Lamivudine/zidovudine
reverse transcriptase inhibitor | |
| Clinical data | |
|---|---|
| Trade names | Combivir |
| AHFS/Drugs.com | Professional Drug Facts |
| MedlinePlus | a601066 |
| License data | |
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| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
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| Identifiers | |
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| PubChem CID | |
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| NIAID ChemDB | |
| CompTox Dashboard (EPA) | |
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Lamivudine/zidovudine, sold under the brand name Combivir among others, is a
Common side effects include headache, feeling tired, nausea, diarrhea, and fever.
Lamivudine/zidovudine was approved for medical use in the United States in 1997, and in the European Union in 1998.
Medical uses
It is indicated for use in combination with an additional antiretroviral agent for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.[3][5]
Pregnancy
Lamividine/zidovudine is categorized 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 effects
The most common adverse effects of Lamividine/zidovudine are similar to other NRTI's and includes
Interactions
Drug-drug interactions
Lamividine/zidovudine interacts with stavudine and zalcitabine by competing intracellularly for activation and results in inhibiting phosphorylation.[3][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 interactions
Half 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 action
The combination of lamivudine and zidovudine is composed of two nucleotide reverse transcriptase inhibitors (NRTIs).[3]
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.[14] 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.[citation needed]
Lamividuine and zidovudine combination therapy is believed to work synergistically together to prevent mutations in the HIV virus, which can contribute to drug resistance.[15]
Pharmacokinetics
Lamivudine 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.[3]
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.[3]
Lamivudine and zidovudine are not extensively metabolized by CYP450 liver enzymes.[citation needed]
History
Lamivudine/zidovudine (brand name Combivir) was introduced to the market with FDA approval 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.[16]
Society and culture
Lamivudine/zidovudine is on the World Health Organization's List of Essential Medicines.[6]
Drug formulations
Drug formulations: tablets by mouth
- Combivir: lamivudine 150 mg and zidovudine 300 mg (scored). It is marketed by ViiV Healthcare.
- Generic: lamivudine 150 mg and zidovudine 300 mg.
References
- FDA. Retrieved 22 October 2023.
- ^ ISBN 9789241547659.
- ^ a b c d e f g h i "Combivir- lamivudine and zidovudine tablet, film coated". DailyMed. 10 May 2019. Retrieved 29 May 2020.
- ^ ISBN 9781284057560.
- ^ a b "Combivir EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 29 May 2020.
- ^ hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- PMID 15467577.
- PMID 18472979.
- S2CID 10271162.
- ^ PMID 10647802.
- ^ "Drugs for HIV Infection" (PDF). The Medical Letter, Inc. October 2006. Archived from the original (PDF) on 5 March 2017. Retrieved 9 November 2016.
- .
- ^ a b c "Summary of Product Characteristics: Lamivudine, Nevirapine and Zidovudine Tablets" (PDF). May 2011. Archived from the original (PDF) on 9 November 2016.
- ^ "Combivir". www.catie.ca. Archived from the original on 8 November 2016. Retrieved 8 November 2016.
- ^ "Combivir | ViiV Healthcare". www.viivhealthcare.com. Archived from the original on 5 May 2016. Retrieved 8 November 2016.
- PMID 18472979.
