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| Lamivudine | Nucleoside analoguereverse transcriptase inhibitor |
| Zidovudine | Nucleoside analoguereverse transcriptase inhibitor |
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| Trade names | Combivir |
| AHFS/Drugs.com | Professional Drug Facts |
| MedlinePlus | a601066 |
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| Routes of administration | By mouth |
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Lamivudine/zidovudine, sold under the brand nameCombivir among others, is afixed-dose combinationantiretroviral medication used to treatHIV/AIDS.[1] It contains twoantiretroviral medications,lamivudine andzidovudine.[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 includebone marrow suppression,muscle damage, worsening ofhepatitis B if previously infected,high blood lactate andliver enlargement.[1][3] It may be part of a recommended treatment duringpregnancy.[1] The medications are both of thenucleoside reverse transcriptase inhibitor (NRTI) class.[1] They work by blocking the action of theenzyme,reverse transcriptase, that the virus requires to reproduce.[2]
Lamivudine/zidovudine was approved for medical use in the United States in 1997, and in the European Union in 1998.[2][4] It is on theWorld Health Organization's List of Essential Medicines.[5] It is available as ageneric medication.[3]
It is indicated for use in combination with an additionalantiretroviral agent for the treatment ofhuman immunodeficiency virus type 1 (HIV-1) infection.[2][4]
Lamividine/zidovudine is categorizedpregnancy category C in the United States, meaning there are potential risks to the baby during pregnancy, but potential benefits may outweigh the risks.[6] Data supports the safety of this combination during pregnancy and is often preferred over other fixed dose combinations during pregnancy.[7]
The most common adverse effects of Lamividine/zidovudine are similar to other NRTI's and includesheadache,neutropenia,anemia,nausea,vomiting,myopathy and nail pigmentation.[8][9] More serious and potentially life-threatening adverse effects reported includelactic acidosis withhepatic steatosis, but this rare adverse event is mostly associated with Zidovudine.[9] HIV-positive patients with chronichepatitis 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.[10]
Lamividine/zidovudine interacts withstavudine andzalcitabine by competing intracellularly for activation and results in inhibitingphosphorylation.[2][11] There is also a known interaction withnephrotoxic or bone marrow suppressive agents (e.g.doxorubicin) which increases the risk of hematologic toxicity of zidovudine.[12] Monitoring renal function and hematologic tests can be used to assess these potential interactions.[12]
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.[12]
The combination oflamivudine andzidovudine is composed of two nucleotidereverse transcriptase inhibitors (NRTIs).[2]
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.[13] Lamivudine and zidovudine act as nucleoside analogs, which are substrates for the human nucleosidekinases. 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.[14]
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.[2]
Zidovudine is also well absorbed in the body and penetrates into the cerebrospinal fluid. Oral bioavailability is 75% and primarily metabolized by the liver byglucuronidation. The primary metabolite is GZDV, an inactive metabolite produced afterfirst pass metabolism. The half-life of zidovudine is 0.5 to 3 hours and binds poorly to plasma proteins.[2]
Lamivudine and zidovudine are not extensively metabolized byCYP450 liver enzymes.[citation needed]
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.[15]
Lamivudine/zidovudine is on theWorld Health Organization's List of Essential Medicines.[5]
Drug formulations: tablets by mouth
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