Zidovudine


Continuing Education Activity

Zidovudine is a medication used in the management and treatment of HIV-1. It is in the nucleoside reverse transcriptase inhibitor class of medications. This activity reviews the indications, action, and contraindications for zidovudine as a valuable agent in the treatment of HIV-1. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the interprofessional healthcare team in the treatment of patients with HIV-1 and related conditions.

Objectives:

  • Identify the mechanism of action of zidovudine.
  • Describe the potential adverse effects of zidovudine.
  • Outline the appropriate monitoring toxicity of zidovudine.
  • Explain the interprofessional team strategies for improving care coordination and communication to advance zidovudine and improve outcomes.

Indications

Human immunodeficiency virus or HIV primarily disrupts CD4+ T cells, thus compromising the host's immune system. The virus replicates via reverse transcriptase, and if not treated properly, it can progress to acquired immunodeficiency syndrome. It is imperative that providers screen and treat at-risk patient populations. If patients are left untreated, their CD4+ T cell count can drop to dangerous levels leaving the patient susceptible to deadly opportunistic infections and neoplasms. Zidovudine first received approval in the United States in 1987. It is part of a class of medications known as nucleoside reverse transcriptase inhibitors. This class of medications is a crucial aspect of highly active antiretroviral viral therapy (HAART). Zidovudine is indicated for the treatment of the human immunodeficiency virus (HIV-1) in conjunction with other antiretroviral medications. Zidovudine is indicated for the prevention of vertical transmission of the human immunodeficiency virus (HIV-1) between mother and fetus. Zidovudine indications also include the treatment of adult T cell leukemia.[1][2][3][4][5][6]

Mechanism of Action

Zidovudine is a pyrimidine nucleoside reverse transcriptase inhibitor (NRTI) that works primarily through a complex multistep mechanism of action. First, zidovudine is phosphorylated into zidovudine-triphosphate. The phosphorylation of zidovudine inhibits thymidine's ability to integrate into viral DNA through competitively inhibiting viral reverse transcriptase. Zidovudine then incorporates itself into viral DNA. Integration into viral DNA causes chain termination due to the lack of a 3' hydroxyl group. This achieving of chain termination is primarily through zidovudine's unreactive 3′-azido group.[1][2][7]

Administration

Antiretroviral therapy such as zidovudine should be administered promptly following diagnosis of the human immunodeficiency virus (HIV-1). Clinicians ought to pay careful attention to dosing based on the patient's current clinical state as well as for which clinical indication it is being used. Zidovudine has a half-life between 1 to 1.5 hours in patients, a plasma clearance rate of 1.3 L/h/kg, and a renal clearance rate of 0.23 L/h/kg.

Treatment of HIV-1 Infection

  1. Adults: Should receive 600 mg per day with split doses
  2. Dosage for pediatric patients between 6 weeks and 18 years of age is based on body weight and should not be greater than the adult indicated dose. Patients weighing between 4 kg and 9kg will receive a maximum daily dose of 24 mg/kg/day. Patients weighing between 9 kg and 30 kg will receive a maximum daily dose of 18 mg/kg/day. Patients weighing over 30 kg will receive a maximum daily dose of 600 mg/day.
  • Prevention of HIV-1 maternal-fetal transmission: 100 mg five times per day by mouth until the induction of labor. Zidovudine should be given intravenously over one hour at 2 mg/kg while the patient is undergoing labor and delivery. Upon completion of this infusion, patients should receive 1 mg/kg/hour until the clamping of the umbilical cord. The administration of neonatal dosing should be within the first 12 hours after birth. The neonate should receive 2 mg/kg of zidovudine by mouth every 6 hours until the neonate reaches six weeks of age.
  • Special patient populations: Patients with severe anemia or neutropenia should stop treatment until bone marrow recovery is evident. Patients on hemodialysis should receive 100 mg of zidovudine every 6 to 8 hours.[1][4][7][8]

Adverse Effects

Adverse events are extremely common, with patients receiving zidovudine treatment. Up to 84% of patients report adverse effects. The most commonly reported side effects are nausea, vomiting, severe headaches, muscle aches, and insomnia. Hematologic adverse effects occur in up to 45% of patients. These include neutropenia, leukopenia, and anemia. In rare cases, patients may develop pancytopenia. There are reports of severe lactic acidosis and hepatomegaly with steatosis have been reported. Patients with known liver disease should receive careful monitoring.[1][9][10][11]

Contraindications

Zidovudine is contraindicated for any patients with severe life-threatening hypersensitivity reactions to this medication, including anaphylaxis and Stevens-Johnson syndrome. Anaphylaxis may present with difficulty breathing, diffuse rash, and hypotension. Stevens-Johnson syndrome is a very painful blistering skin condition. Prompt discontinuation of zidovudine therapy is critical if any of these symptoms arise.[1]

Monitoring

Patients with hemoglobin less than 9.5 g/dL or a granulocyte count of fewer than 1000 cells/mm3 should practice extreme caution when using zidovudine. Zidovudine has known hematologic toxicity, including anemia, granulocytopenia, neutropenia, and pancytopenia. Although in most cases, the pancytopenia was reversible upon discontinuation. Patients with severe anemias may require a blood transfusion. Patients with signs and symptoms of lactic acidosis and or hepatoxicity should discontinue treatment immediately.[1][10][12]

Toxicity

Zidovudine is a pregnancy category C medication as classified by the now outdated letter system. Clinical trials showed that there was no difference in adverse events in pregnant and nonpregnant patients. Mothers who breastfeed their children are advised not to breastfeed while taking zidovudine because zidovudine is excreted in breast milk. Geriatric populations did not require any different dosing. Patients with hepatic or renal impairment may need dose-related adjustments. There are reports of overdose with zidovudine at doses above 50 grams without any specific constellation of symptoms. There is no recommended treatment for zidovudine overdose at this time. Research has recorded drug interactions between zidovudine and acetaminophen and interactions between zidovudine and probenecid. Patients reported an overall increase in side effects when combining these medications. Patients taking zidovudine in conjunction with acyclovir reported lethargy, insomnia, and a metallic taste in their mouths. All medications that are cytotoxic, nephrotoxic, or cause adverse hematological side effects should be avoided in conjunction with zidovudine.[1][9][10][13]

Enhancing Healthcare Team Outcomes

Understanding the treatment options for the human immunodeficiency virus (HIV-1) is important for nurses, doctors, and pharmacists, all acting as an interprofessional team. Communication is vital to making sure patients receive prompt retroviral therapy, especially when trying to reduce the likelihood of maternal-fetal transmission. The human immunodeficiency virus (HIV-1) requires prompt treatment with antiretroviral therapy to maintain an adequate CD4+ T cell count to prevent some dangerous sequelae that result from a reduced CD4+ T cell count. Clinicians ought to pay special attention to at-risk populations and screen patients with associated risk factors. Prompt treatment with antiretroviral therapies such as zidovudine can provide life-saving immunological support. Zidovudine plays a crucial role in helping prevent the maternal-fetal transmission of the human immunodeficiency virus (HIV-1) in pregnant patients. Zidovudine has not only proven to reduce the likely hood of vertical transmission, but it has also demonstrated the capacity to provide prophylaxis for those children exposed in utero.

Clinicians must provide patient education about the importance of maintaining compliance with zidovudine. This way, patients can maintain an adequate immune response and be less likely to become susceptible to opportunistic infections or neoplasms. This therapy will, in turn, improve the quality of life and survival rates of patients with the human immunodeficiency virus (HIV-1). Patients who are infected and become pregnant should receive proper counseling on treatment that will help prevent vertical maternal-fetal transmission. Human immunodeficiency virus (HIV-1) needs to be on all clinicians' differentials when dealing with certain opportunistic infections, neoplasm, and patient populations. Those who are infected should receive prompt, highly active antiretroviral therapy. Treatment with zidovudine has proven to be effective in several clinical scenarios. Clinicals should consider zidovudine as a part of their treatment algorithm for the human immunodeficiency virus (HIV-1).[1][3][14]

Specialty train HIV care nurses review the importance of compliance with patients, check for side effects, follow up on laboratories, and inform prescribing providers of patient issues. Board-certified infectious disease pharmacists can consult with the prescriber on appropriate dosing and regimen, evaluate interactions, and educate patients. These interprofessional interventions are examples of how coordinated healthcare team dynamics can improve patient outcomes when using zidovudine therapy. [Level 5]


Article Details

Article Author

Zachary Edwards

Article Author

Curtis Ingold

Article Editor:

Chaudhary Ehtsham Azmat

Updated:

5/5/2021 11:55:29 AM

PubMed Link:

Zidovudine

References

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