so specific data are lacking. However, this patient group requires special attention due to age-related decline in renal function and changes in hematological parameters. Appropriate monitoring before and during zidovudine administration is recommended.

Children.

Should be used from birth to prevent mother-to-child transmission.

Overdose.

Symptoms. There are no specific symptoms or signs of acute zidovudine overdose other than those listed in the section "Adverse reactions" (increased fatigue, headache, vomiting, isolated cases of hematological changes). There have been reports of patients ingesting an unknown quantity of zidovudine resulting in plasma levels more than 16 times higher than normal therapeutic levels, but without short-term clinical, biochemical, or hematological consequences.

Treatment. In case of overdose, the patient should be carefully examined to identify signs of intoxication (see section "Adverse reactions"), and appropriate supportive therapy should be administered.

Hemodialysis and peritoneal dialysis have minimal effect on zidovudine elimination but accelerate the elimination of its glucuronide metabolite.

Adverse Reactions

The nature of adverse effects is similar in children and adults.

The frequency of adverse effects is classified according to the following categories: very common (> 1/10), common (> 1/100, < 1/10), uncommon (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000).

Blood and Lymphatic System

Common: anemia (which may require blood transfusions), neutropenia, and leukopenia.

These effects occur more frequently with high-dose regimens (1200–1500 mg daily) and in patients with advanced HIV disease (especially those with poor bone marrow reserve prior to treatment initiation), predominantly in patients with CD4+ cell counts below 100/mm³. Due to these adverse effects, dose reduction or discontinuation of therapy may be necessary (see section "Special Warnings and Precautions for Use"). The incidence of neutropenia is also increased in patients who had low neutrophil counts, hemoglobin levels, and serum vitamin B12 levels at the start of zidovudine therapy.

Uncommon: thrombocytopenia and pancytopenia with bone marrow hypoplasia.

Rare: pure red cell aplasia.

Very rare: aplastic anemia.

Metabolism and Digestive Disorders

Common: hyperlactatemia.

Rare: lactic acidosis (see section "Special Warnings and Precautions for Use"), anorexia.

Redistribution/accumulation of body fat (see section "Special Warnings and Precautions for Use"). The incidence of this phenomenon depends on multiple factors, including the specific antiretroviral drug combination used.

Psychiatric Disorders

Rare: restlessness, depression.

Nervous System Disorders

Very common: headache.

Common: dizziness.

Rare: insomnia, paresthesia, somnolence, decreased mental acuity, seizures.

Cardiovascular System Disorders

Rare: cardiomyopathy.

Respiratory System Disorders

Uncommon: dyspnea.

Rare: cough.

Gastrointestinal Disorders

Very common: nausea.

Common: vomiting, abdominal pain, diarrhea.

Uncommon: flatulence.

Rare: pigmentation of oral mucosa, taste alterations, dyspepsia, pancreatitis.

Hepatobiliary Disorders

Common: elevated liver enzymes and bilirubin levels.

Rare: hepatic disorders, such as severe hepatomegaly with steatosis.

Skin Disorders

Uncommon: rash, pruritus.

Rare: skin and nail pigmentation, urticaria, sweating.

Musculoskeletal System

Common: myalgia.

Uncommon: myopathy.

Renal and Urinary System

Rare: frequent urination.

Reproductive System

Rare: gynecomastia.

General Disorders

Common: malaise.

Uncommon: chills, generalized pain, asthenia.

Rare: shivering, chest pain, influenza-like syndrome.

According to clinical trial data, the incidence of nausea and other common adverse effects significantly decreases after several weeks of zidovudine therapy.

Adverse Effects in Prevention of Maternal-Fetal Transmission

In a placebo-controlled trial (ACTG 076), zidovudine was well tolerated in pregnant women. The frequency of adverse effects was similar to that in the placebo group.

According to the same study, hemoglobin levels in infants treated with zidovudine were slightly lower than in the placebo group, but blood transfusions were not required. Anemia resolved within 6 weeks after completion of zidovudine therapy. Other adverse effects and laboratory abnormalities were similar between the placebo and zidovudine-treated groups. Long-term effects of the drug on the fetus and infant are unknown.

Cases of lactic acidosis, sometimes fatal, associated with severe hepatomegaly and hepatic steatosis have been reported with nucleoside analogues (see section "Special Warnings and Precautions for Use").

Zidovudine treatment has been associated with loss of subcutaneous fat, most prominently in the face, limbs, and buttocks. Patients receiving zidovudine should be regularly monitored for signs of lipoatrophy. If such changes occur, continuation of zidovudine therapy should not be recommended (see section "Special Warnings and Precautions for Use").

Body weight, serum lipid levels, and blood glucose levels may increase during antiretroviral therapy (see section "Special Warnings and Precautions for Use").

In HIV-infected patients with severe immunodeficiency at the initiation of combination antiretroviral therapy, inflammatory reactions to asymptomatic or residual opportunistic infections may occur.

Cases of osteonecrosis have been reported, primarily in patients with confirmed risk factors, long-standing HIV disease, or prolonged antiretroviral therapy.

The frequency of such cases is unknown (see section "Special Warnings and Precautions for Use").

Shelf life. 2 years.

The oral solution is suitable for use for 1 month after first opening.

Storage conditions.

Store at temperatures not exceeding 30°C. Keep out of reach of children.

Packaging.

200 ml in a glass bottle. One bottle with a 10 ml syringe in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

PJSC "Tekhnolog".

Manufacturer's address and location of business activity.

8 Stara Prorizna Street, City of Uman, Cherkasy Region, Ukraine, 20300.