1.COMBIVIR HISTORY
(How was Combivir discovered?)

Combivir is a product of GlaxoSmithKline.

The FDA approved Combivir on September 27, 1997 , for use in combination with other anti-HIV drugs for the treatment of HIV infection in adults and in children more than 12 years old.

Combivir does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.

Note: World-drugs.net sells generic version of Combivir

2.COMBIVIR FACTS

GlaxoSmithKline (GSK) is a world leading research-based pharmaceutical company with a powerful combination of skills and resources that provides a platform for delivering strong growth in today's rapidly changing healthcare environment.

GSK's mission is to improve the quality of human life by enabling people to do more, feel better and live longer.

GlaxoSmithKline is headquartered in the UK and has operations based in the US ; the new company is one of the industry leaders, with an estimated seven per cent of the world's pharmaceutical market.

GSK also has leadership in four major therapeutic areas - anti-infectives, central nervous system (CNS), respiratory and gastro-intestinal/metabolic. In addition, it is a leader in the important area of vaccines and has a growing portfolio of oncology products.

GSK also has a Consumer Healthcare portfolio comprising over-the-counter (OTC) medicines; oral care products and nutritional healthcare drinks, all of which are among the market leaders. 

3.ABOUT COMBIVIR MEDICATION

What are viruses?

A virus is a small infectious organism that must invade a living cell to reproduce (replicate). The virus attaches to a cell, enters it, and releases its DNA or RNA inside the cell. The virus's DNA or RNA is the genetic code containing the information needed to replicate the virus. The viral genetic material takes control of the cell and forces it to replicate the virus. The infected cell usually dies because the virus keeps it from performing its normal functions. Before it dies, however, the cell releases new viruses, which go on to infect other cells.

Some viruses do not kill the cells they infect, but instead alter the cells' functions. Sometimes the infected cell loses control over normal cell division and becomes cancerous. Some viruses that do not kill the cells they infect leave their genetic material in the host cell where it remains dormant for an extended time (latent infection). When the cell is disturbed, the virus may be able to begin growing again and cause disease.

Viruses usually infect one particular type of cell. For example, cold viruses infect only cells of the upper respiratory tract. Additionally, most viruses infect only a few species of plants or animals; some infect only people.

Viruses are transmitted in a variety of ways. Some are swallowed, some are inhaled, and some are transmitted by the bites of insects and other parasites.

The body has a number of defenses against viruses. Physical barriers, such as the skin, discourage easy entry. Infected cells also make interferons, substances that can make non-infected cells more resistant to infection by many viruses.

Drugs that combat viral infections are called antiviral drugs. Antiviral drugs work by interfering with viral replication. Because viruses are tiny and replicate inside cells using the cells' own metabolic pathways, there are only a limited number of metabolic functions that antiviral drugs can target. In contrast, bacteria are relatively large organisms, commonly reproduce by themselves outside of cells, and have many metabolic functions against which antibiotics can be directed. Therefore, antiviral drugs are much more difficult to develop. Antiviral drugs can be toxic to human cells. viruses can develop resistance to antiviral drugs.

Antibiotics are not effective against viral infections, but if a person has a bacterial infection in addition to a viral infection, an antibiotic is often necessary.

Probably the most common viral infections are those of the nose, throat, and airways. These infections include sore throat, sinusitis, the common cold, and influenza. Doctors often refer to these as upper respiratory infections (URIs). In small children, viruses also commonly cause croup and inflammation of the windpipe (laryngitis) or other airways deeper inside the lungs.

Other common viral infections are caused by the herpes viruses. Eight different herpes viruses infect people. Three of these—herpes simplex virus type 1, herpes simplex virus type 2, and varicella-zoster virus—cause infections that produce blisters on the skin. Another herpesvirus, Epstein-Barr virus, causes infectious mononucleosis. Cytomegalovirus is a cause of serious infections in newborns and in people with a weakened immune system. It can also produce an illness similar to infectious mononucleosis in people with a healthy immune system. Human herpesviruses 6 and 7 cause a childhood illness known as roseola infantum. Human herpesvirus 8 has been implicated as a cause of cancer (Kaposi's sarcoma) in people with AIDS. 

All of the herpesviruses cause lifelong infection because the virus remains within its host cell in a dormant (latent) state. Sometimes, the virus reactivates and produces further episodes of disease. Reactivation may occur rapidly or many years after the initial infection. 

What are antiretroviral drugs?

Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. Different antiretroviral drugs act at various stages of the HIV life cycle. Various combinations of three or four drugs are known as HAART or Highly Active Anti Retroviral Therapy.

Treatment guidelines are changing constantly. First came "hit hard, hit early", then came a more conservative approach with a starting point somewhere between 350 and 500 CD4+ T cells/mm³. The latest guidelines use 200 to 350 cells/mm³ as the range to consider starting HAART. However, there remain a range of views on this subject and ultimately the decision to commence or not to commence treatment rests with the patient and their doctor.

Antiretroviral regimens are complex, have serious side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance because of nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions are critical. Treatment should usually be offered to all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy among asymptomatic patients require analysis of real and potential risks and benefits. 

How does Combivir work?

Combivir tablets contain two active ingredients, zidovudine and lamivudine. These are both medicines called nucleoside reverse transcriptase inhibitors. They are used in the treatment of HIV (human immunodeficiency virus) infection.

AIDS (acquired immune deficiency syndrome) is caused by infection with HIV. This virus invades cells of the immune system, particularly the white blood cells known as CD4 T-helper lymphocytes. These cells normally work to activate other cells in the immune system to fight infection. Since HIV kills CD4 T-helper cells, over time the body becomes less able to fight the virus or subsequent infections.

This illustration shows the major sites for potential intervention in the HIV life cycle. 

Abbreviations:

NRTIs = nucleoside reverse transcriptase inhibitors;

NNRTIs = non-nucleoside reverse transcriptase inhibitors

Once the virus is inside the CD4 T-cell it multiplies. Part of the process of viral multiplication involves the conversion of the virus genetic material, RNA, into DNA. This is achieved by a compound essential to the virus, called reverse transcriptase. Reverse transcriptase is a compound known as an enzyme. Combivir works by blocking the action of this enzyme, thereby interfering with the conversion of viral RNA into DNA. This stops the virus from multiplying.

There is no cure for HIV, but Combivir lowers the amount of virus in the body (viral load) and slow the progression of the disease from HIV to AIDS. A combination of several anti-HIV medicines is required to fight the infection because the virus can become resistant to one agent very quickly. Zidovudine and lamivudine are used together to help prevent resistance occurring.   

4.COMBIVIR EFFECTIVENESS
(When is Combivir best taken?)

The pharmacokinetic properties of Combivir in fasting patients are summarized in Table 1. Following oral administration, Combivir is rapidly absorbed and extensively distributed. Binding to plasma protein is low. Approximately 70% of an intravenous dose of Combivir is recovered as unchanged drug in the urine. Metabolism of Combivir is a minor route of elimination. In humans, the only known metabolite is the trans-sulfoxide metabolite.

The pharmacokinetic properties of Combivir in fasting patients are summarized in Table 1. Following oral administration, Combivir is rapidly absorbed and extensively distributed.

Binding to plasma protein is low. Combivir is eliminated primarily by hepatic metabolism. The major metabolite of Combivir is 3-azido-3-deoxy-5-O-b-D-glucopyranuronosylthymidine (GZDV). GZDV area under the curve (AUC) is about 3- fold greater than the Combivir AUC. Urinary recovery of Combivir and GZDV accounts for 14% and 74% of the dose following oral administration, respectively. A second metabolite, 3-amino-3-deoxythymidine (AMT), has been identified in plasma. The AMT AUC was one fifth of the Combivir AUC.

Combivir may be administered with or without food. The extent of lamivudine and zidovudine absorption (AUC) following administration of Combivir with food was similar when compared to fasting healthy subjects (n = 24). 

5.COMBIVIR EFFECTS ON SPECIAL POPULATION
(How do different people react to Combivir?)

After administration of a single dose of Combivir to 13 HIV- infected women, the mean concentration of Combivir was similar in human milk and serum.

Pediatric Patients: Combivir should not be administered to pediatric patients less than 12 years of age because it is a fixed-dose combination that cannot be adjusted for this patient population.

Gender: A pharmacokinetic study in healthy male (n = 12) and female (n = 12) subjects showed no gender differences in Combivir exposure normalized for body weight.

Race: There are no significant racial differences in Combivir pharmacokinetics.

6.COMBIVIR EFFECTS ON MEDICAL CONDITIONS
(How does Combivir affect your existing condition/ailment?)

Impaired Renal Function: Combivir requires dose adjustment in the presence of renal insufficiency, Combivir is not recommended for patients with impaired renal function.

Impaired Hepatic Function : A reduction in the daily dose of Combivir may be necessary in patients with mild to moderate impaired hepatic function or liver cirrhosis. Because Combivir is a fixed-dose combination that cannot be adjusted for this patient population, Combivir is not recommended for patients with impaired hepatic function. 

7.OTHER/ALTERNATE USES OF COMBIVIR
(What else does Combivir treat?)

Combivirmay be used for purposes other as prescribed by your physician. 

8.ADVERSE/SIDE EFFECTS of COMBIVIR
(What are the side effects of Combivir?)

In 4 randomized, controlled trials of Combivir per day, the following selected clinical and laboratory adverse events were observed.

Pancreatitis was observed in 3 of the 656 adult patients (<0.5%) who received Combivir in controlled clinical trials.

Selected laboratory abnormalities observed during therapy are listed in Table below.

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of Combivir. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Combivir.

Body as a Whole : Redistribution/accumulation of body fat.

Cardiovascular : Cardiomyopathy.

Endocrine and Metabolic : Gynecomastia, hyperglycemia.

Gastrointestinal : Oral mucosal pigmentation, stomatitis.

General : Vasculitis, weakness.

Hemic and Lymphatic : Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.

Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbation of hepatitis B.

Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.

Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.

Nervous : Paresthesia, peripheral neuropathy, seizures.

Respiratory: Abnormal breath sounds/wheezing.

Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.