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.
Sunday, May 16, 2010
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.
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 and lamivudine
U.S. BRAND NAMES — Epzicom®
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
DOSING: RENAL IMPAIRMENT — Clcr <50 mL/minute: Use not recommended
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, 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: . HIV: Appropriate use: . Hypersensitivity reactions: . Lactic acidosis/hepatomegaly: .
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom®). 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. Epzicom® 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. Epzicom® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Epzicom® 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 Epzicom® 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 Epzicom® 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).
Disease-related concerns: 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. Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. 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: Due to fixed dose of combination product, use is not recommended with renal impairment (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: Pediatrics: Due to fixed dose of combination product, use is not recommended in children.
DRUG INTERACTIONS
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
Trimethoprim: May decrease the excretion of LamiVUDine. 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 (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV. See individual agents.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Epzicom)
600-300 mg (30): $923.18
MONITORING PARAMETERS — Amylase, bilirubin, blood glucose, serum creatine kinase, liver enzymes, hematologic parameters, triglycerides, viral load, and CD4 count; 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
CANADIAN BRAND NAMES — Kivexa™
INTERNATIONAL BRAND NAMES — Kivexa (AR, AT, AU, BE, BG, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PT, RU, SE, TH, TR, TW, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
PHARMACODYNAMICS / KINETICS — See individual agents.
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
DOSING: RENAL IMPAIRMENT — Clcr <50 mL/minute: Use not recommended
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, 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: . HIV: Appropriate use: . Hypersensitivity reactions: . Lactic acidosis/hepatomegaly: .
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom®). 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. Epzicom® 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. Epzicom® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Epzicom® 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 Epzicom® 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 Epzicom® 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).
Disease-related concerns: 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. Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. 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: Due to fixed dose of combination product, use is not recommended with renal impairment (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: Pediatrics: Due to fixed dose of combination product, use is not recommended in children.
DRUG INTERACTIONS
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
Trimethoprim: May decrease the excretion of LamiVUDine. 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 (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV. See individual agents.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Epzicom)
600-300 mg (30): $923.18
MONITORING PARAMETERS — Amylase, bilirubin, blood glucose, serum creatine kinase, liver enzymes, hematologic parameters, triglycerides, viral load, and CD4 count; 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
CANADIAN BRAND NAMES — Kivexa™
INTERNATIONAL BRAND NAMES — Kivexa (AR, AT, AU, BE, BG, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PT, RU, SE, TH, TR, TW, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
PHARMACODYNAMICS / KINETICS — See individual agents.
Abacavir and lamivudine
U.S. BRAND NAMES — Epzicom®
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
DOSING: RENAL IMPAIRMENT — Clcr <50 mL/minute: Use not recommended
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, 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: . HIV: Appropriate use: . Hypersensitivity reactions: . Lactic acidosis/hepatomegaly: .
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom®). 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. Epzicom® 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. Epzicom® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Epzicom® 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 Epzicom® 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 Epzicom® 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).
Disease-related concerns: 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. Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. 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: Due to fixed dose of combination product, use is not recommended with renal impairment (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: Pediatrics: Due to fixed dose of combination product, use is not recommended in children.
DRUG INTERACTIONS
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
Trimethoprim: May decrease the excretion of LamiVUDine. 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 (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV. See individual agents.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Epzicom)
600-300 mg (30): $923.18
MONITORING PARAMETERS — Amylase, bilirubin, blood glucose, serum creatine kinase, liver enzymes, hematologic parameters, triglycerides, viral load, and CD4 count; 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
CANADIAN BRAND NAMES — Kivexa™
INTERNATIONAL BRAND NAMES — Kivexa (AR, AT, AU, BE, BG, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PT, RU, SE, TH, TR, TW, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
PHARMACODYNAMICS / KINETICS — See individual agents.
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily
DOSING: RENAL IMPAIRMENT — Clcr <50 mL/minute: Use not recommended
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Epzicom®: Abacavir 600 mg and lamivudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — See individual agents.
Postmarketing and/or case reports: Alopecia, anaphylaxis, anemia, aplastic anemia, breath sounds abnormal, CPK increased, erythema multiforme, fat redistribution, hepatic steatosis, hepatitis B exacerbation, hyperglycemia, hypersensitivity reaction, lactic acidosis, lymphadenopathy, muscle weakness, pancreatitis, paresthesia, peripheral neuropathy, rhabdomyolysis, seizure, splenomegaly, Stevens-Johnson syndrome, stomatitis, urticaria, weakness, wheezing
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, 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: . HIV: Appropriate use: . Hypersensitivity reactions: . Lactic acidosis/hepatomegaly: .
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Epzicom®). 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. Epzicom® 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. Epzicom® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Epzicom® 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 Epzicom® 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 Epzicom® 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).
Disease-related concerns: 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. Chronic hepatitis B: [U.S. Boxed Warning]: Following discontinuation of lamivudine, severe acute exacerbations of hepatitis B in patients coinfected with HBV and HIV have been reported. Monitor patients closely for several months following discontinuation of therapy for chronic hepatitis B; clinical exacerbations may occur. 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: Due to fixed dose of combination product, use is not recommended with renal impairment (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: Pediatrics: Due to fixed dose of combination product, use is not recommended in children.
DRUG INTERACTIONS
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
Trimethoprim: May decrease the excretion of LamiVUDine. 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 (show table)
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV. See individual agents.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Tablets (Epzicom)
600-300 mg (30): $923.18
MONITORING PARAMETERS — Amylase, bilirubin, blood glucose, serum creatine kinase, liver enzymes, hematologic parameters, triglycerides, viral load, and CD4 count; 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
CANADIAN BRAND NAMES — Kivexa™
INTERNATIONAL BRAND NAMES — Kivexa (AR, AT, AU, BE, BG, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PT, RU, SE, TH, TR, TW, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor combination.
Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Lamivudine is a cytosine analog. After lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA-dependent DNA polymerase activities of reverse transcriptase.
PHARMACODYNAMICS / KINETICS — See individual agents.
Abacavir
U.S. BRAND NAMES — Ziagen®
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT
Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet:
Ziagen®: 300 mg
DOSAGE FORMS: CONCISE
Solution, oral:
Ziagen®: 20 mg/mL
Tablet:
Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%:
Central nervous system: Headache (7% to 13%)
Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%:
Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%)
Dermatologic: Rash (5% to 6%, children 7%)
Endocrine & metabolic: Triglycerides increased (2% to 6%)
Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%)
Hematologic: Thrombocytopenia (1%)
Hepatic: AST increased (6%)
Neuromuscular & skeletal: Musculoskeletal pain (5% to 6%)
Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (ENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, MI, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS
Boxed warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: 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). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. 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 therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated therapy. Therapy is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir 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 (ie, 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 abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out regardless of HLA-B*5701 status. To report these events on abacavir 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).
Disease-related concerns: 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. Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Adverse events have been observed in some animal reproduction studies. It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission.
In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Solution (Ziagen)
20 mg/mL (240): $132.55
Tablets (Ziagen)
300 mg (60): $545.02
MONITORING PARAMETERS — CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, 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
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Ampi-quim (MX); Filabac (AR); Zepril (AR); Ziagen (AT, AU, BB, BE, BG, BM, BS, BZ, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, IE, IL, IT, JM, KP, NI, NL, NO, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT
Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet:
Ziagen®: 300 mg
DOSAGE FORMS: CONCISE
Solution, oral:
Ziagen®: 20 mg/mL
Tablet:
Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%:
Central nervous system: Headache (7% to 13%)
Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%:
Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%)
Dermatologic: Rash (5% to 6%, children 7%)
Endocrine & metabolic: Triglycerides increased (2% to 6%)
Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%)
Hematologic: Thrombocytopenia (1%)
Hepatic: AST increased (6%)
Neuromuscular & skeletal: Musculoskeletal pain (5% to 6%)
Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (ENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, MI, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS
Boxed warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: 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). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. 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 therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated therapy. Therapy is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir 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 (ie, 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 abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out regardless of HLA-B*5701 status. To report these events on abacavir 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).
Disease-related concerns: 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. Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Adverse events have been observed in some animal reproduction studies. It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission.
In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Solution (Ziagen)
20 mg/mL (240): $132.55
Tablets (Ziagen)
300 mg (60): $545.02
MONITORING PARAMETERS — CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, 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
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Ampi-quim (MX); Filabac (AR); Zepril (AR); Ziagen (AT, AU, BB, BE, BG, BM, BS, BZ, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, IE, IL, IT, JM, KP, NI, NL, NO, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber
Abacavir
U.S. BRAND NAMES — Ziagen®
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT
Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet:
Ziagen®: 300 mg
DOSAGE FORMS: CONCISE
Solution, oral:
Ziagen®: 20 mg/mL
Tablet:
Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%:
Central nervous system: Headache (7% to 13%)
Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%:
Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%)
Dermatologic: Rash (5% to 6%, children 7%)
Endocrine & metabolic: Triglycerides increased (2% to 6%)
Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%)
Hematologic: Thrombocytopenia (1%)
Hepatic: AST increased (6%)
Neuromuscular & skeletal: Musculoskeletal pain (5% to 6%)
Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (ENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, MI, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS
Boxed warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: 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). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. 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 therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated therapy. Therapy is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir 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 (ie, 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 abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out regardless of HLA-B*5701 status. To report these events on abacavir 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).
Disease-related concerns: 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. Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Adverse events have been observed in some animal reproduction studies. It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission.
In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Solution (Ziagen)
20 mg/mL (240): $132.55
Tablets (Ziagen)
300 mg (60): $545.02
MONITORING PARAMETERS — CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, 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
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Ampi-quim (MX); Filabac (AR); Zepril (AR); Ziagen (AT, AU, BB, BE, BG, BM, BS, BZ, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, IE, IL, IT, JM, KP, NI, NL, NO, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents
DOSING: PEDIATRIC — HIV treatment: Oral: 3 months to 16 years: 8 mg/kg body weight twice daily (maximum: 300 mg twice daily) in combination with other antiretroviral agents
(For additional information see "Abacavir: Pediatric drug information")
DOSING: ELDERLY — Refer to adult dosing.
DOSING: HEPATIC IMPAIRMENT
Mild dysfunction (Child-Pugh score 5-6): 200 mg twice daily (oral solution is recommended)
Moderate-to-severe dysfunction: Use is contraindicated by the manufacturer
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, oral:
Ziagen®: 20 mg/mL (240 mL) [strawberry-banana flavor]
Tablet:
Ziagen®: 300 mg
DOSAGE FORMS: CONCISE
Solution, oral:
Ziagen®: 20 mg/mL
Tablet:
Ziagen®: 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — May be administered with or without food.
USE — Treatment of HIV infections in combination with other antiretroviral agents
ADVERSE REACTIONS SIGNIFICANT — Hypersensitivity reactions (which may be fatal) occur in ~5% of patients (see Warnings/Precautions). Symptoms may include anaphylaxis, fever, rash (including erythema multiforme), fatigue, diarrhea, abdominal pain; respiratory symptoms (eg, pharyngitis, dyspnea, cough, adult respiratory distress syndrome, or respiratory failure); headache, malaise, lethargy, myalgia, myolysis, arthralgia, edema, paresthesia, nausea and vomiting, mouth ulcerations, conjunctivitis, lymphadenopathy, hepatic failure, and renal failure.
Note: Rates of adverse reactions were defined during combination therapy with other antiretrovirals (lamivudine and efavirenz or lamivudine and zidovudine). Only reactions which occurred at a higher frequency in adults (except where noted) than in the comparator group are noted. Adverse reaction rates attributable to abacavir alone are not available.
>10%:
Central nervous system: Headache (7% to 13%)
Gastrointestinal: Nausea (7% to 19%, children 9%)
1% to 10%:
Central nervous system: Depression (6%), fever/chills (6%, children 9%), anxiety (5%)
Dermatologic: Rash (5% to 6%, children 7%)
Endocrine & metabolic: Triglycerides increased (2% to 6%)
Gastrointestinal: Diarrhea (7%), vomiting (children 9%), amylase increased (2%)
Hematologic: Thrombocytopenia (1%)
Hepatic: AST increased (6%)
Neuromuscular & skeletal: Musculoskeletal pain (5% to 6%)
Miscellaneous: Hypersensitivity reactions (2% to 9%; may include reactions to other components of antiretroviral regimen), infection (ENT 5%)
<1% (Limited to important or life-threatening): Erythema multiforme, fat redistribution, GGT increased, hepatic steatosis, hepatomegaly, hepatotoxicity, lactic acidosis, MI, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
CONTRAINDICATIONS — Hypersensitivity to abacavir or any component of the formulation (do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status); moderate-to-severe hepatic impairment
WARNINGS / PRECAUTIONS
Boxed warnings: Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: 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). Hypersensitivity reactions: [U.S. Boxed Warning]: Serious and sometimes fatal hypersensitivity reactions have occurred. 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 therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated therapy. Therapy is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (eg, pharyngitis, dyspnea, cough), and GI symptoms (eg, abdominal pain, diarrhea, nausea, vomiting) should discontinue therapy immediately and call for medical attention. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Abacavir 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 (ie, 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 abacavir is restarted following an interruption in therapy, evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out regardless of HLA-B*5701 status. To report these events on abacavir 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).
Disease-related concerns: 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. Hepatic impairment: Use with caution in patients with mild hepatic dysfunction (contraindicated in moderate-to-severe dysfunction). HIV: Appropriate use: Abacavir should always be used as a component of a multidrug regimen.
Special populations: Pediatrics: Safety and efficacy have not been established in children <3 months of age.
DRUG INTERACTIONS
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
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
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Adverse events have been observed in some animal reproduction studies. It is not known if abacavir crosses the human placenta. No increased risk of overall birth defects has been observed following 1st trimester exposure according to data collected by the antiretroviral pregnancy registry. Cases of lactic acidosis/hepatic steatosis syndrome have been reported in pregnant women receiving nucleoside analogues. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy in women receiving nucleoside analogues. Dose adjustment is not needed for pregnancy. The Perinatal HIV Guidelines Working Group considers abacavir to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).
LACTATION — Excretion in breast milk unknown/contraindicated
BREAST-FEEDING CONSIDERATIONS — In infants born to mothers who are HIV positive, HAART while breast-feeding may decrease postnatal infection. However, maternal or infant antiretroviral therapy does not completely eliminate the risk of postnatal HIV transmission.
In the United States where formula is accessible, affordable, safe, and sustainable, complete avoidance of breast-feeding by HIV-infected women is recommended to decrease potential transmission of HIV.
DIETARY CONSIDERATIONS — May be taken with or without food.
PRICING — (data from drugstore.com)
Solution (Ziagen)
20 mg/mL (240): $132.55
Tablets (Ziagen)
300 mg (60): $545.02
MONITORING PARAMETERS — CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, 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
CANADIAN BRAND NAMES — Ziagen®
INTERNATIONAL BRAND NAMES — Abamune (IN); Ampi-quim (MX); Filabac (AR); Zepril (AR); Ziagen (AT, AU, BB, BE, BG, BM, BS, BZ, CH, CL, CN, CO, CR, CZ, DE, DK, DO, ES, FI, FR, GB, GR, GT, GY, HK, HN, IE, IL, IT, JM, KP, NI, NL, NO, PA, PE, PL, PT, RU, SE, SG, SR, SV, TR, TT, TW, VE); Ziagenavir (AR, BR, MX, TH, UY)
MECHANISM OF ACTION — Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
PHARMACODYNAMICS / KINETICS
Absorption: Rapid and extensive absorption
Distribution: Vd: 0.86 L/kg
Protein binding: 50%
Metabolism: Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hours
Time to peak: 0.7-1.7 hours
Excretion: Primarily urine (as metabolites, 1.2% as unchanged drug); feces (16% total dose)
PATIENT INFORMATION — If you experience any of the following: Fever, skin rash, fatigue, nausea, vomiting, diarrhea, abdominal pain, contact your prescriber immediately. This drug is not a cure for HIV infection, nor will it reduce the risk of transmission to others. You will need frequent blood tests to adjust dosage for maximum therapeutic effect. Take as directed; do not discontinue (even if feeling better). You may experience headache or muscle pain or weakness. If you are instructed to stop the medication, do not take this medication in the future. Do not restart without specific instructions by your prescriber
Friday, November 7, 2008
M.BROVITJawa
M.BROVITJawa
Drug Category: Vitamin.
Contents: Syp: Per 5ml: Vits A 2500iu, D 250iu, C 15mg, B1 0.55mg, B2 0.65mg, Nicotinamide 5.5mg.
Regn.No:Pack:Trade Prices:Retail Prices:
Syp(007877):60m(: 15.64:18.40.
Syp(007877):120ml: 28.05:33.00
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