Zidovudine (Retrovir®, AZT)Class:Zi

Zidovudine (Retrovir®, AZT)
Class:
Zidovudine is a thymidine analog in the nucleoside reverse transcriptase inhibitor class.
Antiviral Activity:
Zidovudine is more active against acutely infected cells as compared to chronically infected cells.
Mechanism of Action:
Zidovudine is phosphorylated to zidovudine-triphosphate, which competes with endogenous
nucleotides for incorporation into the viral DNA and once incorporated causes chain termination
due to the lack of a 3’ OH group.
Mechanism of Resistance:
Resistance to NRTIs occurs through two mechanisms; decreased incorporation of NRTIs into the
viral DNA and increased excision of NRTIs from the viral DNA.
Pharmacodynamics:
In vitro IC50 (50% inhibitory concentration) was 0.003 to 0.013mcg/mL and the IC90 (90%
inhibitory concentration) was 0.03 to 0.3 mcg/mL.
Pharmacokinetics:
Zidovudine is well absorbed and undergoes first-pass hepatic glucuronidation to zidovudine
glucuronide. Peak plasma concentrations occur at 0.5-1.0 hour after dosing in the fasted state.
Both zidovudine glucuronide and zidovudine are eliminated through renal excretion with tubular
secretion contributing to the elimination.
Adverse Effects:
Anemia, neutropenia, headache, fatigue, nausea, and myalgia are the most common toxicities.
Dosage:
100mg capsule (100 capsule bottle)
300mg tablet (60 tablet bottle)
Syrup 50mg/5ml (240mg bottle)
Adult: 300mg twice daily
600mg once a day has been studied. This dose has been shown to have antiviral activity. However,
it is less marked and more slowly achieved than 300mg twice a day.
Pediatric:
Preterm Infants (10 mL/min - 300 mg twice daily
Clcr

Results (Indonesian) 1:

AZT (Retrovir®, AZT)Kelas:AZT adalah thymidine analog di kelas inhibitor transkriptase nukleosida.Aktivitas antivirus:AZT lebih aktif terhadap sel yang akut terinfeksi dibandingkan dengan sel yang kronis terinfeksi.Mekanisme Aksi:AZT phosphorylated untuk AZT-trifosfat, yang bersaing dengan endogennukleotida untuk penggabungan ke dalam DNA virus dan setelah dimasukkan penyebab rantai penghentiankarena kurangnya grup 3' OH.Mekanisme perlawanan:Resistensi terhadap NRTIs terjadi melalui dua mekanisme; menurun penggabungan dari NRTIs kevirus DNA dan meningkatkan pengeluaran NRTIs dari DNA virus.Pharmacodynamics:IC50 in vitro (konsentrasi 50% penghambatan) adalah 0.003 untuk 0.013mcg / mL dan IC90 (90%penghambatan konsentrasi) adalah 0.03-0,3 mcg/mL.Farmakokinetik:AZT baik diserap dan mengalami glucuronidation hepatik pertama-pass untuk AZTglukuronida. Kadar plasma puncak terjadi pada 0,5-1,0 jam setelah dosis dalam keadaan berpuasa.AZT glukuronida dan AZT dieliminasi melalui ekskresi renal dengan tabungsekresi pada penghapusan.Efek samping:Anemia, neutropenia, sakit kepala, kelelahan, mual, dan mialgia adalah toksisitas yang paling umum.Dosis:100mg kapsul (100 kapsul botol)300mg tablet (60 tablet botol)Sirup 50mg / 5ml (240mg botol)Dewasa: 300mg dua kali sehari600mg sekali sehari telah dipelajari. Dosis ini telah terbukti memiliki aktivitas antivirus. Namun,it is less marked and more slowly achieved than 300mg twice a day.Pediatric:Preterm Infants (<30 weeks gestational age)Oral: 2 mg/kg q12h IV: 1.5 mg/kg q12h (Both increased to q8h at four weeks of age)Preterm Infants (=30 weeks gestational age)Oral: 2 mg/kg q12h IV: 1.5 mg/kg q12h (Both increased to q8h at two weeks of age)Neonates (within 12 hours after birth through 6 weeks of age)Oral: 2 mg/kg q6h IV: 1.5 mg/kg, infused over 30 minutes, q6hPediatrics (6 weeks to 12 years)Oral: 160 mg/m2 q8h IV intermittent: 120 mg/m2 q6h IV continuous: 20 mg/m2/hrTake with or without foodDisease state based dosing:Clcr >10 mL/min - 300 mg twice dailyClcr <10 mL/min - 300 mg once dailyHemodialysis or continuous ambulatory peritoneal dialysis (CAPD) - 300 mg once dailyHepatic failure – no significant data to make recommendations on dose adjustments Severehepatic failure –the daily dose should be reduced 50% or the dosing interval should be doubled.Contraindications/Warnings/Precautions:Zidovudine should be used with caution in patients who have bone marrow compromise (i.e.granulocyte count <1,000 cells/mm 3 or hemoglobin <9.5 g/dL)Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reportedwith the use of NRTIs.Drug Interactions:The use of zidovudine and stavudine (d4T) concomitantly is contraindicated due to antagonismthat occurs between these two thymidine analogues. Zidovudine plasma concentrations aredecreased 25% by concurrent nevirapine use. Ritonavir induces glucuronidation and has beenfound to reduce the zidovudine AUC by approximately 25%.Ganciclovir, interferon-alpha and other cytotoxic or bone marrow suppressive agents(trimethoprim-sulfamethoxazole, dapsone, pyrimethamine, flucytosine, adriamycin, vinblastine,sulfadiazine, hydroxyurea, vincristine and amphotericin B) may increase the risk of hematologictoxicity associated with zidovudine. Both doxorubicin and ribavirin have demonstrated in vitroinhibition of zidovudine phosphorylation and antagonize its antiviral activity. Probenecidincreases the AUC of zidovudine by 106%.Pregnancy:Category C: Risk unknown. Human studies inadequate.Zidovudine has proven effective in preventing mother to child transmission of HIV infection.Recommended dosing regimen:Women >14 weeks pregnant (continued until onset of labor):100 mg orally 5 times per day OR200 mg orally three times daily OR300 mg orally twice dailyDuring labor and delivery:2 mg/kg (using mother's total body weight) IV over 1 hour then 1 mg/kg/ho ur (using mother's totalbody weight) continuous IV infusion until clamping of the umbilical cordInfant (start within 8 to 12 hours):2mg/kg orally every 6 hours for the first six weeks of lifeMonitoring Requirements:Frequent blood counts in patients with advanced HIV disease, periodic blood counts in patientswith asymptomatic or early HIV disease.Brand names/Manufacturer:Retrovir®GlaxoSmithKline