Canasa Drug Information

is indicated in adults for the treatment of mildly to moderately active ulcerative proctitis. CANASA is an aminosalicylate indicated in adults for the treatment of mildly to moderately active ulcerative proctitis.

Dosage The recommended dosage of CANASA in adults is 1000 mg administered rectally once daily at bedtime for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Safety and effectiveness of CANASA beyond 6 weeks have not been established. Administration Instructions: Evaluate renal function prior to initiation of CANASA therapy . Do not cut or break the suppository.

Retain the suppository for one to three hours or longer, if possible. Drink an adequate amount of fluids If a dose of CANASA is missed, administer as soon as possible, unless it is almost time for next dose. Do not use two CANASA suppositories at the same time to make up for a missed dose.

CANASA suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Keep CANASA away from these surfaces to prevent staining. Dosage The recommended adult dosage is 1000 mg administered rectally once daily at bedtime for 3 to 6 weeks.

Safety and effectiveness beyond 6 weeks have not been established. Administration Instructions: Evaluate renal function prior to initiation of CANASA and periodically while on therapy. Do not cut or break the suppository.

Drink an adequate amount of fluids. Retain the suppository for one to three hours or longer, if possible. CANASA suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel.

Keep CANASA away from these surfaces to prevent staining.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions in adult patients with mildly to moderately active ulcerative proctitis in double-blind, placebo-controlled trials are summarized in the Table 1 below. Table 1: Adverse Reactions Occurring in More Than 1% of Mesalamine Suppository Treated Patients (Comparison to Placebo) Symptom Mesalamine (n = 177) Placebo (n = 84) N % N % Dizziness 5 3 2

Rectal Pain 3 1.8 0 0 Fever 2 1.2 0 0 Rash

2 1.2 0 0 Acne 2 1.2 0 0 Colitis 2 1.2 0 0 In a multicenter, open-label, randomized, parallel group study in 99 patients comparing the CANASA 1000 mg suppository administered nightly to that of the mesalamine 500 mg suppository twice daily. The most common adverse reactions in both groups were headache (14%), flatulence (5%), abdominal pain (5%), diarrhea (3%), and nausea (3%). Three patients discontinued medication because of an adverse reaction; one of these adverse reactions (headache) was deemed possibly related to study medication. The recommended dosage of CANASA is 1000 mg administered rectally once daily at bedtime.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of CANASA or other mesalamine-containing products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: drug fever, fatigue, lupus-like syndrome, medication residue Cardiac Disorders: myocarditis, pericarditis, pericardial effusion Endocrine: Nephrogenic diabetes insipidus Eye disorders : eye swelling Gastrointestinal D isorders : abdominal cramps, abdominal distension, anal pruritus, anorectal discomfort, constipation, feces discolored, flatulence, frequent bowel movements, gastrointestinal bleeding, mucus stools, nausea, painful defecation, pancreatitis, proctalgia, rectal discharge, rectal tenesmus, stomach discomfort, vomiting Hepatic D isorders : cholestatic jaundice, hepatitis, jaundice, Kawasaki-like syndrome including changes in liver enzymes, liver necrosis, liver failure Hematologic D isorders : agranulocytosis, aplastic anemia, thrombocytopenia Neurologi ca l/Psychiatric D isorders : Guillain-Barre syndrome, peripheral neuropathy, transverse myelitis, intracranial hypertension Renal Disorders: interstitial nephritis, renal failure, minimal change disease, nephrolithiasis ○ Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or water treated with hypochlorite containing bleach Respiratory, Thoracic and Mediastinal Disorders: hypersensitivity pneumonitis (including allergic alveolitis, eosinophilic pneumonitis, interstitial pneumonitis), pleuritis/pleurisy Skin and S ubcutaneous T issue D isorder: alopecia, erythema, erythema nodosum, pruritus, psoriasis, pyoderma gangrenosum, urticaria, SJS/TEN, DRESS and AGEP Urogenital: reversible oligospermia

Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs

The concurrent use of mesalamine with known nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions.

Azathioprine or 6- M ercaptopurine

The concurrent use of mesalamine with azathioprine or 6-mercaptopurine and/or other drugs known to cause myelotoxicity may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of CANASA and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.

Interference With Urinary Normetanephrine Measurements Use of mesalamine may lead to spuriously

elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection, because of the similarity in the chromatograms of normetanephrine and mesalamine's main metabolite, N-acetylaminosalicylic acid. Consider an alternative, selective assay for normetanephrine .

Pregnancy Risk Summary Limited published data on mesalamine use in pregnant women are insufficient to inform a drug-associated risk. No evidence of teratogenicity was observed in rats or rabbits when treated during gestation with orally administered mesalamine at doses greater than the recommended human intra-rectal dose ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Reproduction studies have been performed in rats at oral doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of CANASA, based on body surface area) and in rabbits at oral doses up to 495 mg/kg/day (about 5.4 times the recommended human intra-rectal dose of CANASA, based on body surface area) following administration during the period of organogenesis, and have revealed no evidence of impaired fertility or harm to the fetus due to mesalamine.

Pediatric Use The safety and effectiveness of CANASA in pediatric patients for the treatment of mildly to moderately active ulcerative proctitis have not been established. CANASA was evaluated for the treatment of ulcerative proctitis in a 6-week, open-label, single-arm study in 49 patients 5 to 17 years of age, which only included 14 patients with histologically-confirmed cases of ulcerative proctitis. However, efficacy was not demonstrated.

Adverse reactions seen in pediatric patients in this trial (abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea and vomiting) were similar to those seen in adult patients.

is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates or to any ingredients in the suppository vehicle . Known or suspected hypersensitivity to salicylates or aminosalicylates or to any ingredients in the formulation.

Mesalamine absorption from the colon is limited; however, CANASA is an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) involvement. There is no specific antidote for mesalamine overdose. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.