STRIBILD

Treatment-Emergent Adverse Drug Reactionsa (Grades 2-4) Reported in ≥ 2% of Patients in Any Treatment Arm in Studies 102 and 103 (Week 48 and Week 144 analysesb) Week 48 Week 144 STRIBILD ATRIPLA Atazanavir/r + RTV + TRUVADA STRIBILD ATRIPLA Atazanavir + RTV + TRUVADA N=701 N=352 N=355 N=701 N=352 N=355 EYE DISORDERS Ocular icterus 0% 0% 2% 0% 0% 2% GASTROINTESTINAL DISORDERS Diarrhea 2% 1% 3% 2% 2% 3% Nausea 2% 1% 2% 2% 1% 2% GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Fatigue 1% 3% 3% 1% 3% 3% NERVOUS SYSTEM DISORDERS Dizziness <1% 3% 1% <1% 3% 1% Headache 2% 1% 1% 2% 1% 1% PSYCHIATRIC DISORDERS Abnormal dreams <1% 4% <1% <1% 4% <1% Depression <1% 3% 0% <1% 3% 0% SKIN AND SUBCUTANEOUS TISSUE DISORDERS Rash <1% 3% <1% <1% 3% <1% a.

Frequencies of adverse reactions are based on Grade 2-4 treatment-emergent adverse events, attributed to study drugs. b. The cumulative results are reported for each analysis (ie, results from Week 0 to Week 48 are reported for Week 48 analysis and results from Week 0 to Week 144 are reported for Week 144 analysis).

Product Monograph STRIBILD (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) tablets Page 18 of 75 Additional treatment-emergent adverse drug reactions of at least moderate intensity (≥ Grade 2) that occurred in less than 2% of patients treated with STRIBILD in Studies 102 and 103 include vomiting, abdominal pain, dyspepsia, flatulence, insomnia, asthenia, pyrexia, chest pain, myalgia, somnolence, renal failure, Fanconi syndrome, and increased blood creatinine.

Adverse drug reactions of suicidal ideation and suicide attempt occurred in less than 1% of patients receiving elvitegravir or STRIBILD, all of whom had a pre-existing history of depression or psychiatric illness. Of the 701 patients who received STRIBILD for 144 weeks in Studies 102 and 103, renal even ts with laboratory findings consistent with proximal renal tubular injury leading to STRIBILD discontinuation were reported in 4 patients during the first 48 weeks.

These findings largely reversed upon discontinuation of STRIBILD without clinical sequelae. All 4 patients had renal impairment at baseline or were at risk for renal impairment. No additional proximal renal tubular dysfunction cases were reported from Week 48 to Week 144 (see 7 WARNINGS AND PRECAUTIONS, Renal).

In Virologically-Suppressed HIV-Infected Patients No new adverse drug reactions to STRIBILD through Week 48 were identified in 584 virologically stably suppressed patients switching to STRIBILD from a regimen containing a ritonavir-boosted protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI).

In a combined analysis of Studies 115 and 121, the frequency of adverse rea ctions (all grades) was 24% in patients switching to STRIBILD compared to 6% of patients in either group who stayed on their baseline antiretroviral regimen, RTV-boosted PI + TRUVADA or NNRTI + TRUVADA.

Common adverse reactions that occurred in greater than or equal to 2% of patients switching to STRIBILD were nausea (4%), flatulence (2%), and headache (2%). The proportion of patients who discontinued treatment with STRIBILD, the RTV-boosted PI, or the NNRTI due to adverse events, was 2%, 3% and 1%, respectively.

Adverse Reactions from Clinical Trials of the Components of STRIBILD For information on the safety profiles of EMTRIVA, TYBOST, or VIREAD, consult the Product Monographs for these products. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings The frequency of treatment-emergent laboratory abnormalities (Grades 3-4) occurring in at least 2% of […]

4 Administration The recommended dose of STRIBILD is one tablet (containing 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine and 300 mg of tenofovir DF) taken orally once daily with food. 5 Missed Dose If a patient misses a dose of STRIBILD within 12 hours of the time it is usually taken, the patient should take STRIBILD with a meal as soon as possible, and then take the next dose of STRIBILD at the regularly scheduled time.

If a patient misses a dose of STRIBILD by more than 12 hours, the patient should not take the missed dose, but resume the usual dosing schedule. 5 OVERDOSAGE If overdose occurs the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary including monitoring of vital signs and observation of Product Monograph STRIBILD (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) tablets Page 8 of 75 the patient’s clinical status.

Hemodialysis can remove both emtricitabine and tenofovir DF (refer to information below). Elvitegravir Limited clinical experience is available at doses higher than the therapeutic dose of elvitegravir. In one study, boosted elvitegravir equivalent to 2 times the therapeutic dose of 150 mg once daily for 10 days was administered to 42 healthy patients.

No severe adverse reactions were reported. The effects of higher doses are not known. As elvitegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis. Cobicistat Limited clinical experience is available at doses higher than the therapeutic dose of cobicistat.

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

5 hours of emtricitabine dosing (blood flow rate of 400 mL/minute and a dialysate flow rate of 600 mL/minute), however, a single treatment does not significantly affect emtricitabine Cmax or AUC. It is not known whether emtricitabine can be removed by peritoneal dialysis.

Tenofovir DF Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single 300 mg dose of tenofovir DF, a four-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.

For management of a suspected drug overdose, contact your regional poison control centre. 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 2. Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form/ Strength/Composition Non-medicinal Ingredients Oral Tablet 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil) Croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, silicon dioxide, and sodium lauryl sulfate.

The tablets are coated with a coating material containing indigo carmine (FD&C blue #2) aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide and yellow iron oxide. Product Monograph STRIBILD (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil […]

Benzodiazepines orally administered midazolam*, triazolam Triazolam and orally administered midazolam are extensively metabolized by CYP3A4. Coadministration of triazolam or orally administered midazolam with STRIBILD may cause large increases in the concentration of these benzodiazepines.

The potential exists for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression. Beta 2-adrenoceptor agonist salmeterol Coadministration of salmeterol with STRIBILD may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

Direct oral anticoagulants apixaban, rivaroxaban Apixaban and rivaroxaban are primarily metabolized by CYP3A4 and transported by P-gp. Coadministration with STRIBILD may result in increased plasma concentrations of apixaban or rivaroxaban, which may lead to an increased bleeding risk.

Ergot derivatives dihydroergotamine, ergonovine, ergotamine, methylergonovine* Potential for serious and/or life-threatening events such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues.

Product Monograph STRIBILD (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) tablets Page 6 of 75 Drug Class Drugs within class that are contraindicated with STRIBILD Clinical Comment GI motility agents cisapride* Potential for serious and/or life-threatening events such as cardiac arrhythmias.

Herbal products St. John’s Wort (Hypericum perforatum) Patients taking STRIBILD should not use products containing St. John’s wort because coadministration may result in reduced plasma concentrations of elvitegravir and cobicistat. This may result in loss of therapeutic effect and development of resistance.

HMG-CoA reductase inhibitors lovastatin, simvastatin Potential for serious reactions such as myopathy, including rhabdomyolysis. Microsomal triglyceride transfer protein inhibitor lomitapide Potential for increased lomitapide concentrations which may result in markedly increased transaminases.

PDE-5 inhibitors sildenafil† A safe and effective dose in combination with STRIBILD has not been established for sildenafil (Revatio®) when used for the treatment of pulmonary hypertension. There is increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, priapism, and syncope).

*Not marketed in Canada. †For the treatment of pulmonary arterial hypertension.