IMPORTANT SAFETY INFORMATION Prescribing Information

Indication: LEXIVA is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection. The PI-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent. Once-daily administration of LEXIVA/ritonavir is not recommended for adult PI-experienced patients or any pediatric patients.

Important Safety Information: LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir. LEXIVA is contraindicated with ergot derivatives, PROPULSID^®*(cisapride), ORAP^®* (pimozide), VERSED^®* (midazolam), HALCION^®*(triazolam), rifampin, MEVACOR^®* (lovastatin), ZOCOR^®* (simvastatin),RESCRIPTOR^®* (delavirdine), or St. John’s wort (Hypericum perforatum). If LEXIVA is coadministered with ritonavir, TAMBOCOR^®* (flecainide) and RYTHMOL^®* (propafenone) are also contraindicated. CONTINUED BELOW

Resistance

Resistance data from SOLO over 120 weeks
Data from SOLO show no primary PI resistance in virologic failures through 120 weeks

Background: Open-label continuation of LEXIVA/ritonavir QD after a 48-week comparative study of LEXIVA/ritonavir QD versus nelfinavir BID, both administered with abacavir and lamivudine, in treatment-naïve adult patients
Methods: 211 patients from SOLO who had received LEXIVA/ritonavir QD were carried forward to assess long-term virologic suppression, safety, and tolerability of LEXIVA/ritonavir. This analysis examines PI resistance at the time of virologic failure
Results: There were no major protease mutations at the time of first virologic failure in the patients with no baseline resistance who experienced virologic failure (confirmed HIV-1 RNA >1000 copies/mL) over 120 weeks
Conclusions: LEXIVA/ritonavir appears to provide a high genetic barrier to the development of PI resistance at 120 weeks.*

* In the SOLO study, the M461 and 150V mutations were detected in isolates from 1 virologic-failure patient receiving LEXIVA/r once daily at Week 160 (HIV-1 RNA >500 copies/mL). Upon retrospective analysis of stored samples using an ultrasensitive assay, these resistant mutants were traced back to Week 84 (76 weeks prior to clinical virologic failure).¹

1. Sax PE, Xu F, Tisdale M, Elston R. First report of development of resistance to boosted fosamprenavir in an ART-naive subject: virologic and clinical outcome. Poster presented at: 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); December 16-19, 2005; Washington, DC. Poster H-1060.

Important Safety Information

Indication

LEXIVA is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection.

The PI-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent.
Once-daily administration of LEXIVA/ritonavir is not recommended for adult PI-experienced patients or any pediatric patients.

Important Safety Information

LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir
LEXIVA is contraindicated with ergot derivatives, PROPULSID^® (cisapride), ORAP^® (pimozide), VERSED^® (midazolam), HALCION^® (triazolam), rifampin, MEVACOR^® (lovastatin), ZOCOR^® (simvastatin), RESCRIPTOR^® (delavirdine), or St. John's wort (Hypericum perforatum). If LEXIVA is coadministered with ritonavir, TAMBOCOR^® (flecainide) and RYTHMOL^® (propafenone) are also contraindicated
Hyperglycemia, new onset or exacerbations of diabetes mellitus, and spontaneous bleeding in hemophiliacs have been reported with protease inhibitors
Treatment with LEXIVA/r has resulted in increases in the concentration of triglycerides and cholesterol. Triglyceride and cholesterol testing should be performed prior to initiating therapy with LEXIVA and at periodic intervals during therapy
Caution should be exercised when administering LEXIVA to patients with hepatic impairment, including those with hepatitis B or C or marked elevations in transaminases prior to treatment. Increased AST/ALT monitoring should be considered in these patients
LEXIVA taken with oral contraceptives may alter hormonal levels. LEXIVA plus ritonavir taken with oral contraceptives may result in clinically significant hepatic transaminase elevations. Therefore, alternate methods of non-hormonal contraception are recommended
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including LEXIVA. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance," have been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown
LEXIVA should be used with caution in patients with a known sulfonamide allergy
Cases of nephrolithiasis were reported during post-marketing surveillance in HIV-infected patients receiving fosamprenavir calcium. If signs or symptoms of nephrolithiasis occur, temporary interruption or discontinuation of therapy may be considered.
Severe or life-threatening skin reactions were reported in <1% of 700 patients treated with LEXIVA in clinical studies, including 1 case of Stevens-Johnson syndrome
Skin rash (all grades, without regard to causality) occurred in approximately 19% of patients treated with LEXIVA in the pivotal efficacy studies. This led to the discontinuation of LEXIVA in <1% of patients

Other Drug Interactions

Caution should be used when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4, or potentially toxic medications that are metabolized by CYP3A4
Serious and/or life-threatening drug interactions could occur between LEXIVA and CORDARONE^® (amiodarone), lidocaine (systemic), tricyclic antidepressants, and quinidine. Concentration monitoring of these agents is recommended if these agents are used concomitantly with LEXIVA
Particular caution should be used when prescribing phosphodiesterase (PDE-5) inhibitors for erectile dysfunction (eg, sildenafil or vardenafil) in patients receiving LEXIVA
This list of potential drug interactions is not complete

Resistance

Because the potential for HIV cross-resistance among protease inhibitors has not been fully explored, it is unknown what effect therapy with LEXIVA will have on the activity of subsequently administered protease inhibitors
Clinical relevance of resistance data is unknown

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IMPORTANT SAFETY INFORMATION Prescribing Information

Resistance

Resistance data from SOLO over 120 weeks Data from SOLO show no primary PI resistance in virologic failures through 120 weeks

Important Safety Information

Resistance data from SOLO over 120 weeks
Data from SOLO show no primary PI resistance in virologic failures through 120 weeks