Adverse Event Profile

SYMTUZA^®: A Tolerability Profile That Patients Need and That You Can Rely On

Across pivotal trials, no new cases of type 2 diabetes related to SYMTUZA^® or clinically relevant changes in blood pressure over 96 weeks.¹*

Adverse reactions ≥2% in treatment-naïve patients^1,2

*Week 96 was an open-label, single-arm extension, not a primary endpoint.^3,4

^†Includes pooled reported terms: dermatitis, dermatitis allergic, erythema, photosensitivity reaction, rash generalized, rash macular, rash maculopapular, rash morbilliform, rash pruritic, toxic skin eruption, and urticaria.¹

One Grade 3 and no Grade 4 adverse reactions were reported with SYMTUZA^® at 48 weeks.^1‡

In virologically suppressed patients:

The safety profile of SYMTUZA^® was similar to that of treatment-naïve patients¹
Through 48 weeks, the most common treatment-related adverse events were diarrhea (2%, n=16/763) and osteopenia (1%, n=5/763)⁵
Most adverse events were mild to moderate in severity (Grades 1 and 2)⁵
- The most common Grade 3 adverse event was pneumonia, which was reported for 3 (<1%) patients. No Grade 4 adverse events were reported in 2 or more patients

*Week 96 was an open-label, single-arm extension, not a primary endpoint.^3,4

One Grade 3 and no Grade 4 adverse reactions were reported with SYMTUZA^® at 48 weeks.^1‡

In a study of rapid initiation⁶:

of patients (N=109) discontinued due to adverse events over 48 weeks

discontinuations due to weight gain, metabolic, CNS, or GI AEs

Only one patient discontinued due to adverse events
- This patient had allergic dermatitis (Grade 3), pyrexia (Grade 2), and lip swelling (Grade 2)
- All adverse events resolved after discontinuation of study treatment

At 48 weeks, the most common adverse reactions (≥2%, all Grades) in patients rapidly initiating SYMTUZA^® were:

Most adverse reactions during treatment with SYMTUZA^® were mild to moderate in severity (Grade 1 or Grade 2)

Few Grade 3 and 4 clinical laboratory abnormalities occurred in ≥2% of patients (increased bilirubin in 3% of patients, increased ALT in 3% of patients, and increased AST in 5% of patients)

This is not a complete list of all adverse reactions reported with the use of SYMTUZA^®. See Important Safety Information section below for the most common adverse reactions in the treatment-naïve pivotal trial. Please refer to the full Prescribing Information for a complete list of adverse reactions.

^‡Few treatment-naïve patients started a lipid-lowering medication. 1.7% (n=6) of patients in the SYMTUZA^® arm and 0.6% (n=2) in the control arm started a lipid-lowering drug during treatment.²

^§Pooled preferred terms of allergic dermatitis, dermatitis, rash, macular rash, maculopapular rash, papular rash, and pruritic rash.⁶

AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; BL=baseline; CNS=central nervous system; DRV/c=darunavir/cobicistat; FTC=emtricitabine; GI=gastrointestinal; TDF=tenofovir disoproxil fumarate.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B

Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of SYMTUZA^®.

Action: Monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue SYMTUZA^®. If appropriate, anti-hepatitis B therapy may be warranted.

CONTRAINDICATIONS

Do not coadminister SYMTUZA^® and the following drugs due to the potential for serious and/or life-threatening events or loss of therapeutic effect: alfuzosin, carbamazepine, colchicine (in patients with renal and/or hepatic impairment), dronedarone, elbasvir/grazoprevir, ergot derivatives (such as: dihydroergotamine, ergotamine, methylergonovine), ivabradine, lomitapide, lovastatin, lurasidone, oral midazolam, naloxegol, phenobarbital, phenytoin, pimozide, ranolazine, rifampin, St. John’s wort (Hypericum perforatum), sildenafil for pulmonary arterial hypertension, simvastatin, and triazolam.

References: 1. Data on file. Janssen Therapeutics, Division of Janssen Products, LP. 2. SYMTUZA^® [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP. 3. Orkin C, Eron JJ, Rockstroh J, et al; AMBER Study Group. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2020;34(5):707-718. 4. Eron JJ, Orkin C, Cunningham D, et al; EMERALD Study Group. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1. Antiviral Res. 2019;170:104543. 5. Orkin C, Molina JM, Negredo E, et al; EMERALD Study Group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018;5(1):e23-e34. 6. Huhn GD, Crofoot G, Ramgopal M, et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in a rapid-initiation model of care for human immunodeficiency virus type 1 infection: primary analysis of the DIAMOND study. Clin Infect Dis. 2020;71(12):3110-3117.

SYMTUZA®: A Tolerability Profile That Patients Need and That You Can Rely On

SYMTUZA^®: A Tolerability Profile That Patients Need and That You Can Rely On