Combivir

Drug name: Combivir

WARNING

ZIDOVUDINE, ONE OF THE TWO ACTIVE INGREDIENTS IN COMBIVIR, HAS BEEN ASSOCIATED WITH HEMATOLOGIC TOXICITY INCLUDING NEUTROPENIA AND SEVERE ANEMIA, PARTICULARLY IN PATIENTS WITH ADVANCED HUMAN IMMUNODEFICIENCY VIRUS (HIV) DISEASE. PROLONGED USE OF ZIDOVUDINE HAS BEEN ASSOCIATED WITH SYMPTOMATIC MYOPATHY.

LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, INCLUDING FATAL CASES, HAVE BEEN REPORTED WITH THE USE OF NUCLEOSIDE ANALOGUES ALONE OR IN COMBINATION, INCLUDING LAMIVUDINE, ZIDOVUDINE, AND OTHER ANTIRETROVIRALS.

SEVERE ACUTE EXACERBATIONS OF HEPATITIS B HAVE BEEN REPORTED IN PATIENTS WHO ARE CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV AND HAVE DISCONTINUED LAMIVUDINE, WHICH IS ONE COMPONENT OF COMBIVIR. HEPATIC FUNCTION SHOULD BE MONITORED CLOSELY WITH BOTH CLINICAL AND LABORATORY FOLLOW-UP FOR AT LEAST SEVERAL MONTHS IN PATIENTS WHO DISCONTINUE COMBIVIR AND ARE CO-INFECTED WITH HIV AND HBV. IF APPROPRIATE, INITIATION OF ANTI-HEPATITIS B THERAPY MAY BE WARRANTED

Therapeutic actions:

Combivir is an anti-HIV medication. It is in a category of HIV medicines called nucleoside reverse transcriptase inhibitors (NRTIs). Combivir prevents HIV from altering the genetic material of healthy T-cells. This prevents the cells from producing new virus and decreases the amount of virus in the body.
Combivir is marketed by GlaxoSmithKline. It was approved by the U.S. Food and Drug Administration (FDA) for use by people living with HIV in 1997.
Combivir is a combination of two drugs: 300mg of Retrovir® (AZT) and 150mg of Epivir® (3TC). Combivir should be prescribed by a healthcare provider for patients who need both of these drugs. Both of these drugs can still be purchased individually for use in combination with other anti-HIV drugs.
Combivir must be combined with at least one other anti-HIV drug, usually a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI).

Indications: COMBIVIR is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection.

Contraindications and cautions: Patients With HIV and Hepatitis B Virus Co-infection

Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients dually infected with HIV and HBV. In non-HIV-infected patients treated with lamivudine for chronic hepatitis B, emergence of lamivudine-resistant HBV has been detected and has been associated with diminished treatment response (see EPIVIR-HBV package insert for additional information). Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. Posttreatment exacerbations of hepatitis have also been reported (see WARNINGS).

Patients With Impaired Renal Function

Reduction of the dosages of lamivudine and zidovudine is recommended for patients with impaired renal function. Patients with creatinine clearance <50 mL/min should not receive COMBIVIR.

Patients With Impaired Hepatic Function

A reduction in the daily dose of zidovudine may be necessary in patients with mild to moderate impaired hepatic function or liver cirrhosis. COMBIVIR is not recommended for patients with impaired hepatic function.

Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including COMBIVIR. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Fat Redistribution

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and �cushingoid appearance� have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

Information for Patients

COMBIVIR is not a cure for HIV infection and patients may continue to experience illnesses associated with HIV infection, including opportunistic infections. Patients should be advised that the use of COMBIVIR has not been shown to reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Patients should be advised of the importance of taking COMBIVIR exactly as it is prescribed.

Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.

Lamivudine Patients co-infected with HIV and HBV should be informed that deterioration of liver disease has occurred in some cases when treatment with lamivudine was discontinued. Patients should be advised to discuss any changes in regimen with their physician.

Zidovudine Patients should be informed that the important toxicities associated with zidovudine are neutropenia and/or anemia. They should be told of the extreme importance of having their blood counts followed closely while on therapy, especially for patients with advanced HIV disease.

Adverse effects: The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

Bone marrow problems, such as decreased production of red blood cells and/or white blood cells, can occur in people talking Retrovir (AZT), one of the two active drugs in Combivir. Contact your doctor immediately if you develop unusual fatigue, pale skin, sore throat, fever, or chills, which may be signs of bone marrow problems.

Rare but potentially serious side effect of Retrovir, one of the two drugs in Combivir, is myopathy (damage to the muscles, including the heart). People who use Retrovir for a long period of time, meaning several years, are at the greatest risk for myopathy. General symptoms of myopathy include weakness of limbs, usually proximal (located close to the center of the body).

Contact your doctor immediately if you experience nausea, vomiting, or unusual or unexpected stomach discomfort; weakness and tiredness; shortness of breath; weakness in the arms and legs; yellowing of the skin or eyes; or pain in the upper stomach area.

Before taking this medication, tell your doctor if you have: kidney disease; liver disease (including hepatitis B); or low blood cell counts (anemia or low white blood cells).

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Body as a Whole: Redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).

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 severe anemias progressing on therapy), lymphadenopathy, splenomegaly.

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

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.

The side effects listed above may not include all of the side effects reported by the drug's manufacturer.

Interactions: Tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine.

Lamivudine

Trimethoprim (TMP) 160 mg/sulfamethoxazole (SMX) 800 mg once daily has been shown to increase lamivudine exposure (AUC). The effect of higher doses of TMP/SMX on lamivudine pharmacokinetics has not been investigated. No data are available regarding the potential for interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.

Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of COMBIVIR in combination with zalcitabine is not recommended.

Zidovudine Coadministration of ganciclovir, interferon alfa, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.

Concomitant use of COMBIVIR with stavudine should be avoided since an antagonistic relationship with zidovudine has been demonstrated in vitro. In addition, concomitant use of COMBIVIR with doxorubicin or ribavirin should be avoided because an antagonistic relationship with zidovudine has been demonstrated in vitro.

See CLINICAL PHARMACOLOGY for additional drug interactions.

Additional Information: DO NOT SHARE THIS MEDICINE with others. DO NOT USE THIS MEDICINE for other health conditions. KEEP THIS PRODUCT, as well as syringes and needles, if needed during treatment, out of the reach of children. Do not reuse needles, syringes, or other materials.