Fosamprenavir - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • The concomitant use of fosamprenavir with ritonavir and certain other drugs may result in known or potentially significant drug interactions.

Consult the full prescribing information prior to and during treatment for potential drug interactions. ( 5.1 , 7.3 ) • Fosamprenavir should be discontinued for severe skin reactions, including Stevens-Johnson syndrome. • Fosamprenavir should be used with caution in patients with a known sulfonamide allergy. • Use of higher-than-approved doses may lead to transaminase elevations.

Patients with hepatitis B or C are at increased risk of transaminase elevations. • Patients receiving fosamprenavir may develop new onset or exacerbations of diabetes mellitus, hyperglycemia , immune reconstitution syndrome , increase of body fat , and elevated triglyceride and cholesterol concentrations .

Monitor cholesterol and triglycerides prior to therapy and periodically thereafter. • Acute hemolytic anemia has been reported with amprenavir. • Hemophilia: Spontaneous bleeding may occur, and additional factor VIII may be required. • Nephrolithiasis: Cases of nephrolithiasis have been reported with fosamprenavir.

5.1 Risk of Serious Adverse Reactions Due to Drug Interactions Initiation of fosamprenavir/ritonavir, a CYP3A inhibitor, in patients receiving medications metabolized by CYP3A, or initiation of medications metabolized by CYP3A in patients already receiving fosamprenavir/ritonavir may increase plasma concentrations of medications metabolized by CYP3A.

Initiation of medications that inhibit or induce CYP3A may increase or decrease concentrations of fosamprenavir/ritonavir, respectively.

These interactions may lead to: • clinically significant adverse reactions, potentially leading to severe, life-threatening, or fatal events from greater exposures of concomitant medications. • clinically significant adverse reactions from greater exposures of fosamprenavir/ritonavir. • loss of therapeutic effect of fosamprenavir/ritonavir and possible development of resistance.

See Table 6 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Drug Interactions ] .

Consider the potential for drug interactions prior to and during therapy with fosamprenavir/ritonavir; review concomitant medications during therapy with fosamprenavir/ritonavir; and monitor for the adverse reactions associated with the concomitant medications [see Contraindications , Drug Interactions ] .

5.2 Skin Reactions Severe and life-threatening skin reactions, including 1 case of Stevens-Johnson syndrome among 700 subjects treated with fosamprenavir in clinical trials.

Treatment with fosamprenavir should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms [see Adverse Reactions ] .

5.3 Sulfa Allergy Fosamprenavir should be used with caution in patients with a known sulfonamide allergy.

Fosamprenavir contains a sulfonamide moiety.

The potential for cross-sensitivity between drugs in the sulfonamide class and fosamprenavir is unknown.

In a clinical trial of fosamprenavir used as the sole protease inhibitor, rash occurred in 2 of 10 subjects (20%) with a history of sulfonamide allergy compared with 42 of 126 subjects (33%) with no history of sulfonamide allergy.

In 2 clinical trials of fosamprenavir plus low-dose ritonavir, rash occurred in 8 of 50 subjects (16%) with a history of sulfonamide allergy compared with 50 of 412 subjects (12%) with no history of sulfonamide allergy.

5.4 Hepatic Toxicity Use of fosamprenavir with ritonavir at higher-than-recommended dosages may result in transaminase elevations and should not be used [see Dosage and Administration , Overdosage ] .

Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for developing or worsening of transaminase elevations.

Appropriate laboratory testing should be conducted prior to initiating therapy with fosamprenavir and patients should be monitored closely during treatment.

5.5 Diabetes/Hyperglycemia New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia have been reported during postmarketing surveillance in HIV-1– infected patients receiving protease inhibitor therapy.

Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events.

In some cases, diabetic ketoacidosis has occurred.

In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases.

Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and causal relationships between protease inhibitor therapy and these events have not been established.

5.6 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including fosamprenavir.