Adult Dosing

Treatment of HIV-1 infection

• 1 tablet PO bid

Note:

• Not recommended in adolescents or adults <40 kg as it is a fixed-dose tablet that cannot be dose adjusted

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

Note:

• Not recommended in adolescents or adults <40 kg as it is a fixed-dose tablet that cannot be dose adjusted

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of HIV-1 infection in combination with other antiretrovirals or as monotherapy

• Hypersensitivity to any of the ingredients of the product
• Hepatic impairment
• Weight <40 kg
• CrCl <50 mL/min

• Serious and occasionally fatal hypersensitivity reactions, typically with multi-organ involvement, may be associated with abacavir
• Promptly discontinue therapy should any evidence or suspicion of hypersensitivity reaction occur
• Following a hypersensitivity reaction to abacavir, never restart therapy or any other abacavir-containing product as more severe symptoms including life-threatening hypotension and death may occur within hours
• Patients who carry the HLA-B*5701 allele are highly susceptible for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy, screen patients for the HLA-B*5701 allele; this approach has been found to decrease the risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. HLA-B*5701-negative patients may develop a suspected hypersensitivity reaction to abacavir
• Reintroduction of therapy or any other abacavir-containing product, even in patients having no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions that can occur within hours
• Hematologic toxicity, including neutropenia and severe anemia, has been associated with the use of zidovudine, particularly in patients with advanced HIV-1 infection. Prolonged use of zidovudine has been associated with symptomatic myopathy
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Discontinue therapy if clinical or laboratory findings suggestive of lactic acidosis or significant hepatotoxicity occur
• Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue therapy and are co-infected with HIV and HBV. Initiation of anti-hepatitis B therapy may be warranted

Renal Dose Adjustment (Based on CrCl)

• <50 mL/min: Contraindicated (dose adjustment not possible with fixed-dose combination)

Hepatic Dose Adjustment

• Hepatic impairment: Contraindicated (dose adjustment not possible with fixed-dose combination)

See Supplemental Patient Information

• Product is a fixed-dose combination of 3 nucleoside analogues namely abacavir, lamivudine, and zidovudine; intended only for patients whose regimen would otherwise include these three components
• Serious and occasionally fatal hypersensitivity reactions, typically with multi-organ involvement, may be associated with this drug [US Black Box Warning]
• Permanently discontinue therapy should any evidence or suspicion of hypersensitivity reaction occur [US Black Box Warning]
• Patients who carry the HLA-B*5701 allele are highly susceptible for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy, screen patients for the HLA-B*5701 allele; this approach has been found to decrease the risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. HLA-B*5701-negative patients may develop a suspected hypersensitivity reaction to abacavir [US Black Box Warning]
• Therapy is not recommended for HLA-B*5701-positive patients; consider therapy only with close medical supervision and under exceptional circumstances when the potential benefit outweighs the risk
• Skin patch testing is used as a research tool; avoid using it as a aid in the clinical diagnosis of abacavir hypersensitivity
• Hypersensitivity to abacavir is a multi-organ clinical syndrome characterized by a sign or symptom in two or more of the following groups: fever, rash, GI (nausea, vomiting, diarrhea, or abdominal pain), constitutional (generalized malaise, fatigue, or achiness), and respiratory (dyspnea, cough, or pharyngitis)
• Anaphylaxis, renal failure, liver failure, hypotension, adult respiratory distress syndrome, respiratory failure, and death have occurred in association with hypersensitivity reactions. Physical findings include lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), maculopapular/urticarial rash, and erythema multiforme; hypersensitivity reactions have occurred without rash
• Laboratory abnormalities associated with hypersensitivity include elevated LFTs, elevated creatinine phosphokinase, elevated creatinine, and lymphopenia
• Discontinue therapy as soon as a hypersensitivity reaction is suspected. Permanently discontinue therapy if hypersensitivity cannot be ruled out in order to minimize the risk of a life-threatening hypersensitivity reaction
• Following a hypersensitivity reaction to abacavir, never restart therapy as more severe symptoms including life-threatening hypotension and death may occur [US Black Box Warning]
• Carefully evaluate the reason for discontinuation of therapy while considering re-initiation of therapy to ensure that the patient did not have symptoms of a hypersensitivity reaction; screen all patients of unknown HLA-B*5701 status for the allele prior to therapy re-initiation
• Permanently discontinue therapy and avoid re-initiation of abacavir if hypersensitivity cannot be ruled out on clinical grounds even in the absence of the HLA-B*5701 allele, due to the potential for a severe or even fatal reaction
• If symptoms consistent with hypersensitivity are not identified, reintroduce therapy with continuous monitoring for symptoms of a hypersensitivity reaction
• Register patients in an Abacavir Hypersensitivity Registry
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. Discontinue therapy if clinical or laboratory findings suggestive of lactic acidosis or significant hepatotoxicity occur [US Black Box Warning]. Obesity and prolonged nucleoside exposure may be the possible risk factors
• Periodically monitor blood counts for HIV-1-infected individuals and in patients with asymptomatic or early HIV-1 disease
• Hematologic toxicity, including neutropenia and severe anemia, has been associated with the use of zidovudine, particularly in patients with advanced HIV-1 infection [US Black Box Warning]
• Administer therapy cautiously in patients who have bone marrow compromise evidenced by granulocyte count <1,000 cells/mm³ or hemoglobin <9.5 g/dL
• Periodic blood counts are strongly recommended to detect severe anemia or neutropenia in HIV-infected individuals receiving therapy, particularly those with advanced HIV disease. Consider dosage interruption if anemia or neutropenia develops
• Symptomatic myopathy and myositis have been associated with prolonged use of zidovudine [US Black Box Warning]
• In patients co-infected with HIV-1 and hepatitis B, acute exacerbation of hepatitis has been reported after discontinuation of this drug; closely monitor hepatic function (laboratory and clinical) for at least several months after stopping treatment. Initiate anti-hepatitis B therapy if indicated [US Black Box Warning]
• Hepatic decompensation, sometimes fatal, has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon alfa with or without ribavirin. Closely monitor such patients for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia. Consider discontinuation of therapy as medically appropriate
• Dose reduction or discontinuation of interferon alfa, ribavirin, or both is recommended if worsening clinical toxicities are observed, including hepatic decompensation
• Exacerbation of anemia may occur in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine; concomitant administration of ribavirin with this drug is not advised
• Consider potential for cross-resistance between abacavir and other NRTIs when choosing new therapeutic regimens in therapy-experienced patients
• Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients co-infected with HIV-1 and HBV
• Immune reconstitution syndrome may occur in patients treated with combination antiretroviral therapy. Autoimmune disorders have also been reported to occur in the setting of immune reconstitution
• Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have occurred in patients receiving antiretroviral therapy
• Avoid concomitant administration with other products that contain abacavir, lamivudine, or zidovudine as one of their components

Cautions: Use cautiously in:

• Risk of hepatic disease
• Risk of cardiac disease
• Coronary heart disease
• Hypertension
• Hyperlipidemia
• Diabetes mellitus
• Obesity
• Smoking
• Female patients
• Myelosuppression
• Prolonged nucleoside treatment
• Baseline viral load >100,000

Supplemental Patient Information

• Advise patients to read the medication guide and warning card every time to obtain any new information that may be present about the medication
• Inform patients that this drug is not a cure for HIV-1 infection and they may continue to experience illnesses associated with HIV infection such as opportunistic infections. Advise patients to seek medical help for any significant health changes
• Advise HIV-infected mothers not to breastfeed their infants due to the risk of HIV transmission

Pregnancy Category:C

Breastfeeding: HIV-infected mothers generally should not breastfeed their infants. Exclusive breastfeeding for 6 months is recommended for HIV-infected mothers in countries where no acceptable, feasible, sustainable and safe replacement feeding is available to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding. In these settings, abrupt weaning at 4 months does not reduce the risk of HIV transmission or produce an overall health benefit compared to continued breastfeeding, and increases the risk of infant death in HIV-infected infants. Extended antiretroviral prophylaxis in breastfed infants reduces the rate of HIV transmission during breastfeeding by about half, but the optimal regimen and duration of prophylaxis has not yet been defined. Abacavir/lamivudine/zidovudine has been successfully used as part of a regimen that decreases mother-to-child transmission of HIV. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 5 January 2011). The Centers for Disease Control and Prevention recommend that HIV-infected mothers should not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Lamivudine and zidovudine are excreted in human milk. As per manufacturer's data, HIV-infected mothers should be instructed not to breastfeed their infants during therapy.

• CV: Severe hypotension, myocardial infarction
• GI: Hepatic failure, severe hepatomegaly with steatosis, hepatotoxicity, pancreatitis, nausea, diarrhea, vomiting, anorexia, abdominal pain, mouth ulceration
• GU: Renal failure
• CNS: Headache, malaise, fatigue, insomnia, dizziness, seizures
• NEURO: Paresthesias, peripheral neuropathy
• RESP: Acute respiratory distress syndrome, respiratory failure, URTI
• MUSC: Myopathy, rhabdomyolysis, myalgia, arthralgia
• DERM: Erythema multiforme, toxic epidermal necrolysis, rash, urticaria
• IMMU: Immune reconstitution syndrome, autoimmune disorders
• METABOLIC: Lipodystrophy, lactic acidosis
• HEMA: Severe anemia, neutropenia
• LAB TESTS: Elevated LFTs, elevated amylase
• HYPERSENSITIVITY: Severe hypersensitivity reactions, anaphylaxis, Stevens-Johnson syndrome
• MISC: Death, post-treatment HBV exacerbation, fever, chills

Abacavir

• Nucleoside reverse transcriptase inhibitor; inhibits replication of HIV by incorporating into HIV DNA and production of incomplete, nonfunctional DNA
• Oral bioavailability: mean 86 %
• Metabolized by liver; CYP450: None
• Excretion: Urine 82.2% (1.2% unchanged), feces 16%
• Half-life: 1.45 +/- 0.32 hrs

Lamivudine

• Nucleoside reverse transcriptase inhibitor; phosphorylated intra-cellularly to its active metabolite, lamivudine-5'-triphosphate (3TC-TP); principal mode of action of 3TC-TP is the inhibition of HIV-1 reverse transcriptase and HBV polymerase resulting in DNA chain termination
• Mean oral bioavailability 86 %
• Metabolism is a minor route of elimination
• Excretion: Renal (primarily unchanged)
• Half-life: 5-7 hrs

Zidovudine

• Nucleoside reverse transcriptase inhibitor; inhibits replication of retroviruses, including human immunodeficiency virus, by interfering with viral RNA-directed DNA polymerase and acts as a chain terminator of DNA synthesis
• Oral bioavailability: 64 +/- 10 %
• Primarily metabolized in the liver via glucuronidation; CYP450: Unknown
• Excretion: Primarily urine; 14% unchanged and 74% as metabolites
• Half-life: 0.5-3 hrs

US Trade Name(s)

• Trizivir

US Availability

abacavir/lamivudine/zidovudine (generic)

• TABS: 300 mg/150 mg/300 mg

Trizivir (abacavir/lamivudine/zidovudine)

• TABS: 300 mg/150 mg/300 mg

Canadian Trade Name(s)

• Trizivir

Canadian Availability

Trizivir (abacavir/lamivudine/zidovudine)

• TABS: 300 mg/150 mg/300 mg

UK Trade Name(s)

• Trizivir

UK Availability

Trizivir (abacavir/lamivudine/zidovudine)

• TABS: 300 mg/150 mg/300 mg

Australian Trade Name(s)

• Trizivir

Australian Availability

Trizivir (abacavir/lamivudine/zidovudine)

• TABS: 300 mg/150 mg/300 mg

[Outline]

Antimicrobials

Antiviral Agents

Antiviral Combinations

Infectious Disease

Antiviral Agents

Antiviral Combinations

Pricing data from www.DrugStore.com in U.S.A.

• Trizivir 300-150-300 MG TABS [Bottle] (VIIV HEALTHCARE)
  60 mg = $1562.95
  180 mg = $4374.97

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

Drug Name: Trizivir (abacavir 300 MG / lamivudine 150 MG / zidovudine 300 MG) Oral Tablet

Ingredient(s): Abacavir mixture with Lamivudine and Zidovudine

Imprint: GX;LL1

Color(s): Blue

Shape: Oval

Size (mm): 21.00

Score: 1

Inactive Ingredient(s): magnesium stearate / cellulose, microcrystalline / sodium starch glycolate type a potato / fd&c blue no. 2 / hypromellose / polyethylene glycol / titanium dioxide / ferric oxide yellow

Drug Label Author:
GlaxoSmithKline LLC

DEA Schedule:
Non-Scheduled