Canasa

Description

The active ingredient in CANASA 1000 mg suppositories for rectal use is mesalamine, also known as mesalazine or 5-aminosalicylic acid (5-ASA). Chemically, mesalamine is 5-amino-2-hydroxybenzoic acid and is classified as an aminosalicylate. Each CANASA rectal suppository contains 1000 mg of mesalamine (USP) in a base of Hard Fat, NF. The empirical formula is C7H7NO3, with a molecular weight of 153.14.

Uses and Indications

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

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

The recommended adult dosage of CANASA is 1000 mg, administered rectally once daily at bedtime for a duration of 3 to 6 weeks. The safety and effectiveness of CANASA beyond 6 weeks have not been established.

Prior to initiating therapy with CANASA, healthcare professionals should evaluate the patient's renal function and continue to monitor it periodically throughout the treatment course.

For administration, it is important to note the following instructions:

• The suppository should not be cut or broken prior to use.

• Patients are advised to drink an adequate amount of fluids to facilitate the administration.

• After insertion, the suppository should be retained for one to three hours, or longer if possible, to maximize its therapeutic effect.

Additionally, healthcare professionals should inform patients that CANASA suppositories may cause staining of surfaces that come into direct contact with them, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. It is recommended to keep CANASA away from these surfaces to prevent any potential staining.

Contraindications

Use is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any components of the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Patients with known renal impairment or those taking nephrotoxic drugs require careful evaluation of the risks and benefits associated with CANASA therapy. It is essential to monitor renal function regularly, and treatment should be discontinued if there is any deterioration in renal status.

Mesalamine-Induced Acute Intolerance Syndrome may present symptoms that are challenging to differentiate from an exacerbation of ulcerative colitis. Therefore, healthcare professionals should closely monitor patients for any worsening of symptoms and discontinue treatment if acute intolerance syndrome is suspected.

In cases where a hypersensitivity reaction is suspected, including conditions such as myocarditis and pericarditis, immediate evaluation is warranted, and treatment should be discontinued. Additionally, patients with known liver impairment should be assessed for the risks and benefits of continuing therapy.

At the first signs or symptoms of severe cutaneous adverse reactions or any other indications of hypersensitivity, treatment should be halted, and further evaluation should be considered. Patients with pre-existing skin conditions are advised to minimize sun exposure, wear protective clothing, and apply a broad-spectrum sunscreen when outdoors to mitigate the risk of skin reactions.

It is important to note that mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is crucial to prevent stone formation.

Healthcare professionals should be aware that spuriously elevated test results may occur with liquid chromatography with electrochemical detection in patients receiving CANASA. To avoid this issue, an alternative, selective assay for urinary normetanephrine should be utilized.

Regular monitoring of renal function is recommended for patients with known renal impairment or those on nephrotoxic medications. Furthermore, due to the potential interference with standard tests, it is advisable to use an alternative, selective assay for urinary normetanephrine.

Side Effects

Patients may experience a range of adverse reactions while using this medication, categorized by frequency and seriousness.

Common adverse reactions occurring in clinical trials (≥ 1%) include dizziness (3%), rectal pain (1.8%), fever (1.2%), rash (1.2%), acne (1.2%), and colitis (1.2%). Other frequently reported reactions include headache (14%), flatulence (5%), abdominal pain (5%), diarrhea (3%), and nausea (3%).

In addition to these common reactions, postmarketing experience has identified several serious adverse reactions across various systems.

Body as a Whole: Reports include drug fever, fatigue, lupus-like syndrome, and medication residue.

Cardiac Disorders: Serious conditions such as myocarditis, pericarditis, and pericardial effusion have been noted.

Endocrine Disorders: Nephrogenic diabetes insipidus has been reported.

Eye Disorders: Eye swelling has been observed.

Gastrointestinal Disorders: A wide range of gastrointestinal issues has been reported, including abdominal cramps, abdominal distension, anal pruritus, anorectal discomfort, constipation, feces discoloration, flatulence, frequent bowel movements, gastrointestinal bleeding, mucus stools, nausea, painful defecation, pancreatitis, proctalgia, rectal discharge, rectal tenesmus, stomach discomfort, and vomiting.

Hepatic Disorders: Serious hepatic conditions such as cholestatic jaundice, hepatitis, jaundice, Kawasaki-like syndrome (including changes in liver enzymes), liver necrosis, and liver failure have been documented.

Hematologic Disorders: Cases of agranulocytosis, aplastic anemia, and thrombocytopenia have been reported.

Neurological/Psychiatric Disorders: Serious neurological conditions, including Guillain-Barre syndrome, peripheral neuropathy, transverse myelitis, and intracranial hypertension, have been observed.

Renal Disorders: Adverse renal effects include interstitial nephritis, renal failure, minimal change disease, nephrolithiasis, and urine discoloration due to contact with mesalamine.

Respiratory, Thoracic and Mediastinal Disorders: Hypersensitivity pneumonitis (including allergic alveolitis, eosinophilic pneumonitis, and interstitial pneumonitis) and pleuritis/pleurisy have been reported.

Skin and Subcutaneous Tissue Disorders: Severe cutaneous adverse reactions such as alopecia, erythema, erythema nodosum, pruritus, psoriasis, pyoderma gangrenosum, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been documented.

Urogenital Disorders: Reversible oligospermia has been reported.

It is important to evaluate the risks and benefits of this medication in patients with known renal or hepatic impairment, and to monitor renal function closely. Discontinuation of treatment is advised if renal function deteriorates or if symptoms of mesalamine-induced acute intolerance syndrome are suspected. Patients should be monitored for hypersensitivity reactions, including myocarditis and pericarditis, and treatment should be discontinued if such reactions occur. Additionally, patients with pre-existing skin conditions should be advised to take precautions against sun exposure.

Finally, it is noted that mesalamine-containing stones may not be detectable by standard imaging techniques, and adequate hydration is essential during treatment. Caution is also advised regarding potential interactions with laboratory tests for urinary normetanephrine, as spurious results may occur.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Canasa (mesalamine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

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. A 6-week, open-label, single-arm study evaluated CANASA in 49 patients aged 5 to 17 years, of which only 14 had histologically-confirmed ulcerative proctitis. Efficacy was not demonstrated in this study. Adverse reactions observed in pediatric patients included abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting, which were consistent with those reported in adult patients.

Geriatric Use

Clinical trials of CANASA did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently from younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products such as CANASA compared to their younger counterparts.

Given these findings, it is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with CANASA. Additionally, when prescribing CANASA to geriatric patients, healthcare providers should consider the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies that may affect treatment outcomes. Careful assessment and monitoring are recommended to ensure the safety and efficacy of CANASA in this population.

Pregnancy

Limited published data on mesalamine use in pregnant patients are insufficient to inform a drug-associated risk. Animal studies have shown no evidence of teratogenicity when mesalamine was administered orally to rats or rabbits during gestation at doses greater than the recommended human intra-rectal dose. Reproductive studies conducted in rats at oral doses up to 320 mg/kg/day (approximately 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) during the period of organogenesis revealed no evidence of impaired fertility or harm to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. 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. It is important to note that adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications. Therefore, healthcare professionals should weigh the potential benefits and risks of mesalamine use in pregnant patients.

Lactation

Mesalamine and its N-acetyl metabolite are present in human milk in undetectable to small amounts. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations ranged from 500 mg to 3 g daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L, while the concentration of the N-acetyl-5-aminosalicylic acid metabolite ranged from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily dosages for an exclusively breastfed infant are 0 to 0.017 mg/kg/day of mesalamine and 0.75 to 2.72 mg/kg/day of N-acetyl-5-aminosalicylic acid.

There are limited reports of diarrhea in breastfed infants, and lactating mothers should monitor their breastfed infants for this condition. There is no information on the effects of mesalamine on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of CANASA to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CANASA and any potential adverse effects on the breastfed child from CANASA or from the underlying maternal conditions.

Renal Impairment

Renal impairment, including conditions such as minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients receiving CANASA, which contains mesalamine or is converted to mesalamine. It is essential to evaluate renal function prior to the initiation of CANASA and to conduct periodic assessments during therapy.

Healthcare professionals should carefully weigh the risks and benefits of administering CANASA to patients with known renal impairment, a history of renal disease, or those taking concomitant nephrotoxic medications. In cases where renal function deteriorates during treatment, CANASA should be discontinued. Additionally, ongoing monitoring of renal function is advised for patients with existing renal impairment or those on nephrotoxic drugs, with discontinuation of CANASA warranted if any decline in renal function is observed.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of hepatic failure when administered CANASA, particularly those with pre-existing liver disease who have previously received other products containing mesalamine.

It is essential to evaluate the risks and benefits of using CANASA in this patient population. Clinicians should carefully consider the patient's liver function and any potential complications associated with treatment. Regular monitoring of liver function tests may be warranted to ensure patient safety and to detect any signs of hepatic deterioration promptly.

Overdosage

In cases of mesalamine overdose, healthcare professionals should be vigilant for symptoms indicative of salicylate toxicity. These symptoms may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, headache, dizziness, confusion, and seizures.

Severe intoxication with salicylates can result in significant complications, including electrolyte imbalances and alterations in blood pH, which may lead to renal and liver dysfunction. Therefore, it is crucial to monitor the patient's renal function closely during the management of an overdose.

Currently, there is no specific antidote available for mesalamine overdose. The primary management strategy involves correcting fluid and electrolyte imbalances through appropriate intravenous therapy. Continuous assessment and supportive care are essential to ensure patient safety and recovery.

Nonclinical Toxicology

Mesalamine has been evaluated for its nonclinical toxicology profile through various studies in animal models.

Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year study conducted in Wistar rats, mesalamine did not result in an increased incidence of neoplastic lesions compared to controls when administered at doses up to 320 mg/kg/day, which is approximately 1.7 times the recommended human intra-rectal dose of CANASA based on body surface area. Mesalamine was found to be non-mutagenic in several assays, including the Ames test, the mouse lymphoma cell (TK +/-) forward mutation test, and the mouse micronucleus test. Additionally, no adverse effects on fertility or reproductive performance were observed in male and female rats at oral doses of mesalamine up to 320 mg/kg/day.

Animal Toxicology Toxicology studies involving mesalamine were performed in rats, mice, rabbits, and dogs, with the kidney identified as the primary target organ for toxicity. In rats, adverse renal effects were noted following a single oral dose of 600 mg/kg (approximately 3.2 times the recommended human intra-rectal dose of CANASA) and at intravenous doses exceeding 214 mg/kg (about 1.2 times the recommended human intra-rectal dose). A 13-week oral gavage toxicity study in rats revealed papillary necrosis and/or multifocal tubular injury in males at a dose of 160 mg/kg (about 0.86 times the recommended human intra-rectal dose) and in both sexes at 640 mg/kg (about 3.5 times the recommended human intra-rectal dose).

In a combined 52-week toxicity and 127-week carcinogenicity study in rats, degeneration of the kidneys and hyalinization of basement membranes and Bowman’s capsule were observed at oral doses of 100 mg/kg/day (approximately 0.54 times the recommended human intra-rectal dose) and higher. A 14-day rectal toxicity study in rabbits indicated that intra-rectal doses up to 800 mg/kg (about 8.6 times the recommended human intra-rectal dose) did not result in any adverse effects.

In a six-month oral toxicity study in dogs, doses of 80 mg/kg (about 1.4 times the recommended human intra-rectal dose) and above led to renal pathology similar to that observed in rats. Furthermore, a rectal toxicity study of mesalamine suppositories in dogs demonstrated that a dose of 166.6 mg/kg (approximately 3 times the recommended human intra-rectal dose) resulted in chronic nephritis and pyelitis. In a 12-month eye toxicity study in dogs, keratoconjunctivitis sicca (KCS) was noted at oral doses of 40 mg/kg (about 0.72 times the recommended human intra-rectal dose) and higher.

Postmarketing Experience

During post-approval use of CANASA and other mesalamine-containing products, various adverse reactions have been reported voluntarily or through surveillance programs. Due to the nature of these reports, which originate from a population of uncertain size, it is not always feasible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Reports include drug fever, fatigue, lupus-like syndrome, and medication residue.

Cardiac Disorders: Cases of myocarditis, pericarditis, and pericardial effusion have been documented.

Endocrine Disorders: Instances of nephrogenic diabetes insipidus have been noted.

Eye Disorders: Eye swelling has been reported.

Gastrointestinal Disorders: Adverse events include abdominal cramps, abdominal distension, anal pruritus, anorectal discomfort, constipation, discolored feces, flatulence, frequent bowel movements, gastrointestinal bleeding, mucus stools, nausea, painful defecation, pancreatitis, proctalgia, rectal discharge, rectal tenesmus, stomach discomfort, and vomiting.

Hepatic Disorders: Reports of cholestatic jaundice, hepatitis, jaundice, Kawasaki-like syndrome (including changes in liver enzymes), liver necrosis, and liver failure have been received.

Hematologic Disorders: Cases of agranulocytosis, aplastic anemia, and thrombocytopenia have been identified.

Neurological/Psychiatric Disorders: Reports include Guillain-Barre syndrome, peripheral neuropathy, transverse myelitis, and intracranial hypertension.

Renal Disorders: Instances of interstitial nephritis, renal failure, minimal change disease, and nephrolithiasis have been documented. Additionally, urine discoloration occurring ex-vivo has been observed due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Respiratory, Thoracic and Mediastinal Disorders: Hypersensitivity pneumonitis (including allergic alveolitis, eosinophilic pneumonitis, and interstitial pneumonitis) and pleuritis/pleurisy have been reported.

Skin and Subcutaneous Tissue Disorders: Adverse reactions include alopecia, erythema, erythema nodosum, pruritus, psoriasis, pyoderma gangrenosum, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

Urogenital Disorders: Reversible oligospermia has been reported.

Patient Counseling

Advise patients to read the FDA-approved patient labeling (Patient Information) thoroughly to understand the proper use and potential risks associated with CANASA. Instruct patients not to cut or break the suppository and to retain it for one to three hours, or longer if possible, to ensure optimal effectiveness.

Encourage patients to drink an adequate amount of fluids during treatment. If a dose of CANASA is missed, patients should administer it as soon as possible, unless it is almost time for the next dose. Patients should be informed not to use two CANASA suppositories at the same time to compensate for a missed dose.

Patients may notice that their urine becomes discolored reddish-brown while taking CANASA, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. Advise patients to monitor their urine flow and to report to their healthcare provider only if the urine is discolored upon leaving the body, before contact with any surface or water.

Inform patients that CANASA suppositories can stain direct contact surfaces, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. It is important to keep CANASA away from these surfaces to prevent staining.

Patients should be made aware that CANASA may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs, including NSAIDs. Periodic monitoring of renal function will be performed while they are on therapy. Advise patients to complete all blood tests ordered by their healthcare provider.

Educate patients on the signs and symptoms of hypersensitivity reactions. Instruct them to discontinue CANASA and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, inform them of the signs and symptoms of worsening liver function and advise them to report any such signs or symptoms to their healthcare provider. Additionally, inform patients about the signs and symptoms of severe cutaneous adverse reactions, instructing them to stop taking CANASA and report to their healthcare provider at the first appearance of such reactions or any other signs of hypersensitivity.

Advise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Instruct patients to drink an adequate amount of fluids during treatment to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine.

Finally, inform elderly patients and those taking azathioprine or 6-mercaptopurine about the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. Advise these patients to complete all blood tests ordered by their healthcare provider.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product below 25ºC (77ºF), although refrigeration is permissible. Care should be taken to keep the product away from direct heat, light, and humidity to maintain its integrity and efficacy. Proper handling and storage conditions are crucial to ensure the product remains effective throughout its shelf life.

Additional Clinical Information

Postmarketing experience has revealed a range of adverse effects associated with the medication. Patients may experience systemic reactions such as drug fever, fatigue, and lupus-like syndrome. Cardiac disorders reported include myocarditis, pericarditis, and pericardial effusion. Endocrine effects may manifest as nephrogenic diabetes insipidus, while ocular symptoms can include eye swelling.

Gastrointestinal disturbances are notable, with patients reporting symptoms such as abdominal cramps, constipation, gastrointestinal bleeding, and pancreatitis, among others. Hepatic disorders have included cholestatic jaundice, hepatitis, and liver failure. Hematologic issues such as agranulocytosis and thrombocytopenia have also been documented. Neurological and psychiatric disorders include Guillain-Barre syndrome and peripheral neuropathy. Renal complications may involve interstitial nephritis and renal failure, with urine discoloration noted due to contact with hypochlorite. Respiratory disorders such as hypersensitivity pneumonitis and pleuritis have been observed, alongside skin reactions including alopecia and severe conditions like SJS/TEN. Lastly, urogenital effects may include reversible oligospermia.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Canasa as submitted by Allergan, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)