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NDC 49702-206 Epzicom
Abacavir Sulfate And Lamivudine Tablet, Film Coated Oral
Viiv Healthcare Company
NDC Product Code: 49702-206 Epzicom
What is NDC 49702-206?
The NDC code 49702-206 is assigned by the FDA to the product Epzicom which is a human prescription drug product labeled by Viiv Healthcare Company. The generic name of Epzicom is abacavir sulfate and lamivudine. The product's dosage form is tablet, film coated and is administered via oral form. The product is distributed in a single package with assigned NDC code 49702-206-13 30 tablet, film coated in 1 bottle . This page includes all the important details about this product, including active and inactive ingredients, pharmagologic classes, product uses and characteristics, UNII information, RxNorm crosswalk and the complete product label.
NDC Product Code 49702-206
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes. Epzicom
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product. Abacavir Sulfate And Lamivudine
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the "Document Type" field of the Structured Product Listing. Human Prescription Drug
Dosage Form Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.
Administration Route(s) What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.
Product Labeler Information What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC. Viiv Healthcare Company
Labeler Code 49702
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. "part 341"). For unapproved drugs, this field will be null. NDA021652
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources. NDA - A product marketed under an approved New Drug Application.
49702 - Viiv Healthcare Company
49702-206 - Epzicom
What are the uses for Epzicom?
This product contains 2 drugs: abacavir and lamivudine. It is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life. Abacavir and lamivudine both belong to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). Abacavir/lamivudine is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, do all of the following: (1) continue to take all HIV medications exactly as prescribed by your doctor, (2) always use an effective barrier method (latex or polyurethane condoms/dental dams) during all sexual activity, and (3) do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Color(s) ORANGE (C48331)
Shape OVAL (C48345)
Size(s) 20 MM
Imprint(s) GS;FC2
Product Packages
Package Description: 30 TABLET, FILM COATED in 1 BOTTLE
Price per Unit: $41.38820 per EA
What are Epzicom Active Ingredients?
An active ingredient is the substance responsible for the medicinal effects of a product specified by the substance's molecular structure or if the molecular structure is not known, defined by an unambiguous definition that identifies the substance. Each active ingredient name is the preferred term of the UNII code submitted.
ABACAVIR SULFATE 600 mg/1
LAMIVUDINE 300 mg/1 - A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.
Epzicom Active Ingredients UNII Codes
ABACAVIR SULFATE (UNII: J220T4J9Q2)
ABACAVIR (UNII: WR2TIP26VS) (Active Moiety)
LAMIVUDINE (UNII: 2T8Q726O95)
LAMIVUDINE (UNII: 2T8Q726O95) (Active Moiety)
What is RxNorm? RxNorm is a normalized naming system for generic and branded drugs that assigns unique concept identifier(s) known as RxCUIs to NDC products.The NDC to RxNorm Crosswalk for this produdct indicates multiple concept unique identifiers (RXCUIs) are associated with this product:
RxCUI: 602393 - abacavir sulfate 600 MG / lamiVUDine 300 MG Oral Tablet
RxCUI: 602393 - abacavir 600 MG / lamivudine 300 MG Oral Tablet
RxCUI: 602393 - abacavir 600 MG / 3TC 300 MG Oral Tablet
RxCUI: 602393 - abacavir (as abacavir sulfate) 600 MG / lamivudine 300 MG Oral Tablet
RxCUI: 602395 - EPZICOM 600 MG / 300 MG Oral Tablet
Epzicom Inactive Ingredients UNII Codes
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for "Unique Ingredient Identifier" and is used to identify each inactive ingredient present in a product.
MAGNESIUM STEARATE (UNII: 70097M6I30)
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
HYPROMELLOSES (UNII: 3NXW29V3WO)
POLYETHYLENE GLYCOL 400 (UNII: B697894SGQ)
POLYSORBATE 80 (UNII: 6OZP39ZG8H)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
Pharmacologic Class(es)
A pharmacologic class is a group of drugs that share the same scientifically documented properties. The following is a list of the reported pharmacologic class(es) corresponding to the active ingredients of this product.
Cytochrome P450 1A1 Inhibitors - [MoA] (Mechanism of Action)
Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor - [EPC] (Established Pharmacologic Class)
Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor - [EPC] (Established Pharmacologic Class)
Nucleoside Reverse Transcriptase Inhibitors - [MoA] (Mechanism of Action)
Abacavir is pronounced as (a ba ka' vir)
Why is abacavir medication prescribed?
Abacavir is used along with other medications to treat human immunodeficiency virus (HIV) infection. Abacavir is in a class of medications called nucleoside reverse trans...
Lamivudine is pronounced as (la mi' vyoo deen)
Why is lamivudine medication prescribed?
Lamivudine (Epivir) is used along with other medications to treat human immunodeficiency virus (HIV) infection. Lamivudine (Epivir-HBV) is used to treat hepatitis B infec...
Epzicom Product Label
FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.
Product Label Table of Contents
WARNING: HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, AND EXACERBATIONS OF HEPATITIS B
1 INDICATIONS AND USAGE
2.1 SCREENING FOR HLAB*5701 ALLELE PRIOR TO STARTING EPZICOM
2.2 RECOMMENDED DOSAGE FOR ADULT PATIENTS
2.3 RECOMMENDED DOSAGE FOR PEDIATRIC PATIENTS
2.4 NOT RECOMMENDED DUE TO LACK OF DOSAGE ADJUSTMENT
3 DOSAGE FORMS AND STRENGTHS
5.1 HYPERSENSITIVITY REACTIONS
5.2 LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS
5.3 PATIENTS WITH HEPATITIS B VIRUS CO-INFECTION
5.4 USE WITH INTERFERON- AND RIBAVIRIN-BASED REGIMENS
5.5 IMMUNE RECONSTITUTION SYNDROME
5.6 FAT REDISTRIBUTION
5.7 MYOCARDIAL INFARCTION
6 ADVERSE REACTIONS
6.1 CLINICAL TRIALS EXPERIENCE IN ADULT SUBJECTS
6.2 CLINICAL TRIALS EXPERIENCE IN PEDIATRIC SUBJECTS
6.3 POSTMARKETING EXPERIENCE
7.1 METHADONE
8.1 PREGNANCY
8.2 LACTATION
8.4 PEDIATRIC USE
8.5 GERIATRIC USE
8.6 PATIENTS WITH IMPAIRED RENAL FUNCTION
8.7 PATIENTS WITH IMPAIRED HEPATIC FUNCTION
10 OVERDOSAGE
12.1 MECHANISM OF ACTION
12.3 PHARMACOKINETICS
12.4 MICROBIOLOGY
13.1 CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
13.2 ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY
14.1 ADULTS
14.2 PEDIATRIC SUBJECTS
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
SPL MEDGUIDE
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of EPZICOM (abacavir and lamivudine). Patients who carry the HLA‑B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA‑B*5701 allele [see Warnings and Precautions (5.1)].
EPZICOM is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701-positive patients [see Contraindications (4), Warnings and Precautions (5.1)]. All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with EPZICOM or reinitiation of therapy with EPZICOM, unless patients have a previously documented HLA‑B*5701 allele assessment. Discontinue EPZICOM immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see Contraindications (4), Warnings and Precautions (5.1)].
Following a hypersensitivity reaction to EPZICOM, NEVER restart EPZICOM or any other abacavir‑containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions (5.1)].
Lactic Acidosis and Severe Hepatomegaly with Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPZICOM if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.2)].
Exacerbations of Hepatitis B
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‑1) and have discontinued lamivudine, which is a 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‑1 and HBV. If appropriate, initiation of anti‑hepatitis B therapy may be warranted [see Warnings and Precautions (5.3)].
EPZICOM, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV‑1) infection.
Screen for the HLA‑B*5701 allele prior to initiating therapy with EPZICOM [see Boxed Warning, Warnings and Precautions (5.1)].
The recommended dosage of EPZICOM for adults is one tablet taken orally once daily, in combination with other antiretroviral agents, with or without food.
The recommended oral dose of EPZICOM for pediatric patients weighing at least 25 kg is one tablet daily in combination with other antiretroviral agents [see Clinical Studies (14.2)]. Before prescribing EPZICOM tablets, pediatric patients should be assessed for the ability to swallow tablets.
Because EPZICOM is a fixed‑dose tablet and cannot be dose adjusted, EPZICOM is not recommended for:
patients with creatinine clearance less than 50 mL per minute [see Use in Specific Populations (8.6)].
patients with mild hepatic impairment. EPZICOM is contraindicated in patients with moderate or severe hepatic impairment [see Contraindications (4), Use in Specific Populations (8.7)].
Use of EPIVIR® (lamivudine) oral solution or tablets and ZIAGEN® (abacavir) oral solution may be considered.
EPZICOM tablets contain 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine. The tablets are modified capsule-shaped, orange, film-coated, and debossed with "GS FC2" on one side with no markings on the reverse side.
EPZICOM is contraindicated in patients:
who have the HLA‑B*5701 allele [see Warnings and Precautions (5.1)].
with prior hypersensitivity reaction to abacavir [see Warnings and Precautions (5.1)] or lamivudine.
with moderate or severe hepatic impairment [see Use in Specific Populations (8.7)].
Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of EPZICOM. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment [see Adverse Reactions (6.1)]. Patients who carry the HLA‑B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA‑B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA‑B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA‑B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.
Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:
All patients should be screened for the HLA‑B*5701 allele prior to initiating therapy with EPZICOM or reinitiation of therapy with EPZICOM, unless patients have a previously documented HLA‑B*5701 allele assessment.
EPZICOM is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA‑B*5701-positive patients.
Before starting EPZICOM, review medical history for prior exposure to any abacavir-containing product. NEVER restart EPZICOM or any other abacavir‑containing product following a hypersensitivity reaction to abacavir, regardless of HLA‑B*5701 status.
To reduce the risk of a life‑threatening hypersensitivity reaction, regardless of HLA‑B*5701 status, discontinue EPZICOM immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications).
If a hypersensitivity reaction cannot be ruled out, do not restart EPZICOM or any other abacavir‑containing products because more severe symptoms, which may include life‑threatening hypotension and death, can occur within hours.
If a hypersensitivity reaction is ruled out, patients may restart EPZICOM. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of EPZICOM or any other abacavir-containing product is recommended only if medical care can be readily accessed.
A Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions should be dispensed with each new prescription and refill.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. See full prescribing information for ZIAGEN (abacavir) and EPIVIR (lamivudine). 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).
Posttreatment Exacerbations of Hepatitis
Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. See full prescribing information for EPIVIR (lamivudine). Patients should be closely monitored with both clinical and laboratory follow‑up for at least several months after stopping treatment.
Emergence of Lamivudine‑Resistant HBV
Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in subjects dually infected with HIV‑1 and HBV. Emergence of hepatitis B virus variants associated with resistance to lamivudine has been reported in HIV‑1‑infected subjects who have received lamivudine‑containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. See full prescribing information for EPIVIR (lamivudine).
Patients receiving interferon alfa with or without ribavirin and EPZICOM should be closely monitored for treatment‑associated toxicities, especially hepatic decompensation. See full prescribing information for EPIVIR (lamivudine). 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 toxicities are observed, including hepatic decompensation (e.g., Child‑Pugh greater than 6) (see full prescribing information for interferon and ribavirin).
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 systems respond 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.
Autoimmune disorders (such as Graves' disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of 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.
In a published prospective, observational, epidemiological trial designed to investigate the rate of myocardial infarction (MI) in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of MI. In a sponsor‑conducted pooled analysis of clinical trials, no excess risk of MI was observed in abacavir‑treated subjects as compared with control subjects. In totality, the available data from the observational cohort and from clinical trials are inconclusive.
As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).
The following adverse reactions are discussed in other sections of the labeling:
Serious and sometimes fatal hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.1)].
Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.2)].
Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.3)].
Hepatic decompensation in patients co-infected with HIV-1 and Hepatitis C [see Warnings and Precautions (5.4)].
Immune reconstitution syndrome [see Warnings and Precautions (5.5)].
Fat redistribution [see Warnings and Precautions (5.6)].
Myocardial infarction [see Warnings and Precautions (5.7)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Serious and Fatal Abacavir-Associated Hypersensitivity Reactions
In clinical trials, serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of EPZICOM [see Boxed Warning, Warnings and Precautions (5.1)]. These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome.
Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with these hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and others did not have a rash). There were reports of erythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevated creatine phosphokinase, elevated creatinine, and lymphopenia and abnormal chest x‑ray findings (predominantly infiltrates, which were localized).
Additional Adverse Reactions with Use of EPZICOM
Therapy‑Naive Adults: Treatment‑emergent clinical adverse reactions (rated by the investigator as moderate or severe) with greater than or equal to 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 listed in Table 1.
Table 1. Treatment‑Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, Greater than or Equal to 5% Frequency) in Therapy‑Naive Adults (CNA30021) through 48 Weeks of Treatment
Adverse Event
ZIAGEN 600 mg q.d.
plus EPIVIR plus Efavirenz
(n = 384)
ZIAGEN 300 mg b.i.d.
Drug hypersensitivitya,b
Depression/Depressed mood
Fatigue/Malaise
Diarrheaa
Abdominal pain/gastritis
Abnormal dreams
aSubjects receiving ZIAGEN 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received ZIAGEN 300 mg twice daily. Five percent (5%) of subjects receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving ZIAGEN 300 mg twice daily. Two percent (2%) of subjects receiving ZIAGEN 600 mg once daily had severe diarrhea while none of the subjects receiving ZIAGEN 300 mg twice daily had this event.
bCNA30024 was a multi‑center, double-blind, controlled trial in which 649 HIV‑1‑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 trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group.
Laboratory Abnormalities: Laboratory abnormalities observed in clinical trials of ZIAGEN were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical trials 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 CNA30021.
Other Adverse Events: In addition to adverse reactions listed above, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT.
The safety of once-daily compared with twice-daily dosing of abacavir and lamivudine, administered as either single products or as EPZICOM, was assessed in the ARROW trial (n = 336). Primary safety assessment in the ARROW (COL105677) trial was based on Grade 3 and Grade 4 adverse events. The frequency of Grade 3 and 4 adverse events was similar among subjects randomized to once-daily dosing compared with subjects randomized to twice-daily dosing. One event of Grade 4 hepatitis in the once-daily cohort was considered as uncertain causality by the investigator and all other Grade 3 or 4 adverse events were considered not related by the investigator. No additional safety issues were identified in pediatric subjects receiving abacavir and lamivudine once-daily compared with historical data in adults [see Adverse Reactions (6.1)].
The following adverse reactions have been identified during postmarketing use. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiovascular: Myocardial infarction.
Skin: Suspected Stevens‑Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases. There have also been reports of erythema multiforme with abacavir use [see Adverse Reactions (6.1)].
Abacavir and Lamivudine
Body as a Whole: Redistribution/accumulation of body fat [see Warnings and Precautions (5.6)].
Digestive: Stomatitis.
Endocrine and Metabolic: Hyperglycemia.
General: Weakness.
Hemic and Lymphatic: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic: Lactic acidosis and hepatic steatosis [see Warnings and Precautions (5.2)], posttreatment exacerbations of hepatitis B [see Warnings and Precautions (5.3)].
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.
In a trial of 11 HIV‑1‑infected subjects receiving methadone‑maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology (12.3)]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to EPZICOM during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Risk Summary
Available data from the APR show no difference in the overall risk of birth defects for abacavir or lamivudine compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population [see Data]. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks gestation. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown.
In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose. However, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose. Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at systemic exposure (AUC) similar to the recommended clinical dose; however, no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (Cmax) 35 times the recommended clinical dose [see Data].
Human Data: Abacavir: Based on prospective reports to the APR of over 2,000 exposures to abacavir during pregnancy resulting in live births (including over 1,000 exposed in the first trimester), there was no difference between the overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of defects in live births was 2.9% (95% CI: 2.0% to 4.1%) following first trimester exposure to abacavir-containing regimens and 2.7% (95% CI: 1.9% to 3.7%) following second/third trimester exposure to abacavir-containing regimens.
Abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see Clinical Pharmacology (12.3)].
Lamivudine: Based on prospective reports to the APR of over 11,000 exposures to lamivudine during pregnancy resulting in live births (including over 4,500 exposed in the first trimester), there was no difference between the overall risk of birth defects for lamivudine compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of birth defects in live births was 3.1% (95% CI: 2.6% to 3.6%) following first trimester exposure to lamivudine-containing regimens and 2.8% (95% CI: 2.5%, 3.3%) following second/third trimester exposure to lamivudine-containing regimens.
Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical trials conducted in South Africa. The trials assessed pharmacokinetics in 16 women at 36 weeks gestation using 150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks gestation using 150 mg lamivudine twice daily with zidovudine, and 10 women at 38 weeks gestation using lamivudine 300 mg twice daily without other antiretrovirals. These trials were not designed or powered to provide efficacy information. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples. In a subset of subjects, amniotic fluid specimens were collected following natural rupture of membranes and confirmed that lamivudine crosses the placenta in humans. Based on limited data at delivery, median (range) amniotic fluid concentrations of lamivudine were 3.9 (1.2 to 12.8)-fold greater compared with paired maternal serum concentration (n = 8).
Animal Data: Abacavir: Abacavir was administered orally to pregnant rats (at 100, 300, and 1,000 mg per kg per day) and rabbits (at 125, 350, or 700 mg per kg per day) during organogenesis (on gestation Days 6 through 17 and 6 through 20, respectively). Fetal malformations (increased incidences of fetal anasarca and skeletal malformations) or developmental toxicity (decreased fetal body weight and crown‑rump length) were observed in rats at doses up to 1,000 mg per kg per day, resulting in exposures approximately 35 times the human exposure (AUC) at the recommended daily dose. No developmental effects were observed in rats at 100 mg per kg per day, resulting in exposures (AUC) 3.5 times the human exposure at the recommended daily dose. In a fertility and early embryo-fetal development study conducted in rats (at 60, 160, or 500 mg per kg per day), embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) or toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at doses up to 500 mg per kg per day. No developmental effects were observed in rats at 60 mg per kg per day, resulting in exposures (AUC) approximately 4 times the human exposure at the recommended daily dose. Studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta. In pregnant rabbits, no developmental toxicities and no increases in fetal malformations occurred at up to the highest dose evaluated, resulting in exposures (AUC) approximately 9 times the human exposure at the recommended dose.
Lamivudine: Lamivudine was administered orally to pregnant rats (at 90, 600, and 4,000 mg per kg per day) and rabbits (at 90, 300 and 1,000 mg per kg per day and at 15, 40, and 90 mg per kg per day) during organogenesis (on gestation Days 7 through 16 [rat] and 8 through 20 [rabbit]). No evidence of fetal malformations due to lamivudine was observed in rats and rabbits at doses producing plasma concentrations (Cmax) approximately 35 times higher than human exposure at the recommended daily dose. Evidence of early embryolethality was seen in the rabbit at systemic exposures (AUC) similar to those observed in humans, but there was no indication of this effect in the rat at plasma concentrations (Cmax) 35 times higher than human exposure at the recommended daily dose. Studies in pregnant rats showed that lamivudine is transferred to the fetus through the placenta. In the pre-and postnatal development study in rats, lamivudine was administered orally at doses of 180, 900, and 4,000 mg per kg per day from gestation Day 6 through postnatal Day 20). In the study, development of the offspring, including fertility and reproductive performance, were not affected by the maternal administration of lamivudine.
The Centers for Disease Control and Prevention recommend that HIV‑1‑infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV‑1 infection. Abacavir and lamivudine are present in human milk. There is no information on the effects of abacavir and lamivudine on the breastfed infant or the effects of the drug on milk production. Because of the potential for (1) HIV‑1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving EPZICOM.
The dosing recommendations in this population are based on the safety and efficacy established in a controlled trial conducted using either the combination of EPIVIR and ZIAGEN or EPZICOM [see Dosage and Administration (2.3), Adverse Reactions (6.2), Clinical Studies (14.2)].
In pediatric patients weighing less than 25 kg, use of abacavir and lamivudine as single products is recommended to achieve appropriate dosing.
Clinical trials of abacavir and lamivudine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, caution should be exercised in the administration of EPZICOM in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Dosage and Administration (2.4), Use in Specific Populations (8.6, 8.7)].
EPZICOM is not recommended for patients with creatinine clearance less than 50 mL per min because EPZICOM is a fixed-dose combination and the dosage of the individual components cannot be adjusted. If a dose reduction of lamivudine, a component of EPZICOM, is required for patients with creatinine clearance less than 50 mL per min, then the individual components should be used [see Clinical Pharmacology (12.3)].
EPZICOM is a fixed-dose combination and the dosage of the individual components cannot be adjusted. If a dose reduction of abacavir, a component of EPZICOM, is required for patients with mild hepatic impairment (Child-Pugh Class A), then the individual components should be used [see Clinical Pharmacology (12.3)].
The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment; therefore, EPZICOM is contraindicated in these patients [see Contraindications (4)].
There is no known specific treatment for overdose with EPZICOM. If overdose occurs, the patient should be monitored, and standard supportive treatment applied as required.
Abacavir: It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.
Lamivudine: Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event.
EPZICOM
EPZICOM tablets contain the following 2 synthetic nucleoside analogues: abacavir (ZIAGEN, also a component of TRIZIVIR®) and lamivudine (also known as EPIVIR or 3TC) with inhibitory activity against HIV‑1.
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.
Abacavir Sulfate
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 g per mol. It has the following structural formula:
abacavir sulfate structural formula - epzicom spl graphic 01
Abacavir sulfate is a white to off‑white solid and is soluble in water.
In vivo, abacavir sulfate dissociates to its free base, abacavir. Dosages 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 g per mol. It has the following structural formula:
Lamivudine is a white to off‑white crystalline solid and is soluble in water.
EPZICOM is an antiretroviral agent [see Microbiology (12.4)].
Pharmacokinetics in Adults
In a single-dose, 3-way crossover bioavailability trial of 1 EPZICOM tablet versus 2 ZIAGEN tablets (2 x 300 mg) and 2 EPIVIR tablets (2 x 150 mg) administered simultaneously in healthy subjects (n = 25), there was no difference in the extent of absorption, as measured by the area under the plasma concentration-time curve (AUC) and maximal peak concentration (Cmax), of each component.
Abacavir: Following oral administration, abacavir is rapidly absorbed and extensively distributed. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, Cmax was 4.26 ± 1.19 mcg per mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg•hour per mL. Binding of abacavir to human plasma proteins is approximately 50% and was independent of concentration. Total blood and plasma drug-related radioactivity concentrations are identical, demonstrating that abacavir readily distributes into erythrocytes. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide.
Lamivudine: Following oral administration, lamivudine is rapidly absorbed and extensively distributed. After multiple-dose oral administration of lamivudine 300 mg once daily for 7 days to 60 healthy subjects, steady-state Cmax (Cmax,ss) was 2.04 ± 0.54 mcg per mL (mean ± SD) and the 24-hour steady-state AUC (AUC24,ss) was 8.87 ± 1.83 mcg•hour per mL. Binding to plasma protein is low. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine. Metabolism of lamivudine is a minor route of elimination. In humans, the only known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after 12 hours).
In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 enzymes.
The pharmacokinetic properties of abacavir and lamivudine in fasting subjects are summarized in Table 2.
Table 2. Pharmacokinetic Parametersa for Abacavir and Lamivudine in Adults
Oral bioavailability (%)
86 ± 25
n = 6
Apparent volume of distribution (L/kg)
0.86 ± 0.15
Systemic clearance (L/h/kg)
Renal clearance (L/h/kg)
Elimination half-life (h)
5 to 7b
aData presented as mean ± standard deviation except where noted.
bApproximate range.
Effect of Food on Absorption of EPZICOM
EPZICOM may be administered with or without food. Administration with a high-fat meal in a single-dose bioavailability trial 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 with fasted conditions (n = 25). These results are similar to those from previous trials of the effect of food on abacavir and lamivudine tablets administered separately.
Renal Impairment: EPZICOM: The effect of renal impairment on the combination of abacavir and lamivudine has not been evaluated (see the U.S. prescribing information for the individual abacavir and lamivudine components).
Hepatic Impairment: EPZICOM: The effect of hepatic impairment on the combination of abacavir and lamivudine has not been evaluated (see the U.S. prescribing information for the individual abacavir and lamivudine components).
Pregnancy: Abacavir: Abacavir pharmacokinetics were studied in 25 pregnant women during the last trimester of pregnancy receiving abacavir 300 mg twice daily. Abacavir exposure (AUC) during pregnancy was similar to those in postpartum and in HIV-infected non-pregnant historical controls. Consistent with passive diffusion of abacavir across the placenta, abacavir concentrations in neonatal plasma cord samples at birth were essentially equal to those in maternal plasma at delivery.
Lamivudine: Lamivudine pharmacokinetics were studied in 36 pregnant women during 2 clinical trials conducted in South Africa. Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.
Pediatric Patients: Abacavir and Lamivudine: The pharmacokinetic data for abacavir and lamivudine following administration of EPZICOM in pediatric subjects weighing 25 kg and above are limited. The dosing recommendations in this population are based on the safety and efficacy established in a controlled trial conducted using either the combination of EPIVIR and ZIAGEN or EPZICOM. Refer to the EPIVIR and ZIAGEN USPI for pharmacokinetic information on the individual products in pediatric patients [see Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Studies (14.2)].
Geriatric Patients: The pharmacokinetics of abacavir and lamivudine have not been studied in subjects over 65 years of age.
Gender: There are no significant or clinically relevant gender differences in the pharmacokinetics of the individual components (abacavir or lamivudine) based on the available information that was analyzed for each of the individual components.
Race: There are no significant or clinically relevant racial differences in pharmacokinetics of the individual components (abacavir or lamivudine) based on the available information that was analyzed for each of the individual components.
The drug interactions described are based on trials conducted with abacavir or lamivudine as single entities; no drug interaction trials have been conducted with EPZICOM.
Cytochrome P450 Enzymes: 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.
Abacavir: Lamivudine and/or Zidovudine: Fifteen HIV‑1‑infected subjects were enrolled in a crossover‑designed drug interaction trial evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.
Lamivudine: Zidovudine: No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed in 12 asymptomatic HIV‑1-infected adult subjects given a single dose of zidovudine (200 mg) in combination with multiple doses of lamivudine (300 mg every 12 h).
Ethanol: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure.
Methadone: In a trial of 11 HIV‑1‑infected subjects receiving methadone‑maintenance therapy (40 mg and 90 mg daily), with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased 22% (90% CI: 6% to 42%) [see Drug Interactions (7)]. The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir.
Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine, stavudine, and zidovudine. However, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV‑1/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n = 18), stavudine (n = 10), or zidovudine (n = 6) were coadministered as part of a multi‑drug regimen to HIV‑1/HCV co‑infected subjects [see Warnings and Precautions (5.4)].
Interferon Alfa: There was no significant pharmacokinetic interaction between lamivudine and interferon alfa in a trial of 19 healthy male subjects.
The effects of other coadministered drugs on abacavir or lamivudine are provided in Table 3.
Table 3. Effect of Coadministered Drugs on Abacavir or Lamivudine
Coadministered
Drug and Dose
Concentrations of Abacavir or Lamivudine
Concentration of Coadministered Drug
Single 600 mg
↑41%
90% CI:
↔ a
750 mg every 8 h x 7 to 10 days
1% to 20%
Trimethoprim 160 mg/
800 mg daily x 5 days
↑ = Increase; ↔ = No significant change; AUC = Area under the concentration versus time curve; CI = Confidence interval.
aThe drug-drug interaction was only evaluated in males.
Abacavir: 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.
Lamivudine: 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.
Antiviral Activity
Abacavir: The antiviral activity of abacavir against HIV‑1 was assessed in a number of cell lines including primary monocytes/macrophages and peripheral blood mononuclear cells (PBMCs). EC50 values ranged from 3.7 to 5.8 microM (1 microM = 0.28 mcg per mL) and 0.07 to 1.0 microM against HIV‑1IIIB and HIV‑1BaL, respectively, and the mean EC50 value was 0.26 ± 0.18 microM against 8 clinical isolates. The median EC50 values of abacavir were 344 nM (range: 14.8 to 676 nM), 16.9 nM (range: 5.9 to 27.9 nM), 8.1 nM (range: 1.5 to 16.7 nM), 356 nM (range: 35.7 to 396 nM), 105 nM (range: 28.1 to 168 nM), 47.6 nM (range: 5.2 to 200 nM), 51.4 nM (range: 7.1 to 177 nM), and 282 nM (range: 22.4 to 598 nM) against HIV‑1 clades A-G and group O viruses (n = 3 except n = 2 for clade B), respectively. The EC50 values against HIV-2 isolates (n = 4) ranged from 0.024 to 0.49 microM.
Lamivudine: The antiviral activity of lamivudine against HIV‑1 was assessed in a number of cell lines including monocytes and PBMCs using standard susceptibility assays. EC50 values were in the range of 0.003 to 15 microM (1 microM = 0.23 mcg per mL). The median EC50 values of lamivudine were 60 nM (range: 20 to 70 nM), 35 nM (range: 30 to 40 nM), 30 nM (range: 20 to 90 nM), 20 nM (range: 3 to 40 nM), 30 nM (range: 1 to 60 nM), 30 nM (range: 20 to 70 nM), 30 nM (range: 3 to 70 nM), and 30 nM (range: 20 to 90 nM) against HIV-1 clades A-G and group O viruses (n = 3 except n = 2 for clade B), respectively. The EC50 values against HIV-2 isolates (n = 4) ranged from 0.003 to 0.120 microM in PBMCs. Ribavirin (50 microM) used in the treatment of chronic HCV infection decreased the anti-HIV‑1 activity of lamivudine by 3.5‑fold in MT‑4 cells.
The combination of abacavir and lamivudine has demonstrated antiviral activity in cell culture against non‑subtype B isolates and HIV‑2 isolates with equivalent antiviral activity as for subtype B isolates. Neither abacavir, nor lamivudine, were antagonistic to all tested anti-HIV agents. See full prescribing information for ZIAGEN (abacavir) and EPIVIR (lamivudine). Ribavirin, used in the treatment of HCV infection, decreased the anti-HIV-1 potency of abacavir/lamivudine reproducibly by 2- to 6-fold in cell culture.
HIV‑1 isolates with reduced susceptibility to the combination of abacavir and lamivudine have been selected in cell culture with amino acid substitutions K65R, L74V, Y115F, and M184V/I emerging in HIV‑1 RT. M184V or I substitutions resulted in high-level resistance to lamivudine and an approximately 2-fold decrease in susceptibility to abacavir. Substitutions K65R, L74M, or Y115F with M184V or I conferred a 7- to 8-fold reduction in abacavir susceptibility, and combinations of three substitutions were required to confer more than an 8-fold reduction in susceptibility.
Cross-Resistance
Cross‑resistance has been observed among nucleoside reverse transcriptase inhibitors (NRTIs). The combination of abacavir/lamivudine has demonstrated decreased susceptibility to viruses with a K65R substitution with or without an M184V/I substitution, viruses with L74V plus the M184V/I substitution, and viruses with thymidine analog mutation substitutions (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219E/R/H/Q/N) plus M184V. An increasing number of TAMs is associated with a progressive reduction in abacavir susceptibility.
Abacavir: Abacavir was administered orally at 3 dosage levels to separate groups of mice and rats in 2-year carcinogenicity studies. Results showed an increase in the incidence of malignant and non-malignant tumors. Malignant tumors occurred in the preputial gland of males and the clitoral gland of females of both species, and in the liver of female rats. In addition, non-malignant tumors also occurred in the liver and thyroid gland of female rats. These observations were made at systemic exposures in the range of 6 to 32 times the human exposure at the recommended dose of 600 mg.
Lamivudine: Long‑term carcinogenicity studies with lamivudine in mice and rats showed no evidence of carcinogenic potential at exposures up to 10 times (mice) and 58 times (rats) the human exposures at the recommended dose of 300 mg.
Mutagenicity
Abacavir: Abacavir induced chromosomal aberrations both in the presence and absence of metabolic activation in an in vitro cytogenetic study in human lymphocytes. Abacavir was mutagenic in the absence of metabolic activation, although it was not mutagenic in the presence of metabolic activation in an L5178Y mouse lymphoma assay. Abacavir was clastogenic in males and not clastogenic in females in an in vivo mouse bone marrow micronucleus assay. Abacavir was not mutagenic in bacterial mutagenicity assays in the presence and absence of metabolic activation.
Lamivudine: Lamivudine was mutagenic in an L5178Y mouse lymphoma assay and clastogenic in a cytogenetic assay using cultured human lymphocytes. Lamivudine was not mutagenic in a microbial mutagenicity assay, in an in vitro cell transformation assay, in a rat micronucleus test, in a rat bone marrow cytogenetic assay, and in an assay for unscheduled DNA synthesis in rat liver.
Impairment of Fertility
Abacavir: Abacavir did not affect male or female fertility in rats at a dose associated with exposures (AUC) approximately 3.3 times (male) or 4.1 times (female) those in humans at the clinically recommended dose.
Lamivudine: Lamivudine did not affect male or female fertility in rats at doses up to 4,000 mg per kg per day, associated with concentrations approximately 42 times (male) or 63 times (female) higher than the concentrations (Cmax) in humans at the dose of 300 mg.
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 at a dose of 600 mg. The clinical relevance of this finding has not been determined.
One EPZICOM tablet given once daily is an alternative regimen to EPIVIR tablets 300 mg once daily plus ZIAGEN tablets 2 x 300 mg once daily as a component of antiretroviral therapy.
The following trial was conducted with the individual components of EPZICOM.
Therapy-Naive Adults
CNA30021 was an international, multicenter, double-blind, controlled trial in which 770 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with EPIVIR 300 mg once daily and efavirenz 600 mg once daily. The double-blind treatment duration was at least 48 weeks. Trial participants had a mean age of 37 years; were male (81%), white (54%), black (27%), and American Hispanic (15%). The median baseline CD4+ cell count was 262 cells per mm3 (range: 21 to 918 cells per mm3) and the median baseline plasma HIV-1 RNA was 4.89 log10 copies per mL (range: 2.60 to 6.99 log10 copies per mL).
The outcomes of randomized treatment are provided in Table 4.
Table 4. Outcomes of Randomized Treatment through Week 48 (CNA30021)
plus EPIVIR plus
Efavirenz
Respondera
64% (71%)
Virologic failureb
11% (5%)
Discontinued due to adverse reactions
Discontinued due to other reasonsc
aSubjects achieved and maintained confirmed HIV-1 RNA less than 50 copies per mL (less than 400 copies per mL) through Week 48 (Roche AMPLICOR Ultrasensitive HIV-1 MONITOR® standard test version 1.0).
bIncludes viral rebound, failure to achieve confirmed less than 50 copies per mL (less than 400 copies per mL) by Week 48, and insufficient viral load response.
cIncludes consent withdrawn, lost to follow-up, protocol violations, clinical progression, and other.
After 48 weeks of therapy, the median CD4+ cell count increases from baseline were 188 cells per mm3 in the group receiving ZIAGEN 600 mg once daily and 200 cells per mm3 in the group receiving ZIAGEN 300 mg twice daily. Through Week 48, 6 subjects (2%) in the group receiving ZIAGEN 600 mg once daily (4 CDC classification C events and 2 deaths) and 10 subjects (3%) in the group receiving ZIAGEN 300 mg twice daily (7 CDC classification C events and 3 deaths) experienced clinical disease progression. None of the deaths were attributed to trial medications.
ARROW (COL105677) was a 5-year, randomized, multicenter trial which evaluated multiple aspects of clinical management of HIV-1 infection in pediatric subjects. HIV-1–infected, treatment-naïve subjects aged 3 months to 17 years were enrolled and treated with a first-line regimen containing abacavir and lamivudine, dosed twice daily according to World Health Organization recommendations. After a minimum of 36 weeks of treatment, subjects were given the option to participate in Randomization 3 of the ARROW trial, comparing the safety and efficacy of once-daily dosing with twice-daily dosing of abacavir and lamivudine, in combination with a third antiretroviral drug, for an additional 96 weeks. Virologic suppression was not a requirement for participation at baseline for Randomization 3. At baseline for Randomization 3 (following a minimum of 36 weeks of twice-daily treatment), 75% of subjects in the twice-daily cohort were virologically suppressed, compared with 71% of subjects in the once-daily cohort.
Of the 1,206 original ARROW subjects, 669 participated in Randomization 3. Subjects randomized to receive once-daily dosing (n = 336) and who weighed at least 25 kg received abacavir 600 mg and lamivudine 300 mg, as either the single entities or as EPZICOM.
The proportions of subjects with HIV-1 RNA less than 80 copies per mL through 96 weeks are shown in Table 5. The differences between virologic responses in the two treatment arms were comparable across baseline characteristics for gender and age.
Table 5. Virologic Outcome of Randomized Treatment at Week 96a (ARROW Randomization 3)
Abacavir plus Lamivudine
Twice-Daily Dosing
Once-Daily Dosing
HIV-1 RNA <80 copies/mLb
HIV-1 RNA ≥80 copies/mLc
No virologic data
Discontinued due to adverse event or death
Discontinued study for other reasonsd
Missing data during window but on study
aAnalyses were based on the last observed viral load data within the Week 96 window.
bRisk difference (95% CI) of response rate is -2.4% (-9% to 5%) at Week 96.
cIncludes subjects who discontinued due to lack or loss of efficacy or for reasons other than an adverse event or death, and had a viral load value of greater than or equal to 80 copies per mL, or subjects who had a switch in background regimen that was not permitted by the protocol.
dOther includes reasons such as withdrew consent, loss to follow-up, etc. and the last available HIV-1 RNA less than 80 copies per mL (or missing).
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 49702-206-13).
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) (see USP Controlled Room Temperature).
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Inform patients:
that a Medication Guide and Warning Card summarizing the symptoms of the abacavir hypersensitivity reaction and other product information will be dispensed by the pharmacist with each new prescription and refill of EPZICOM, and instruct the patient to read the Medication Guide and Warning Card every time to obtain any new information that may be present about EPZICOM. The complete text of the Medication Guide is reprinted at the end of this document.
to carry the Warning Card with them.
how to identify a hypersensitivity reaction [see Warnings and Precautions (5.1), Medication Guide].
that if they develop symptoms consistent with a hypersensitivity reaction they should call their healthcare provider right away to determine if they should stop taking EPZICOM.
that a hypersensitivity reaction can worsen and lead to hospitalization or death if EPZICOM is not immediately discontinued.
to not restart EPZICOM or any other abacavir-containing product following a hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
that if they have a hypersensitivity reaction, they should dispose of any unused EPZICOM to avoid restarting abacavir.
that a hypersensitivity reaction is usually reversible if it is detected promptly and EPZICOM is stopped right away.
that if they have interrupted EPZICOM for reasons other than symptoms of hypersensitivity (for example, those who have an interruption in drug supply), a serious or fatal hypersensitivity reaction may occur with reintroduction of abacavir.
to not restart EPZICOM or any other abacavir‑containing product without medical consultation and only if medical care can be readily accessed by the patient or others.
Lactic Acidosis/Hepatomegaly with Steatosis
Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogues and other antiretrovirals. Advise patients to stop taking EPZICOM if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.2)].
Patients with Hepatitis B or C Co-infection
Advise patients co-infected with HIV‑1 and HBV that worsening of liver disease has occurred in some cases when treatment with lamivudine was discontinued. Advise patients to discuss any changes in regimen with their physician [see Warnings and Precautions (5.3)].
Inform patients with HIV‑1/HCV co-infection that hepatic decompensation (some fatal) has occurred in HIV‑1/HCV co-infected patients receiving combination antiretroviral therapy for HIV‑1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.4)].
Immune Reconstitution Syndrome
Advise patients to inform their healthcare provider immediately of any signs and symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when EPZICOM is started [see Warnings and Precautions (5.5)].
Redistribution/Accumulation of Body Fat
Inform patients 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 [see Warnings and Precautions (5.6)].
Pregnancy Registry
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to EPZICOM during pregnancy [see Use in Specific Populations (8.1)].
Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)].
Instruct patients that if they miss a dose of EPZICOM, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose [see Dosage and Administration (2)].
Availability of Medication Guide
Instruct patients to read the Medication Guide before starting EPZICOM and to re-read it each time the prescription is renewed. Instruct patients to inform their physician or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.
EPIVIR, EPZICOM, TRIZIVIR, and ZIAGEN are registered trademarks of the ViiV Healthcare group of companies.
The other brands listed are trademarks of their respective owners and are not trademarks of the ViiV Healthcare group of companies. The makers of these brands are not affiliated with and do not endorse the ViiV Healthcare group of companies or its products.
Manufactured for:
ViiV Healthcare
Research Triangle Park, NC 27709
Lamivudine is manufactured under agreement from
Shire Pharmaceuticals Group plc
Basingstoke, UK
©2017 the ViiV Healthcare group of companies. All rights reserved.
EPZ:13PI
EPZICOM® (ep' zih com)
(abacavir and lamivudine)
What is the most important information I should know about EPZICOM?
EPZICOM can cause serious side effects, including:
Serious allergic reactions (hypersensitivity reaction) that can cause death have happened with EPZICOM and other abacavir-containing products. Your risk of this allergic reaction is much higher if you have a gene variation called HLA‑B*5701. Your healthcare provider can determine with a blood test if you have this gene variation.
If you get a symptom from 2 or more of the following groups while taking EPZICOM, call your healthcare provider right away to find out if you should stop taking EPZICOM.
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 list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you at all times.
If you stop EPZICOM because of an allergic reaction, never take EPZICOM (abacavir and lamivudine) or any other abacavir‑containing medicine (TRIUMEQ®, TRIZIVIR® or ZIAGEN®) again.
If you have an allergic reaction, dispose of any unused EPZICOM. Ask your pharmacist how to properly dispose of medicines.
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 healthcare provider 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 healthcare provider tells you that you can take EPZICOM again, start taking it when you are around medical help or people who can call a healthcare provider if you need one.
Build-up of acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take EPZICOM. Lactic acidosis is a serious medical emergency that can cause death. Call your healthcare provider right away if you get any of the following symptoms that could be signs of lactic acidosis:
• feel very weak or tired • feel cold, especially in your arms and legs
• unusual (not normal) muscle pain • feel dizzy or light-headed
• trouble breathing • have a fast or irregular heartbeat
• stomach pain with nausea and vomiting
Serious liver problems can happen in people who take EPZICOM. In some cases, these serious liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following signs or symptoms of liver problems:
• your skin or the white part of your eyes • loss of appetite for several days or longer
turns yellow (jaundice) • nausea
• dark or "tea-colored" urine • pain, aching, or tenderness on the right side
• light-colored stools (bowel movements) of your stomach area
You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking nucleoside analogue medicines for a long time.
Worsening of hepatitis B virus in people who have HIV-1 infection. If you have HIV-1 and hepatitis B virus (HBV) infection, your HBV may get worse (flare-up) if you stop taking EPZICOM. A "flare-up" is when your HBV infection suddenly returns in a worse way than before. Worsening liver disease can be serious and may lead to death
Do not run out of EPZICOM. Refill your prescription or talk to your healthcare provider before your EPZICOM is all gone.
Do not stop EPZICOM without first talking to your healthcare provider.
If you stop taking EPZICOM, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your liver.
Resistant Hepatitis B Virus (HBV). If you have HIV-1 and hepatitis B, the hepatitis B virus can change (mutate) during your treatment with EPZICOM and become harder to treat (resistant).
Use with interferon and ribavirin‑based regimens. Worsening of liver disease that has caused death has happened in people infected with both HIV-1 and hepatitis C virus who are taking antiretroviral medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking EPZICOM and interferon with or without ribavirin tell your healthcare provider if you have any new symptoms.
What is EPZICOM?
EPZICOM is a prescription HIV-1 (Human Immunodeficiency Virus-type 1) medicine used with other antiretroviral medicines to treat HIV-1 infection. HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). EPZICOM contains 2 prescription medicines, abacavir (ZIAGEN) and lamivudine (EPIVIR®).
EPZICOM should not be used in children weighing less than 55 pounds (25 kg).
When used with other antiretroviral medicines to treat HIV-1 infection, EPZICOM may help:
reduce the amount of HIV-1 in your blood. This is called "viral load".
increase the number of CD4+ (T) cells in your blood, that help fight off other infections.
Reducing the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may help improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).
EPZICOM does not cure HIV-1 infection or AIDS. You must keep taking HIV-1 medicines to control HIV-1 infection and decrease HIV-related illnesses.
Who should not take EPZICOM?
Do not take EPZICOM if you:
have a certain type of gene variation called the HLA-B*5701 allele. Your healthcare provider will test you for this before prescribing treatment with EPZICOM.
are allergic to abacavir or any of the ingredients in EPZICOM. See the end of this Medication Guide for a complete list of ingredients in EPZICOM.
have liver problems.
What should I tell my healthcare provider before taking EPZICOM?
Before you take EPZICOM tell your healthcare provider if you:
have been tested and know whether or not you have a particular gene variation called HLA‑B*5701.
have or have had liver problems, including hepatitis B or C virus infection.
have kidney problems.
have heart problems, smoke, or have diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes.
drink alcohol or take medicines that contain alcohol.
are pregnant or plan to become pregnant. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
Pregnancy Registry. There is a pregnancy registry for women who take antiretroviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
are breastfeeding or plan to breastfeed. Do not breastfeed if you take EPZICOM.
You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Some medicines interact with EPZICOM. Keep a list of your medicines to show your healthcare provider and pharmacist. You can ask your healthcare provider or pharmacist for a list of medicines that interact with EPZICOM. Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take EPZICOM with other medicines.
Tell your healthcare provider if you take:
any other medicine to treat HIV-1
medicines to treat hepatitis viruses such as interferon or ribavirin
How should I take EPZICOM?
Take EPZICOM exactly as your healthcare provider tells you.
Do not change your dose or stop taking EPZICOM without talking with your healthcare provider. If you miss a dose of EPZICOM, take it as soon as you remember. Do not take 2 doses at the same time. If you are not sure about your dosing, call your healthcare provider.
Stay under the care of a healthcare provider while taking EPZICOM.
EPZICOM may be taken with or without food.
Tell your healthcare provider if your child has trouble swallowing EPZICOM tablets.
Do not run out of EPZICOM. The virus in your blood may increase and the virus may become harder to treat. When your supply starts to run low, get more from your healthcare provider or pharmacy
If you take too much EPZICOM, call your healthcare provider or go to the nearest hospital emergency room right away.
What are the possible side effects of EPZICOM?
EPZICOM can cause serious side effects including:
See "What is the most important information I should know about EPZICOM?"
Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after you start taking EPZICOM.
Changes in body fat can happen in people who take HIV-1 medicines. These changes may include an increased amount of fat in the upper back and neck ("buffalo hump"), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
Heart attack (myocardial infarction). Some HIV-1 medicines including EPZICOM may increase your risk of heart attack.
The most common side effects of EPZICOM include:
• trouble sleeping • nausea
• depression • diarrhea
• headache • rash
• tiredness • fever
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of EPZICOM. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.
How should I store EPZICOM?
Store EPZICOM at 59°F to 86°F (15°C 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 purposes other than those listed in a Medication Guide. 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.
If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for the information about EPZICOM that is written for health professionals.
For more information go to www.EPZICOM.com or call 1-877-844-8872.
What are the ingredients in EPZICOM?
Active ingredients: abacavir sulfate and lamivudine
Inactive ingredients: magnesium stearate, microcrystalline cellulose, sodium starch glycolate.
Tablet film coating contains: OPADRY® orange YS-1-13065-A made of FD&C Yellow No. 6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide.
Manufactured for: by:
ViiV Healthcare GlaxoSmithKline
Research Triangle Park, NC 27709 Research Triangle Park, NC 27709
Lamivudine is manufactured under agreement from Shire Pharmaceuticals Group plc, Basingstoke, UK
EPIVIR, EPZICOM, TRIUMEQ, TRIZIVIR, and ZIAGEN are registered trademarks of the ViiV Healthcare group of companies.
EPZ:12MG
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised: 03/2017
PRINCIPAL DISPLAY PANEL
EPZICOM®
600 mg 300 mg
Each tablet contains 600 mg of abacavir as abacavir sulfate and 300 mg of lamivudine.
See prescribing information for dosage information.
Store at 25oC (77oF); excursions permitted to 15o to 30oC (59o to 86oF) (see USP Controlled Room Temperature).
Notice to Authorized Dispenser:
Each time EPZICOM is dispensed, give the patient a Medication Guide and Warning Card from the carton.
©2017 the ViiV Healthcare group of companies
10000000146406 Rev. 5/17
Epzicom 30 count carton - epzicom spl graphic 03


Alphabet's new project, code named Malta, is an inexpensive system that takes full advantage of renewable energy by storing it for up to several weeks in flexible locations. Nobel prize-winning Stanford physics professor Robert Laughlin designed a theoretical system that stores electricity as heat and cold. This stored energy can be kept for days, or even weeks, until it's needed.
Here's how it works: Renewable energy is collected from wind or solar farms on the grid and sent to Malta's energy storage system. This electrical energy drives a heat pump (a machine that converts electrical energy into thermal energy by creating a temperature difference). The heat is stored in high temperature molten salt, while the cold is stored in a chilled low temperature liquid similar to antifreeze. The temperature difference is then reconverted by a heat engine back into electrical energy and sent back to the grid when needed.
This system benefits from inexpensive components, with much of it using conventional technology. Salt is easily extracted from the earth and can be used multiple times to store heat without degrading or emitting toxic byproducts. Malta uses flexible siting, so it isn't dependent on weather conditions or specific locations. It can be close to the renewable energy source or near a location with high demand on the grid. The system is also long-lasting and easy to expand, as the salt tanks can be charged and re-charged thousands of times—possibly for up to 40 years, which is three times longer than other current storage options.
After over two years of building CAD drawings, running extensive computer simulations and 3D printing parts, the team has detailed engineering designs that are almost ready to be turned into actual machinery. They are moving quickly to test commercial viability and are looking for innovative industry partners to help bring the system to life. The next step in the process is to build a megawatt-scale prototype plant large enough to prove that the technology can work at a commercial scale.


text:
American College of Surgeons Media Press Releases 2019 Press Releases MBSAQIP manual presents updated program standards for overweight and obese patients
American Joint Committee on Cancer announces new leaders for 2020
A peer support program can help surgeons deal with adverse events that happen during surgery
ACS Commends Ways and Means Exercise of Jurisdiction over Surprise Billing
American College of Surgeons Opposes Alexander, Pallone, Walden Surprise Billing Plan
Older adults who "train" for a major operation spend less time in the hospital
Safe and effective pain control after surgery for children and teens addressed by ACS and APSA
Wichita Falls surgeon Beth H. Sutton, MD, FACS, elected Chair of the Board of Regents of the American College of Surgeons
Dr. Timothy W. Mullett is the New Chair-Elect of the ACS Commission on Cancer
New framework for humanitarian health systems to improve civilian care in conflict zones
ACS NSQIP recognizes 88 hospitals for achieving meritorious surgical patient care outcomes
Winston-Salem trauma surgeon Dr. J. Wayne Meredith is new ACS President-Elect
When a major injury occurs again in children, it's too often no accident
Five-year breast cancer survival rates at a safety net hospital rival national averages
Surgeons report that 12-hour shifts improve patient outcomes, lower costs vs. 24-hour call shifts
Gallbladder removal operation linked to better outcomes when performed soon after hospital admission
American College of Surgeons Honors Five Members with Surgical Humanitarian and Volunteerism Awards
Artificial intelligence outperforms clinicians' judgment in triaging postoperative patients for intensive care in a pilot test
Medical scribes have a positive impact on surgeons and residents
Adults 85 years and older generally fare well after colon cancer operations
ACS NSQIP surgical risk calculator accurately and reliably predicts four quality-of-life outcomes for geriatric surgical patients
Postoperative opioid prescribing and use drop significantly with no change in patient-reported pain control or satisfaction after state imposes regulations
Smartphone data can help surgeons understand a patient's recovery
General surgery residents who often experience mistreatment during residency training are at a greater risk of burnout and suicidal thoughts
Alexandria surgeon Vice Admiral Raquel C. Bono, MD, FACS, honored for inspiring women in surgery
Honorary Fellowship in the American College of Surgeons is awarded to 12 prominent surgeons
Chattanooga surgeon R. Phillip Burns, MD, FACS, honored with 2019 Distinguished Service Award of the American College of Surgeons
New York City surgeon Valerie W. Rusch, MD, FACS, is installed as the 100th President of the American College of Surgeons
American College of Surgeons Clinical Congress Convenes in San Francisco Next Week
ACS Academy of Master Surgeon Educators Admits its Second Class into Membership
Large-scale enhanced recovery program improves outcomes for bariatric surgery patients
More than 1 million people around the world have now been trained to Stop the Bleed
New risk/benefit calculator can predict possible outcomes for bariatric surgery patients
ACS comments on the continual occurrence of firearm deaths and injuries in the U.S.
Delay from breast cancer diagnosis to chemotherapy after a cancer operation may shorten survival for patients
Researchers identify four characteristics in older patients associated with an inability to return home after an operation
ACS introduces a new standardized program for hospitals devoted to high-quality surgical care for older adults
ACS and HBS Institute for Strategy and Competitiveness partner to develop value measurement tool for hospitals
MBSAQIP manual presents updated program standards for overweight and obese patients
American College of Surgeons Opposes the Lower Health Care Costs Act
Minneapolis surgeon Dr. Henry Buchwald receives 2019 Jacobson Innovation Award
National surgical care program opens enrollment for new cohort of hospitals
American College of Surgeons applauds congressional passage of PAHPAI (H.R. 269/ S. 1379)
More than half of patients in pain management study took no opioids after operations
American College of Surgeons applauds Ruiz/Roe legislative framework to address surprise medical bills
Just released: Proceedings from inaugural Medical Summit on Firearm Injury Prevention
American College of Surgeons opposes "Stop Surprise Medical Bills" legislation
Standards for quality surgical care for older adults finalized
Online tool gives surgeons and their patients probabilities for the success of their ventral hernia repair operation
May is our nation's first ever National Stop the Bleed Month
Save the date: San Francisco will host ACS Clinical Congress October 27-31
New trauma care pathway reduces delirium and likelihood of returning to the hospital
Save the date: ACS Quality and Safety Conference convenes in Washington, DC, July 19-22
Traffic accidents involving moose are 13 times more likely to result in human death
Frailty May Be a New Screening Criterion for Fitness for an Operation
Medicaid expansion led to increase in screening for colorectal cancer patients in Kentucky
Inaugural Firearm Injury Prevention Summit Held
Gallbladder Removal Operation During Pregnancy Associated with Adverse Maternal Outcomes
Kidney Transplantation to Minority Patients with a Different Blood Type Is Safe
Genetically modified virus injection into tumor can treat metastatic melanoma
African-Americans May Live Longer After Liver Transplant if Their Donors Are the Same Race
News from the American College of Surgeons
Devin Rose
Sally Garneski
Email: pressinquiry@facs.org
Optimal Resources for Metabolic and Bariatric Surgery manual presents updated program standards for overweight and obese patients
Third version of nationally recognized standards manual includes a designation for bariatric and metabolic surgery centers to now offer patients non-surgical interventions along with a quality improvement project requirement.
CHICAGO (July 11, 2019): The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), a joint quality program of the American College of Surgeons (ACS) and the American Society for Metabolic and Bariatric Surgery (ASMBS), has released its third version of program standards to take effect in October 2019. The updated standards, outlined in Optimal Resources for Metabolic and Bariatric Surgery, include a new designation level for facilities offering non-surgical treatment for obesity, as well as a requirement for accredited centers to implement one new quality improvement initiative each year.
In the United States, more than 11 million people suffer from severe obesity and an estimated 93 million people are obese. The comorbidities associated with obesity range from diabetes and heart disease to certain types of cancers. Bariatric surgical procedures have been shown to reduce obesity, improve mortality, and decrease the health risks from chronic diseases like cardiomyopathy and diabetes.
The MBSAQIP standards provide guidance for facilities to build the structure that enables them to provide safe, high-quality care to all metabolic and bariatric patients. Programs seeking MBSAQIP accreditation are required to meet eight overarching standards which outline the framework for program scope and governance, facilities and equipment resources, patient care protocols, data surveillance, and more.
Accredited centers are required to enter every metabolic and bariatric procedure performed for the treatment of obesity-related diseases into the MBSAQIP Registry. This Registry collects prospective, risk-adjusted, clinically rich data based on standardized definitions. Reports from the Registry provide site-specific data that gives participating centers the ability to benchmark their outcomes and compare their results with aggregate national comparison data in the system.
Currently, there are more than 800 MBSAQIP-accredited centers in the United States and Canada, and more than 200,000 bariatric cases are captured annually in the MBSAQIP Registry. The program is celebrating its five-year anniversary in 2019.
An important new accreditation level in the 2019 standards manual is the Obesity Medicine Qualification Accreditation option. This accreditation option provides an additional designation level for facilities that offer non-surgical treatment for patients who are overweight or have Class I, II, or III obesity. Centers with this designation employ nutritional interventions, physical activity, behavioral change, and pharmacotherapy to treat patients. Additionally, these centers will collect and document specific data elements in which they will monitor patient outcomes against medical weight loss interventions.
"Obesity is a chronic, pervasive disease that requires involvement from the entire 'house of medicine.' Our new designation of the obesity medicine qualification is in recognition of new treatment options and providers available to our patients in need," said John Morton, MD, MPH, FACS, FASMBS, Chair of the ACS Committee for Metabolic and Bariatric Surgery. Dr. Morton is also the incoming vice chair for quality and division chief of bariatric and minimally invasive surgery at the Yale School of Medicine, New Haven, CT.
"As we've seen in other fields such as oncology or cardiology, care is best when it is multi-modal and multidisciplinary. In combination, obesity medicine and bariatric surgery can enhance the safety and efficacy of precision treatment for the patient with obesity," Dr. Morton said.
Another standard which has been enhanced requires all accredited centers to measure, evaluate, and improve their performance through at least one quality improvement initiative each year. Centers that are high outliers on the semiannual risk-adjusted report, or SAR must develop initiatives to address their high outlier status. These initiatives can target areas for improvement including patient experience or education, internal processes, clinical pathways, or other issues related to providing high-quality care to patients.
"These updated standards will help the bariatric and metabolic surgery programs build on our already established success with surgical quality improvement for overweight and obese patients," said ACS Executive Director David B. Hoyt, MD, FACS. "By implementing these program standards, participating centers, as well as new centers seeking accreditation, will be able to raise the bar on surgical quality for their patients."
"With these standards, we have identified specific strategies for bariatric surgery centers to improve their outcomes for patients who seek surgical treatment and for those who seek to achieve weight loss non-surgically in a medically supervised, supportive environment. Patients who seek treatment at an accredited center will receive care that it is tailored to their individual needs, and is based on the best evidence available in the field," explained Clifford Y. Ko, MD, MS, MSHS, FACS, FASCRS, Director, ACS Division of Research and Optimal Patient Care.
MBSAQIP is no longer accepting applications under the 2016 standards, and instead will begin accepting applications from new centers in August of 2019. All centers currently accredited under MBSAQIP must be in compliance with the 2019 standards by October of 2019.
More information on the application process is available here. For further information, please contact mbsaqip@facs.org.
"FACS" designates that a surgeon is a Fellow of the American College of Surgeons.
About the American College of Surgeons
The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 82,000 members and is the largest organization of surgeons in the world. For more information, visit www.facs.org.
About the American Society for Metabolic and Bariatric Surgery
The ASMBS is the largest organization for bariatric surgeons in the nation. It is a non-profit organization that works to advance the art and science of bariatric surgery and is committed to educating medical professionals and the lay public about bariatric surgery as an option for the treatment of morbid obesity, as well as the associated risks and benefits. It encourages its members to investigate and discover new advances in obesity, while maintaining a steady exchange of experiences and ideas that may lead to improved outcomes for morbidly obese patients. For more information, visit www.asmbs.org.

redpajama_set_name: RedPajamaCommonCrawl


text:
Showing 10 Services filtered by 'P'
Peer mentor service for adults and older people
Information about peer support workers for adults and older people.
Peer mentor service for people using forensic services
Providing community peer mentor support services for people using forensic services.
Perinatal community mental health service in Teesside
Providing community mental health support to women who are experiencing mental health difficulties during pregnancy or in the first year after they have had their baby in Teesside.
Perinatal community nursery nurse service
Information about our perinatal community nursery nurse service for women, and their babies and families, during the antenatal and postnatal period.
Perinatal mental health service in Durham and Darlington
Providing community perinatal mental health services for adult women who are experiencing mental health difficulties during pregnancy or in the first year after they have had their baby in Durham and Darlington.
Perinatal mental health service in North Yorkshire and York
Providing community perinatal mental health services for adult women in North Yorkshire and York.
Providing advice on the safe and appropriate use of medicines. This webpage contains a link to our choice and medication website.
Psychological wellbeing practitioners for children in North Yorkshire
Information about psychological wellbeing practitioners for children. Psychological wellbeing practitioners identify common mental health disorders and help children and young people to feel empowered and have tools for life.
Psychosis and early intervention service in Redcar and Cleveland
Providing community psychosis and early intervention services for adults in Redcar and Cleveland.
Area: Middlesbrough, Redcar, Teesside
Psychosis service in Stockton-on-Tees for adults
A community mental health service for adults in Stockton-on-Tees, who suffer with severe and persistent mental health problems, such as schizophrenia, psychosis and bi polar disorder.


Bernie Sanders and Hillary Clinton are going at it over Elizabeth Warren's critique of Hillary's handling of a bankruptcy bill.
TAPPER: Her response has been, among other things, to say, "Nobody can point to a vote that I have ever changed because of this."
Elizabeth Warren wrote -- I'm just quoting Elizabeth Warren -- "The bill was essentially the same, but Hillary Rodham Clinton was not."
And Warren basically charges that, because Hillary Clinton had taken $140,000 from banks, she did change her vote.
Now, that's Warren saying it, not you.
TAPPER: But do you think that's an example of Clinton changing her vote?
This is what I think. I think you have a corrupt campaign finance system. I think you have the Koch brothers, billionaires, ExxonMobil. You have Wall Street. You have pharmaceutical companies pouring huge amounts of money into our political process, undermining American democracy.
...TAPPER: OK. But your campaign did send out this excerpt from Elizabeth Warren, and she directly said that Clinton in her view changed her vote.
SANDERS: Well, that's Elizabeth's point. I think the point that we wanted to note -- I suspect the point that the campaign tried to make was to identify a particular vote that Secretary Clinton cast. And, by the way, they're sending out 10 things a day attacking me. I should -- just to set the record straight on that.
Sorry, no sale on "that's Elizabeth's point," because it was Bernie's campaign that sent it around. That's a little gutless. What's even weirder, though, is Sanders explaining what he "suspects" his campaign of doing, as if he's some gumshoe on the trail of an elusive serial killer. He seems genuinely not to be in control of his political operation, which naturally makes you wonder what a Sanders White House would be like.
CLINTON: -- that would protect women. But now let me finish, George, because this has been bandied about and I just want to set the record straight. And so then three years later, part of the -- part of what Senator -- Senator Warren said, you played. You didn't play the whole thing, because we've been allies. I faced a tough decision and I stood up for women and children. I went to the Senate floor, said that was exactly what I was doing. Then the bill did not pass. It never became law. And then when the next bill came up, 2005, women's issues were taken care of because I had made that a point back in 2001. And so then I was against that bill. I didn't get a chance to actually vote against it because Bill was in the hospital having a heart procedure. But I put a statement out. I was against it. So I'm happy to set this record straight. And I really want to, once again, call out the Sanders campaign, which claims they like to run a positive campaign. But they have been quite artful in raising questions and trying to cast doubts about my record.
CLINTON: I have a public record. I have never, ever been influenced in a view or a vote by anyone who has given me any kind of money. So I'm just going to keep setting the record straight.
I give Hillary credit for coming up with a substantive defense here, but this is also a no sale. If her argument is that she made a pragmatic compromise to try and get something good into a bad bill, that's fine, but it was a bad compromise. Taking on the sanders campaign is a good move, though I question the wisdom of tiptoeing around Elizabeth Warren the way she is. She's not going to get Warren's endorsement, but showing the strength to push back directly on her would display some political courage.