SYMTUZA® Dosing Information & Instructions | SYMTUZA® (darunavir/cobicistat/emtricitabine/tenofovir alafenamide)

Dosing & Administration

One tablet, once daily with food.

Not Actual Size

The smallest darunavir coformulation available.
SYMTUZA^® is a complete regimen that is smaller than PREZCOBIX^®.

If desired, patients have the option to split the pill into 2 pieces. The whole dose should be taken immediately after splitting. When splitting SYMTUZA^®, a standard tablet splitter may be used.

Recommended Dosage

SYMTUZA® is a 4-drug fixed-dose combination product containing 800 mg of darunavir (DRV), 150 mg of cobicistat (COBI), 200 mg of emtricitabine (FTC), and 10 mg of tenofovir alafenamide (TAF).

The recommended dosage of SYMTUZA® is 1 tablet taken orally once daily with food in adults and pediatric patients weighing at least 40 kg. For patients who are unable to swallow the whole tablet, SYMTUZA® may be split into 2 pieces using a tablet splitter, and the entire dose should be consumed immediately after splitting.

Not Recommended in Patients With Severe Renal Impairment

SYMTUZA® is not recommended in patients with creatinine clearance below 30 mL per minute.

Not Recommended During Pregnancy

SYMTUZA® is not recommended during pregnancy because of substantially lower exposures of darunavir and cobicistat during the second and third trimesters.

SYMTUZA® should not be initiated in pregnant individuals. An alternative regimen is recommended for those who become pregnant during therapy with SYMTUZA®.

Testing Prior to Initiation of SYMTUZA^®

Prior to or when initiating SYMTUZA^®, and during treatment with SYMTUZA^®, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.

Not Recommended in Patients With Severe Hepatic Impairment

SYMTUZA® is not recommended for use in patients with severe hepatic impairment (Child-Pugh Class C).

Not Recommended in Pediatric Patients Weighing <40 kg

The safety and effectiveness of SYMTUZA® have not been established and is not recommended in pediatric patients weighing less than 40 kg.

Lactation

The Centers for Disease Control and Prevention recommends that HIV-infected mothers in the United States must not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.

DOSAGE FORMS AND STRENGTHS

Each SYMTUZA® tablet contains darunavir ethanolate equivalent to 800 mg of darunavir, 150 mg of cobicistat, 200 mg of emtricitabine (FTC), and tenofovir alafenamide fumarate equivalent to 10 mg of tenofovir alafenamide (TAF). The yellow to yellowish-brown capsule-shaped, film-coated tablet is debosed with "8121" on one side and "JG" on other side.

Drugs that are contraindicated

Alpha 1-adrenoreceptor agonist	alfuzosin
Anticonvulsants	carbamazepine, phenobarbital, phenytoin
Anti-gout	colchicine in patients with renalor hepatic impairment
Antimycobacterial	rifampin
Antipsychotics	lurasidone, pimozide
Cardiac disorders	dronedarone, ivabradine, ranolazine
Ergot derivatives	dihydroergotamine, ergotamine, methylergonovine
GI motility agent	cisapride
Herbal product	St. John’s wort
Hepatitis C direct-acting antivirals	elbasvir/grazoprevir
Lipid modifying agents	lomitapide, lovastatin, simvastatin
Opioid antagonist	naloxegol
PDE-5 inhibitor	sildenafil for treatment of pulmonary arterial hypertension
Sedative/hypnotics	midazolam (oral), triazolam

Coadministration not recommended^*

Anticoagulant	rivaroxaban
Anticonvulsants	eslicarbazepine, oxcarbazepine
Antifungal	voriconazole
Antimycobacterials	rifabutin, rifapentine
Systemic/inhaled/nasal/ophthalmic corticosteroids	betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, mometasone, triamcinolone
Hepatitis C direct-acting antivirals	glecaprevir/pibrentasvir
Immunosuppressant/neoplastic	everolimus, irinotecan
Inhaled beta agonist	salmeterol
PDE-5 inhibitor	avanafil
Platelet aggregation inhibitors	clopidogrel, ticagrelor

*Recommendations are based on drug interaction trials conducted with components of SYMTUZA^®, as individual agents or in combination, or are predicted interactions.

GI=gastrointestinal; PDE-5=phosphodiesterase type 5; STR=single-tablet regimen.

Reference: 1. SYMTUZA^® [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP.

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, cisapride, 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.

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) and cases of liver injury, including some fatalities, have been reported in patients receiving darunavir, a component of SYMTUZA^®. Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse reactions.

Action: Monitor liver function prior to initiating and during therapy, especially in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases. Patients with evidence of new or worsening liver function should consider discontinuing SYMTUZA^®. SYMTUZA^® is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).
Severe Skin Reactions: In patients receiving darunavir, a component of SYMTUZA^®, severe skin reactions may occur, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis. These include conditions accompanied by fever and/or elevations of transaminases.

Action: Discontinue SYMTUZA^® immediately if signs or symptoms of severe skin reactions develop. These can include but are not limited to severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Risk of Serious Adverse Reactions or Loss of Virologic Response Due to Drug Interactions: Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
Immune Reconstitution Syndrome: Patients receiving SYMTUZA^® may develop new onset or exacerbations of immune reconstitution syndrome.
New Onset or Worsening Renal Impairment: Renal impairment, including cases of acute renal failure and Fanconi syndrome, has been reported with the use of tenofovir prodrugs. In clinical trials of SYMTUZA^®, there were no cases of proximal renal tubulopathy, including Fanconi syndrome, reported in the SYMTUZA^® group through Week 48. SYMTUZA^® is not recommended in patients with creatinine clearance below 30 mL per minute. Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including nonsteroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

Action: Prior to initiating or during treatment, on a clinically appropriate schedule, monitor serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue SYMTUZA^® in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Patients who experience a confirmed increase in serum creatinine of greater than 0.4 mg/dL should be closely monitored for renal safety.
Sulfa Allergy: Darunavir contains a sulfonamide moiety. The incidence and severity of rash were similar in subjects with or without a history of sulfonamide allergy.

Action: Monitor patients with a known sulfonamide allergy.
Lactic Acidosis/Severe Hepatomegaly With Steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of SYMTUZA^®, and tenofovir disoproxil fumarate (TDF), another prodrug of tenofovir, alone or in combination with other antiretrovirals.

Action: Discontinue SYMTUZA^® in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.
Diabetes Mellitus/Hyperglycemia: New-onset or exacerbations of pre-existing diabetes mellitus and hyperglycemia have been reported in patients receiving protease inhibitors.

Action: Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required.
Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving antiretroviral therapy.
Hemophilia: Patients with hemophilia may develop an increase in bleeding events.

ADVERSE REACTIONS

The most common clinical adverse reactions (all grades) occurring in at least 2% of treatment-naïve patients were diarrhea, rash,* nausea, fatigue, headache, abdominal discomfort, and flatulence.

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

Grade 2-4 laboratory abnormalities have been reported in patients receiving SYMTUZA^®, including elevations in serum creatinine, liver function tests, triglycerides, total cholesterol, low-density lipoproteins, and glucose levels. This is not a complete list of all adverse reactions reported with the use of SYMTUZA^®. Please refer to the full Prescribing Information for a complete list of adverse drug reactions.

USE IN SPECIFIC POPULATIONS

Pregnancy: SYMTUZA^® is not recommended for use during pregnancy and should not be initiated in pregnant individuals because of substantially lower exposures of darunavir and cobicistat during pregnancy.

Lactation: The Centers for Disease Control and Prevention recommends that HIV-infected mothers in the United States must not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection.
Pediatric Use: The safety and effectiveness of SYMTUZA^® have not been established and is not recommended in pediatric patients weighing less than 40 kg.
Consult the full Prescribing Information for SYMTUZA^® for additional information on the Uses in Specific Populations.

Please see full Prescribing Information, including Boxed WARNING for SYMTUZA^®.

cp-62076v5

The Protective Barrier to Resistance of Darunavir in a Convenient STR¹

Dosing & Administration

DOSAGE FORMS AND STRENGTHS

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The Protective Barrier to Resistance of Darunavir in a Convenient STR1

Dosing & Administration

DOSAGE FORMS AND STRENGTHS

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Healthcare Professionals

The Protective Barrier to Resistance of Darunavir in a Convenient STR¹