SYMTUZA

and 14 CLINICAL TRIALS. 1 Pediatrics Pediatrics (≥12 and <18 years of age with body weight ≥40 kg) Pediatrics (≥12 years of age with body weight ≥40 kg): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of SYMTUZA in pediatric patients has been established.

Therefore, Health Canada has authorized an indication for pediatric use. (see 4 DOSAGE AND ADMINISTRATION and 7 WARNINGS AND PRECAUTIONS). 2 Geriatrics Geriatrics (≥65 years of age) Limited information is available on the use of SYMTUZA® in patients aged 65 and over (see 4 DOSAGE AND ADMINISTRATION, 7 WARNINGS AND PRECAUTIONS, and 10 CLINICAL PHARMACOLOGY).

Therefore, SYMTUZA® should be used with caution in elderly patients. 2 CONTRAINDICATIONS SYMTUZA® is contraindicated in patients who are hypersensitive to darunavir, cobicistat, emtricitabine, tenofovir alafenamide, or to any ingredient in the formulation or component of the container.

For a complete listing, see the

). There is no specific antidote for overdose with SYMTUZA®. Treatment of overdose with SYMTUZA® consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Since darunavir and cobicistat are highly protein bound, dialysis is unlikely to be beneficial in significant removal of the active substances.

Darunavir Single doses up to 3,200 mg of the oral solution of darunavir alone and up to 1,600 mg of the tablet formulation of darunavir co-administered with ritonavir have been administered to healthy volunteers without untoward symptomatic effects.

Since darunavir is highly protein bound, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Cobicistat Limited clinical experience with cobicistat is available at doses higher than the therapeutic dose.

In two studies, a single dose of cobicistat 400 mg was administered to a total of 60 healthy subjects. No severe adverse reactions were reported. The effects of higher doses are not known. Since cobicistat is highly protein bound, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis.

0 Page 8 of 64 Emtricitabine Limited clinical experience is available at doses higher than the therapeutic dose of EMTRIVA. In one clinical pharmacology study, single doses of emtricitabine 1200 mg (6 times the dose in GENVOYA/DESCOVY) were administered to 11 subjects.

No severe adverse reactions were reported. The effects of higher doses are not known. 5 hours of emtricitabine dosing. It is not known whether emtricitabine can be removed by peritoneal dialysis. Tenofovir Alafenamide Limited clinical experience is available at doses higher than the therapeutic dose of tenofovir alafenamide.

A single supratherapeutic dose of 125 mg tenofovir alafenamide was administered to 48 healthy subjects. No serious adverse reactions were reported. The effects of higher doses are unknown. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

). 2 Geriatrics Geriatrics (≥65 years of age) Limited information is available on the use of SYMTUZA® in patients aged 65 and over (see 4 DOSAGE AND ADMINISTRATION, 7 WARNINGS AND PRECAUTIONS, and 10 CLINICAL PHARMACOLOGY). Therefore, SYMTUZA® should be used with caution in elderly patients.

2 CONTRAINDICATIONS SYMTUZA® is contraindicated in patients who are hypersensitive to darunavir, cobicistat, emtricitabine, tenofovir alafenamide, or to any ingredient in the formulation or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING section of the Product Monograph.

SYMTUZA® is contraindicated in patients with severe (Child-Pugh Class C) hepatic insufficiency. Darunavir and cobicistat are both inhibitors of the cytochrome P450 3A (CYP3A) isoform. Administration of SYMTUZA® is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index).

Darunavir and cobicistat are both substrates of the cytochrome P450 3A (CYP3A) isoform. Co-administration of SYMTUZA® is contraindicated with potent CYP3A inducers as it may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and development of resistance.

4 Drug-Drug Interactions, Table 6). 0 Page 5 of 64 Table 1: Drugs that are Contraindicated with SYMTUZA® Drug Class Drugs within Class that are Contraindicated with SYMTUZA® Alpha 1-Adrenoreceptor Antagonist alfuzosin Antiarrhythmics/Antianginals amiodarone, dronedarone, ivabradine, lidocaine (systemic) Anti-coagulants apixaban, dabigatran, rivaroxaban Anti-convulsants carbamezepine, phenobarbital, phenytoin Anti-gout colchicine (in patients with renal and/or hepatic impairment) Antimycobacterial rifampin Ergot Derivatives dihydroergotamine, ergonovine, ergotamine Hepatitis C Virus Direct-Acting Antivirals elbasvir/grazoprevir Herbal Products St.

08/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ......................................................................................

2 TABLE OF CONTENTS ........................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ...............................................................

4 1 INDICATIONS ............................................................................................................... 1 Pediatrics .............................................................................................................

2 Geriatrics ............................................................................................................. 4 2 CONTRAINDICATIONS ................................................................................................

4