| 词条 | Lamivudine/zidovudine |
| 释义 |
| verifiedrevid = 399728371 | image = Lamivudine and zidovudine.svg | width = 150 | type = combo | component1 = Lamivudine | class1 = Nucleoside analogue reverse transcriptase inhibitor | component2 = Zidovudine | class2 = Nucleoside analogue reverse transcriptase inhibitor | Drugs.com = {{Drugs.com|pro|Combivir}} | tradename = Combivir | MedlinePlus = a601066 | pregnancy_AU = | pregnancy_US = C | pregnancy_category = | licence_EU = yes | legal_AU = | legal_CA = | legal_UK = POM | legal_US = Rx-only | legal_status = | routes_of_administration = by mouth | CAS_number = | ATC_prefix = J05 | ATC_suffix = AR01 | PubChem = 160352 | DrugBank = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 21106283 | NIAID_ChemDB = 031479 }}Lamivudine/zidovudine, sold under the brand name Combivir among others, is a medication used to treat HIV/AIDS.[1] It is a combination of two antiretroviral medications, lamivudine and zidovudine.[1] It is used together with other antiretrovirals.[1] It is taken by mouth twice a day.[1][2] Common side effects include headache, feeling tired, nausea, diarrhea, and fever.[2] Severe side effects may include bone marrow suppression, muscle damage, worsening of hepatitis B if previously infected, high blood lactate and liver enlargement.[1][8] It may be part of a recommended treatment during pregnancy.[1] The medications are both of the nucleoside reverse transcriptase inhibitor (NRTI) class.[1] They work by blocking the action of the enzyme, reverse transcriptase, that the virus requires to reproduce.[2] Lamivudine/zidovudine was approved for medical use in the United States in 1997.[2] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] It is available as a generic medication.[8] The wholesale cost in the developing world is about US$6.90 to $29.64 per month.[4] As of 2015 the cost for a typical month of medication in the United States more than $200.[5] Medical usesIt is FDA approved for use in combination with an additional antiretroviral agent for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.[6] PregnancyLamividine/zidovudine is pregnancy category C in the United States, meaning there are potential risks to the baby during pregnancy, but potential benefits may outweigh the risks.[7] Data supports the safety of this combination during pregnancy and is often preferred over other fixed dose combinations during pregnancy.[8] Side effectsThe most common adverse effects of Lamividine/zidovudine are similar to other NRTI's and includes headache, neutropenia, anemia, nausea, vomiting, myopathy and nail pigmentation.[9][10] More serious and potentially life-threatening adverse effects reported include lactic acidosis with hepatic steatosis, but this rare adverse event is mostly associated with Zidovudine.[10] HIV-positive patients with chronic hepatitis B virus (HBV) infections are at risk for potential flares of hepatitis that can occur with abrupt discontinuation of Lamividine/zidovudine because Lamivudine is also used in low doses for treatment against active HBV.[11] InteractionsDrug-drug interactionsLamividine/zidovudine interacts with Stavudine and Zalcitabine by competing intracellularly for activation and results in inhibiting phosphorylation.[24][12] There is also a known interaction with nephrotoxic or bone marrow suppressive agents (e.g. doxorubicin) which increases the risk of hematologic toxicity of zidovudine.[13] Monitoring renal function and hematologic tests can be used to assess these potential interactions.[13] Drug-food interactionsHalf lives of Lamivudine and Zidovudine are not affected by food and absorption rates were slowed when taken with food but were not clinically significant, therefore, Lamivudine/zidovudine may be taken with or without food.[13] Mechanism of actionThe combination of lamivudine and zidovudine is composed of two nucleotide reverse transcriptase inhibitors (NRTIs).[14] Lamivudine and zidovudine both competitively inhibit and reduce the activity of reverse transcriptase (RT) causing HIV infected cells to decrease the number of viruses in the body.[15] Lamivudine and zidovudine act as nucleoside analogs, which are substrates for the human nucleoside kinases. The initial phosphorylation step is crucial for the drug's activity, then converted into the active 5’-triphosphate form by host kinases. The drug is then incorporated to the end of the growing chain of the viral DNA causing the chain to be terminated, where nucleotides can no longer be added to the growing viral DNA. Lamividuine and zidovudine combination therapy is believed to work synergistically together to prevent mutations in the HIV virus, which can contribute to drug resistance.[16] PharmacokineticsLamivudine is well absorbed in the body and distributes widely into the extravascular space. Oral bioavailability is >80% and overall metabolism is insignificant where approximately 95% of the drug is found unchanged in the urine. The only known metabolite found in humans is trans-sulfoxide. The half-life of lamivudine is 10 to 15 hours and binds poorly to plasma proteins.[17] Zidovudine is also well absorbed in the body and penetrates into the cerebrospinal fluid. Oral bioavailability is 75% and primarily metabolized by the liver by glucuronidation. The primary metabolite is GZDV, an inactive metabolite produced after first pass metabolism. The half-life of zidovudine is 0.5 to 3 hours and binds poorly to plasma proteins.[17] Lamivudine and zidovudine are not extensively metabolized by CYP450 liver enzymes. HistoryLamivudine/Zidovudine (brand name Combivir) was introduced to the market with FDA licensure in 1997. Its impact in history is significant as it was the first combination therapy with a fixed dose for HIV-positive people, and soon solidified its title as a gold standard as it was the most prescribed NRTI in initial HIV treatment for newly diagnosed patients. The arrival of Combivir was seen as a new revolution in HIV therapy, with its improved toxicity profile and tolerability, especially compared to the undesirable side effects of lone AZT therapy or the unfavorable facial and lipoatrophy seen in Stavudine monotherapy at that time.[18] Society and cultureLamivudine/Zidovudine is on the World Health Organization's List of Essential Medicines, the 2015 list of necessary medications.[19] Drug formulationsDrug formulations: tablets by mouth
References1. ^1 2 3 4 5 6 {{cite book|title=WHO Model Formulary 2008|date=2009|publisher=World Health Organization|isbn=9789241547659|pages=157, 161|url=http://apps.who.int/medicinedocs/documents/s16879e/s16879e.pdf|accessdate=8 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20161213060118/http://apps.who.int/medicinedocs/documents/s16879e/s16879e.pdf|archivedate=13 December 2016|df=}} 2. ^1 2 3 {{cite web|title=Combivir - FDA prescribing information, side effects and uses|url=https://www.drugs.com/pro/combivir.html|website=www.drugs.com|accessdate=10 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20161108140647/https://www.drugs.com/pro/combivir.html|archivedate=8 November 2016|df=}} 3. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}} 4. ^{{cite web|title=Lamivudine + Zidovudine|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=457&searchYear=2014|website=International Drug Price Indicator Guide|accessdate=8 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20170305004844/http://mshpriceguide.org/en/single-drug-information/?DMFId=457&searchYear=2014|archivedate=5 March 2017|df=}} 5. ^1 2 {{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=59}} 6. ^{{Cite web|url=https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Combivir/pdf/COMBIVIR.PDF|title=Highlight of Prescribing Information: Combivir|last=|first=|date=Nov 2015|website=|access-date=|deadurl=no|archiveurl=https://web.archive.org/web/20161109154410/https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Combivir/pdf/COMBIVIR.PDF|archivedate=2016-11-09|df=}} 7. ^{{cite journal|title=Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy|journal=American Journal of Obstetrics and Gynecology|volume=191|issue=3|pages=985–992|doi=10.1016/j.ajog.2004.05.061|pmid=15467577|date=September 2004|last1=Heather Watts|first1=D.|last2=Covington|first2=Deborah L.|last3=Beckerman|first3=Karen|last4=Garcia|first4=Patricia|last5=Scheuerle|first5=Angela|last6=Dominguez|first6=Kenneth|last7=Ross|first7=Brenda|last8=Sacks|first8=Susan|last9=Chavers|first9=Scott|last10=Tilson|first10=Hugh}} 8. ^{{Cite journal|last=Portsmouth|first=Simon D|last2=Scott|first2=Christopher J|date=2016-11-09|title=The renaissance of fixed dose combinations: Combivir|journal=Therapeutics and Clinical Risk Management|volume=3|issue=4|pages=579–583|issn=1176-6336|pmc=2374941|pmid=18472979}} 9. ^{{Cite journal|last=Esser|first=Stefan|last2=Helbig|first2=Doris|last3=Hillen|first3=Uwe|last4=Dissemond|first4=Joachim|last5=Grabbe|first5=Stephan|date=2007-09-01|title=Side effects of HIV therapy|journal=JDDG: Journal der Deutschen Dermatologischen Gesellschaft|language=en|volume=5|issue=9|pages=745–754|doi=10.1111/j.1610-0387.2007.06322.x|pmid=17760894|issn=1610-0387|df=}} 10. ^1 {{Cite journal|last=Carpenter|first=Charles C. 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D.|title = The renaissance of fixed dose combinations: Combivir|journal = Therapeutics and Clinical Risk Management|volume = 3|issue = 4|pages = 579–583|last2 = Scott|first2 = C. J.|pmid = 18472979}} 19. ^{{Cite web|url=http://www.who.int/medicines/publications/essentialmedicines/en/|title=WHO Model Lists of Essential Medicines|website=World Health Organization|language=en-GB|access-date=2016-11-07|deadurl=no|archiveurl=https://web.archive.org/web/20161102075222/http://www.who.int/medicines/publications/essentialmedicines/en/|archivedate=2016-11-02|df=}} 20. ^1 {{Cite web|url=http://www.healthline.com/health/hiv-aids/cost-of-treatment#1|title=The Cost of HIV Treatment|last=|first=|date=2015-04-02|website=|access-date=2016-11-16|deadurl=no|archiveurl=https://web.archive.org/web/20161125112739/http://www.healthline.com/health/hiv-aids/cost-of-treatment#1|archivedate=2016-11-25|df=}} External links
4 : Fixed dose combination (antiretroviral)|Hepatotoxins|World Health Organization essential medicines|RTT |
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