Zidovudine adverse reactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Hematologic toxicity, including neutropenia and anemia [see Boxed Warning, Warnings and Precautions (5.1)].
- Symptomatic myopathy [see Boxed Warning, Warnings and Precautions (5.2)].
- Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.3)].
- Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.4)].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults: The frequency and severity of adverse reactions associated with the use of RETROVIR are greater in patients with more advanced infection at the time of initiation of therapy.
Table 3 summarizes adverse reactions reported at a statistically significant greater incidence for subjects receiving RETROVIR in a monotherapy trial.
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In addition to the adverse reactions listed in Table 3, adverse reactions observed at an incidence of ≥5% in any treatment arm in clinical trials (NUCA3001, NUCA3002, NUCB3001, and NUCB3002) were abdominal cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, insomnia, musculoskeletal pain, myalgia, and neuropathy. Additionally, in these trials hyperbilirubinemia was reported at an incidence of ≤0.8%.
Selected laboratory abnormalities observed during a clinical trial of monotherapy with RETROVIR are shown in Table 4.
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Pediatrics: The clinical adverse reactions reported among adult recipients of RETROVIR may also occur in pediatric patients.
Trial ACTG 300: Selected clinical adverse reactions and physical findings with a ≥5% frequency during therapy with EPIVIR® (lamivudine) Oral Suspension 4 mg/kg twice daily plus RETROVIR 160 mg/m2 3 times daily compared with didanosine in therapy-naive (≤56 days of antiretroviral therapy) pediatric subjects are listed in Table 5.
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Selected laboratory abnormalities experienced by therapy-naive (≤56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.
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Macrocytosis was reported in the majority of pediatric subjects receiving RETROVIR 180 mg/m2 every 6 hours in open-label trials. Additionally, adverse reactions reported at an incidence of <6% in these trials were congestive heart failure, decreased reflexes, ECG abnormality, edema, hematuria, left ventricular dilation, nervousness/irritability, and weight loss.
Use for the Prevention of Maternal-Fetal Transmission of HIV-1: In a randomized, double-blind, placebo-controlled trial in HIV-1-infected women and their neonates conducted to determine the utility of RETROVIR for the prevention of maternal-fetal HIV-1 transmission, RETROVIR Syrup at 2 mg/kg was administered every 6 hours for 6 weeks to neonates beginning within 12 hours following birth. The most commonly reported adverse reactions were anemia (hemoglobin <9.0 g/dL) and neutropenia (<1,000 cells/mm3). Anemia occurred in 22% of the neonates who received RETROVIR and in 12% of the neonates who received placebo. The mean difference in hemoglobin values was less than 1.0 g/dL for neonates receiving RETROVIR compared with neonates receiving placebo. No neonates with anemia required transfusion and all hemoglobin values spontaneously returned to normal within 6 weeks after completion of therapy with RETROVIR. Neutropenia in neonates was reported with similar frequency in the group that received RETROVIR (21%) and in the group that received placebo (27%). The long-term consequences of in utero and infant exposure to RETROVIR are unknown.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of RETROVIR. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to RETROVIR.
Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain, redistribution/accumulation of body fat [see Warnings and Precautions (5.7)].
Cardiovascular: Cardiomyopathy, syncope.
Endocrine: Gynecomastia.
Eye: Macular edema.
Gastrointestinal: Dysphagia, flatulence, oral mucosa pigmentation, mouth ulcer.
General: Sensitization reactions including anaphylaxis and angioedema, vasculitis.
Hemic and Lymphatic: Aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia.
Hepatobiliary Tract and Pancreas: Hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis, pancreatitis.
Musculoskeletal: Increased CPK, increased LDH, muscle spasm, myopathy and myositis with pathological changes (similar to that produced by HIV-1 disease), rhabdomyolysis, tremor.
Nervous: Anxiety, confusion, depression, dizziness, loss of mental acuity, mania, paresthesia, seizures, somnolence, vertigo.
Respiratory: Dyspnea, rhinitis, sinusitis.
Skin: Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweat, urticaria.
Special Senses': Amblyopia, hearing loss, photophobia, taste perversion. Urogenital: Urinary frequency, urinary hesitancy.[1]
References
Adapted from the FDA Package Insert.