Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®

PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.

DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).

(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")

DOSING: ELDERLY — Use with caution.

DOSING: RENAL IMPAIRMENT — Clcr ≤ 50 mL/minute: Avoid use.

DOSING: HEPATIC IMPAIRMENT — Use contraindicated.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

DOSAGE FORMS: CONCISE
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer without regard to food or water.

USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®

ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.

The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.

>10%:
Central nervous system: Headache (13%), malaise (12%), fatigue (12%)
Gastrointestinal: Nausea (19%)

1% to 10%:
Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%)
Dermatologic: Rash (5%)
Endocrine & metabolic: Triglycerides increased (2% grade 3-4)
Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%)
Hematologic: Neutropenia (5%)
Hepatic: ALT increased (6%)
Neuromuscular & skeletal: CPK increased (7%)
Otic: Ear infection (5%)
Respiratory: Nose/throat infection (5%)
Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)

Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome

CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status.

WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients testing positive for the presence of the HLA-B*5701 allele are at an increased risk for hypersensitivity reactions. Screening for HLA-B*5701 allele status is recommended prior to initiating abacavir-containing therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated abacavir therapy. Trizivir® is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.

Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. Coronary heart disease: Use may increase risk of myocardial infarction; use caution in patients with risks for coronary heart disease; modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be minimized prior to use. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr ≤ 50 mL/minute.

Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.

Special populations: Adolescents and Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.

DRUG INTERACTIONS
Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy

Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification

DOXOrubicin: May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification

DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination

Fluconazole: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification

Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy

Probenecid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Abacavir. Risk C: Monitor therapy

Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification

Rifamycin Derivatives: May increase the metabolism of Zidovudine. Exceptions: Rifabutin. Risk D: Consider therapy modification

Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination

Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy

Valproic Acid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Zalcitabine: LamiVUDine may diminish the therapeutic effect of Zalcitabine. Risk D: Consider therapy modification

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.

PREGNANCY RISK FACTOR — C

PREGNANCY IMPLICATIONS — See individual agents.

LACTATION — See individual agents.

BREAST-FEEDING CONSIDERATIONS — See individual agents.

DIETARY CONSIDERATIONS — May be taken without regard to food or water.

PRICING — (data from drugstore.com)
Tablets (Trizivir)
300-150-300 mg (60): $1431.91

MONITORING PARAMETERS — Blood glucose, CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, bilirubin, serum transaminases, triglycerides, serum amylase; HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele; signs and symptoms of pancreatitis; observe for appearance of opportunistic infections

CANADIAN BRAND NAMES — Trizivir®

INTERNATIONAL BRAND NAMES — Tricivir (AR, CN); Trivudin (AR); Trizivir (AT, AU, BE, BG, CH, CL, CO, CR, CZ, DE, DK, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PE, PT, RU, SE, TR, TW, UY, VE)

MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.

PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.

Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®

PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)

DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.

DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).

(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")

DOSING: ELDERLY — Use with caution.

DOSING: RENAL IMPAIRMENT — Clcr ≤ 50 mL/minute: Avoid use.

DOSING: HEPATIC IMPAIRMENT — Use contraindicated.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

DOSAGE FORMS: CONCISE
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Administer without regard to food or water.

USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®

ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.

The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.

>10%:
Central nervous system: Headache (13%), malaise (12%), fatigue (12%)
Gastrointestinal: Nausea (19%)

1% to 10%:
Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%)
Dermatologic: Rash (5%)
Endocrine & metabolic: Triglycerides increased (2% grade 3-4)
Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%)
Hematologic: Neutropenia (5%)
Hepatic: ALT increased (6%)
Neuromuscular & skeletal: CPK increased (7%)
Otic: Ear infection (5%)
Respiratory: Nose/throat infection (5%)
Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)

Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome

CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status.

WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.

Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients testing positive for the presence of the HLA-B*5701 allele are at an increased risk for hypersensitivity reactions. Screening for HLA-B*5701 allele status is recommended prior to initiating abacavir-containing therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated abacavir therapy. Trizivir® is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.

Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. Coronary heart disease: Use may increase risk of myocardial infarction; use caution in patients with risks for coronary heart disease; modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be minimized prior to use. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr ≤ 50 mL/minute.

Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.

Special populations: Adolescents and Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.

DRUG INTERACTIONS
Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy

Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification

DOXOrubicin: May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification

DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination

Fluconazole: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification

Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy

Probenecid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Abacavir. Risk C: Monitor therapy

Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification

Rifamycin Derivatives: May increase the metabolism of Zidovudine. Exceptions: Rifabutin. Risk D: Consider therapy modification

Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination

Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy

Valproic Acid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy

Zalcitabine: LamiVUDine may diminish the therapeutic effect of Zalcitabine. Risk D: Consider therapy modification

ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.

PREGNANCY RISK FACTOR — C

PREGNANCY IMPLICATIONS — See individual agents.

LACTATION — See individual agents.

BREAST-FEEDING CONSIDERATIONS — See individual agents.

DIETARY CONSIDERATIONS — May be taken without regard to food or water.

PRICING — (data from drugstore.com)
Tablets (Trizivir)
300-150-300 mg (60): $1431.91

MONITORING PARAMETERS — Blood glucose, CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, bilirubin, serum transaminases, triglycerides, serum amylase; HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele; signs and symptoms of pancreatitis; observe for appearance of opportunistic infections

CANADIAN BRAND NAMES — Trizivir®

INTERNATIONAL BRAND NAMES — Tricivir (AR, CN); Trivudin (AR); Trizivir (AT, AU, BE, BG, CH, CL, CO, CR, CZ, DE, DK, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PE, PT, RU, SE, TR, TW, UY, VE)

MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.

PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.

Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®
MEXICAN BRAND NAMES — Trizivir
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
What key warnings should I know about before taking this medicine?
This medicine may cause liver damage and a change in the acid levels in the blood. Closely review the section in this leaflet which lists when to call healthcare provider. Pregnancy, obesity, and/or prolonged therapy may increase the risk.
Dangerous allergic reactions can occur. Tell healthcare provider about any fever, rash, feeling tired, nausea, vomiting, diarrhea, belly pain, flu-like symptoms, sore throat, cough, or difficulty breathing. Do not restart this medicine if you have had an allergic reaction.
This medicine may cause muscle aches and stiffness if it is used for long periods of time. Closely review the section in this leaflet which lists when to call healthcare provider.
Please read the medication guide given to you.
REASONS NOT TO TAKE THIS MEDICINE If you have an allergy to abacavir, lamivudine, zidovudine, or any other part of this medicine. Tell healthcare provider if you are allergic to any medicine. Make sure to tell about the allergy and how it affected you. This includes telling about rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other symptoms involved. If you have liver disease. If you are pregnant or may be pregnant. If you are breast-feeding.
What is this medicine used for? This medicine is used to treat HIV infection.
How does it work? Abacavir, lamivudine, and zidovudine work to injure the virus and fight the infection.
How is it best taken? To gain the most benefit, do not miss doses. Use prescription as directed, even if feeling better. Take this medicine with or without food. Take with food if it causes an upset stomach.
What do I do if I miss a dose? (does not apply to patients in the hospital) Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and return to your regular schedule. Do not take a double dose or extra doses. Do not change dose or stop medicine. Talk with healthcare provider.
What are the precautions when taking this medicine? If this medicine is stopped because you have an allergy to it, do not restart it. It can cause a much more dangerous effect if restarted. If this medicine is stopped for any other reason, do not restart it without talking to healthcare provider. It could be very dangerous to restart on your own. If medicine changes for HIV infection, make sure to ask healthcare provider about hepatitis B treatment. Wear disease medical alert identification. Do not run out of this medicine. Check medicines with healthcare provider. This medicine may not mix well with other medicines. If you have kidney disease, talk with healthcare provider. If you have liver disease, talk with healthcare provider. Avoid alcohol (includes wine, beer, and liquor). You may not be alert. Avoid driving, doing other tasks or activities until you see how this medicine affects you. To protect against sexually-transmitted diseases, use a latex condom. Use birth control that you can trust to prevent pregnancy while taking this medicine. Breast-feeding is not recommended in HIV disease.
What are some possible side effects of this medicine? Anemia and low white blood cell count. Headache. Nausea or vomiting. Small frequent meals, frequent mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Diarrhea. Not hungry. Irritated pancreas can rarely occur.
What should I monitor? Change in condition being treated. Is it better, worse, or about the same? Check blood work regularly. Talk with healthcare provider. Follow up with healthcare provider.
REASONS TO CALL HEALTHCARE PROVIDER IMMEDIATELY If you suspect an overdose, call your local poison control center immediately or dial 911. Signs of a life-threatening reaction. These include wheezing; chest tightness; fever; itching; bad cough; blue skin color; fits; or swelling of face, lips, tongue, or throat. Allergic reaction (fever, rash, feeling tired, nausea/vomiting, diarrhea, belly pain, sore throat, cough, difficulty breathing, or flu-like symptoms). Stop medicine and talk with healthcare provider right away! Difficulty breathing. Severe belly pain. Severe nausea or vomiting. Severe diarrhea. Dark urine or yellow skin or eyes. Feeling extremely tired or weak. Any rash. No improvement in condition or feeling worse.
How should I store this medicine? Store at room temperature. Protect tablets from moisture. Do not store in a bathroom or kitchen.
GENERAL STATEMENTS If you have a life-threatening allergy, wear allergy identification at all times. Do not share your medicine with others and do not take anyone else's medicine. Keep all medicine out of the reach of children and pets. Keep a list of all your medicines (prescription, natural products, supplements, vitamins, over-the-counter) with you. Give this list to healthcare provider (doctor, nurse, nurse practitioner, pharmacist, physician assistant). Talk with healthcare provider before starting any new medicine, including over-the-counter, natural products, or vitamins.

Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®
MEXICAN BRAND NAMES — Trizivir
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
What key warnings should I know about before taking this medicine?
This medicine may cause liver damage and a change in the acid levels in the blood. Closely review the section in this leaflet which lists when to call healthcare provider. Pregnancy, obesity, and/or prolonged therapy may increase the risk.
Dangerous allergic reactions can occur. Tell healthcare provider about any fever, rash, feeling tired, nausea, vomiting, diarrhea, belly pain, flu-like symptoms, sore throat, cough, or difficulty breathing. Do not restart this medicine if you have had an allergic reaction.
This medicine may cause muscle aches and stiffness if it is used for long periods of time. Closely review the section in this leaflet which lists when to call healthcare provider.
Please read the medication guide given to you.
REASONS NOT TO TAKE THIS MEDICINE If you have an allergy to abacavir, lamivudine, zidovudine, or any other part of this medicine. Tell healthcare provider if you are allergic to any medicine. Make sure to tell about the allergy and how it affected you. This includes telling about rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other symptoms involved. If you have liver disease. If you are pregnant or may be pregnant. If you are breast-feeding.
What is this medicine used for? This medicine is used to treat HIV infection.
How does it work? Abacavir, lamivudine, and zidovudine work to injure the virus and fight the infection.
How is it best taken? To gain the most benefit, do not miss doses. Use prescription as directed, even if feeling better. Take this medicine with or without food. Take with food if it causes an upset stomach.
What do I do if I miss a dose? (does not apply to patients in the hospital) Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and return to your regular schedule. Do not take a double dose or extra doses. Do not change dose or stop medicine. Talk with healthcare provider.
What are the precautions when taking this medicine? If this medicine is stopped because you have an allergy to it, do not restart it. It can cause a much more dangerous effect if restarted. If this medicine is stopped for any other reason, do not restart it without talking to healthcare provider. It could be very dangerous to restart on your own. If medicine changes for HIV infection, make sure to ask healthcare provider about hepatitis B treatment. Wear disease medical alert identification. Do not run out of this medicine. Check medicines with healthcare provider. This medicine may not mix well with other medicines. If you have kidney disease, talk with healthcare provider. If you have liver disease, talk with healthcare provider. Avoid alcohol (includes wine, beer, and liquor). You may not be alert. Avoid driving, doing other tasks or activities until you see how this medicine affects you. To protect against sexually-transmitted diseases, use a latex condom. Use birth control that you can trust to prevent pregnancy while taking this medicine. Breast-feeding is not recommended in HIV disease.
What are some possible side effects of this medicine? Anemia and low white blood cell count. Headache. Nausea or vomiting. Small frequent meals, frequent mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Diarrhea. Not hungry. Irritated pancreas can rarely occur.
What should I monitor? Change in condition being treated. Is it better, worse, or about the same? Check blood work regularly. Talk with healthcare provider. Follow up with healthcare provider.
REASONS TO CALL HEALTHCARE PROVIDER IMMEDIATELY If you suspect an overdose, call your local poison control center immediately or dial 911. Signs of a life-threatening reaction. These include wheezing; chest tightness; fever; itching; bad cough; blue skin color; fits; or swelling of face, lips, tongue, or throat. Allergic reaction (fever, rash, feeling tired, nausea/vomiting, diarrhea, belly pain, sore throat, cough, difficulty breathing, or flu-like symptoms). Stop medicine and talk with healthcare provider right away! Difficulty breathing. Severe belly pain. Severe nausea or vomiting. Severe diarrhea. Dark urine or yellow skin or eyes. Feeling extremely tired or weak. Any rash. No improvement in condition or feeling worse.
How should I store this medicine? Store at room temperature. Protect tablets from moisture. Do not store in a bathroom or kitchen.
GENERAL STATEMENTS If you have a life-threatening allergy, wear allergy identification at all times. Do not share your medicine with others and do not take anyone else's medicine. Keep all medicine out of the reach of children and pets. Keep a list of all your medicines (prescription, natural products, supplements, vitamins, over-the-counter) with you. Give this list to healthcare provider (doctor, nurse, nurse practitioner, pharmacist, physician assistant). Talk with healthcare provider before starting any new medicine, including over-the-counter, natural products, or vitamins.

Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them

Abacavir, lamivudine, and zidovudine

U.S. BRAND NAMES — Trizivir®
SYNONYMS — 3TC, Abacavir, and AZT; 3TC, Abacavir, and ZDV; 3TC, Abacavir, and Zidovudine; 3TC, ABC, and AZT; 3TC, ABC, and ZDV; Abacavir, 3TC, and AZT; Abacavir, 3TC, and ZDV; Abacavir, Lamivudine, and Azidothymidine; Abacavir, Zidovudine, and Lamivudine; ABC, 3TC, and AZT; ABC, 3TC, and ZDV; Azidothymidine, Abacavir, and Lamivudine; Azidothymidine, Lamivudine and Abacavir; AZT, Abacavir, and 3TC; AZT, Abacavir, and Lamivudine; AZT, ABC, and 3TC; Compound S, Abacavir, and 3TC; Compound S, Abacavir, and Lamivudine; Compound S, ABC, and 3TC; Lamivudine, Abacavir, and Zidovudine; Lamivudine, Zidovudine, and Abacavir; ZDV, Abacavir, and 3TC; ZDV, Abacavir, and Lamivudine; ZDV, ABC, and 3TC; Zidovudine, Abacavir, and Lamivudine
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir, lamivudine, and zidovudine: Drug information")
Children: Not intended for pediatric use; product is a fixed-dose combination
Adolescents <40 kg: Not recommended; product is a fixed-dose combination
Adolescents 40 kg and Adults: 1 tablet twice daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regard to meals
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended; data on the use of this triple NRTI combination regimen in patients with baseline viral loads >100,000 copies/mL is limited)
ADVERSE REACTIONS — See Abacavir, Lamivudine, and Zidovudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir, potentially fatal hypersensitivity reactions may occur (see Warnings)
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir, lamivudine, and zidovudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis) and GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Trizivir®, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If abacavir, Trizivir®, or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Trizivir®, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Trizivir® in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir, lamivudine, and zidovudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation, neutropenia, and anemia; consider discontinuation of abacavir, lamivudine, and zidovudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Zidovudine is associated with hematologic toxicity including granulocytopenia and severe anemia requiring transfusions; use with caution in patients with ANC <1000 cells/mm3 or hemoglobin <9.5 g/dL; discontinue treatment in children with an ANC <500 cells/mm3 until marrow recovery is observed; use of erythropoietin, or filgrastim may be necessary in some patients; prolonged use of zidovudine may cause myositis and myopathy; zidovudine has been shown to be carcinogenic in rats and mice.
Trizivir® contains abacavir, lamivudine, and zidovudine as a fixed-dose combination; do not use in patients weighing <40 kg, in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine and zidovudine dosage adjustment, or in patients with hepatic dysfunction (Note: Patients with mild to moderate hepatic dysfunction or liver cirrhosis require zidovudine dosage adjustment; abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Trizivir® with abacavir, lamivudine, emtricitabine, or zidovudine-containing products.
DRUG INTERACTIONS — See Abacavir, Lamivudine, and Zidovudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption (see Yuen, 2001).
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, anemia, bone marrow suppression, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, platelets, hemoglobin, MCV, reticulocyte count, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests. HIV patients should be screened for hepatitis B infection before starting lamivudine (see Warnings).
STABILITY — Store at room temperature 25ºC (77ºF)
MECHANISM OF ACTION — See Abacavir, Lamivudine, and Zidovudine
PHARMACOKINETICS — One Trizivir® tablet is bioequivalent, in the extent (AUC) and rate of absorption (peak concentration and time to peak concentration), to one abacavir 300 mg tablet, one lamivudine 150 mg tablet, plus one zidovudine 300 mg tablet; See Abacavir, Lamivudine, and Zidovudine
PATIENT INFORMATION — Trizivir® is not a cure for HIV. Take Trizivir® every day as prescribed; do not change dose or discontinue without physician's advice. If Trizivir® is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information")
Trizivir® contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reaction. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir, lamivudine, and zidovudine. Stop taking Trizivir® and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain), flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Trizivir® (or abacavir, Ziagen®, or Epzicom™), never take Trizivir®, abacavir, Ziagen®, or Epzicom™ again.
Trizivir® contains zidovudine which may cause a decrease in white blood cells or red blood cells (anemia); routine blood tests can help detect these blood problems. Zidovudine may also cause muscle weakness with prolonged use, which may be a serious problem; notify physician if muscle weakness occurs.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir, lamivudine, and zidovudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Trizivir®, inform your physician about your medical conditions, including any blood, kidney, or liver problems (including hepatitis B infection). Do not take Trizivir ® with Combivir ®, Emtriva™, Epivir®, Epivir-HBV®, Epzicom®, Retrovir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them

Abacavir and lamivudine

U.S. BRAND NAMES — Epzicom™
CANADIAN BRAND NAMES — Kivexa™
SYNONYMS — 3TC and ABC; 3TC and Abacavir; Abacavir and 3TC; ABC and 3TC; Lamivudine and Abacavir
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir and lamivudine: Drug information")
Children and Adolescents <18 years of age: Not intended for pediatric use; product is a fixed-dose combination; safety and efficacy has not been established in pediatric patients
Adolescents 18 years of age and Adults: 1 tablet daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regards to meals.
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended)
ADVERSE REACTIONS — See Abacavir and Lamivudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir; potentially fatal hypersensitivity reactions may occur (see Warnings).
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir and lamivudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis), GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Epzicom™, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, or reactions to other medications). If abacavir, Epzicom™ or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Epzicom™, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Epzicom™ in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir and lamivudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation; consider discontinuation of abacavir and lamivudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Epzicom™ contains abacavir and lamivudine as a fixed-dose combination; do not use in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine dosage adjustment or in patients with hepatic dysfunction (Note: Abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Epzicom™ with abacavir, lamivudine, or emtricitabine-containing products.
DRUG INTERACTIONS — See Abacavir and Lamivudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption; in a single dose study, a high-fat meal did not change bioavailability or peak concentrations.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, hemoglobin, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests; HIV patients should be screened for hepatitis B before starting lamivudine (see Warnings)
STABILITY — Store at room temperature 25ºC (77ºF).
MECHANISM OF ACTION — See Abacavir and Lamivudine
PHARMACOKINETICS — One Epzicom™ tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets; see Abacavir and Lamivudine
PATIENT INFORMATION — Epzicom™ is not a cure for HIV. Take Epzicom™ every day as prescribed; do not change dose or discontinue without physician's advice. If Epzicom™ is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir and lamivudine: Patient drug information")
Epzicom™ contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reactions. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir and lamivudine. Stop taking Epzicom™ and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain); flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Epzicom™ (or abacavir, Ziagen®, or Trizivir®), never take Epzicom™, abacavir, Ziagen®, or Trizivir® again.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir and lamivudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Epzicom™, inform your physician about your medical conditions, including any kidney or liver problems (including hepatitis B infection). Do not take Epzicom™ with Combivir®, Emtriva™, Epivir®, Epivir-HBV®, Trizivir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them.
A high rate of early virologic failure in therapy-naive adult HIV patients has been observed with the once-daily three-drug combination therapy of abacavir, lamivudine, and tenofovir; this antiretroviral regimen is currently not recommended; any patient currently receiving this regimen should be closely monitored for virologic failure and considered for treatment modification

Abacavir and lamivudine

U.S. BRAND NAMES — Epzicom™
CANADIAN BRAND NAMES — Kivexa™
SYNONYMS — 3TC and ABC; 3TC and Abacavir; Abacavir and 3TC; ABC and 3TC; Lamivudine and Abacavir
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir and lamivudine: Drug information")
Children and Adolescents <18 years of age: Not intended for pediatric use; product is a fixed-dose combination; safety and efficacy has not been established in pediatric patients
Adolescents 18 years of age and Adults: 1 tablet daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regards to meals.
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended)
ADVERSE REACTIONS — See Abacavir and Lamivudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir; potentially fatal hypersensitivity reactions may occur (see Warnings).
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir and lamivudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis), GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Epzicom™, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, or reactions to other medications). If abacavir, Epzicom™ or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Epzicom™, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Epzicom™ in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir and lamivudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation; consider discontinuation of abacavir and lamivudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Epzicom™ contains abacavir and lamivudine as a fixed-dose combination; do not use in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine dosage adjustment or in patients with hepatic dysfunction (Note: Abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Epzicom™ with abacavir, lamivudine, or emtricitabine-containing products.
DRUG INTERACTIONS — See Abacavir and Lamivudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption; in a single dose study, a high-fat meal did not change bioavailability or peak concentrations.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, hemoglobin, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests; HIV patients should be screened for hepatitis B before starting lamivudine (see Warnings)
STABILITY — Store at room temperature 25ºC (77ºF).
MECHANISM OF ACTION — See Abacavir and Lamivudine
PHARMACOKINETICS — One Epzicom™ tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets; see Abacavir and Lamivudine
PATIENT INFORMATION — Epzicom™ is not a cure for HIV. Take Epzicom™ every day as prescribed; do not change dose or discontinue without physician's advice. If Epzicom™ is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir and lamivudine: Patient drug information")
Epzicom™ contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reactions. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir and lamivudine. Stop taking Epzicom™ and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain); flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Epzicom™ (or abacavir, Ziagen®, or Trizivir®), never take Epzicom™, abacavir, Ziagen®, or Trizivir® again.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir and lamivudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Epzicom™, inform your physician about your medical conditions, including any kidney or liver problems (including hepatitis B infection). Do not take Epzicom™ with Combivir®, Emtriva™, Epivir®, Epivir-HBV®, Trizivir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them.
A high rate of early virologic failure in therapy-naive adult HIV patients has been observed with the once-daily three-drug combination therapy of abacavir, lamivudine, and tenofovir; this antiretroviral regimen is currently not recommended; any patient currently receiving this regimen should be closely monitored for virologic failure and considered for treatment modification

Abacavir, lamivudine, and zidovudine: Drug information

(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information" and see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
U.S. BRAND NAMES — Trizivir®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%: Central nervous system: Headache (13%), malaise (12%), fatigue (12%) Gastrointestinal: Nausea (19%)
1% to 10%: Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%) Dermatologic: Rash (5%) Endocrine & metabolic: Triglycerides increased (2% grade 3-4) Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%) Hematologic: Neutropenia (5%) Hepatic: ALT increased (6%) Neuromuscular & skeletal: CPK increased (7%) Otic: Ear infection (5%) Respiratory: Nose/throat infection (5%) Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir.
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)Tablets (Trizivir) 300-150-300 mg (60): $1154.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose with zidovudine include nausea, vomiting, headache, dizziness, drowsiness, lethargy, confusion, and hematologic changes. Myocardial degeneration has been documented in animals during long-term high-dose toxicology studies; clinical relevance is unknown. Treatment is symptom-directed and supportive. Peritoneal dialysis and hemodialysis have little to no effect on the removal of the components of Trizivir®.
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.

Abacavir, lamivudine, and zidovudine: Drug information

(For additional information see "Abacavir, lamivudine, and zidovudine: Patient drug information" and see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
U.S. BRAND NAMES — Trizivir®
PHARMACOLOGIC CATEGORY Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE Tablet: Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%: Central nervous system: Headache (13%), malaise (12%), fatigue (12%) Gastrointestinal: Nausea (19%)
1% to 10%: Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%) Dermatologic: Rash (5%) Endocrine & metabolic: Triglycerides increased (2% grade 3-4) Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%) Hematologic: Neutropenia (5%) Hepatic: ALT increased (6%) Neuromuscular & skeletal: CPK increased (7%) Otic: Ear infection (5%) Respiratory: Nose/throat infection (5%) Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir.
WARNINGS / PRECAUTIONS Box warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
RESTRICTIONS — An FDA-approved medication guide and warning card (summarizing symptoms of hypersensitivity) must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm.
DRUG INTERACTIONS — See individual agents.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)Tablets (Trizivir) 300-150-300 mg (60): $1154.51
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms of overdose with zidovudine include nausea, vomiting, headache, dizziness, drowsiness, lethargy, confusion, and hematologic changes. Myocardial degeneration has been documented in animals during long-term high-dose toxicology studies; clinical relevance is unknown. Treatment is symptom-directed and supportive. Peritoneal dialysis and hemodialysis have little to no effect on the removal of the components of Trizivir®.
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.