ZIDOVUDINE tablet, film coated

국가: 미국

언어: 영어

출처: NLM (National Library of Medicine)

유효 성분:

ZIDOVUDINE (UNII: 4B9XT59T7S) (ZIDOVUDINE - UNII:4B9XT59T7S)

제공처:

Aurobindo Pharma Limited

INN (국제 이름):

ZIDOVUDINE

구성:

ZIDOVUDINE 300 mg

관리 경로:

ORAL

처방전 유형:

PRESCRIPTION DRUG

치료 징후:

Zidovudine tablets, a nucleoside reverse transcriptase inhibitor, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Zidovudine tablets are indicated for the prevention of maternal-fetal HIV-1 transmission [see Dosage and Administration (2.3)].  The indication is based on a dosing regimen that included 3 components:   - antepartum therapy of HIV-1 infected mothers - intrapartum therapy of HIV-1 infected mothers - post-partum therapy of HIV-1 exposed neonate Points to consider prior to initiating zidovudine tablets in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:   - In most cases, zidovudine tablets for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs. - Prevention of HIV-1 transmission in women who have received zidovudine tablets for a prolonged period before pregnancy has not been evaluated. - Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy with zidovudine tablets during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 week's gestation. Zidovudine tablets are contraindicated in patients who have had a potentially life-threatening hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulation. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to zidovudine during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no difference in the overall risk of birth defects for zidovudine compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population (see Data) . The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks' gestation. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown. Hyperlactatemia, which may be due to mitochondrial dysfunction, has been reported in infants with in utero exposure to zidovudine-containing products. These events were transient and asymptomatic in most cases. There have been few reports of developmental delay, seizures, and other neurological disease. However, a causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum has not been established (see Data) . In an animal reproduction study, administration of oral zidovudine to female rats prior to mating and throughout gestation resulted in embryotoxicity at doses that produced systemic exposure (AUC) approximately 33 times higher than exposure at the recommended clinical dose. However, no embryotoxicity was observed after oral administration of zidovudine to pregnant rats during organogenesis at doses that produced systemic exposure (AUC) approximately 117 times higher than exposures at the recommended clinical dose. Administration of oral zidovudine to pregnant rabbits during organogenesis resulted in embryotoxicity at doses that produced systemic exposure (AUC) approximately 108 times higher than exposure at the recommended clinical dose. However, no embryotoxicity was observed at doses that produced systemic exposure (AUC) approximately 23 times higher than exposures at the recommended clinical dose (see Data) . Data Human Data: Based on prospective reports to the APR of over 13,000 exposures to zidovudine during pregnancy resulting in live births (including over 4,000 exposed in the first trimester), there was no difference between the overall risk of birth defects for zidovudine compared with the background birth defect rate of 2.7% in a U.S. reference population of the MACDP. The prevalence of birth defects in live births was 3.2% (95% CI: 2.7% to 3.8%) following first trimester exposure to zidovudine-containing regimens and 2.8% (95% CI: 2.5% to 3.2%) following second/third trimester exposure to zidovudine-containing regimens. A randomized, double-blind, placebo-controlled trial was conducted in HIV-1-infected pregnant women to determine the utility of zidovudine for the prevention of maternal-fetal HIV-1-transmission [see Clinical Studies (14.3)] . Zidovudine treatment during pregnancy reduced the rate of maternal-fetal HIV-1 transmission from 24.9% for infants born to placebo-treated mothers to 7.8% for infants born to mothers treated with zidovudine. There were no differences in pregnancy-related adverse events between the treatment groups. Of the 363 neonates that were evaluated, congenital abnormalities occurred with similar frequency between neonates born to mothers who received zidovudine and neonates born to mothers who received placebo. The observed abnormalities included problems in embryogenesis (prior to 14 weeks) or were recognized on ultrasound before or immediately after initiation of study drug. Zidovudine has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see Clinical Pharmacology (12.3)] . There have been reports of mild, transient elevations in serum lactate levels, which may be due to mitochondrial dysfunction, in neonates and infants exposed in utero or peri-partum to zidovudine-containing products. There have been few reports of developmental delay, seizures, and other neurological disease. However, a causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum has not been established. The clinical relevance of transient elevations in serum lactate is unknown. Animal Data: A study in pregnant rats (at 50, 150, or 450 mg per kg per day starting 26 days prior to mating through gestation to postnatal Day 21) showed increased fetal resorptions at doses that produced systemic exposures (AUC) approximately 33 times higher than exposure at the recommended daily human dose (300 mg twice daily). However, in an oral embryo-fetal development study in rats (at 125, 250, or 500 mg per kg per day on gestation Days 6 through 15), no fetal resorptions were observed at doses that produced systemic exposure (AUC) approximately 117 times higher than exposures at the recommended daily human dose. An oral embryo-fetal development study in rabbits (at 75, 150, or 500 mg per kg per day on gestation Day 6 through 18) showed increased fetal resorptions at the 500 mg per kg per day dose, which produced systemic exposures (AUC) approximately 108 times higher than exposure at the recommended daily human dose; however, no fetal resorptions were noted at doses up to 150 mg per kg per day, which produced systemic exposure (AUC) approximately 23 times higher than exposures at the recommended daily human dose. These oral embryo-fetal development studies in the rat and rabbit revealed no evidence of fetal malformations with zidovudine. In another developmental toxicity study, pregnant rats (dosed at 3,000 mg per kg per day from Days 6 through 15 of gestation) showed marked maternal toxicity and an increased incidence of fetal malformations at exposures greater than 300 times the recommended daily human dose based on AUC. However, there were no signs of fetal malformations at doses up to 600 mg per kg per day. Risk Summary The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Zidovudine is present in human milk. There is no information on the effects of zidovudine on the breastfed infant or the effects of the drug on milk production. Because of the potential for (1) HIV-1 transmission (in HIV negative infants), (2) developing viral resistance (in HIV positive infants), and (3) adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving zidovudine. Zidovudine has been studied in HIV-1-infected pediatric subjects aged at least 6 weeks who had HIV-1-related symptoms or who were asymptomatic with abnormal laboratory values indicating significant HIV-1-related immunosuppression. Zidovudine has also been studied in neonates perinatally exposed to HIV-1 [see Dosage and Administration (2.2), Adverse Reactions (6.1) , Clinical Pharmacology (12.3), Clinical Studies (14.2, 14.3)] . Clinical studies of zidovudine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Unchanged zidovudine and its glucuronide metabolite (formed in the liver) are primarily eliminated from the body by renal excretion. In patients with severely impaired renal function (CrCl less than 15 mL per min), dosage reduction is recommended [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)] . Zidovudine is primarily eliminated by hepatic metabolism and zidovudine concentrations appear to be increased in patients with impaired hepatic function, which may increase the risk of hematologic toxicity. Frequent monitoring of hematologic toxicities is advised. There are insufficient data to recommend dose adjustment of zidovudine in patients with impaired hepatic function or liver cirrhosis [see Dosage and Administration (2.6), Clinical Pharmacology (12.3)] .

제품 요약:

Zidovudine Tablets USP, 300 mg are white colored, biconvex, round, film-coated tablets debossed with ‘D’ on one side and ‘11’ on other side.                      Bottle of 60                               NDC 65862-024-60                      6 x 10 Unit-dose Tablets           NDC 65862-024-10 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

승인 상태:

Abbreviated New Drug Application

제품 특성 요약

ZIDOVUDINE - ZIDOVUDINE TABLET, FILM COATED
AUROBINDO PHARMA LIMITED
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZIDOVUDINE
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ZIDOVUDINE TABLETS.
ZIDOVUDINE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1987
WARNING: RISK OF HEMATOLOGICAL TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND
SEVERE HEPATOMEGALY WITH STEATOSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
_ _
HEMATOLOGIC TOXICITY INCLUDING NEUTROPENIA AND SEVERE ANEMIA HAVE BEEN
ASSOCIATED
WITH THE USE OF ZIDOVUDINE. (5.1)
SYMPTOMATIC MYOPATHY ASSOCIATED WITH PROLONGED USE OF ZIDOVUDINE.
(5.3)
LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING
FATAL CASES, HAVE
BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES INCLUDING
ZIDOVUDINE. SUSPEND
TREATMENT IF CLINICAL OR LABORATORY FINDINGS SUGGESTIVE OF LACTIC
ACIDOSIS OR
PRONOUNCED HEPATOTOXICITY OCCUR. (5.4)
INDICATIONS AND USAGE
Zidovudine tablets are a nucleoside analogue reverse transcriptase
inhibitor indicated for:
Treatment of Human Immunodeficiency Virus (HIV-1) infection in
combination with other antiretroviral
agents. (1.1)
Prevention of maternal-fetal HIV-1 transmission. (1.2)
DOSAGE AND ADMINISTRATION
• Treatment of HIV-1 infection:
Adults: Recommended oral dosage is 300 mg twice a day with other
antiretroviral agents. For patients
who are unable to take the oral formulations, the recommended
intravenous dose is 1 mg per kg infused
over 1 hour every 4 hours. (2.1)
Pediatric patients (aged 4 weeks to less than 18 years): Dosage should
be calculated based on body
weight not to exceed adult dose. (2.2)
• Prevention of maternal-fetal HIV-1 transmission:
Specific dosage instructions for mother and infant. (2.3)
• Patients with severe anemia and/or neutropenia:
Dosage interruption may be necessary. (2.4)
• Renal impairment: Recommended oral dosage in hemodialysis or
peritoneal dialysis or in patients with
creatinine clearance (CrCl) le