text:
//    Openbravo POS is a point of sales application designed for touch screens.
//    Copyright (C) 2007-2009 Openbravo, S.L.
//    http://www.openbravo.com/product/pos
//
//    This file is part of Openbravo POS.
//
//    Openbravo POS is free software: you can redistribute it and/or modify
//    it under the terms of the GNU General Public License as published by
//    the Free Software Foundation, either version 3 of the License, or
//    (at your option) any later version.
//
//    Openbravo POS is distributed in the hope that it will be useful,
//    but WITHOUT ANY WARRANTY; without even the implied warranty of
//    MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
//    GNU General Public License for more details.
//
//    You should have received a copy of the GNU General Public License
//    along with Openbravo POS.  If not, see <http://www.gnu.org/licenses/>.

package com.openbravo.pos.pda.struts.actions;

import javax.servlet.http.HttpServletRequest;
import javax.servlet.http.HttpServletResponse;
import org.apache.struts.action.ActionForm;
import org.apache.struts.action.ActionMapping;
import org.apache.struts.action.ActionForward;

/**
 *
 * @author jaroslawwozniak
 */
public class LogoutAction extends org.apache.struts.action.Action {

    /* forward name="success" path="" */
    private final static String SUCCESS = "success";

    /**
     * This is the action called from the Struts framework.
     * @param mapping The ActionMapping used to select this instance.
     * @param form The optional ActionForm bean for this request.
     * @param request The HTTP Request we are processing.
     * @param response The HTTP Response we are processing.
     * @throws java.lang.Exception
     * @return
     */
    public ActionForward execute(ActionMapping mapping, ActionForm form,
            HttpServletRequest request, HttpServletResponse response)
            throws Exception {

        request.getSession().invalidate();
        return mapping.findForward(SUCCESS);
    }
}

redpajama_set_name: RedPajamaGithub


CSI Life's new Medicare Supplement has a commission structure unlike any other carrier. John Hockaday explains how it works, and why it's so great.
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text:
張重文
Chung-Wen Chang
工業化國家跨期經常帳與貨幣存量之研究
Money and Intertemporal Current Accounts among Industrialize Countries
翁銘章
Ming-Jang Weng
經濟學系
社會及行為科學學門
經濟學類
經常帳、貨幣存量、向量自我迴歸、消費偏向效果
current account、money stock、VAR、consumption-tilting effect
下載:103
論文名稱: 工業化國家跨期經常帳與貨幣存量之研究 頁數: 98
校(院)所組別: 國立暨南國際大學管理學院經濟學研究所
畢業時間及提要別: 九十一學年度第二學期碩士論文提要
研究生: 張重文 指導教授: 翁銘章 博士
論文提要內容:
"未雨綢繆"為Campbell於1987年所發表文章中的一個著名的理論,指出消費的多寡取決於對未來經濟前景的理性預期,話雖如此,但在一個高度發展的國家裡,個人消費行為時常受到各種原因所影響,例如:時間偏好率、利率、通貨膨脹…等,因而一個理性的消費者應該將全部因素納入自己的消費考量中,在此同時,消費決策亦會彼此牽連而影響到經常帳及匯率。
基於消費平滑與恆常所得假說的觀點,我們依循Ghosh(1995a)的方法程序來估計一國的經常帳,並且將"貨幣"此一重要總體經濟因素納入跨期經常帳的研究方法中,用來解釋理論與實際經常帳之間的離異,藉以發掘該因素的重要性。
本文研究中囊括了五個主要的工業化國家來分析,並加入"貨幣" 作為探究其經常帳表現的重要性要素之一,這五個國家分別是:日本、加拿大、德國、美國及英國。根據所獲得的實證結果,不僅是如傳統文獻所強調的國民現金流量(national cash flow,本國國民產出減去投資及政府支出)而且在本文新加入的貨幣存量也都反映出它們對決定經常帳路徑的影響力,甚而,貨幣存量在我們的延伸方法裡亦扮演著解釋傳統方法所無法解釋的一個決定性角色。
總括而言,此五大工業化國家的經常帳,在面對國民現金流量及貨幣存量的變動時,的確能夠扮演一個平滑消費的緩衝器。
Title of Thesis:Money and Intertemporal Current Accounts among Industrialize Countries
Name of Institute:Graduate Institute of Economics, National Chi-Nan University, Taiwan
Graduate Date: June, 2002 Degree Conferred: Master
Name of Student: Chung-Wen Chang Advisor: Dr. Ming-Jang Weng
"Save for a rainy day", a well known theory proposed in Campbell (1987), indicates that the current consumption depends on the rational prospect of future economy. Nevertheless, within a highly developed economy, individual''s consumption is often affected by various factors, for instance, the rate of time preference, interest rates and inflation, …etc. Therefore, a rational representative consumer should take all possible information available to them into consideration in making decisions regarding optimal consumption; meanwhile, this will in turn affects current accounts and domestic credit as well.
Based on the viewpoints of consumption-smoothing and permanent income hypothesis, we modify Ghosh (1995a)''s methodology to incorporate one of important macroeconomic variables, "money" into the intertemporal approach to the current account to explore its influence in explaining the difference between theoretical and actual current accounts.
In this study, five major industrialized countries are investigated adding money as one of key elements: Japan, Canada, Germany, the US and UK. According to the empirical findings, not only the national cash flow (output minus investment and government expenditure) as stated in the literatures but money stock reflect their influence in determinating the dynamic behavior of current account aslo. Therefore, money does play a crucial role in our extensive method in explaining what traditional method can not explain.
As a whole, the current accounts of these five major industrialized countries indeed acts as a buffer to smooth consumption in facing fluctuations of shocks to national cash flow and money stock.
1 Introduction 1
1.1 Preliminary ……………………………………………….…… 1
1.2 The Motivation and Purpose ………………………………….. 8
1.3 Structure ………………………………………………………. 11
2 Literature Review 14
3 Theoretical Model And Econometric Method 27
3.1 The Present-value Model of the Current Account …………….. 28
3.2 The Extension of Present-value Model of the Current Account . 38
3.3 Econometric Method ………………………………………….. 44
3.3.1 Unit Root Test …………………………………………….. 44
3.3.2 Cointegration Test ………………………………………… 47
3.3.3 Vector Autoregression Model …………………………….. 49
3.3.4 Granger Causality Test ……………………………………. 51
3.3.5 Wald Test ………………………………………………….. 53
4 Empirical Evidence 61
4.1 Empirical Specification ………………………………………... 61
4.1.1 Data Source ………………………………………………... 61
4.1.2 Sample Period …………………………………………….. 62
4.1.3 Data Treatments …………………………………………… 62
4.1.4 Choice of World Interest Rate and Inflation Rate ………… 62
4.1.5 Variable ……………………………………………………. 63
4.2 Results ………………………………………………………….. 64
4.2.1 Unit Root and Cointegration Test …………………………. 64
4.2.2 Present-value Estimation ………………………………….. 66
5 Conclusion 86
4.1 Test for Unit Roots ……………………………………………… 73
4.2 Estimation for Consumption-tilting Effects (θ, θ1) ……………... 74
4.3 The Model Choice ……………………………………………… 75
4.4 Determination of Optimal Lag ………………………………….. 75
4.5 Japan's VAR Results ……………………………………………. 76
4.6 Canada's VAR Results ………………………………………….. 76
4.7 US's VAR Results ………………………………………………. 77
4.8 UK's VAR Results ……………………………………………… 77
4.9 Germany's VAR Results ………………………………………... 78
4.10 Germany1's VAR Results ………………………………………... 78
4.11 The Monetary Effect …………………………………………….. 79
4.12 Wald Test, etc. …………………………………………………… 79
1.1 Relationship GDP and current account for Japan ………………... 4
1.2 Relationship GDP and current account for the US ………………. 4
1.3 Relationship GDP and current account for Canada ……………… 5
1.4 Relationship GDP and current account for Germany ……………. 6
1.5 Relationship GDP and current account for the UK ……………… 7
1.6 Relationship money stock and current account for Japan ……….. 9
1.7 Relationship money stock and current account for the US ………. 9
1.8 Relationship money stock and current account for Canada …….. 10
1.9 Relationship money stock and current account for Germany …... 12
1.10 Relationship money stock and current account for the UK ……... 12
3.1 Relationship GDP and current account with money adjusted for Japan …………………………………………………………….. 56
3.2 Relationship money stock and current account with money adjusted for Japan …………………………………………………………. 56
3.3 Relationship money stock and current account with money adjusted for Canada ……………………………………………………….. 57
3.5 Relationship GDP and current account with money adjusted for the US ……………………………………………………………….. 58
3.6 Relationship money stock and current account with money adjusted for the US ………………………………………………………... 58
3.7 Relationship GDP and current account with money adjusted for the UK ……………………………………………………………….. 59
3.8 Relationship money stock and current account with money adjusted for the UK ……………………………………………………….. 59
3.9 Relationship GDP and current account with money adjusted for Germany ………………………………………………………… 60
3.10 Relationship money stock and current account with money adjusted for Germany …………………………………………………….. 60
4.1 Japan: actual and predicted current accounts using traditional and new approaches ………………………………………………….. 80
4.2 Canada: actual and predicted current accounts using traditional and new approaches ………………………………………………….. 81
4.3 US: actual and predicted current accounts using traditional and new approaches ………………………………………………………. 82
4.4 UK: actual and predicted current accounts using traditional and new approaches ………………………………………………………. 83
4.5 Germany: actual and predicted current accounts using traditional and new approaches …………………………………………………. 84
4.6 Germany: actual and predicted current accounts using traditional and new approaches ………………………………………………….. 85
[1] Agenor, P.R., C. Bismut, P. Cashin and C.J. McDermott, "Consumption Smoothing and the Current Account: Evidence for France, 1970-1996," Journal of International Money and Finance, 1999, vol.18, pp.1-12.
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[15] Ghosh, A. and J. Ostry, "The Current Account in Developing Countries: A Perspective from the Consumption-Smoothing Approach," World Bank Economic Review, 1995, vol.9, pp.305-333.
[16] Hall, Robert E., "Stochastic Implications of the Life Cycle-Permanent Income Hypothesis: Theory and Evidence," Journal of Political Economy, 1978, vol.86, pp.971-987.
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[31] Shibata, Akihisa and Mototsugu Shintani, "Capital Mobility in the World Economy: an Alternative Test," Journal of International Money and Finance, 1998, vol.17, pp.741-756.
[32] Trehan, Bharat and Carl E. Walsh, "Testing Intertemporal Budget Constraints: Theory and Applications to US Federal Budget and Current Account Deficits," Journal of Monet, Credit and Banking, 1991, vol.23, pp.206-223.
[33] Weng, Ming-Jang, "Recent Developments of the Intertemporal Current Accounts in the US and Japan," Mimeo, 2001.
[34] Wu, Jyh-Lin, Stilianos Fountas and Show-lin Chen, "Testing for the Sustainability of the Ccurrent Account Deficit in two Industrial Countries," Economics Letters, 1996, vol.52, pp.193-198.
[35] Wu, Jyh-Lin, "Mean Reversion of the Current Account: Evidence from the Panel Data Unit-root Test" Economics Letters, 2000, vol.66, pp.215-222.
[36] Yan, Ho-Don, "Intertemporal Current Account Balance and the East Asian Currency Crises," International Advances in Economic Research, 1999, vol.5, pp.277-288.
[37] Yan, Ho-Don, "Puzzles from Current Account Imbalances: a Comparison between Japan and the United States," Mimeo, 2000.
1. 日本、韓國與台灣加權股價指數連動關係之實證研究
2. 貨幣存量對經常帳動態之影響-G4工業化國家之研究
3. 經常帳決定理論之現值模型檢定-以台灣與南韓為例
4. 美、加、墨之跨國經常帳關聯
5. 台、日、韓之跨國長期經常帳關聯
6. 美日經常帳之動態關聯研究
1. 8.陳昭儀, "增強創造力的方法", 資優教育季刊 第54期, 1995。
2. 7.陳明溥, "ICAI之發展趨勢─智慧型電腦輔助教學", 資訊與教育 第31期, 1991。
3. 4.侯文娟, "智慧型教學系統", 資訊與教育 第39期, 1994。
2. 購買力平價說對匯率動態解釋能力?-不同開發程度國家匯率實證結果
3. 快速經濟成長下人力資本投資報酬率的變化─台灣實證
4. 商業銀行逾放款之研究─應用距離函數法
5. 人壽保費定價--界限選擇權及跳躍序列模型的應用
6. 男性婚姻溢酬之實證分析-以台灣地區為例
7. 廠商研發支出的租稅效果
8. 緩長記憶之虛假迴歸檢定
9. 雙重狀態貝它係數之國際資本資產訂價模式建構與檢測-國際主要股價指數報酬實證研究
10. 人力資本的代間移轉--家庭背景對子女教育成就的影響
11. 日本與美國近來的經常帳關聯
12. 社會資本與均衡路徑未定性
13. 中央銀行干預及總體經濟訊息變數對匯率波動性的影響
14. 不對稱複佔下之研發
15. 家庭背景對子女教育成就之影響

redpajama_set_name: RedPajamaCommonCrawl


Manager, Fleet/Lease Manager, and National Account Manager.
She became KCI Kansas City's Assistant General Manager of Sales in 2013, and in 2017, became the McConkey Auction Group's Vice President of National Sales.
Spokane, Kansas City and Seattle lanes. She currently serves as Secretary of the National Auto Auction Association's Western Zone Board.


After purchasing this Audio/Video you will receive an email with a link to watch and download your sessions.
Healthy desire comes from the real self and from a genuine place in the heart, but envy comes from a very different place. Envy is not about simple healthy desire; envy defines the good as "that which I don't have". It devalues what I do have, comparing it to what I don't have but want. We believe something will make us happy, yet when we get that thing, the cycle starts all over. Envy idealizes what we don't have, creating emptiness within us. Join Dr. Cloud as he helps you understand the destructive effects of envy, how it develops, and how to begin to change this pattern in your life. He will show you how to get your desires connected to your heart and your real self, and loosen the hold caused by this pattern of envy. There is hope!


text:
The temperate rainforests of the Russian Far East are within the Russian federal subjects Primorsky Krai and Khabarovsk Krai and contains the Sikhote-Alin mountain range. Found within the Russian Federation, this area is one of the most productive and diverse forests in the world and also contains one of the highest endangered species densities on Earth. While most temperate rainforests around the world have retained only a fraction of their historical range, these forests maintain the majority of their former range and almost all of their historical biodiversity. The region is also notable for having what has become the last remaining large tract of viable habitat for the critically endangered Amur tiger and Amur leopard.

History
The Russian Federation contains one sixth of the world's land mass and around half of the country's territory is what could be considered continuous wilderness, with large expanses of boreal forests providing relatively untouched habitat for an extremely wide diversity of species. The temperate rainforests are located at the intersection of the Pacific tectonic plate and the Eurasian continent's plate in far southeastern Russia, forming an area with a unique set of characteristics seen no where else in the world. During the last glacial maximum, the area was not glaciated, allowing for the development of a complex ecosystem containing species with origins in Siberia's boreal forest and Manchuria's subtropical forests. Historically these forests ranged from the southeastern Pacific coast of Russia, North Korea, and into northern China, however large amounts of human development (in China especially) has limited the forest to its current range in the Russian Far East. In 2001, UNESCO recognized a 1.5 million hectare area of forest in the central part of the Sikhote-Alin mountains as a World Heritage Site in Russia, citing the area as one of the most unique and valuable areas of intact forest in the world

Geography
These forests are found dispersed throughout the Sikhote-Alin mountain range, which extend over 1000 km along the west coast of the Sea of Japan. The mountains have a maximum height of 1850 m, while the average elevation within the range is around 1000 m. The major rivers include the Ussuri, which acts as the western border with China and empties into the Amur river, which in turn flows northeast to empties into the Sea of Okhotsk. The Bikin and Iman rivers act as tributaries to the Ussuri, flowing west from the Sikhote-Alin mountain range.

Climate
Known as the "Ussuri taiga," this region of Russia has long, cold winters and fairly mild summers to go along with a mean precipitation of 800–1000 mm per year. During the summer and fall, a monsoonal influence brings tropical storms and typhoons coming from the southeast, resulting in substantial rainfall. Fog occurs as a result of difference in temperatures between the continent and the ocean, resulting in more moderate temperatures, higher humidities; helping to prevent substantial water loss from occurring due to evapotranspiration. Continental winds coming in from Siberia bring cooler, dry air during winter, resulting in lighter precipitation (30–50 cm of snow). Winters can be long and bitterly cold with January mean temperatures ranging from -15 to -20 °C and snow covering the forest floor from October to April. The driest parts of the year are from April to June and September to October, which also happen to coincide with the greatest threat of forest fire.

Species
The forests fall in the transition zone between two biomes: the southern Asian hardwood forest and the northern coniferous forest. There have been around 2500 species of vascular plants and 300 vertebrate species recorded in Primorsky Krai.

The forest is a mix of broadleaf and conifer, with the forest type becoming more conifer dominated at higher elevations and more broad-leaf-conifer mixed at the lower elevations and within valleys. The most common species include the Korean pine (Pinus koraiensis) and Manchurian fir (Abies holophylla) at the lowest elevations and coastlines. Jezo spruce (Picea jezoensis) and Khingan fir (Abies nephrolepis) are common species to be found from 700–1400 meters. Other tree species include Mongolian oak (Quercus mongolica), silver birch (Betula platyphylla), Scots pine (Pinus sylvestris), trembling aspen (Populus tremula), Siberian dwarf pine (Pinus pumila), Erman's birch (Betula ermanii), and Dahurian larch (Larix gmelinii), a deciduous conifer common throughout, but dominant in the northernmost reaches of the forest The Amur region of Russia holds the last remaining habitats for the critically endangered Siberian tiger, Amur leopard, and Manchurian sika deer. It has been estimated that there are less the 600 tigers. and around 90 leopards left in the wild. The area also contains populations of Asiatic black bears, Kamchatka brown bears, and Mongolian grey wolves, as the Russian Far East, altogether, might probably be the only place in the world where endangered tigers, leopards, bears, and grey wolves coexist. This region also happens to be some of the last of habitat of the Blakiston's fish owl (Bubo blakistoni); along with being the world's largest owl, it is unique in the way that it eats fish (primarily Masu salmon) and relies on old growth forests along river banks to hunt, nest, and breed. The Siberian grouse is similar to the spruce grouse and Franklin's grouse of North America, and can be found in the dense, remote pockets of broadleaf, coniferous and deciduous forests of Far East Russia. Common ungulates include red deer, roe deer, wild boar, Manchurian moose, and musk deer.

Forest structure and disturbances
Fire and logging constitute the primary disturbances in this area, both of which are occurring at an increasing frequency. Illegal logging practices, along with a political climate more favorable to multinational logging corporations has drastically increased the amount of timber taken per year. The occurrence of Korean pine in dominant forests has been declining as more common and more intense wildfires start to take their toll on the species, limiting its ability to recover and changing areas that were once dominated by old growth Korean pine to Mongolian oak and birch forests. Above 700–800 meters in altitude, the forest type transitions from broadleaf to coniferous, dominated by Jezo spruce and Manchurian fir. The further to the north, the altitudinal gradient decreases with the increase in latitude, resulting in coniferous forests at sea level at 47° N latitude.

Conservation
Under the USSR control, conservation strategies focused on the creation and a network of strictly protected nature reserves, called zapovednik and partially protected wildlife refuges, called zakaznik. These conservation strategies were largely successful and well maintained, as 85 zapovedniks and 26 national parks remained within Russian control after the fall of the Soviet Union in December 1991. Following the break up, a period of economic hardship has ensued in Russia, resulting in conservation funding cuts and increases in illegal logging and poaching, casting serious doubt on the viabilities of the protected areas and the many rare and endemic species that they contain.

Conservation policies have been falling from federal control down to a regional level, which creates funding and enforcement challenges, but also allows for a more grass-roots, bottom up approach to conservation, which despite the challenges has seen some success. Much of the recent funding for conservation studies and implementation of legislation comes from donors and organizations in the United States, where investing in conserving the biodiversity in the Russian Far East is seen as a good economic investment. At a species level, Korean pine is a highly valued type of timber, and although the logging of the species is restricted, illegal logging practices thrive due to a lack of enforcement. Korean pine forests also receive the most interest when it comes to conservationists, as they have been found to have the highest densities of tigers and their prey. Because of this, it appears that the longevity of the temperate rain forests in the Russian Far East will most likely depend on the success of the habitat conservation efforts for the endangered species found there, particularly those for the Amur tiger.

References

External links
 Zhuravlev, Yu. N., ed. (2000) Стратегия сохранения биоразнообразия Сихотэ-Алиня = A Biodiversity Conservation Strategy for the Sikhote-Alin' Vladivostok: Russian Academy of Sciences, Far Eastern Branch

Ecoregions of Russia
Temperate broadleaf and mixed forests
Temperate coniferous forests
Temperate rainforests
Geography of the Russian Far East

redpajama_set_name: RedPajamaWikipedia


NEW YORK – AUGUST 14: Jayson Werth #28 of the Philadelphia Phillies bats against the New York Mets on August 14, 2010 at Citi Field in the Flushing neighborhood of the Queens borough of New York City.
Are Phils on verge of dynasty?
Given the wretched history of the game's losingest franchise, it seems out of place to suggest such a question. Well, don't look now, but the Phillies are trying to become the first team since the 1942-44 Cardinals to win three consecutive NL pennants, and they could win a few more before they're done. They've gotten here despite injuries that would have crippled most teams. Crazy stuff happens in the playoffs, but Philly, with its pitchers and hitters on a roll, has to be considered the favorite to go all the way.
Can Reds hit their way to NLCS?
Generally, relying on hitting to win in the playoffs against A-list pitchers isn't good business. But that's where the Reds find themselves. Their pitchers are no match for the Phillies' Big Three of Roy Halladay, Roy Oswalt and Cole Hamels, so they're going to have to get it done with their bats. They're certainly capable, having led the league in hitting (.271), home runs (187) and runs per game (4.9). Likely NL MVP Joey Votto hit .393 vs. the Phillies during the season, but this is a different Phillies team. They finished 21-6 in September, the best record in baseball.
Will Edinson Volquez step up?
Three months ago, when the Rockies visited Cincinnati after the all-star break, Volquez was making his first start after months of rehabbing his way back from Tommy John surgery. Today, Volquez is the Reds' starter for the series opener against the Phillies. Dusty Baker doesn't have the likes of Halladay or Oswalt, so he went with the hot hand. Volquez in his final four starts: 27 2/3 innings, six runs allowed and 31 strikeouts. If he can be that guy in the opener, and if the Reds can steal one to start the series, they may have a chance. If not, they could be gone in a hurry.
As we speak, Werth's agent, Scott Boras, is probably putting together a book of reasons why Werth should get paid $100 million-plus when he becomes a free agent. But nothing his agent says can jack up Werth's price more than performing in the playoffs. How much has Werth progressed in recent years? He was a platooner vs. lefties for Jim Tracy in Los Angeles. This year, he hit 20 home runs against right-handers.


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The Coos Bay Area Zonta Service Foundation is affiliated with Zonta International, a leading global organization of professionals empowering women worldwide through service and advocacy.The Coos Bay Area Club was chartered in 1953 and grants thousands of dollars in scholarships annually.Each scholarship is eligible to help cover tuition, fees, books, supplies, and if applicable, dormitory housing including a meal plan charged to a recipient's account at any accredited college, university or trade school within the United States.
Applicants will demonstrate an interest in working to support Zonta's mission:To improve the legal, political, economic, educational, health or professional status of women.
For all scholarships, preference is given to applicants who exhibit financial need and who have graduated from a Coos County high school or have lived in Coos County for 5 years.
Applicants are eligible to apply for one or more scholarships.
Recommendation letters cannot be written by family members.
Field of study must be in an accredited business or business-related program.
Open to Women of any age within the Coos County area.
Must complete minimum 36 college credits by end of Spring term 2020.
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Must plan to attend accredited institution; full time (12 credits) in Fall of 2019.
Scoring will be based on:scholastic ability, essay and recommendation letters (2).
Recipients of this scholarship are automatically entered into the District 8 Scholarship competition to earn an additional $2,000 if selected.
To obtain background information about this scholarship, go to:https://www.zonta.org/Global-Impact/Education/Women-in-Business-Scholarship.
Field of study focus must be in Science, Technology, Engineering or Math.
Open to ALL individuals within the Coos County area.
Cumulative GPA must be 3.0 or higher.
Open to high school or college students.
Any field of study is accepted.
Must complete minimum 36 college credit by end of Spring term 2020.
Cumulative GPA must be 2.5 or higher.
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Are living or studying in a Zonta district/region.
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Scoring will be based on:Academic performance, essay content and volunteer work. Recipients of this scholarship may be nominated for the District 8 Scholarship competition to earn an additional $2,000 if selected.
Open to women within the Coos County area.
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In the essay, provide a brief explanation why education was interrupted.
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Scoring will be based on:scholastic ability; content of essay and recommendation letters (2).
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In the essay, explain what you plan to do with your certification.
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Describe in your essay how your involvement in Z-Club has impacted you.
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One electronic copy OR one hard copy of your full application must be submitted and postmarked by March 20, 2019. See Application Check List for complete instructions and address.
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YOUNG WOMEN IN PUBLIC AFFAIRS cash award applications are due MARCH 1, 2019.The winning recipient's application will be forwarded to the district level for an opportunity for another award.All other scholarship applications are due APRIL 1, 2019.
Submit this application electronically OR mail complete application to Zonta Scholarship Committee, P.O. Box 245, North Bend, OR 97459 submitted and postmarked by MARCH 1, 2019.


text:
Label: ZIDOVUDINE tablet, film coated
Packager: Lannett Company, Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ZIDOVUDINETABLETS 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)
Zidovudine is 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)
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) less than 15 mL per minute is 100 mg every 6 to 8 hours. Equivalent intraveneous dosing is approximately 1 mg per kg every 6 to 8 hours.( 2.5)
Tablets: 300 mg ( 3)
Hypersensitivity to zidovudine or any of the components (e.g., anaphylaxis, Stevens-Johnson syndrome). ( 4)
See boxed warning for information about the following: hematologic toxicity, myopathy, and lactic acidosis and severe hepatomegaly. ( 5.1, 5.3, 5.4)
Exacerbation of anemia has been reported in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine. Coadministration of ribavirin and zidovudine is not advised. ( 5.5)
Hepatic decompensation, (some fatal), has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy and interferon alfa with/without ribavirin. Discontinue zidovudine as medically appropriate and consider dose reduction or discontinuation of interferon alfa, ribavirin, or both. ( 5.5)
Zidovudine tablets should not be administered with other zidovudine-containing combination products. ( 5.6)
Immune reconstitution syndrome ( 5.6) and lipoatrophy ( 5.7) have been reported in patients treated with combination antiretroviral therapy.
Most commonly reported adverse reactions (incidence greater than or equal to 15%) in adult HIV-1 clinical trials were headache, malaise, nausea, anorexia, and vomiting. ( 6.1)
Most commonly reported adverse reactions (incidence greater than or equal to 15%) in pediatric HIV-1 clinical trials were fever and cough. ( 6.1)
Most commonly reported adverse reactions in neonates (incidence greater than or equal to 15%) in the prevention of maternal-fetal transmission of HIV-1 clinical trial were anemia and neutropenia. ( 6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-800-325-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Avoid use with stavudine. ( 7.1)
Avoid use with doxorubicin. ( 7.2)
Bone marrow suppressive/cytotoxic agents: May increase the hematologic toxicity of zidovudine. ( 7.3)
Lactation: Women infected with HIV should be instructed not to breastfed due to potential for HIV transmission ( 8.2)
See 17 for PATIENT COUNSELING INFORMATION.
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Treatment of HIV-1
1.2 Prevention of Maternal-Fetal HIV-1 Transmission
2 DOSAGE AND ADMINISTRATION
2.1 Adults – Treatment of HIV-1 Infection
2.2 Pediatric Patients (Aged 4 Weeks to Less Than 18 Years)
2.4 Patients with Severe Anemia and/or Neutropenia
2.5 Patients with Renal Impairment
2.6 Patients with Hepatic Impairment
3 DOSAGE FORMS AND STRENGTHS
5 WARNINGS AND PRECAUTIONS
5.1 Hematologic Toxicity/Bone Marrow Suppression
5.3 Myopathy
5.4 Lactic Acidosis/Severe Hepatomegaly with Steatosis
5.5 Use with Interferon- and Ribavirin-based Regimens in HIV-1/HCV Co-infected Patients
5.6 Immune Reconstitution Syndrome
5.7 Lipoatrophy
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 Antiretroviral Agents
7.2 Doxorubicin
7.3 Hematologic/Bone Marrow Suppressive/Cytotoxic Agents
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
12.4 Microbiology
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Adults
14.2 Pediatric Patients
14.3 Prevention of Maternal-Fetal HIV-1 Transmission
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
Sections or subsections omitted from the full prescribing information are not listed.
Zidovudine tablets have been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease [see Warnings and Precautions (5.1)].
Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.3)].
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including zidovudine and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)].
Zidovudine, a nucleoside reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Zidovudine is 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 three 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 in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:
In most cases, zidovudine 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 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 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.
The recommended oral dose of zidovudine tablets is 300 mg twice daily in combination with other antiretroviral agents.
Healthcare professionals should pay special attention to accurate calculation of the dose of zidovudine, transcription of the medication order, dispensing information, and dosing instructions to minimize risk for medication dosing errors.
Prescribers should calculate the appropriate dose of zidovudine for each child based on body weight (kg) and should not exceed the recommended adult dose.
Before prescribing zidovudine tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow a zidovudine tablet, the zidovudine syrup formulation should be prescribed.
The recommended oral dosage in pediatric patients aged 4 weeks to less than 18 years and weighing greater than or equal to 4 kg is provided in Table 1. Zidovudine syrup should be used to provide accurate dosage when whole tablets are not appropriate.
Table 1: Recommended Pediatric Oral Dosage of Zidovudine
Body Weight (kg)
Total Daily Dose
Dosage Regimen and Dose
Three Times Daily
4 to < 9
24 mg/kg/day
12 mg/kg
≥ 9 to < 30
600 mg/day
Alternatively, dosing for zidovudine can be based on body surface area (BSA) for each child. The recommended oral dose of zidovudine is 480 mg per m 2 per day in divided doses (240 mg per m 2 twice daily or 160 mg per m 2 three times daily). In some cases the dose calculated by mg per kg will not be the same as that calculated by BSA.
The recommended dosage regimen for administration to pregnant women (greater than 14 weeks of pregnancy) and their neonates is:
Maternal Dosing
100 mg orally 5 times per day until the start of labor [see Clinical Studies (14.3)] . During labor and delivery, intravenous zidovudine should be administered at 2 mg per kg (total body weight) over 1 hour followed by a continuous intravenous infusion of 1 mg per kg per hour (total body weight) until clamping of the umbilical cord.
Neonatal Dosing
Start neonatal dosing within 12 hours after birth and continue through 6 weeks of age. Neonates unable to receive oral dosing may be administered zidovudine intravenously. See Table 2 for dosing recommendations.
Table 2. Recommended Neonatal Dosages of Zidovudine
Dose and Dosage Regimen
8 mg/kg/day
2 mg/kg every 6 hours
1.5 mg/kg infused over 30 minutes, every 6 hours
Significant anemia (hemoglobin less than 7.5 g per dL or reduction greater than 25% of baseline) and/or significant neutropenia (granulocyte count less than 750 cells per mm 3 or reduction greater than 50% from baseline) may require a dose interruption until evidence of marrow recovery is observed [see Warnings and Precautions (5.1)]. In patients who develop significant anemia, dose interruption does not necessarily eliminate the need for transfusion. If marrow recovery occurs following dose interruption, resumption in dose may be appropriate using adjunctive measures such as epoetin alfa at recommended doses, depending on hematologic indices such as serum erythropoietin level and patient tolerance.
In patients maintained on hemodialysis or peritoneal dialysis or with creatinine clearance (CrCl) by Cockcroft-Gault less than 15 mL per min, the recommended oral dosage is 100 mg every 6 to 8 hours. The intravenous dosing regimen equivalent to the oral administration of 100 mg every 6 to 8 hours is approximately 1 mg per kg every 6 to 8 hours [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
There are insufficient data to recommend dose adjustment of zidovudine in patients with impaired hepatic function or liver cirrhosis. Frequent monitoring of hematologic toxicities is advised [see Use in Specific Populations (8.7)].
Zidovudine tablets are white, biconvex, round, film-coated tablets debossed with "S2" on one side and blank on the other side.
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 formulations.
Zidovudine should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count less than 1,000 cells per mm 3 or hemoglobin less than 9.5 g per dL. Hematologic toxicities appear to be related to pretreatment bone marrow reserve and to dose and duration of therapy. In patients with advanced symptomatic HIV-1 disease, anemia and neutropenia were the most significant adverse events observed. In patients who experience hematologic toxicity, a reduction in hemoglobin may occur as early as 2 to 4 weeks, and neutropenia usually occurs after 6 to 8 weeks. There have been reports of pancytopenia associated with the use of zidovudine, which was reversible in most instances after discontinuance of the drug. However, significant anemia, in many cases requiring dose adjustment, discontinuation of zidovudine, and/or blood transfusions, has occurred during treatment with zidovudine alone or in combination with other antiretrovirals.
Frequent blood counts are strongly recommended to detect severe anemia or neutropenia in patients with poor bone marrow reserve, particularly in patients with advanced HIV-1 disease who are treated with zidovudine. For HIV-1-infected individuals and patients with asymptomatic or early HIV-1 disease, periodic blood counts are recommended. If anemia or neutropenia develops, dosage interruption may be needed [see Dosage and Administration (2.4)].
Myopathy and myositis with pathological changes, similar to that produced by HIV-1 disease, have been associated with prolonged use of zidovudine.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including zidovudine. A majority of these cases have been in women. Female sex and obesity may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues. Treatment with zidovudine should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations.
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as zidovudine. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with zidovudine in HIV-1/HCV co-infected subjects [see Clinical Pharmacology (12.3)] , exacerbation of anemia due to ribavirin has been reported when zidovudine is part of the HIV regimen. Coadministration of ribavirin and zidovudine is not advised. Consideration should be given to replacing zidovudine in established combination HIV-1/HCV therapy, especially in patients with a known history of zidovudine-induced anemia.
Hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and zidovudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia.
Discontinuation of zidovudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6) (see the complete prescribing information for interferon and ribavirin).
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including zidovudine. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
Treatment with zidovudine has been associated with loss of subcutaneous fat. The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to a non-zidovudine-containing regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine and other zidovudine- containing products, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy.
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Hematologic toxicity, including neutropenia and anemia [see Boxed Warning, Warnings and Precautions (5.1)].
Symptomatic myopathy [see Boxed Warning, Warnings and Precautions (5.3)].
Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.4)].
Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.5)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The frequency and severity of adverse reactions associated with the use of zidovudine are greater in patients with more advanced infection at the time of initiation of therapy.
Table 3 summarizes adverse reactions reported at a statistically significant greater incidence for subjects receiving oral Zidovudine in a monotherapy trial.
Table 3. Percentage (%) of Subjects with Adverse Reactions (Greater Than or Equal to 5% Frequency) in Asymptomatic HIV-1 Infection (ACTG 019)
Zidovudine 500 mg/day
9% *
In addition to the adverse reactions listed in Table 3, adverse reactions observed at an incidence of greater than or equal to 5% in any treatment arm in clinical trials (NUCA3001, NUCA3002, NUCB3001 and NUCB3002) were abdominal cramps, abdominal pain, arthralgia, chills, dyspepsia, fatigue, insomnia, musculoskeletal pain, myalgia, and neuropathy. Additionally, in these trials hyperbilirubinemia was reported at an incidence of less than or equal to 0.8%.
Selected laboratory abnormalities observed during a clinical trial of monotherapy with oral zidovudine are shown in Table 4.
Table 4. Frequencies of Selected (Grade 3/4) Laboratory Abnormalities in Subjects with Asymptomatic HIV-1 Infection (ACTG 019)
ULN = Upper limit of normal.
(Abnormal Level)
Anemia (Hgb < 8 g/dL)
Granulocytopenia (< 750 cells/mm 3)
Thrombocytopenia (platelets < 50,000/mm 3)
ALT (> 5 x ULN)
AST (> 5 x ULN)
The adverse reactions reported during IV administration of zidovudine injection are similar to those reported with oral administration; neutropenia and anemia were reported most frequently. Long-term IV administration beyond 2 to 4 weeks has not been studied in adults and may enhance hematologic adverse reactions. Local reaction, pain, and slight irritation during IV administration occur infrequently.
The clinical adverse reactions reported among adult recipients of zidovudine may also occur in pediatric patients.
Trial ACTG 300: Selected clinical adverse reactions and physical findings with a greater than or equal to 5% frequency during therapy with EPIVIR ® (lamivudine) oral suspension 4 mg per kg twice daily plus zidovudine 160 mg per m 2 3 times daily compared with didanosine in therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 5.
Table 5. Selected Clinical Adverse Reactions and Physical Findings (Greater Than or Equal to 5% Frequency) in Pediatric Subjects in Trial ACTG 300
Includes pain, discharge, erythema, or swelling of an ear.
EPIVIR plus zidovudine tablets
Didanosine
Abnormal breath sounds/wheezing
Signs or symptoms of ears *
Nasal discharge or congestion
Selected laboratory abnormalities experienced by therapy-naive (less than or equal to 56 days of antiretroviral therapy) pediatric subjects are listed in Table 6.
Table 6. Frequencies of Selected (Grade 3/4) Laboratory Abnormalities in Pediatric Subjects in Trial ACTG 300
ANC = Absolute neutrophil count.
Neutropenia (ANC < 400 cells/mm 3)
ALT (> 10 x ULN)
AST (> 10 x ULN)
Lipase (> 2.5 x ULN)
Total amylase (> 2.5 x ULN)
Macrocytosis was reported in the majority of pediatric subjects receiving zidovudine 180 mg per m 2 every 6 hours in open-label trials. Additionally, adverse reactions reported at an incidence of less than 6% in these trials were congestive heart failure, decreased reflexes, ECG abnormality, edema, hematuria, left ventricular dilation, nervousness/irritability, and weight loss.
Use for the Prevention of Maternal-Fetal Transmission of HIV-1
In a randomized, double-blind, placebo-controlled trial in HIV-1-infected women and their neonates conducted to determine the utility of zidovudine for the prevention of maternal-fetal HIV-1 transmission, zidovudine syrup at 2 mg per kg was administered every 6 hours for 6 weeks to neonates beginning within 12 hours following birth. The most commonly reported adverse reactions were anemia (hemoglobin less than 9.0 g per dL) and neutropenia (less than 1,000 cells per mm 3). Anemia occurred in 22% of the neonates who received zidovudine and in 12% of the neonates who received placebo. The mean difference in hemoglobin values was less than 1 g per dL for neonates receiving zidovudine compared with neonates receiving placebo. No neonates with anemia required transfusion and all hemoglobin values spontaneously returned to normal within 6 weeks after completion of therapy with zidovudine. Neutropenia in neonates was reported with similar frequency in the group that received zidovudine (21%) and in the group that received placebo (27%). The long-term consequences of in utero and infant exposure to zidovudine are unknown.
The following adverse reactions have been identified during post-approval use of zidovudine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: Back pain, chest pain, flu-like syndrome, generalized pain, redistribution/
accumulation of body fat [see Warnings and Precautions (5.7)].
Cardiovascular:Cardiomyopathy, syncope.
Eye: Macular edema.
Gastrointestinal: Constipation, dysphagia, flatulence, oral mucosa pigmentation, mouth ulcer.
General: Sensitization reactions including anaphylaxis and angioedema, vasculitis.
Hematologic: Aplastic anemia, hemolytic anemia, leukopenia, lymphadenopathy, pancytopenia with marrow hypoplasia, pure red cell aplasia.
Hepatobiliary: Hepatitis, hepatomegaly with steatosis, jaundice, lactic acidosis, pancreatitis.
Musculoskeletal: Increased CPK, increased LDH, muscle spasm, myopathy and myositis with pathological changes (similar to that produced by HIV-1 disease), rhabdomyolysis, tremor.
Nervous: Anxiety, confusion, depression, dizziness, loss of mental acuity, mania, paresthesia, seizures, somnolence, vertigo.
Reproductive System and Breast: Gynecomastia.
Respiratory: Dyspnea, rhinitis, sinusitis.
Skin and Subcutaneous Tissue: Changes in skin and nail pigmentation, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, sweating, urticaria.
Special Senses: Amblyopia, hearing loss, photophobia, taste perversion.
Renal and Urinary: Urinary frequency, urinary hesitancy.
Stavudine
Concomitant use of zidovudine with stavudine should be avoided since an antagonistic relationship has been demonstrated in vitro.
Nucleoside Analogues Affecting DNA Replication
Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of zidovudine against HIV-1; concomitant use of such drugs should be avoided.
Concomitant use of zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated in vitro.
Coadministration of ganciclovir, interferon alfa, ribavirin, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RETROVIR 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).
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.
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)] .
Acute overdoses of zidovudine have been reported in pediatric patients and adults. These involved exposures up to 50 grams. No specific symptoms or signs have been identified following acute overdosage with zidovudine apart from those listed as adverse events such as fatigue, headache, vomiting, and occasional reports of hematological disturbances. Patients recovered without permanent sequelae. Hemodialysis and peritoneal dialysis appear to have a negligible effect on the removal of zidovudine while elimination of its primary metabolite, 3ʹ‑azido-3ʹ-deoxy-5ʹ- O-β- D-glucopyranuronosylthymidine (GZDV), is enhanced. If overdose occurs, the patient should be monitored for evidence of toxicity and given standard supportive treatment as required.
Zidovudine (formerly called azidothymidine [AZT]), is a pyrimidine nucleoside analogue active against HIV-1. The chemical name of zidovudine is 3ʹ-Azido-3ʹ-deoxythymidine; it has the following structural formula:
Zidovudine is a white to yellowish powder with a molecular weight of 267.24 and a solubility of 20.1 mg per mL in water at 25°C. The molecular formula is C 10H 13N 5O 4.
Zidovudine tablets are for oral administration. Each film-coated tablet contains 300 mg of zidovudine and the inactive ingredients hypromellose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, polyethylene glycol, titanium dioxide, polyvinyl alcohol-part hydrolyzed, talc and lecithin soya.
Zidovudine is an antiretroviral agent [see Microbiology (12.4)] .
Absorption and Bioavailability
Following IV dosing, dose-independent kinetics was observed over the range of 1 to 5 mg per kg. The mean steady-state peak and trough concentrations of zidovudine at 2.5 mg per kg every 4 hours were 1.1 and 0.1 mcg per mL, respectively.
In adults, following oral administration, zidovudine is rapidly absorbed and extensively distributed, with peak serum concentrations occurring within 0.5 to 1.5 hours. The AUC was equivalent when zidovudine was administered as zidovudine tablets or syrup compared with zidovudine capsules. The pharmacokinetic properties of zidovudine in fasting adult subjects are summarized in Table 7.
Table 7. Zidovudine Pharmacokinetic Parameters in Adult Subjects
Median [range] for 50 paired samples drawn 1 to 8 hours after the last dose in subjects on chronic therapy with zidovudine.
Approximate range.
Mean ± SD
(except where noted)
Oral bioavailability (%)
(n = 5)
Apparent volume of distribution (L/kg)
Cerebrospinal fluid (CSF):plasma ratio *
0.6 [0.04 to 2.62]
Systemic clearance (L/h/kg)
Renal clearance (L/h/kg)
0.34 ± 0.05
Elimination half-life (h) †
0.5 to 3
The apparent volume of distribution of zidovudine is 1.6 ± 0.6 L per kg (Table 7); and binding to plasma protein is low (less than 38%).
Metabolism and Elimination
Zidovudine is primarily eliminated by hepatic metabolism. The major metabolite of zidovudine is GZDV. GZDV AUC is about 3-fold greater than the zidovudine AUC. Urinary recovery of zidovudine and GZDV accounts for 14% and 74%, respectively, of the dose following oral administration and 18% and 60%, respectively, following IV dosing. A second metabolite, 3ʹ-amino-3ʹ‑deoxythymidine (AMT), has been identified in the plasma following single-dose IV administration of zidovudine. The AMT AUC was one-fifth of the zidovudine AUC. Pharmacokinetics of zidovudine were dose independent at oral dosing regimens ranging from 2 mg per kg every 8 hours to 10 mg per kg every 4 hours.
Effect of Food on Absorption
Zidovudine may be administered with or without food. The zidovudine AUC was similar when a single dose of zidovudine was administered with food.
Patients with Renal Impairment: Zidovudine clearance was decreased resulting in increased zidovudine and GZDV half-life and AUC in subjects with impaired renal function (n = 14) following a single 200-mg oral dose (Table 8). Plasma concentrations of AMT were not determined. No dose adjustment is recommended for patients with CrCl greater than or equal to 15 mL per min.
Table 8. Zidovudine Pharmacokinetic Parameters in Subjects with Severe Renal Impairment *
Data are expressed as mean ± standard deviation.
Control Subjects
(Normal Renal Function)
Subjects With Renal Impairment
CrCl (mL/min)
Zidovudine AUC (ng•h/mL)
Zidovudine half-life (h)
1 ± 2
Hemodialysis and Peritoneal Dialysis: The pharmacokinetics and tolerance of zidovudine were evaluated in a multiple-dose trial in subjects undergoing hemodialysis (n = 5) or peritoneal dialysis (n = 6) receiving escalating oral doses up to 200 mg 5 times daily for 8 weeks. Daily doses of 500 mg or less were well tolerated despite significantly elevated GZDV plasma concentrations. Apparent zidovudine oral clearance was approximately 50% of that reported in subjects with normal renal function. Hemodialysis and peritoneal dialysis appeared to have a negligible effect on the removal of zidovudine, whereas GZDV elimination was enhanced. A dosage adjustment is recommended for patients undergoing hemodialysis or peritoneal dialysis [see Dosage and Administration (2.5)] .
Patients with Hepatic Impairment: Data describing the effect of hepatic impairment on the pharmacokinetics of zidovudine are limited. However, zidovudine is eliminated primarily by hepatic metabolism and it appears that zidovudine clearance is decreased and plasma concentrations are increased in subjects with hepatic impairment. 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)] .
Pediatric Patients: Zidovudine pharmacokinetics have been evaluated in HIV-1-infected pediatric subjects (Table 9).
Patients Aged 3 Months to 12 Years: Overall, zidovudine pharmacokinetics in pediatric patients older than 3 months are similar to those in adult patients. Proportional increases in plasma zidovudine concentrations were observed following administration of oral solution from 90 to 240 mg per m 2 every 6 hours. Oral bioavailability, terminal half-life, and oral clearance were comparable to adult values. As in adult subjects, the major route of elimination was by metabolism to GZDV. After IV dosing, about 29% of the dose was excreted in the urine unchanged, and about 45% of the dose was excreted as GZDV [see Dosage and Administration (2.2)] .
Patients Aged Less Than 3 MonthsZidovudine pharmacokinetics have been evaluated in pediatric subjects from birth to 3 months of life. Zidovudine elimination was determined immediately following birth in eight neonates who were exposed to zidovudine in utero. The half-life was 13 ± 5.8 hours. In neonates less than or equal to 14 days, bioavailability was greater, total body clearance was slower, and half-life was longer than in pediatric subjects older than 14 days. For dose recommendations for neonates [see Dosage and Administration (2.3)] .
Table 9. Zidovudine Pharmacokinetic Parameters in Pediatric Subjects *
Data presented as mean ± standard deviation except where noted.
Median [range].
Birth to 14 Days
Aged 14 Days to
Aged 3 Months to
CSF:plasma ratio
0.68 [0.03 to 3.25] †
CL (L/h/kg)
Elimination half-life (h)
Pregnant Women: Zidovudine pharmacokinetics have been studied in a Phase I trial of eight women during the last trimester of pregnancy. Zidovudine pharmacokinetics were similar to those of nonpregnant adults. Consistent with passive transmission of the drug across the placenta, zidovudine concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see Use in Specific Populations (8.1)] .
Although data are limited, methadone maintenance therapy in five pregnant women did not appear to alter zidovudine pharmacokinetics.
Geriatric Patients: Zidovudine pharmacokinetics have not been studied in subjects over 65 years of age.
Male and Female Patients: A pharmacokinetic trial in healthy male (n = 12) and female (n = 12) subjects showed no differences in zidovudine AUC when a single dose of zidovudine was administered as the 300 mg zidovudine tablet.
Drug Interaction Studies
[See Drug Interactions (7)].
Table 10. Effect of Coadministered Drugs on Zidovudine AUC *
↑ = Increase; ↓ = Decrease; ↔ = no significant change; AUC = area under the concentration versus time curve; CI = confidence interval.
This table is not all inclusive.
Estimated range of percent difference.
Note: ROUTINE DOSE MODIFICATION OF ZIDOVUDINE IS NOT WARRANTED WITH COADMINISTRATION OF THE FOLLOWING DRUGS.
Coadministered Drug and Dose
Zidovudine
Oral Dose
Zidovudine Concentrations
Concentration of Coadministered Drug
750 mg every 12 h with food
every 8 h
↑31%
23% to 78% †
500 mg twice daily
100 mg every
4 h x 7 days
↓12%
↓34% to ↑14%
400 mg daily
95% CI:
Lamivudine
300 mg every 12 h
single 200 mg
30 mg to 90 mg daily
Nelfinavir
750 mg every 8 h x
2 mg/kg every
↑106%
100% to 170% †
Not Assessed
600 mg daily x
q 8 h x 14 days
250 mg or 500 mg every 8 h x 4 days
64% to 130% †
Phenytoin: Phenytoin plasma levels have been reported to be low in some patients receiving zidovudine, while in one case a high level was documented. However, in a pharmacokinetic interaction trial in which 12 HIV-1-positive volunteers received a single 300-mg phenytoin dose alone and during steady-state zidovudine conditions (200 mg every 4 hours), no change in phenytoin kinetics was observed. Although not designed to optimally assess the effect of phenytoin on zidovudine kinetics, a 30% decrease in oral zidovudine clearance was observed with phenytoin.
Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine, stavudine, and zidovudine. However, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV-1/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n = 18), stavudine (n = 10), or zidovudine (n = 6) were coadministered as part of a multi-drug regimen to HIV-1/HCV co-infected subjects [see Warnings and Precautions (5.5)] .
Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5ʹ-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. ZDV-TP is a weak inhibitor of the cellular DNA polymerases α and γ and has been reported to be incorporated into the DNA of cells in culture.
Antiviral Activity
The antiviral activity of zidovudine against HIV-1 was assessed in a number of cell lines including monocytes and fresh human peripheral blood lymphocytes. The EC50 and EC90 values for zidovudine were 0.01 to 0.49 microM (1 microM = 0.27 mcg per mL) and 0.1 to 9 microM, respectively. HIV-1 from therapy-naive subjects with no amino acid substitutions associated with resistance gave median EC50 values of 0.011 microM (range: 0.005 to 0.110 microM) from Virco (n = 92 baseline samples) and 0.0017 microM (0.006 to 0.0340 microM) from Monogram Biosciences (n = 135 baseline samples). The EC50 values of zidovudine against different HIV-1 clades (A-G) ranged from 0.00018 to 0.02 microM, and against HIV-2 isolates from 0.00049 to 0.004 microM. Zidovudine was not antagonistic to tested anti-HIV agents with the exception of stavudine where an antagonistic relationship with zidovudine has been demonstrated in cell culture. Ribavirin has been found to inhibit the phosphorylation of zidovudine in cell culture.
HIV 1 isolates with reduced susceptibility to zidovudine have been selected in cell culture and were also recovered from subjects treated with zidovudine. Genotypic analyses of the isolates selected in cell culture and recovered from zidovudine-treated subjects showed thymidine analog mutation (TAMs) substitutions in the HIV-1 RT (M41L, D67N, K70R, L210W, T215Y or F, and K219E/R/H/Q/N/Q) that confer zidovudine resistance. In general, higher levels of resistance were associated with greater number of substitutions. In some subjects harboring zidovudine-resistant virus at baseline, phenotypic sensitivity to zidovudine was restored by 12 weeks of treatment with lamivudine and zidovudine.
Cross-Resistance
Cross-resistance has been observed among NRTIs. TAM substitutions are selected by zidovudine and confer cross-resistance to abacavir, didanosine, stavudine, and tenofovir.
Zidovudine was administered orally at three dosage levels to separate groups of mice and rats (60 females and 60 males in each group). Initial single daily doses were 30, 60, and 120 mg per kg per day in mice and 80, 220, and 600 mg per kg per day in rats. The doses in mice were reduced to 20, 30, and 40 mg per kg per day after Day 90 because of treatment-related anemia, whereas in rats only the high dose was reduced to 450 mg per kg per day on Day 91 and then to 300 mg per kg per day on Day 279.
In mice, seven late-appearing (after 19 months) vaginal neoplasms (five nonmetastasizing squamous cell carcinomas, one squamous cell papilloma, and one squamous polyp) occurred in animals given the highest dose. One late-appearing squamous cell papilloma occurred in the vagina of a middle-dose animal. No vaginal tumors were found at the lowest dose.
In rats, two late-appearing (after 20 months), nonmetastasizing vaginal squamous cell carcinomas occurred in animals given the highest dose. No vaginal tumors occurred at the low or middle dose in rats. No other drug-related tumors were observed in either sex of either species.
At doses that produced tumors in mice and rats, the estimated drug exposure (as measured by AUC) was approximately 3 times (mouse) and 24 times (rat) the estimated human exposure at the recommended therapeutic dose of 100 mg every 4 hours.
It is not known how predictive the results of rodent carcinogenicity studies may be for humans.
Two transplacental carcinogenicity studies were conducted in mice. One study administered zidovudine at doses of 20 mg per kg per day or 40 mg per kg per day from gestation Day 10 through parturition and lactation with dosing continuing in offspring for 24 months postnatally. The doses of zidovudine administered in this study produced zidovudine exposures approximately 3 times the estimated human exposure at recommended doses. After 24 months, an increase in incidence of vaginal tumors was noted with no increase in tumors in the liver or lung or any other organ in either gender. These findings are consistent with results of the standard oral carcinogenicity study in mice, as described earlier. A second study administered zidovudine at maximum tolerated doses of 12.5 mg per day or 25 mg per day (approximately 1000 mg per kg nonpregnant body weight or approximately 450 mg per kg of term body weight) to pregnant mice from Days 12 through 18 of gestation. There was an increase in the number of tumors in the lung, liver, and female reproductive tracts in the offspring of mice receiving the higher dose level of zidovudine.
Zidovudine was mutagenic in a 5178Y/TK +/- mouse lymphoma assay, positive in an in vitro cell transformation assay, clastogenic in a cytogenetic assay using cultured human lymphocytes, and positive in mouse and rat micronucleus tests after repeated doses. It was negative in a cytogenetic study in rats given a single dose.
Impairment of Fertility
Zidovudine, administered to male and female rats at doses up to 450 mg per kg per day, which is 7 times the recommended adult dose (300 mg twice daily) based on body surface area, had no effect on fertility based on conception rates.
Therapy with zidovudine has been shown to prolong survival and decrease the incidence of opportunistic infections in patients with advanced HIV-1 disease and to delay disease progression in asymptomatic HIV-1-infected patients.
Zidovudine in combination with other antiretroviral agents has been shown to be superior to monotherapy for one or more of the following endpoints: delaying death, delaying development of AIDS, increasing CD4+ cell counts, and decreasing plasma HIV-1 RNA.
The clinical efficacy of a combination regimen that includes zidovudine was demonstrated in trial ACTG 320. This trial was a multi-center, randomized, double-blind, placebo-controlled trial that compared zidovudine 600 mg per day plus EPIVIR 300 mg per day to zidovudine plus EPIVIR plus indinavir 800 mg three times daily. The incidence of AIDS-defining events or death was lower in the triple-drug–containing arm compared with the 2-drug–containing arm (6.1% versus 10.9%, respectively).
Monotherapy
In controlled trials of treatment-naive subjects conducted between 1986 and 1989, monotherapy with zidovudine, as compared with placebo, reduced the risk of HIV-1 disease progression, as assessed using endpoints that included the occurrence of HIV-1-related illnesses, AIDS-defining events, or death. These trials enrolled subjects with advanced disease (BW 002), and asymptomatic or mildly symptomatic disease in subjects with CD4+ cell counts between 200 and 500 cells per mm 3 (ACTG 016 and ACTG 019). A survival benefit for monotherapy with zidovudine was not demonstrated in the latter two trials. Subsequent trials showed that the clinical benefit of monotherapy with zidovudine was time limited.
ACTG 300 was a multi-center, randomized, double-blind trial that provided for comparison of EPIVIR plus zidovudine to didanosine monotherapy. A total of 471 symptomatic, HIV-1-infected therapy-naive pediatric subjects were enrolled in these two treatment arms. The median age was 2.7 years (range: 6 weeks to 14 years), the mean baseline CD4+ cell count was 868 cells per mm 3, and the mean baseline plasma HIV-1 RNA was 5.0 log 10 copies per mL. The median duration that subjects remained on trial was approximately 10 months. Results are summarized in Table 11.
Table 11. Number of Subjects (%) Reaching a Primary Clinical Endpoint (Disease Progression or Death)
HIV disease progression or death (total)
Physical growth failure
Central nervous system deterioration
CDC Clinical Category C
The utility of zidovudine for the prevention of maternal-fetal HIV-1 transmission was demonstrated in a randomized, double-blind, placebo-controlled trial (ACTG 076) conducted in HIV-1-infected pregnant women with CD4+ cell counts of 200 to 1,818 cells per mm 3 (median in the treated group: 560 cells per mm 3) who had little or no previous exposure to zidovudine. Oral zidovudine was initiated between 14 and 34 weeks of gestation (median 11 weeks of therapy) followed by IV administration of zidovudine during labor and delivery. Following birth, neonates received oral zidovudine syrup for 6 weeks. The trial showed a statistically significant difference in the incidence of HIV-1 infection in the neonates (based on viral culture from peripheral blood) between the group receiving zidovudine and the group receiving placebo. Of 363 neonates evaluated in the trial, the estimated risk of HIV-1 infection was 7.8% in the group receiving zidovudine and 24.9% in the placebo group, a relative reduction in transmission risk of 68.7%. Zidovudine was well tolerated by mothers and infants. There was no difference in pregnancy-related adverse events between the treatment groups.
Zidovudine 300-mg tablets are supplied as white, biconvex, round, film-coated tablets containing 300 mg of zidovudine per tablet. Each tablet has one side debossed with "S2" and blank on the other side.
Bottles of 60 (NDC 0527-1905-06).
Hypersensitivity Reactions
Inform patients that potentially life-threatening hypersensitivity reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) can occur while receiving zidovudine tablets. Instruct patients to immediately contact their healthcare provider if they develop rash, as it may be a sign of a more serious reaction. Advise patients that it is very important that they remain under a healthcare provider's care during treatment with zidovudine tablets [ see Contraindications (4)].
Neutropenia and Anemia
Inform patients that the major toxicities of zidovudine tablets are neutropenia and/or anemia. The frequency and severity of these toxicities are greater in patients with more advanced disease and in those who initiate therapy later in the course of their infection. Advise patients that if toxicity develops, they may require transfusions or drug discontinuation. Advise patients of the extreme importance of having their blood counts followed closely while on therapy, especially for patients with advanced symptomatic HIV-1 disease [see Boxed Warning, Warnings and Precautions (5.1)] .
Inform patients that myopathy and myositis with pathological changes, similar to that produced by HIV-1 disease, have been associated with prolonged use of zidovudine tablets [see Boxed Warning, Warnings and Precautions (5.3)] .
Lactic Acidosis/Hepatomegaly with Steatosis
Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogues and other antiretrovirals. Advise patients to stop taking zidovudine tablets if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Boxed Warning, Warnings and Precautions (5.4)] .
HIV-1/HCV Co-infection
Inform patients with HIV-1/HCV co-infection that hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.5)] .
Immune Reconstitution Syndrome
Advise patients to inform their healthcare provider immediately of any signs and symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when zidovudine tablets are started [see Warnings and Precautions (5.6)].
Advise patients that loss of subcutaneous fat may occur in patients receiving zidovudine tablets and that they will be regularly assessed during therapy [see Warnings and Precautions (5.7)] .
Common Adverse Reactions
Inform patients that the most commonly reported adverse reactions in adult patients being treated with zidovudine tablets were headache, malaise, nausea, anorexia, and vomiting. The most commonly reported adverse reactions in pediatric patients receiving zidovudine tablets were fever, cough, and digestive disorders. Patients also should be encouraged to contact their physician if they experience muscle weakness, shortness of breath, symptoms of hepatitis or pancreatitis, or any other unexpected adverse events while being treated with zidovudine tablets [see Adverse Reactions (6)] .
Advise patients that other medications may interact with zidovudine tablets and certain medications, including ganciclovir, interferon alfa, and ribavirin, may exacerbate the toxicity of zidovudine tablets [see Drug Interactions (7)] .
Inform pregnant women considering the use of zidovudine tablets during pregnancy for prevention of HIV-1 transmission to their infants that transmission may still occur in some cases despite therapy.
Pregnancy Registry
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to zidovudine tablets during pregnancy [see Use in Specific Populations (8.1)] .
Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)] .
Instruct patients that if they miss a dose of zidovudine tablets, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose [ see Dosage and Administration (2)].
EPIVIR is registered trademarks of the ViiV Healthcare group of companies.
Sunshine Lake Pharma Co., Ltd.
Guangdong Province 523808
Lannett Company, Inc.
PRINCIPAL DISPLAY PANEL – 300 mg
Each tablet contains 300 mg of zidovudine.
Usual Dosage: See package insert for Dosage and Administration.
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Preserve in tight, light-resistant containers.
Philadelphia, PA19136
Guangdong Province, China
Rev. 11/19
zidovudine tablet, film coated
ZIDOVUDINE (UNII: 4B9XT59T7S) (ZIDOVUDINE - UNII:4B9XT59T7S) ZIDOVUDINE 300 mg
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)
POLYVINYL ALCOHOL (UNII: 532B59J990)
LECITHIN, SOYBEAN (UNII: 1DI56QDM62)
Color white (white) Score no score
Flavor Imprint Code S;2
NDC:0527-1905-06 60 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 03/25/2014
Labeler - Lannett Company, Inc. (002277481)
1 199663 zidovudine 300 MG Oral Tablet PSN
2 199663 zidovudine 300 MG Oral Tablet SCD
3 199663 AZT 300 MG Oral Tablet SY
https://dailymed.nlm.nih.gov/dailymed/labelrss.cfm?setid=425faad5-8dbc-455b-a8c3-60bdf0e2ce54