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 debossed with "8121" on one side and "JG" on other side.

These recommendations are based on drug interaction trials conducted with the components of SYMTUZA®, as individual agents or in combination, or are predicted interactions. No drug interaction trials have been performed with SYMTUZA^® or with all the components administered together.³

Examples of drugs that are contraindicated³

Alpha 1-adrenoreceptor antagonist	alfuzosin
Anticonvulsants	carbamazepine, phenobarbital, phenytoin
Antigout	colchicine in patients with renal and/or hepatic impairment
Antimycobacterial	rifampin
Antipsychotics	lurasidone, pimozide
Cardiac disorders	dronedarone, ivabradine, ranolazine
Ergot derivatives	dihydroergotamine, ergotamine, methylergonovine
Hepatitis C direct-acting antivirals	elbasvir/grazoprevir
Herbal product	St. John’s wort (Hypericum perforatum)
Lipid-modifying agents	lomitapide, lovastatin, simvastatin
Opioid antagonist	naloxegol
PDE-5 inhibitor	sildenafil when used for treatment of pulmonary arterial hypertension
Sedatives/hypnotics	midazolam, triazolam

Examples of drugs where coadministration is not recommended³

Anticoagulant	rivaroxaban
Anticonvulsants	eslicarbazepine, oxcarbazepine
Antifungal	voriconazole
Antimycobacterials	rifabutin, rifapentine
corticosteroids	betamethasone, budesonide, ciclesonide, dexamethasone (systemic), 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

The information presented here is a subset of clinical information in Table 4 of the Prescribing Information; it is not a complete list of all information in Table 4.

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

Reference: 1. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Updated January 20, 2022. Accessed March 8, 2022. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines
2. Data on file. Janssen Therapeutics, Division of Janssen Products, LP. 3. SYMTUZA® [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products, LP.4. Crauwels HM, Baugh B, Van Landuyt E, et al. Bioequivalence of the once-daily single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide compared to combined intake of the separate agents and the effect of food on bioavailability. Clin Pharmacol Drug Dev. 2019;8(4):480-491.

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

Darunavir and cobicistat are both inhibitors and substrates of the cytochrome P450 3A (CYP3A) isoform. SYMTUZA^® should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events. In addition, co-administration of SYMTUZA^® with CYP3A inducers is expected to lower plasma concentrations of darunavir and cobicistat which may lead to loss of efficacy of darunavir and development of resistance.

Action: Examples of drugs that are contraindicated for co-administration with SYMTUZA^® due to the potential for serious and/or life-threatening events or loss of therapeutic effect are listed below: 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.

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: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)-containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events. SYMTUZA^® is not recommended in patients with estimated 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-62076v10

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

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Healthcare Professionals

The Protective Barrier to Resistance of Darunavir in a Convenient STR¹