RxPRODUCT NEWS: PROFILE: Trizivir (abacavir sulfate, lamivudine, and zidovudine)

GlaxoSmithKline's Trizivir (abacavirsulfate, lamivudine, andzidovudine) has received traditionalapproval from the FDA for thetreatment of HIV. Trizivir, approved foradults with HIV who weigh over 40 kg,is a fixed-dose combination regimenof 3 nucleoside reverse transcriptaseinhibitors. Traditional approval requiresextended clinical trials lasting atleast 48 weeks. Accelerated approval,which requires data from clinical trialslasting only 24 weeks, was granted toTrizivir in 2000. GlaxoSmithKline promotesTrizivir's fixed-dose regimen toincrease patient compliance through asimplified twice-a-day administrationwithout regard to food or water.¹

Pharmacology

Abacavir, a carbocyclic syntheticnucleoside analogue, is converted toan active metabolite that inhibits HIV-1 reverse transcriptase activity. Lamivudineand zidovudine are both syntheticnucleoside analogues that areconverted intracellularly to activemetabolites. These metabolites inhibitreverse transcriptase activity throughDNA chain termination.²

Clinical Trial

A 48-week clinical trial involved theindividual components of Trizivir. In amulticenter, double-blind, controlledstudy, 562 HIV-infected therapy-naïveadults were randomized into 2 groups:one group received abacavir 300 mgtwice daily and Combivir (lamivudine150 mg and zidovudine 300 mg) twicedaily, while the other group receivedindinavir 800 mg 3 times a day plusCombivir twice daily. At the end of thestudy, both treatment groups displayedsimilar efficacy. These resultssuggest that treatment with the componentsof Trizivir is as effective astreatment with a protease inhibitor.³

Safety

Abacavir has been associated withsevere and often fatal hypersensitivityreactions in about 3% to 5% of patientswho use it. Trizivir should never beused in patients with a history ofhypersensitivity to abacavir; upon reintroduction,more severe symptomsmay develop within hours and possiblyresult in death.⁴ Symptoms of abacavirhypersensitivity include 2 or more ofthe following: fever; rash; gastrointestinalupset, such as nausea, vomiting,diarrhea, or abdominal pain; constitutionalsymptoms, such as generalizedmalaise, fatigue, or aches; and respiratorysymptoms, such as dyspnea, cough,or pharyngitis.

Patients must be aware of the potentialfor hypersensitivity to abacavirand educated to identify a hypersensitivityreaction. GlaxoSmithKline providespatients with a summary of thesymptoms of hypersensitivity on aMedication Guide and Warning Card.Patients should carry the WarningCard at all times.²

Hematologic toxicity, such as neutropeniaand anemia, has been linkedto zidovudine, especially in patientswith advanced HIV.²

Antiretrovirals, including abacavir,lamivudine, and zidovudine, havebeen associated with severe hepatomegalywith steatosis and lactic acidosis,often with fatal results.² Hepaticfunction should be monitored closelyin HIV patients with concomitantinfection with hepatitis B virus whohave discontinued lamivudine, whichis a component of Trizivir.² Trizivirshould not be used in patients withimpaired hepatic function or creatinineclearance less than 50 mL/min.²

Trizivir should be used cautiously inpatients with bone marrow suppression(granulocytes less than 1000cells/m³ or hemoglobin less than 9.5g/dL).²

Myopathy and myositis have beenobserved with zidovudine therapy andmay result with Trizivir as well.²

The following drugs may alter oneor more of the components of Trizivir:nelfinavir, trimethoprim/sulfamethoxazole,atovaquone, fluconazole, methadone,probenecid, ritonavir, valproicacid, and ethanol.²

The most commonly reported sideeffects include nausea; vomiting;malaise; fatigue; headache; diarrhea;fever; depressive disorders; rash; anxiety;ear, nose, and throat infections;and viral respiratory infections.^2-4

Dr. Holmberg is a pharmacist with PhoenixChildren's Hospital, Phoenix, Ariz.

For a list of references, send a stamped, self-addressedenvelope to: References Department,Attn. A. Stahl, Pharmacy Times,241 Forsgate Drive, Jamesburg, NJ 08831; orsend an e-mail request to: astahl@ascendmedia.com.