MEZERA

1 Dosing Considerations • Hepatic Impairment: MEZERA is contraindicated in patients with severe hepatic impairment. In patients with mild to moderate liver function impairment, caution should be exercised and MEZERA should be used only if the expected benefit clearly outweighs the risks to the patient.

Appropriate assessments and monitoring of liver function should be performed prior to and during treatment, at the discretion of the treating physician (see 2 CONTRAINDICATIONS, and 7 WARNINGS AND PRECAUTIONS, Hepatic). • Renal Impairment: MEZERA is contraindicated in patients with severe renal impairment.

In patients with mild to moderate renal function impairment, caution should be exercised and MEZERA should be used only if the benefits outweigh the risks. Appropriate assessments of renal function should be done prior to initiation of therapy and periodically while on treatment especially during the initial phase of treatment (see 2 CONTRAINDICATIONS, and 7 WARNINGS AND PRECAUTIONS, Renal).

• Hematologic: Blood test for differential blood count is recommended prior to and during treatment, at the discretion of the treating physician, given the risk of serious blood dyscrasias when MEZERA is used alone or concomitantly with 6-mercaptopurine or azathioprine.

MEZERA should be used only if the benefits clearly outweigh the risks in patients with underlying bleeding or clotting disorders (see 7 WARNINGS AND PRECAUTIONS, Hematologic). 2 Recommended Dose and Dosage Adjustment • Daily dosing is continued until a significant response is achieved or the patient achieves remission.

Treatment should be continued for at least 6 weeks, to reach endoscopic and/or histological remission. • Health Canada has not authorized an indication for pediatric use. Suppositories The usual dose of MEZERA suppositories is one suppository containing 1 g of mesalazine, self- administered once daily at bedtime.

The suppository should be retained for 1 to 3 hours or longer to achieve the maximum benefit. While the effect of the suppositories may be seen within 3 to 21 days, the usual course of therapy would be from 3 to 6 weeks depending on symptoms and sigmoidoscopic findings.

Foam The usual dose for MEZERA foam enema is two actuations (each containing 1 g mesalazine for a total daily dose of 2 g mesalazine) to be administered once daily at bedtime. If the patient has difficulty in holding the amount of foam released with two actuations, the foam can also be administered in two divided doses: one at bedtime and the other during the night (after evacuation of the first single dose) or in the early morning.

1 Adverse Reaction Overview The most common adverse drug reactions were in the gastrointestinal system. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. Therefore, the adverse reaction rates observed in the clinical trials, 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 useful in identifying and approximating rates of adverse drug reactions in real-world use. MEZERA (mesalazine) Page 11 of 39 Suppositories In a 6-week, single-blind, randomized, multi-centre clinical study (SAS-6/UCA) to compare the efficacy and safety of MEZERA 1 g suppositories (1 g mesalazine/day) vs.

mesalazine 500 mg suppositories (500 mg TID) in patients with acute ulcerative proctitis, 200 patients received MEZERA 1 g suppositories, and 203 patients received mesalazine 500 mg suppositories. 2% in the 1 g and 500 mg suppository groups respectively.

Most adverse reactions were mild or moderate in severity. 1% in the MEZERA foam enema (2 g mesalazine/day) and placebo foam enema groups respectively. Most adverse reactions were mild or moderate in severity. 3 Less Common Clinical Trial Adverse Reactions Other less common (<1%) drug-related adverse events reported with MEZERA rectal formulations in the pivotal clinical studies for suppository or foam enema included the following: Eye disorders: Visual disturbance.

Gastrointestinal disorders:

Anal/perianal burning/discomfort, abdominal distension, colic, meteorism.

General disorders and administration site conditions:

Application site irritation, application site pain, malaise.

, Skin 12/2021 7 WARNINGS AND PRECAUTIONS, General 12/2023 7 WARNINGS AND PRECAUTIONS, Renal 12/2023 7 WARNINGS AND PRECAUTIONS, Sensitivity/Resistance 12/2023 7 WARNINGS AND PRECAUTIONS, Skin 12/2023 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 ...............................................................................................................

4 2 CONTRAINDICATIONS ................................................................................................. 4 4 DOSAGE AND ADMINISTRATION ................................................................................. 6 5 OVERDOSAGE..............................................................................................................

6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 6 7 WARNINGS AND PRECAUTIONS .................................................................................. 10 8 ADVERSE REACTIONS ................................................................................................

13 9 DRUG INTERACTIONS ................................................................................................ 15 10 CLINICAL PHARMACOLOGY .......................................................................................

15 11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 19 12 SPECIAL HANDLING INSTRUCTIONS ........................................................................... 19 PART II: SCIENTIFIC INFORMATION .......................................................................................

73m2) (see 7 WARNINGS AND PRECAUTIONS, Renal). • patients with severe hepatic impairment (see 7 WARNINGS AND PRECAUTIONS, Hepatic). g. Aspirin®), 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. • patients with existing gastric or duodenal ulcer. • patients with urinary tract obstructions. • infants under 2 years of age. MEZERA (mesalazine) Page 5 of 39