EPZICOM™
(abacavir sulfate and lamivudine)
Tablets

EPZICOM contains 2 nucleoside analogues (abacavir sulfate and lamivudine) and is intended only for patients whose regimen would otherwise include these 2 components.

Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate, a component of EPZICOM. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or achiness), and (5) respiratory (including dyspnea, cough, or pharyngitis). Discontinue EPZICOM as soon as a hypersensitivity reaction is suspected. Permanently discontinue EPZICOM if hypersensitivity cannot be ruled out, even when other diagnoses are possible.

Following a hypersensitivity reaction to abacavir, NEVER restart EPZICOM or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.

Reintroduction of EPZICOM or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours (see WARNINGS and PRECAUTIONS: Information for Patients).

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, and other antiretrovirals (see WARNINGS).

Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) and have discontinued lamivudine, which is one component of EPZICOM. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue EPZICOM and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted (see WARNINGS).

EPZICOM Tablets contain the following 2 synthetic nucleoside analogues: abacavir sulfate (ZIAGEN^®, also a component of TRIZIVIR^®) and lamivudine (also known as EPIVIR^® or 3TC) with inhibitory activity against HIV.

EPZICOM Tablets are for oral administration. Each orange, film-coated tablet contains the active ingredients 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (Opadry^® orange YS-1-13065-A) that is made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.

The chemical name of abacavir sulfate is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C₁₄H₁₈N₆O)_2•H₂SO₄ and a molecular weight of 670.76 daltons. It has the following structural formula:

Abacavir sulfate is a white to off-white solid with a solubility of approximately 77 mg/mL in distilled water at 25°C.

In vivo, abacavir sulfate dissociates to its free base, abacavir. All dosages for abacavir sulfate are expressed in terms of abacavir.

The chemical name of lamivudine is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine has also been referred to as (-)2′,3′-dideoxy, 3′-thiacytidine. It has a molecular formula of C₈H₁₁N₃O₃S and a molecular weight of 229.3 daltons. It has the following structural formula:

Lamivudine is a white to off-white crystalline solid with a solubility of approximately 70 mg/mL in water at 20°C.

Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3′-OH group in the incorporated nucleotide analogue prevents the formation of the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.CBV-TP is a weak inhibitor of cellular DNA polymerases α, β, and γ.

Lamivudine is a synthetic nucleoside analogue. Intracellularly lamivudine is phosphorylated to its active 5′-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. CBV-TP and 3TC-TP are weak inhibitors of cellular DNA polymerases α, β, and γ.

HIV-1 isolates with reduced susceptibility to the combination of abacavir and lamivudine have been selected in cell culture and have also been obtained from patients failing abacavir/lamivudine-containing regimens. Genotypic characterization of abacavir/lamivudine-resistant viruses selected in cell culture identified amino acid substitutions M184V/I, K65R, L74V, and Y115F in HIV-1 RT.

Genotypic analysis of isolates selected in cell culture and recovered from abacavir-treated patients demonstrated that amino acid substitutions K65R, L74V, Y115F, and M184V/I in HIV-1 RT contributed to abacavir resistance. Genotypic analysis of isolates selected in cell culture and recovered from lamivudine-treated patients showed that the resistance was due to a specific amino acid substitution in HIV-1 RT at codon 184 changing the methionine to either isoleucine or valine (M184V/I). In a study of therapy-naive adults receiving ZIAGEN 600 mg once daily (n = 384) or 300 mg twice daily (n = 386) in a background regimen of lamivudine 300 mg and efavirenz 600 mg once daily (Study CNA30021), the incidence of virologic failure at 48 weeks was similar between the 2 groups (11% in both arms). Genotypic (n = 38) and phenotypic analyses (n = 35) of virologic failure isolates from this study showed that the RT mutations that emerged during abacavir/lamivudine once-daily and twice-daily therapy were K65R, L74V, Y115F, and M184V/I. The abacavir- and lamivudine-associated resistance mutation M184V/I was the most commonly observed mutation in virologic failure isolates from patients receiving abacavir/lamivudine once daily (56%, 10/18) and twice daily (40%, 8/20).

Thirty-nine percent (7/18) of the isolates from patients who experienced virologic failure in the abacavir once-daily arm had a >2.5-fold decrease in abacavir susceptibility with a median-fold decrease of 1.3 (range 0.5 to 11) compared with 29% (5/17) of the failure isolates in the twice-daily arm with a median-fold decrease of 0.92 (range 0.7 to 13). Fifty-six percent (10/18) of the virologic failure isolates in the once-daily abacavir group compared to 41% (7/17) of the failure isolates in the twice-daily abacavir group had a >2.5-fold decrease in lamivudine susceptibility with median-fold changes of 81 (range 0.79 to >116) and 1.1 (range 0.68 to >116) in the once-daily and twice-daily abacavir arms, respectively.

Cross-resistance has been observed among nucleoside reverse transcriptase inhibitors. Viruses containing abacavir and lamivudine resistance-associated mutations, namely, K65R, L74V, M184V, and Y115F, exhibit cross-resistance to didanosine, emtricitabine, lamivudine, tenofovir, and zalcitabine in cell culture and in patients. The K65R mutation can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine; the L74V mutation can confer resistance to abacavir, didanosine, and zalcitabine; and the M184V mutation can confer resistance to abacavir, didanosine, emtricitabine, lamivudine, and zalcitabine.

The combination of abacavir/lamivudine has demonstrated decreased susceptibility to viruses with the mutations K65R with or without the M184V/I mutation, viruses with L74V plus the M184V/I mutation, and viruses with thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219 E/R/H/Q/N) plus M184V. An increasing number of TAMs is associated with a progressive reduction in abacavir susceptibility.

EPZICOM may be administered with or without food. Administration with a high-fat meal in a single-dose bioavailability study resulted in no change in AUClast, AUC∞, and Cmax for lamivudine. Food did not alter the extent of systemic exposure to abacavir (AUC∞), but the rate of absorption (Cmax) was decreased approximately 24% compared to fasted conditions (n = 25). These results are similar to those from previous studies of the effect of food on abacavir and lamivudine tablets administered separately.

See PRECAUTIONS: Pregnancy.

See PRECAUTIONS: Nursing Mothers.

See PRECAUTIONS: Drug Interactions. The drug interactions described are based on studies conducted with the individual nucleoside analogues. In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 enzymes nor do they inhibit or induce this enzyme system; therefore, it is unlikely that clinically significant drug interactions will occur with drugs metabolized through these pathways.

EPZICOM Tablets, in combination with other antiretroviral agents, are indicated for the treatment of HIV-1 infection.

Additional important information on the use of EPZICOM for treatment of HIV-1 infection:

• EPZICOM is one of multiple products containing abacavir. Before starting EPZICOM, review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir.
• In one controlled study (CNA30021), more patients taking ZIAGEN 600 mg once daily had severe hypersensitivity reactions compared to patients taking ZIAGEN 300 mg twice daily.
• As part of a triple-drug regimen, EPZICOM Tablets are recommended for use with antiretroviral agents from different pharmacological classes and not with other nucleoside/nucleotide reverse transcriptase inhibitors.

See WARNINGS, ADVERSE REACTIONS, and Description of Clinical Studies.

EPZICOM Tablets are contraindicated in patients with previously demonstrated hypersensitivity to abacavir or to any other component of the product (see WARNINGS). Following a hypersensitivity reaction to abacavir, NEVER restart EPZICOM or any other abacavir-containing product. Fatal rechallenge reactions have been associated with readministration of abacavir to patients with a prior history of a hypersensitivity reaction to abacavir (see WARNINGS and PRECAUTIONS).

EPZICOM Tablets are contraindicated in patients with hepatic impairment (see CLINICAL PHARMACOLOGY).

Serious and sometimes fatal hypersensitivity reactions have been associated with EPZICOM and other abacavir-containing products. To minimize the risk of a life-threatening hypersensitivity reaction, permanently discontinue EPZICOM if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Important information on signs and symptoms of hypersensitivity, as well as clinical management, is presented below.

Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups.

Group 1: Fever

Group 2: Rash

Group 3: Gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain)

Group 4: Constitutional (including generalized malaise, fatigue, or achiness)

Group 5: Respiratory (including dyspnea, cough, or pharyngitis)

Hypersensitivity to abacavir following the presentation of a single sign or symptom has been reported infrequently.

Hypersensitivity to abacavir was reported in approximately 8% of 2,670 patients (n = 206) in 9 clinical trials (range: 2% to 9%) with enrollment from November 1999 to February 2002. Data on time to onset and symptoms of suspected hypersensitivity were collected on a detailed data collection module. The frequencies of symptoms are shown in Figure 1. Symptoms usually appeared within the first 6 weeks of treatment with abacavir, although the reaction may occur at any time during therapy. Median time to onset was 9 days; 89% appeared within the first 6 weeks; 95% of patients reported symptoms from 2 or more of the 5 groups uled above.

Figure 1: Hypersensitivity-Related Symptoms Reported with ≥10% Frequency in Clinical Trials (n = 206 Patients)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir and lamivudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering EPZICOM to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with EPZICOM should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

In clinical trials in non-HIV-infected patients treated with lamivudine for chronic HBV, clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. These exacerbations have been detected primarily by serum ALT elevations in addition to re-emergence of HBV DNA. Although most events appear to have been self-limited, fatalities have been reported in some cases. Similar events have been reported from post-marketing experience after changes from lamivudine-containing HIV treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV and HBV. The causal relationship to discontinuation of lamivudine treatment is unknown. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of posttreatment exacerbations of hepatitis.

In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as lamivudine, a component of EPZICOM. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV/HCV co-infected patients (see CLINICAL PHARMACOLOGY: Drug Interactions), hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and EPZICOM should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of EPZICOM should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicitiesare observed, including hepatic decompensation (e.g., Childs Pugh >6) (see the complete prescribing information for interferon and ribavirin).

EPZICOM contains fixed doses of 2 nucleoside analogues, abacavir and lamivudine, and should not be administered concomitantly with other abacavir-containing and/or lamivudine-containing products (ZIAGEN, EPIVIR, COMBIVIR^®, or TRIZIVIR).

The complete prescribing information for all agents being considered for use with EPZICOM should be consulted before combination therapy with EPZICOM is initiated.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including EPZICOM. 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.

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.

Pregnancy Category C. There are no adequate and well-controlled studies of EPZICOM in pregnant women. Reproduction studies with abacavir and lamivudine have been performed in animals (see Abacavir and Lamivudine sections below). EPZICOM should be used during pregnancy only if the potential benefits outweigh the risks.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV infection.

Safety and effectiveness of EPZICOM in pediatric patients have not been established.

Clinical studies of abacavir and lamivudine did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. EPZICOM is not recommended for patients with impaired renal function or impaired hepatic function (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a ≥5% frequency during therapy with ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily are uled in Table 4.

* Patients receiving ZIAGEN 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared to patients who received ZIAGEN 300 mg twice daily. Five percent (5%) of patients receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared to 2% of patients receiving ZIAGEN 300 mg twice daily. Two percent (2%) of patients receiving ZIAGEN 600 mg once daily had severe diarrhea while none of the patients receiving ZIAGEN 300 mg twice daily had this event.

†Study CNA30024 was a multi-center, double-blind, controlled study in which 649 HIV-infected, therapy-naive adults were randomized and received either ZIAGEN (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily) or zidovudine (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily). CNA30024 used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the study, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 patients in the abacavir group and 3% of 325 patients in the zidovudine group.

Laboratory abnormalities observed in clinical studies of ZIAGEN were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical studies of EPIVIR were thrombocytopenia and elevated levels of bilirubin, amylase, and lipase.

The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in Study CNA30021.

In addition to adverse reactions uled above, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT.

The following reactions have been identified during post-approval use of abacavir and lamivudine. 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 abacavir and/or lamivudine.

There is no known antidote for abacavir. It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.

One case of an adult ingesting 6 grams of lamivudine was reported; there were no clinical signs or symptoms noted and hematologic tests remained normal. It is not known whether lamivudine can be removed by peritoneal dialysis or hemodialysis.

A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill. To facilitate reporting of hypersensitivity reactions and collection of information on each case, an Abacavir Hypersensitivity Registry has been established. Physicians should register patients by calling 1-800-270-0425.

The recommended oral dose of EPZICOM for adults is one tablet daily, in combination with other antiretroviral agents (see INDICATIONS AND USAGE: Description of Clinical Studies, PRECAUTIONS, MICROBIOLOGY, and CLINICAL PHARMACOLOGY).

EPZICOM can be taken with or without food.

Because it is a fixed-dose tablet, EPZICOM should not be prescribed for patients requiring dosage adjustment such as those with creatinine clearance <50 mL/min, those with hepatic impairment, or those experiencing dose-limiting adverse events. Use of EPIVIR Oral Solution and ZIAGEN Oral Solution may be considered.

EPZICOM is available as tablets. Each tablet contains 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine. The tablets are orange, film-coated, modified capsule-shaped, and debossed with GS FC2 on one side with no markings on the reverse side. They are packaged as follows:

Bottles of 30 Tablets (NDC 0173-0742-00).

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature).

Myocardial degeneration was found in mice and rats following administration of abacavir for 2 years. The systemic exposures were equivalent to 7 to 24 times the expected systemic exposure in humans. The clinical relevance of this finding has not been determined.

EPZICOM™ (ep' zih com)Tablets

Generic name: abacavir sulfate and lamivudine

Read the Medication Guide that comes with Epzicom before you start taking it and each time you get a refill because there may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. Be sure to carry your Epzicom Warning Card with you at all times.

What is the most important information I should know about Epzicom?

• Serious Allergic Reaction to Abacavir. Epzicom contains abacavir (also contained in Ziagen^®and Trizivir^®). Patients taking Epzicom may have a serious allergic reaction (hypersensitivity reaction) that can cause death. If you get a symptom from 2 or more of the following groups while taking Epzicom, stop taking Epzicom and call your doctor right away.

  	Symptom(s)
  Group 1	Fever
  Group 2	Rash
  Group 3	Nausea, vomiting, diarrhea, abdominal (stomach area) pain
  Group 4	Generally ill feeling, extreme tiredness, or achiness
  Group 5	Shortness of breath, cough, sore throat

A ul of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you.

If you stop Epzicom because of an allergic reaction,NEVER take Epzicom (abacavir sulfate and lamivudine)or any other abacavir-containing medicine (Ziagen and Trizivir) again. If you take Epzicom or any other abacavir-containing medicine again after you have had an allergic reaction, WITHIN HOURS you may get life-threatening symptoms that may include very low blood pressure or death.

If you stop Epzicom for any other reason, even for a few days, and you are not allergic to Epzicom, talk with your doctor before taking it again. Taking Epzicom again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If your doctor tells you that you can take Epzicom again, start taking it when you are around medical help or people who can call a doctor if you need one.

• Lactic Acidosis. Some HIV medicines, including Epzicom, can cause a rare but serious condition called lactic acidosis with liver enlargement (hepatomegaly). Nausea and tiredness that don't get better may be symptoms of lactic acidosis. In some cases this condition can cause death. Women, overweight people, and people who have taken HIV medicines like Epzicom for a long time have a higher chance of getting lactic acidosis and liver enlargement. Lactic acidosis is a medical emergency and must be treated in the hospital.
• Worsening of hepatitis B virus (HBV) infection. Patients with HBV infection, who take Epzicom and then stop it, may get “flare-ups” of their hepatitis. “Flare-up” is when the disease suddenly returns in a worse way than before. If you have HBV infection, your doctor should closely monitor your liver function for several months after stopping Epzicom. You may need to take anti-HBV medicines.
• Use with interferon- and ribavirin-based regimens. Worsening of liver disease (sometimes resulting in death) has occurred in patients infected with both HIV and hepatitis C virus who are taking anti-HIV medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking Epzicom as well as interferon with or without ribavirin and you experience side effects, be sure to tell your doctor.

Epzicom can have other serious side effects. Be sure to read the section below entitled "What are the possible side effects of Epzicom?"

What is Epzicom?

Epzicom is a prescription medicine used to treat HIV infection. Epzicom includes 2 medicines: abacavir (Ziagen) and lamivudine or 3TC (Epivir^®). See the end of this Medication Guide for a complete ul of ingredients in Epzicom. Both of these medicines are called nucleoside analogue reverse transcriptase inhibitors (NRTIs). When used together, they help lower the amount of HIV in your blood. This helps to keep your immune system as healthy as possible so that it can help fight infection.

Different combinations of medicines are used to treat HIV infection. You and your doctor should discuss which combination of medicines is best for you.

• Epzicom does not cure HIV infection or AIDS. We do not know if Epzicom will help you live longer or have fewer of the medical problems that people get with HIV or AIDS. It is very important that you see your doctor regularly while you are taking Epzicom.
• Epzicom does not lower the risk of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood. For your health and the health of others, it is important to always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood. Never use or share dirty needles.

Who should not take Epzicom?

Do not take Epzicom if you:

• have ever had a serious allergic reaction (a hypersensitivity reaction) to Epzicom or any other medicine that has abacavir as one of its ingredients (Trizivir and Ziagen). See the end of this Medication Guide for a complete ul of ingredients in Epzicom. If you have had such a reaction, return all of your unused Epzicom to your doctor or pharmacist.
• have a liver that does not function properly.
• are less than 18 years of age.

Before starting Epzicom tell your doctor about all your medical conditions, including if you:

• are pregnant or planning to become pregnant. We do not know if Epzicom will harm your unborn child. You and your doctor will need to decide if Epzicom is right for you. If you use Epzicom while you are pregnant, talk to your doctor about how you can be on the Antiviral Pregnancy Registry for Epzicom.
• are breastfeeding. Some of the ingredients in Epzicom can be passed to your baby in your breast milk. It is not known if they could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.
• have liver problems including hepatitis B virus infection.
• have kidney problems.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• methadone
• Hivid^® (zalcitabine, ddC)
• Epivir or Epivir-HBV^® (lamivudine, 3TC), Ziagen (abacavir sulfate), Combivir^® (lamivudine and zidovudine), or Trizivir (abacavir sulfate, lamivudine, and zidovudine).

How should I take Epzicom?

• Take Epzicom by mouth exactly as your doctor prescribes it. The usual dose is 1 tablet once a day. Do not skip doses.
• You can take Epzicom with or without food.
• If you miss a dose of Epzicom, take the missed dose right away. Then, take the next dose at the usual time.
• Do not let your Epzicom run out.
• Starting Epzicom again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to it before. If you run out of Epzicom even for a few days, you must ask your doctor if you can start Epzicom again. If your doctor tells you that you can take Epzicom again, start taking it when you are around medical help or people who can call a doctor if you need one.
• If you stop your anti-HIV drugs, even for a short time, the amount of virus in your blood may increase and the virus may become harder to treat.
• If you take too much Epzicom, call your doctor or poison control center right away.

What should I avoid while taking Epzicom?

• Do not take Epivir (lamivudine, 3TC), Combivir^{(lamivudine and zidovudine), Ziagen (abacavir sulfate), or Trizivir (abacavir sulfate, lamivudine, and zidovudine) while taking Epzicom. Some of these medicines are already in Epzicom.}
• Do not take zalcitabine (Hivid, ddC) while taking Epzicom.

Avoid doing things that can spread HIV infection, as Epzicom does not stop you from passing the HIV infection to others.

• Do not share needles or other injection equipment.
• Do not share personal lis that can have blood or body fluids on them, like toothbrushes and razor blades.
• Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom or other barrier method to lower the chance of sexual contact with semen, vaginal secretions, or blood.
• Do not breastfeed. Epzicom can be passed to babies in breast milk and could harm the baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

What are the possible side effects of Epzicom?

Epzicom can cause the following serious side effects:

• Serious allergic reaction that can cause death. (See "What is the most important information I should know about Epzicom?" at the beginning of this Medication Guide.)
• Lactic acidosis with liver enlargement (hepatomegaly) that can cause death. (See "What is the most important information I should know about Epzicom?" at the beginning of this Medication Guide.)
• Worsening of HBV infection. (See "What is the most important information I should know about Epzicom?" at the beginning of this Medication Guide.)
• Changes in immune system. When you start taking HIV medicines, your immune system may get stronger and could begin to fight infections that have been hidden in your body, such as pneumonia, herpes virus, or tuberculosis. If you have new symptoms after starting your HIV medicines, be sure to tell your doctor.
• Changes in body fat. These changes have happened in patients taking antiretroviral medicines like Epzicom. The changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the back, chest, and stomach area. Loss of fat from the legs, arms, and face may also happen. The cause and long-term health effects of these conditions are not known.

The most common side effects with Epzicom are trouble sleeping, depression, headache, tiredness, dizziness, nausea, diarrhea, rash, fever, stomach pain, abnormal dreams, and anxiety. Most of these side effects did not cause people to stop taking Epzicom.

This ul of side effects is not complete. Ask your doctor or pharmacist for more information.

How should I store Epzicom?

• Store Epzicom at room temperature between 59° to 86°F (15° to 30°C).
• Keep Epzicom and all medicines out of the reach of children.

General information for safe and effective use of Epzicom

Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use Epzicom for a condition for which it was not prescribed. Do not give Epzicom to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Epzicom. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for the information that is written for healthcare professionals or call 1-888-825-5249.

What are the ingredients in Epzicom?

Active ingredients: abacavir sulfate and lamivudine

Inactive ingredients: Each film-coated Epzicom Tablet contains the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (Opadry^® orange YS-1-13065-A) that is made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.

March 2006 MG-036

This Medication Guide has been approved by the US Food and Drug Administration.

GlaxoSmithKline

Research Triangle Park, NC 27709

Lamivudine is manufactured under agreement from

Shire Pharmaceuticals Group plc

Basingstoke, UK

©2006, GlaxoSmithKline. All rights reserved.

October 2006 RL-2319