Pharmacy Editor: Jay W. Marks, MD

GENERIC NAME: lamivudine and zidovudine

BRAND NAME: Combivir

DRUG CLASS AND MECHANISM: Combivir is an oral drug that is a combination of lamivudine (Epivir) and zidovudine (Retrovir). It is used for the treatment of infections with the human immunodeficiency virus (HIV). Lamivudine and zidovudine are in a class of drugs called reverse transcriptase inhibitors that also includes zalcitabine (Hivid) and didanosine (Videx).

During infection with HIV, the HIV virus multiplies within the body's cells. The newly-formed viruses are released from the cells and then spread throughout the body where they infect other cells. In this manner, the infection continually spreads to new, uninfected cells that the body is continually producing, and HIV infection is perpetuated. When producing new viruses, the HIV virus must manufacture new DNA for each virus. Reverse transcriptase is the enzyme that the virus uses to form this new DNA. Lamivudine and zidovudine block the activity of reverse transcriptase and block the production of DNA and new viruses. (Specifically, lamivudine is converted within the body to its active form, lamivudine triphosphate, and zidovudine is converted to its active form, zidovudine triphosphate. The active forms are similar to the naturally occurring deoxycytidine triphosphate and thymidine triphosphate, respectively, chemicals that are used by reverse transcriptase to make DNA. The reverse transcriptase uses lamivudine triphosphate and zidovudine triphosphate instead of the naturally-occurring deoxycytidine triphosphate and thymidine triphosphate for making DNA, and these active forms of the drugs interfere with the activity of reverse transcriptase.)

The effectiveness of either lamivudine or zidovudine when used alone may decrease as the HIV virus develops resistance to the effects of the individual drugs. By combining lamivudine and zidovudine, it is more difficult for the HIV virus to develop resistance to therapy since it must develop resistance to both drugs. As a result, Combivir is more effective than lamivudine or zidovudine alone. Combivir does not kill existing HIV virus, and it is not a cure for HIV. Combivir was approved by the FDA in September, 1997.

GENERIC AVAILABLE: No.

PRESCRIPTION: Yes.

PREPARATIONS: Tablets: 150/300 mg (lamivudine/zidovudine)

STORAGE: Store at 2-30°C (36-86°F).

PRESCRIBED FOR: Combivir is used, in combination with other agents, for the treatment of HIV infection.

DOSING: For the treatment of HIV infection the recommended oral dose for adults or children greater than 12 years of age is one tablet twice daily. Combivir is administered without regard to meals since food does not affect its absorption.

DRUG INTERACTIONS: Fluconazole (Diflucan), probenecid, trimethoprim (Trimpex) and valproic acid (Depakote) reduce the elimination of zidovudine and therefore increase the blood concentration of zidovudine. This can lead to increased side effects from zidovudine.

PREGNANCY: Use of Combivir during pregnancy has not been adequately evaluated.

NURSING MOTHERS: Use of Combivir by nursing mothers has not been studied. HIV infected mothers should not breast feed because of the potential risk of transmitting HIV to an infant that is not infected.

SIDE EFFECTS: The most serious side effects of Combivir are a decrease in blood cells, muscle pain (myopathy) or muscle breakdown (rhabdomyolysis), liver enlargement and metabolic disturbance (lactic acidosis). Other side effects include chills, rash, abdominal pain, nausea and vomiting, weight loss, headache, cough and insomnia. Accumulation or redistribution of fat may also occur.

Reference: FDA Prescribing Information