ELYXYB

1 Dosing Considerations • The safety and efficacy of treating multiple migraine attacks with ELYXYB in a one-month period has not been studied. Therefore, ELYXYB should be used for the fewest number of days per month as needed, based on individual treatment goals, in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (see 2 CONTRAINDICATIONS; 3 SERIOUS WARNINGS AND PRECAUTIONS BOX; 7 WARNINGS AND PRECAUTIONS).

• ELYXYB is not indicated for prophylaxis of migraine. 8 mL) taken orally, with or without food. 8 mL). The safety and efficacy of a second dose in a 24-hour period have not been studied. ELYXYB should be used for the fewest number of days per month, as needed.

Hepatic Impairment:

Mild: No dose adjustment is needed for patients with mild hepatic impairment (Child-Pugh 5-6).

Moderate:

Caution should be exercised in administrating celecoxib to patients with moderate hepatic ELYXYB (celecoxib oral solution) Page 7 of 51 impairment based on history of celecoxib administration in those patients. 4 Administration).

Severe:

ELYXYB is contraindicated in patients with severe hepatic impairment (Child-Pugh > 9) (see 2 CONTRAINDICATIONS). 3 Pharmacokinetics, Special Populations and Conditions). ELYXYB is contraindicated in patients with severe renal impairment (estimated creatinine clearance < 30 mL/min) (see 2 CONTRAINDICATIONS).

CYP2C9 Poor Metabolizers or Concomitant use of CYP2C9 inhibitors:

Caution should be exercised in administrating celecoxib to patients who are known, or suspected to be, CYP2C9 poor metabolizers based on previous history/experience with other CYP2C9 substrates or to patients who are concomitantly treated with CYP2C9 inhibitors.

3 Pharmacokinetics, Special Populations and Conditions). Pediatrics (< 18 years of age) Health Canada has not authorized an indication for pediatric use (see 2 CONTRAINDICATIONS). 4 Administration Patients must drink the entire amount of ELYXYB directly from the bottle.

ELYXYB can be taken with or without food. , patients with moderate hepatic impairment, who are CYP2C9 poor metabolizers or taking concomitant CYP2C9 inhibitors): Patients must use an oral dosing syringe to precisely measure the prescribed amount of ELYXYB.

1 Clinical Trials by Indication). The most common (at least 1% of patients who received ELYXYB and greater than placebo) adverse reaction in Phase 3 studies were dysgeusia and nausea. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be ELYXYB (celecoxib oral solution) Page 18 of 51 useful for identifying and approximating rates of adverse drug reactions in real-world use.

Table 1 lists all adverse events, regardless of causality, occurring in ≥ 1% of patients receiving a single dose of ELYXYB in these studies and that occurred at a higher incidence than in the placebo groups. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings No clinically meaningful hematologic, clinical chemistry or urinalysis findings were identified for any clinical studies of ELYXYB.

In clinical trials with celecoxib capsules, an increased incidence of hyperchloremia in patients receiving celecoxib compared with patients on placebo was observed. Other laboratory abnormalities that occurred more frequently in the patients receiving celecoxib included hypophosphatemia, and elevated urea.

These laboratory abnormalities were also seen in patients who received comparator NSAIDs in these studies. The clinical significance of these abnormalities has not been established. 5 Post-Market Adverse Reactions Additional reports of serious adverse events temporally associated with celecoxib during worldwide post-marketing experience are included below.

Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or clearly establish a causal relationship to celecoxib exposure.

). The safety and efficacy of treating multiple migraine attacks with ELYXYB in a one-month-period have not been studied. Therefore, ELYXYB should be used for the fewest number of days per month as needed, based on individual treatment goals, in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (see 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS).

3 Pediatrics). 4 Geriatrics). 2 CONTRAINDICATIONS ELYXYB is contraindicated in: • The perioperative pain setting of Coronary Artery Bypass Graft (CABG) surgery. Although ELYXYB has NOT been studied in this patient population, a selective COX-2 inhibitor NSAID studied in such a setting has led to an increased incidence of cardiovascular/thromboembolic events, deep surgical infections and sternal wound complications (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).

• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition. • Women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants. • Severe uncontrolled heart failure.

• Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

ELYXYB (celecoxib oral solution) Page 5 of 51 • Patients who have demonstrated allergic-type reactions to sulfonamides. e. complete or partial syndrome of ASA-intolerance - rhinosinusitis, urticaria/angioedema, nasal polyps, asthma).

Fatal anaphylactoid reactions have occurred in such individuals. Individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction. The potential for cross-reactivity between different NSAIDs must be kept in mind (see 7 WARNINGS AND PRECAUTIONS, Immune, Anaphylactoid Reactions).

and 7 WARNINGS AND PRECAUTIONS). The safety and efficacy of treating multiple migraine attacks with ELYXYB in a one-month-period have not been studied. Therefore, ELYXYB should be used for the fewest number of days per month as needed, based on individual treatment goals, in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (see 2 CONTRAINDICATIONS and 7 WARNINGS AND PRECAUTIONS).

3 Pediatrics). 4 Geriatrics). 2 CONTRAINDICATIONS ELYXYB is contraindicated in: • The perioperative pain setting of Coronary Artery Bypass Graft (CABG) surgery. Although ELYXYB has NOT been studied in this patient population, a selective COX-2 inhibitor NSAID studied in such a setting has led to an increased incidence of cardiovascular/thromboembolic events, deep surgical infections and sternal wound complications (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).

• The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition. • Women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants. • Severe uncontrolled heart failure.

• Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

ELYXYB (celecoxib oral solution) Page 5 of 51 • Patients who have demonstrated allergic-type reactions to sulfonamides. e. complete or partial syndrome of ASA-intolerance - rhinosinusitis, urticaria/angioedema, nasal polyps, asthma).

Fatal anaphylactoid reactions have occurred in such individuals. Individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction. The potential for cross-reactivity between different NSAIDs must be kept in mind (see 7 WARNINGS AND PRECAUTIONS, Immune, Anaphylactoid Reactions).