Baraclude^®
(entecavir)
Baraclude^® (entecavir) Tablets
Baraclude^® (entecavir) Oral Solution

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with antiretrovirals.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted (see WARNINGS: Exacerbations of Hepatitis after Discontinuation of Treatment).

Limited clinical experience suggests there is a potential for the development of resistance to HIV (human immunodeficiency virus) nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated. Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). See WARNINGS: Co-infection with HIV.

BARACLUDE^® is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). The chemical name for entecavir is 2-amino-1,9-dihydro-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one, monohydrate. Its molecular formula is C₁₂H₁₅N₅O₃•H₂O, which corresponds to a molecular weight of 295.3. Entecavir has the following structural formula:

Entecavir is a white to off-white powder. It is slightly soluble in water (2.4 mg/mL), and the pH of the saturated solution in water is 7.9 at 25° ± 0.5° C.

BARACLUDE film-coated tablets are available for oral administration in strengths of 0.5 mg and 1 mg of entecavir. BARACLUDE 0.5-mg and 1-mg film-coated tablets contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone, and magnesium stearate. The tablet coating contains titanium dioxide, hypromellose, polyethylene glycol 400, polysorbate 80 (0.5-mg tablet only), and iron oxide red (1-mg tablet only). BARACLUDE Oral Solution is available for oral administration as a ready-to-use solution containing 0.05 mg of entecavir per milliliter. BARACLUDE Oral Solution contains the following inactive ingredients: maltitol, sodium citrate, citric acid, methylparaben, propylparaben, and orange flavor.

Entecavir, a guanosine nucleoside analogue with activity against HBV polymerase, is efficiently phosphorylated to the active triphosphate form, which has an intracellular half-life of 15 hours. By competing with the natural substrate deoxyguanosine triphosphate, entecavir triphosphate functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Entecavir triphosphate is a weak inhibitor of cellular DNA polymerasesα, β, and δ and mitochondrial DNA polymerase γ with K_i values ranging from 18 to >160 µM.

Entecavir inhibited HBV DNA synthesis (50% reduction, EC₅₀) at a concentration of 0.004 µM in human HepG2 cells transfected with wild-type HBV. The median EC₅₀ value for entecavir against lamivudine-resistant HBV (rtL180M, rtM204V) was 0.026 µM (range 0.010-0.059 µM).

The coadministration of HIV nucleoside reverse transcriptase inhibitors (NRTIs) with BARACLUDE is unlikely to reduce the antiviral efficacy of BARACLUDE against HBV or of any of these agents against HIV. In HBV combination assays in cell culture, abacavir, didanosine, lamivudine, stavudine, tenofovir, or zidovudine were not antagonistic to the anti-HBV activity of entecavir over a wide range of concentrations. In HIV antiviral assays, entecavir was not antagonistic to the cell culture anti-HIV activity of these six NRTIs at >4 times the C_max of entecavir.

The single- and multiple-dose pharmacokinetics of entecavir were evaluated in healthy subjects and subjects with chronic hepatitis B infection.

BARACLUDE (entecavir) is indicated for the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

This indication is based on histologic, virologic, biochemical, and serologic responses in nucleoside-treatment-naive and lamivudine-resistant adult subjects with HBeAg-positive or HBeAg-negative chronic HBV infection with compensated liver disease and on more limited data in adult subjects with HIV/HBV co-infection who have received prior lamivudine therapy.

The safety and efficacy of BARACLUDE were evaluated in three Phase 3 active-controlled trials. These studies included 1633 subjects 16 years of age or older with chronic hepatitis B infection (serum HBsAg-positive for at least 6 months) accompanied by evidence of viral replication (detectable serum HBV DNA, as measured by the bDNA hybridization or PCR assay). Subjects had persistently elevated ALT levels ≥1.3 times the upper limit of normal (ULN) and chronic inflammation on liver biopsy compatible with a diagnosis of chronic viral hepatitis. The safety and efficacy of BARACLUDE were also evaluated in a study of 68 subjects co-infected with HBV and HIV.

BARACLUDE is contraindicated in patients with previously demonstrated hypersensitivity to entecavir or any component of the product.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy, including entecavir. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted (see ADVERSE REACTIONS: Exacerbations of Hepatitis after Discontinuation of Treatment).

BARACLUDE has not been evaluated in HIV/HBV co-infected patients who were not simultaneously receiving effective HIV treatment. Limited clinical experience suggests there is a potential for the development of resistance to HIV nucleoside reverse transcriptase inhibitors if BARACLUDE is used to treat chronic hepatitis B virus infection in patients with HIV infection that is not being treated (see MICROBIOLOGY: Antiviral Activity, Antiviral Activity against HIV). Therefore, therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART). Before initiating BARACLUDE therapy, HIV antibody testing should be offered to all patients. BARACLUDE has not been studied as a treatment for HIV infection and is not recommended for this use.

A patient package insert (PPI) for BARACLUDE is available for patient information.

Patients should remain under the care of a physician while taking BARACLUDE. They should discuss any new symptoms or concurrent medications with their physician.

Patients should be advised to take BARACLUDE on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal).

Patients should be informed that deterioration of liver disease may occur in some cases if treatment is discontinued, and that they should discuss any change in regimen with their physician.

Patients should be offered HIV antibody testing before starting BARACLUDE therapy. They should be informed that if they have HIV infection and are not receiving effective HIV treatment, BARACLUDE may increase the chance of HIV resistance to HIV medication (see WARNINGS: Co-infection with HIV).

Patients should be advised that treatment with BARACLUDE has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination (see Labor and Delivery).

Since entecavir is primarily eliminated by the kidneys (see CLINICAL PHARMACOLOGY: Metabolism and Elimination), coadministration of BARACLUDE with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug. Coadministration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir disoproxil fumarate did not result in significant drug interactions. The effects of coadministration of BARACLUDE with other drugs that are renally eliminated or are known to affect renal function have not been evaluated, and patients should be monitored closely for adverse events when BARACLUDE is coadministered with such drugs.

Long-term oral carcinogenicity studies of entecavir in mice and rats were carried out at exposures up to approximately 42 times (mice) and 35 times (rats) those observed in humans at the highest recommended dose of 1 mg/day. In mouse and rat studies, entecavir was positive for carcinogenic findings.

In mice, lung adenomas were increased in males and females at exposures 3 and 40 times those in humans. Lung carcinomas in both male and female mice were increased at exposures 40 times those in humans. Combined lung adenomas and carcinomas were increased in male mice at exposures 3 times and in female mice at exposures 40 times those in humans. Tumor development was preceded by pneumocyte proliferation in the lung, which was not observed in rats, dogs, or monkeys administered entecavir, supporting the conclusion that lung tumors in mice may be a species-specific event. Hepatocellular carcinomas were increased in males and combined liver adenomas and carcinomas were also increased at exposures 42 times those in humans. Vascular tumors in female mice (hemangiomas of ovaries and uterus and hemangiosarcomas of spleen) were increased at exposures 40 times those in humans. In rats, hepatocellular adenomas were increased in females at exposures 24 times those in humans; combined adenomas and carcinomas were also increased in females at exposures 24 times those in humans. Brain gliomas were induced in both males and females at exposures 35 and 24 times those in humans. Skin fibromas were induced in females at exposures 4 times those in humans.

It is not known how predictive the results of rodent carcinogenicity studies may be for humans.

Entecavir was clastogenic to human lymphocyte cultures. Entecavir was not mutagenic in the Ames bacterial reverse mutation assay using S. typhimurium and E. coli strains in the presence or absence of metabolic activation, a mammalian-cell gene mutation assay, and a transformation assay with Syrian hamster embryo cells. Entecavir was also negative in an oral micronucleus study and an oral DNA repair study in rats. In reproductive toxicology studies, in which animals were administered entecavir at up to 30 mg/kg for up to 4 weeks, no evidence of impaired fertility was seen in male or female rats at systemic exposures >90 times those achieved in humans at the highest recommended dose of 1 mg/day. In rodent and dog toxicology studies, seminiferous tubular degeneration was observed at exposures ≥35 times those achieved in humans. No testicular changes were evident in monkeys.

There are no studies in pregnant women and no data on the effect of BARACLUDE on transmission of HBV from mother to infant. Therefore, appropriate interventions should be used to prevent neonatal acquisition of HBV.

Entecavir is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Mothers should be instructed not to breast-feed if they are taking BARACLUDE.

Safety and effectiveness of entecavir in pediatric patients below the age of 16 years have not been established.

Clinical studies of BARACLUDE did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Entecavir is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION: Renal Impairment).

Clinical studies of BARACLUDE did not include sufficient numbers of subjects from some racial/ethnic minorities (black/African American, Hispanic) to determine whether they respond differently to treatment with the drug. There are no significant racial differences in entecavir pharmacokinetics.

Assessment of adverse reactions is based on four studies (AI463014, AI463022, AI463026, and AI463027) in which 1720 subjects with chronic hepatitis B infection received double-blind treatment with BARACLUDE 0.5 mg/day (n=679), BARACLUDE 1 mg/day (n=183), or lamivudine (n=858) for up to 2 years. Median duration of therapy was 69 weeks for BARACLUDE-treated subjects and 63 weeks for lamivudine-treated subjects in Studies AI463022 and AI463027 and 73 weeks for BARACLUDE-treated subjects and 51 weeks for lamivudine-treated subjects in Studies AI463026 and AI463014. The safety profiles of BARACLUDE and lamivudine were comparable in these studies. The safety profile of BARACLUDE 1 mg (n=51) in HIV/HBV co-infected subjects enrolled in Study AI463038 was similar to that of placebo (n=17) through 24 weeks of blinded treatment and similar to that seen in non-HIV infected subjects (see WARNINGS: Co-infection with HIV).

The most common adverse events of any severity with at least a possible relation to study drug for BARACLUDE-treated subjects were headache, fatigue, dizziness, and nausea. The most common adverse events among lamivudine-treated subjects were headache, fatigue, and dizziness. One percent of BARACLUDE-treated subjects in these four studies compared with 4% of lamivudine-treated subjects discontinued for adverse events or abnormal laboratory test results. Also see WARNINGS and PRECAUTIONS.

Selected clinical adverse events of moderate-severe intensity and considered at least possibly related to treatment occurring during therapy in four clinical studies in which BARACLUDE was compared with lamivudine are presented in Table 7.

Frequencies of selected treatment-emergent laboratory abnormalities reported during therapy in four clinical trials of BARACLUDE compared with lamivudine are uled in Table 8.

Among BARACLUDE-treated subjects in these studies, on-treatment ALT elevations >10 X ULN and >2 X baseline generally resolved with continued treatment. A majority of these exacerbations were associated with a ≥2 log₁₀/mL reduction in viral load that preceded or coincided with the ALT elevation. Periodic monitoring of hepatic function is recommended during treatment.

An exacerbation of hepatitis or ALT flare was defined as ALT >10 X ULN and >2 X the subject’s reference level (minimum of the baseline or last measurement at end of dosing). For all subjects who discontinued treatment (regardless of reason), Table 9 presents the proportion of subjects in each study who experienced post-treatment ALT flares. In these studies, a subset of subjects was allowed to discontinue treatment at or after 52 weeks if they achieved a protocol-defined response to therapy. If BARACLUDE is discontinued without regard to treatment response, the rate of post-treatment flares could be higher.

There is no experience of entecavir overdosage reported in patients. Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

Following a single 1-mg dose of entecavir, a 4-hour hemodialysis session removed approximately 13% of the entecavir dose.

The recommended dose of BARACLUDE for chronic hepatitis B virus infection in nucleoside-treatment-naive adults and adolescents 16 years of age and older is 0.5 mg once daily.

The recommended dose of BARACLUDE in adults and adolescents (≥16 years of age) with a history of hepatitis B viremia while receiving lamivudine or known lamivudine resistance mutations is 1 mg once daily.

BARACLUDE should be administered on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal).

BARACLUDE (entecavir) Oral Solution contains 0.05 mg of entecavir per milliliter. Therefore, 10 mL of the oral solution provides a 0.5-mg dose and 20 mL provides a 1-mg dose of entecavir.

In subjects with renal impairment, the apparent oral clearance of entecavir decreased as creatinine clearance decreased (see CLINICAL PHARMACOLOGY: Pharmacokinetics, Special Populations). Dosage adjustment is recommended for patients with creatinine clearance <50 mL/min, including patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), as shown in Table 10. The once-daily dosing regimens are preferred.

No dosage adjustment is necessary for patients with hepatic impairment.

The optimal duration of treatment with BARACLUDE for patients with chronic hepatitis B infection and the relationship between treatment and long-term outcomes such as cirrhosis and hepatocellular carcinoma are unknown.

BARACLUDE^® (entecavir) Tablets and Oral Solution are available in the following strengths and configurations of plastic bottles with child-resistant closures:

BARACLUDE Oral Solution is a ready-to-use product; dilution or mixing with water or any other solvent or liquid product is not recommended. Each bottle of the oral solution is accompanied by a dosing spoon that is calibrated in 1-mL increments up to 10 mL. Patients should be instructed to hold the spoon in a vertical position and fill it gradually to the mark corresponding to the prescribed dose. Rinsing of the dosing spoon with water is recommended after each daily dose.

BARACLUDE Tablets should be stored in a tightly closed container at 25° C (77° F); excursions permitted between 15-30° C (59-86° F) [see USP Controlled Room Temperature].

BARACLUDE Oral Solution should be stored in the outer carton at 25° C (77° F); excursions permitted between 15-30° C (59-86° F) [see USP Controlled Room Temperature]. Protect from light. After opening, the oral solution can be used up to the expiration date on the bottle. The bottle and its spans should be discarded after the expiration date.

US Patent No: 5,206,244. Other patents pending.

Baraclude^® (BEAR ah klude)
(generic name = entecavir)
Tablets and Oral Solution

Read the Patient Information that comes with BARACLUDE before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.

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

• Some people who have taken medicines like BARACLUDE (a nucleoside analogue) have developed a serious condition called lactic acidosis (buildup of an acid in the blood). Lactic acidosis is a medical emergency and must be treated in the hospital. Call your healthcare provider right away if you get any of the following signs of lactic acidosis.
  • You feel very weak or tired.
  • You have unusual (not normal) muscle pain.
  • You have trouble breathing.
  • You have stomach pain with nausea and vomiting.
  • You feel cold, especially in your arms and legs.
  • You feel dizzy or light-headed.
  • You have a fast or irregular heartbeat.
• Some people who have taken medicines like BARACLUDE have developed serious liver problems called hepatotoxicity, with liver enlargement (hepatomegaly) and fat in the liver (steatosis). Call your healthcare provider right away if you get any of the following signs of liver problems.
  • Your skin or the white part of your eyes turns yellow (jaundice).
  • Your urine turns dark.
  • Your bowel movements (stools) turn light in color.
  • You don’t feel like eating food for several days or longer.
  • You feel sick to your stomach (nausea).
  • You have lower stomach pain.
• Your hepatitis B infection may get worse or become very serious if you stop BARACLUDE.
  • Take BARACLUDE exactly as prescribed.
  • Do not run out of BARACLUDE.
  • Do not stop BARACLUDE without talking to your healthcare provider.

  Your healthcare provider will need to monitor your health and do regular blood tests to check your liver if you stop BARACLUDE. Tell your healthcare provider right away about any new or unusual symptoms that you notice after you stop taking BARACLUDE.

• If you have or get HIV (human immunodeficiency virus) infection be sure to discuss your treatment with your doctor. If you are taking BARACLUDE to treat chronic hepatitis B and are not taking medicines for your HIV at the same time, some HIV treatments that you take in the future may be less likely to work. You are advised to get an HIV test before you start taking BARACLUDE and anytime after that when there is a chance you were exposed to HIV. BARACLUDE will not help your HIV infection.

What is BARACLUDE?

BARACLUDE is a prescription medicine used for chronic infection with hepatitis B virus (HBV) in adults who also have active liver damage.

• BARACLUDE will not cure HBV.
• BARACLUDE may lower the amount of HBV in the body.
• BARACLUDE may lower the ability of HBV to multiply and infect new liver cells.
• BARACLUDE may improve the condition of your liver.

It is important to stay under your healthcare provider’s care while taking BARACLUDE. Your healthcare provider will test the level of the hepatitis B virus in your blood regularly.

Does BARACLUDE lower the risk of passing HBV to others?

BARACLUDE does not stop you from spreading HBV to others by sex, sharing needles, or being exposed to your blood. Talk with your healthcare provider about safe sexual practices that protect your partner. Never share needles. Do not share personal lis that can have blood or body fluids on them, like toothbrushes or razor blades. A shot (vaccine) is available to protect people at risk from becoming infected with HBV.

Who should not take BARACLUDE?

Do not take BARACLUDE if you are allergic to any of its ingredients. The active ingredient in BARACLUDE is entecavir. See the end of this leaflet for a complete ul of ingredients in BARACLUDE. Tell your healthcare provider if you think you have had an allergic reaction to any of these ingredients.

BARACLUDE has not been studied in children and is not recommended for anyone less than 16 years old.

What should I tell my healthcare provider before I take BARACLUDE?

Tell your healthcare provider about all of your medical conditions, including if you:

• have kidney problems. Your BARACLUDE dose or dose schedule may need to be adjusted.
• are pregnant or planning to become pregnant. It is not known if BARACLUDE is safe to use during pregnancy. It is not known whether BARACLUDE helps prevent a pregnant mother from passing HBV to her baby. You and your healthcare provider will need to decide if BARACLUDE is right for you. If you use BARACLUDE while you are pregnant, talk to your healthcare provider about the BARACLUDE Pregnancy Registry.
• are breast-feeding. It is not known if BARACLUDE can pass into your breast milk or if it can harm your baby. Do not breast-feed if you are taking BARACLUDE.

Tell your healthcare provider about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. BARACLUDE may interact with other medicines that leave the body through the kidneys.

Know the medicines you take. Keep a ul of your medicines with you to show your healthcare provider and pharmacist.

How should I take BARACLUDE?

• Take BARACLUDE exactly as prescribed. Your healthcare provider will tell you how much BARACLUDE to take. Your dose will depend on whether you have been treated for HBV infection before and what medicine you took. The usual dose of BARACLUDE Tablets is either 0.5 mg (one white tablet) or 1 mg (one pink tablet) once daily by mouth. The usual dose of BARACLUDE Oral Solution is either 10 mL or 20 mL once daily by mouth. Your dose may be lower or you may take BARACLUDE less often than once a day if you have kidney problems.
• Take BARACLUDE once a day on an empty stomach to help it work better. Empty stomach means at least 2 hours after a meal and at least 2 hours before the next meal. To help you remember to take your BARACLUDE, try to take it at the same time each day.
• If you are taking BARACLUDE Oral Solution, carefully measure your dose with the spoon provided, as follows:
  • 1)Hold the spoon in a vertical (upright) position and fill it gradually to the mark corresponding to the prescribed dose. Holding the spoon with the volume marks facing you, check that it has been filled to the proper mark.
  • 2) Swallow the medicine directly from the measuring spoon.
  • 3)After each use, rinse the spoon with water and allow it to air dry.
  
  If you lose the spoon, call your pharmacist or healthcare provider for instructions.
• Do not change your dose or stop taking BARACLUDE without talking to your healthcare provider. Your hepatitis B symptoms may get worse or become very serious if you stop taking BARACLUDE. After you stop taking BARACLUDE, it is important to stay under your healthcare provider’s care. Your healthcare provider will need to do regular blood tests to check your liver.
• If you forget to take BARACLUDE, take it as soon as you remember and then take your next dose at its regular time. If it is almost time for your next dose, skip the missed dose. Do not take two doses at the same time. Call your healthcare provider or pharmacist if you are not sure what to do.
• When your supply of BARACLUDE starts to run low, get more from your healthcare provider or pharmacy. Do not run out of BARACLUDE (entecavir).
• If you take more than the prescribed dose of BARACLUDE, call your healthcare provider right away.

What are the possible side effects of BARACLUDE?

BARACLUDE may cause the following serious side effects (see“What is the most important information I should know about BARACLUDE?”):

• lactic acidosis and liver problems.
• a worse or very serious hepatitis if you stop taking it.

The most common side effects of BARACLUDE are headache, tiredness, dizziness, and nausea. Less common side effects include diarrhea, indigestion, vomiting, sleepiness, and trouble sleeping. In some patients, the results of blood tests that measure how the liver or pancreas is working may worsen.

These are not all the side effects of BARACLUDE. The ul of side effects is not complete at this time because BARACLUDE is still under study. Report any new or continuing symptom to your healthcare provider. If you have questions about side effects, ask your healthcare provider. Your healthcare provider may be able to help you manage these side effects.

How should I store BARACLUDE?

• Store BARACLUDE Tablets or Oral Solution at room temperature, 59° to 86° F (15° to 30° C). They do not require refrigeration. Do not store BARACLUDE Tablets in a damp place such as a bathroom medicine cabinet or near the kitchen sink.
• Keep the container tightly closed. BARACLUDE Oral Solution should be stored in the original carton and protected from light.
• Throw away BARACLUDE when it is outdated or no longer needed by flushing tablets down the toilet or pouring the oral solution down the sink.
• Keep BARACLUDE and all medicines out of the reach of children and pets.

General information about BARACLUDE: Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use BARACLUDE for a condition for which it was not prescribed. Do not give BARACLUDE to other people, even if they have the same symptoms you have. It may harm them. The leaflet summarizes the most important information about BARACLUDE. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about BARACLUDE that is written for healthcare professionals. You can also call 1-800-321-1335 or visit the BARACLUDE website at www.Baraclude.com.

What are the ingredients in BARACLUDE?

Active Ingredient: entecavir

Inactive Ingredients in BARACLUDE Tablets: lactose monohydrate, microcrystalline cellulose, crospovidone, povidone, magnesium stearate, titanium dioxide, hypromellose, polyethylene glycol 400, polysorbate 80 (0.5-mg tablet only), and iron oxide red (1-mg tablet only).

Inactive Ingredients in BARACLUDE Oral Solution: maltitol, sodium citrate, citric acid, methylparaben, propylparaben, and orange flavor.

Bristol-Myers Squibb Company
Princeton, NJ 08543 USA

This Patient Information Leaflet has been approved by the U.S. Food and Drug Administration.
1195459A3

Rev July 2007