Zidovudine and lamivudine – active components of the drug, represent selective inhibitors of the reverse transcriptase of HIV-1 and HIV-2. This highly efficient combination is manifested through the synergy of active substances. Lamivudine exhibits a synergistically abilities relatively zidovudine and enhances its therapeutic effect. Clinical trials has also shown that Combivir has a depressing effect on the multiplication of HIV in the cells of the body. Once in the body, these components are metabolized under the action of intracellular kinases to form the 5′-triphosphates (TF). The resulting metabolites are substrates for HIV reverse transcriptase and competitively inhibit the enzyme.
The mechanism of action of Combivir occurs due to the fat that zidovudine and lamivudine are included in the chain of viral DNA in the form of monophosphate forms, than cause breakage of the chain. Triphosphate forms of these components have a similar ability to a much lesser extent.
During carrying out a mono therapy with nucleoside reverse transcriptase inhibitors there were recorded mutations of resistance and, consequently, the decrease in therapeutic activity to virtually zero. The results of the clinical trials of Combivir confirmed the reduction in HIV-1 viral load and increase of CD4 cells. It was also confirmed by a significant slowing of disease progression and a significant reduction in the number of deaths. Thanks to the previously mentioned synergistic effect, the use of a combination of zidovudine and lamivudine slows down the development of resistance to zidovudine of patients who were not treated previously with antiretroviral therapy (ART). The drug can be purchased on our website.
Combivir is endowed with a good capacity for absorption of the mucosal surface of the gastrointestinal tract. Physico-chemical and pharmacokinetic studies of Combivir proved that simultaneous food intake as the intake of crushed tablets does not have a significant impact on the absorbability of the drug and clinical effect. Combivir has a high oral bioavailability (zidovudine – 60-70%, lamivudine – 80-85%). The maximum concentration of these components in the organism is observed already after 0.5 and 0.75 hours and is 1.8 and 1.5 mg/ml, respectively. Components of the drug are able to penetrate into the CNS and cerebrospinal fluid. The average ratio of concentrations of zidovudine and cerebrospinal fluid in serum is 0.5, lamivudine – 0.12 in 2-4 hours after administration of Combivir. The half-life of lamivudine is from 5 to 7 hours.
The removing of Combivir from human body is provided by excretory renal function. It is known that zidovudine is excreted in the form of the metabolite 5’-glucuronide of zidovudine, and lamivudine is not metabolized but excreted unchanged. If a patient has documented violations of the kidneys, it increases the risk of accumulation of the drug in the body. Therefore, when buying a drug on our website you will extend your treatment with Combivir. Patients with renal and also hepatic failure in history must be cautious and monitor their condition, as patients with these disorders are at risk.
There are no data of pharmacokinetic studies of Combivir in gerontology (older than 65 years) due to the fact that the main age category of HIV-infected patients is in the range of 20-40 years and the majority of clinical trials of antiretroviral drugs are conducted in this category of patients.
Similar studies in pediatric patients (from 6 months. to 12 years) showed the similarity of the pharmacokinetics of the drug in children with that of adult patients, but there was a reduction in absolute bioavailability of lamivudine to 55-65%. There was recorded an increase in parameters of systemic clearance in children, they are reduced simultaneously with the maturation of the child’s body and it corresponds to the level, which is defined in adult patients at the age of 12 years.
Indications for use
Combivir is prescribed to adults and children with body weight more than 14 kg if they have HIV.
The method of application.
Combivir is taken with or without food. Combivir tablet should be swallowed as a whole. If it causes difficulties, it is possible to chop a tablet and mix it with a small amount of soft food or liquid. However, a necessary condition for achieving the desired therapeutic effect is receiving the entire quantity of the mixture immediately after its preparation.
The correction of the dose of Combivir is made only by a doctor. It may reduce or increase of the dose, and the abolition of one of the components of the drug. In this case, a patient is prescribed a required component in the form of a single-agent preparation or (for example, Retrovir (AZT) or Epivir (lamivudine)).
Individual selection of the dosing is guaranteed in the following cases:
the presence of renal or hepatic insufficiency history of the patient;
anemia or neutropenia;
elderly age (over 65 years) is due to the lack of clinical trials of the drug in these patients.
Most often in gerontology they use monopreparations of the components of Combivir, taking into account the physiological characteristics of the organism of patients.