Adverse Effects of Zidovudine Overdose

Introduction

Zidovudine is an antiviral drug used in combination with other medications to treat human immunodeficiency virus (HIV) infection. It belongs to a class of medications named nucleoside reverse transcriptase inhibitors (NRTI). Zidovudine cannot cure human immunodeficiency virus infection (HIV). It works by decreasing the chance of developing human immunodeficiency virus (HIV) infection and related illnesses and complications. Even though Zidovudine helps to reduce the progression of infection in patients infected with human immunodeficiency virus (HIV), its overdose will cause adverse health effects to the body. Neurotoxicity and hematological toxicity are observed in patients with Zidovudine overdose.

What Is Zidovudine?

Zidovudine, also named azidothymidine (AZT), is an analog of thymidine (pyrimidine deoxynucleoside). They selectively inhibit the reverse enzyme transcriptase in the human immunodeficiency virus (HIV). Viruses use the reverse transcriptase enzyme to make DNA from an RNA template. This double-stranded DNA, formed by reverse transcriptase enzymes, will be integrated with the genetic material of the infected human cell during infection. Thus Zidovudine helps to reduce the progress of viral infection by inhibiting the action of the reverse transcriptase enzyme.

What Are the Uses of Zidovudine?

• Prevention of Human Immunodeficiency Virus (HIV) - In combination with other antiretroviral drugs (Lamivudine), it is used for post-exposure prophylaxis (PEP). Post-exposure prevention or prophylaxis is done after accidental exposure to human immunodeficiency virus (HIV) contaminated body fluids, tissues, and blood. It usually happens with healthcare workers. Zidovudine is given to human immunodeficiency virus-infected pregnant women to reduce the chance of passing the viral infection (HIV) to the baby.

• Treatment of Human Immunodeficiency Virus (HIV) - In combination with other antiretroviral drugs, Zidovudine is given twice daily for the treatment of the human immunodeficiency virus (HIV).To control the human immunodeficiency virus (HIV) infection and reduce its resistance, multiple antiviral drugs are used. It is named highly active antiretroviral therapy (HAART).

• Antibacterial Action - In combination with other antibacterial agents, Zidovudine can be used against multidrug-resistant gram negative-bacteria.

What Are the Side Effects of Using Zidovudine?

Some patients may develop side effects after Zidovudine use. It depends on their body's reaction to the drug.

It includes the following:

• Headache.

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• Trouble sleeping.

• Constipation.

• Rash.

• Joint pain.

• Itching.

• Heartburn.

• Peeling of the skin.

• Muscle weakness.

• Weight loss.

• Stomach cramps.

• Blistering of skin.

• Hives.

• Swelling of eyes, tongue, and face.

What Is the Normal Dosing Regimen for Zidovudine?

1. Oral Dose for Human Immunodeficiency Virus (HIV) Infection - For adults, 300 milligrams two times a day with other antiviral medications. The dose depends on the body weight of infants (four weeks of age) and children.

• Weight more than 30 kilograms - 60 milligrams per day in divided doses.

• Weight less than 30 kilograms (up to nine kilograms) - 18 milligrams per kilogram in divided doses.

• Weight less than nine kilograms (up to four kilograms) - 24 milligrams per kilogram per day in divided doses.

2. Oral Dose for Prevention of Human Immunodeficiency Virus (HIV) Infection in Pregnant Women - It is given to prevent the spread of human immunodeficiency virus (HIV) infection from pregnant women to their babies during pregnancy and birth.

• Pregnant Women - It is given after 14 weeks of pregnancy, up to childbirth 100 milligrams, five times a day, is given.

• Newborn Infants - The dose depends on the body weight of the newborn. The normal dose followed is two milligrams per kilogram of body weight every six hours, starting from 12 hours after birth until six weeks of age.

What Is Zidovudine Overdose?

The dosage of Zidovudine depends on the patient's age and the severity of the infection. For normal adults, 300 milligrams are given twice a day (a total of 600 milligrams per day). Zidovudine doses must be monitored regularly to avoid toxicity due to overdose. Studies have shown an increased risk of developing neurotoxicity and hematological toxicity with Zidovudine overdose.

The toxic reactions associated with Zidovudine overdose include the following:

• At high doses, Zidovudine may inhibit the DNA polymerase enzyme used by normal human cells for cell division and cause cell damage. They can also act on mitochondrial DNA polymerase enzymes and cause damage to skeletal and cardiac muscles (myositis).

• Anemia is often associated with Zidovudine overdose. There will be reduced red blood cells in the body, causing reduced oxygen availability to tissues and organs. It will result in fatigue, dizziness, headache, skin pallor, shortness of breath, and a fast heart rate.

• Neutropenia (low neutrophil count) is also observed with Zidovudine overdose. There will be a very low count of neutrophils (white blood cells) in the body, which will cause increased susceptibility to infection.

• Elevations of bilirubin levels are observed with Zidovudine overdose. Bilirubin is a yellow-orange pigment produced in the body as a result of red blood cell breakdown.

• Neurotoxicity is an important effect associated with Zidovudine overdose. Alterations in protein and lipid metabolism, oxidative stress, and mitochondrial damage will cause neurotoxicity. Zidovudine overdose will induce cellular stress and neuronal damage. Disrupted nerve cell activity will cause seizures.

• Gastrointestinal irritations are common after a Zidovudine overdose. In addition, there will be gastrointestinal symptoms like cramps, diarrhea, and loss of appetite during a Zidovudine overdose.

• Myopathy induced by Zidovudine overdose will cause muscle fatigue, wasting, and weakness. Patients taking Zidovudine for a long period of time are often associated with muscular diseases.

• Zidovudine overdose may cause life-threatening liver damage and result in a life-threatening condition called lactic acidosis (too much lactic acid in the blood).

• Headache and severe nausea are seen in patients due to increased levels of Zidovudine in the body.

Conclusion

Zidovudine, combined with other antiviral drugs, is used to prevent and reduce human immunodeficiency virus (HIV) infection. They can also prevent the spread of human immunodeficiency viral infection (HIV) from pregnant women to children and after accidental exposure to body fluids containing human immunodeficiency virus (HIV). The dosing regimen for Zidovudine is calculated based on the patient's body weight and clinical conditions. Proper monitoring of the dose must be done in each patient to rule out toxicity related to Zidovudine overdose.