Zidovudine (AZT) was first synthesized in 1964 as a potential anti-cancer drug but failed in that role, it was approved by the FDA in 1987 as the first antiretroviral treatment for HIV/AIDS. Zidovudine is used to reduce the progression of HIV in individuals, whether they experience severe symptoms, mild symptoms, or none at all. It is also used to help prevent the transmission of HIV from pregnant women to their babies during pregnancy and childbirth.
BRAND NAMES
Retrovir-
Capsules: 100 mg capsules for oral use.
Tablets: 300 mg tablets for oral use.
Oral solution/syrup: 10 mg of zidovudine per mL.
MECHANISM OF ACTION
Zidovudine (AZT) is an antiretroviral medication classified as a nucleoside reverse transcriptase inhibitor (NRTI) and is used in the treatment of HIV. After intracellular phosphorylation to its active triphosphate form, it mimics thymidine, one of the natural DNA nucleosides. During viral DNA synthesis by reverse transcriptase, AZT is incorporated into the growing DNA chain. However, unlike natural thymidine, AZT lacks a 3'-hydroxyl (-OH) group, which is essential for forming the next phosphodiester bond in DNA elongation. As a result, its incorporation causes chain termination, halting viral DNA synthesis and thereby inhibiting HIV replication.
PHARMACOKINETICS
Absorption
Zidovudine is well absorbed after oral administration, but its absorption can be highly variable between individuals and is affected by food and certain health conditions. Its absorption is also subject to first-pass metabolism, which reduces its overall bioavailability.
Distribution
Zidovudine has an apparent volume of distribution of about 1.6 ± 0.6L/kg.
Metabolism
Zidovudine is metabolized primarily through three pathways: glucuronidation, phosphorylation, and reduction. Glucuronidation is the main pathway for zidovudine elimination, whereas phosphorylation is essential for activating the drug so it can exert its antiviral effects.
Excretion
60–75% of the drug is excreted in urine in the form of glucuronide.14–20% is excreted as unchanged zidovudine.
PHARMACODYNAMICS
Zidovudine’s primary pharmacodynamic action involves inhibiting HIV-1 reverse transcriptase by mimicking natural nucleotides and competing for incorporation into the viral DNA chain. Once incorporated, it acts as a chain terminator, preventing further DNA elongation and stopping viral replication.
ADMINISTRATION
Zidovudine is administered orally or intravenously as part of combination therapy, as monotherapy is not recommended due to the risk of drug resistance. However, the injectable formulation is not readily available. Adult oral dosing 300 mg twice daily.
DOSAGE AND STRENGTHS
Oral tablets: 300 mg
Oral capsules: 100 mg
Oral solution (syrup): 10 mg/mL
IV injection: 10 mg/mL
DRUG INTERACTIONS
Zidovudine has a range of drug interactions, most notably with other antiretrovirals like stavudine and ribavirin, as well as with drugs that cause bone marrow suppression, such as certain cancer therapies and antibiotics. Other interactions involve medications like probenecid and rifampin that can alter zidovudine's blood levels, and drugs with overlapping toxicities that increase risks of muscle or liver damage. Always consult a healthcare professional about all medications and supplements to safely manage these potential interactions.
FOOD INTERACTIONS
Zidovudine may be taken with or without food; however, taking it with a meal can help minimize nausea, which is a common side effect. While a high-fat meal may slightly slow absorption, it doesn't significantly impact the overall drug amount absorbed. Alcohol should be avoided as it can weaken the immune system and increase the risk of bleeding. Always inform your doctor about any supplements, as high doses of vitamins or minerals can interact with HIV medication.
CONTRAINDICATIONS
Use is contraindicated in individuals with a history of severe, life-threatening allergic reactions to any ingredient in the formulation. Contra-indicated in neonates with hyperbilirubinemia requiring treatment other than phototherapy or if serum transaminases are more than 5 times normal levels.
SIDE EFFECTS
Hepatotoxicity Gastrointestinal issues.
Headache.
Fatigue and malaise.
Insomnia.
Muscle and joint pain.
Nail pigmentation.
Myopathy.
Hematologic toxicity.
Severe skin reactions.
OVER DOSE
In cases of zidovudine overdose, the most significant risk is metabolic acidosis with high lactate levels, which can be fatal.
Seizures.
Neurological effects.
Muscular issues.
Metabolic acidosis.
Hepatotoxicity.
Hematological toxicity.
Gastrointestinal issues.
TOXICITY
Zidovudine toxicity can cause serious and potentially fatal side effects, primarily affecting the blood, liver, and muscles. The drug's main mechanism of toxicity involves damage to mitochondria, the energy-producing parts of cells.
