Balsalazide disodium Capsule

Balsalazide disodium capsules are indicated for the treatment of mildly to moderately active ulcerative colitis in patients 5 years of age and older.

Limitations of Use:

Safety and effectiveness of balsalazide disodium capsules beyond 8 weeks in pediatric patients 5 years to 17 years of age and 12 weeks in adults have not been established.

Balsalazide disodium capsules are contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the components of balsalazide disodium capsules or balsalazide metabolites [see Warnings and Precautions ( 5.3), Adverse Reactions ( 6.2), Description ( 11)] .

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of mesalamine, the active moiety of balsalazide disodium capsules [see Adverse Reactions ( 6.2)].

Discontinue balsalazide disodium capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

The following clinically significant adverse reactions are described elsewhere in labeling:

1. Renal Impairment [see Warnings and Precautions ( 5.1)]
2. Mesalamine-Induced Acute Intolerance Syndrome [see Warnings and Precautions ( 5.2)]
3. Hypersensitivity Reactions [see Warnings and Precautions ( 5.3)]
4. Hepatic Failure [see Warnings and Precautions ( 5.4)]
5. Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5)]
6. Upper Gastrointestinal Tract Obstruction [see Warnings and Precautions ( 5.6)]
7. Photosensitivity [see Warnings and Precautions ( 5.7)]
8. Nephrolithiasis [see Warnings and Precautions ( 5.8)]

• Renal Impairment: Assess renal function at the beginning of treatment and periodically during treatment. Evaluate the risks and benefits in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function. Discontinue if renal function deteriorates. (5.1, 7.1, 8.6)

• Mesalamine-Induced Acute Intolerance Syndrome: Symptoms may be difficult to distinguish from an exacerbation of ulcerative colitis; monitor for worsening symptoms; discontinue treatment if acute intolerance syndrome is suspected. (5.2)

• Hypersensitivity Reactions, including Myocarditis and Pericarditis

: Evaluate patients immediately and discontinue if a hypersensitivity reaction is suspected. (5.3)

• Hepatic Failure

: Evaluate the risks and benefits in patients with known liver impairment. (5.4)

• Severe Cutaneous Adverse Reactions

: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation (5.5)

• Upper Gastrointestinal Tract Obstruction

: Avoid in patients with pyloric stenosis or other organic or functional obstruction. (5.6)

• Photosensitivity

: Advise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. (5.7)

• Nephrolithiasis

: Stones containing mesalamine, the active moiety in balsalazide disodium capsules, are undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment with balsalazide disodium capsules. (5.8)

• Interference with Laboratory Tests

: Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection. (5.9) 5.1 Renal Impairment

Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients given products such as balsalazide disodium capsules that release mesalamine into the gastrointestinal tract. Evaluate renal function prior to initiation of balsalazide disodium capsules and periodically while on therapy. Evaluate the risks and benefits of using balsalazide disodium capsules in patients with known renal impairment, a history of renal disease or taking nephrotoxic drugs. Discontinue balsalazide disodium capsules if renal function deteriorates while on therapy

[see Drug Interactions (7.1), Use in Specific Populations (8.6)]. 5.2 Mesalamine-Induced Acute Intolerance Syndrome

Balsalazide is converted to mesalamine, which has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache, and rash. Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with balsalazide disodium capsules. 5.3 Hypersensitivity Reactions

Some patients have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to balsalazide disodium capsules or to other compounds that contain or are converted to mesalamine. Mesalamine-induced hypersensitivity reactions may present as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis and hematologic abnormalities. Evaluate patients immediately if signs or symptoms of a hypersensitivity reaction are present. Discontinue balsalazide disodium capsules if an alternative etiology for the signs and symptoms cannot be established. 5.4 Hepatic Failure

There have been reports of hepatic failure in patients with pre-existing liver disease who have been administered mesalamine. Because balsalazide is converted to mesalamine, evaluate the risks and benefits of using balsalazide disodium capsules in patients with known liver impairment. 5.5 Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of mesalamine, the active moiety of balsalazide disodium capsules

[see Adverse Reactions (6.2)].

Discontinue balsalazide disodium capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Upper Gastrointestinal Tract Obstruction

Pyloric stenosis or other organic or functional obstruction in the upper gastrointestinal tract may cause prolonged gastric retention of balsalazide disodium capsules, which would delay mesalamine release in the colon. Avoid balsalazide disodium capsules in patients at risk of upper gastrointestinal tract obstruction. 5.7 Photosensitivity

Patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema have reported more severe photosensitivity reactions. Advise patients to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. 5.8 Nephrolithiasis

Cases of nephrolithiasis have been reported with the use of mesalamine, the active moiety of balsalazide disodium capsules, including stones with 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment with balsalazide disodium capsules. 5.9 Interference with Laboratory Tests

Use of balsalazide disodium capsules, which is converted to 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 the main metabolite of mesalamine, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective assay for normetanephrine.

Adults:

The recommended dosage in adults is 2.25 g (three 750 mg capsules) three times daily for up to 8 weeks. Some patients in the adult clinical trials required treatment for up to 12 weeks.

Pediatric Patients 5 Years to 17 Years of Age:

The recommended dosage in pediatric patients 5 years to 17 years of age is either:

1. 2.25 g (three 750 mg capsules) three times daily for up to 8 weeks;
2. OR:
3. 750 mg (one capsule) three times daily for up to 8 weeks.

Use of balsalazide disodium capsules in the pediatric population for more than 8 weeks has not been evaluated in clinical trials [see Clinical Studies ( 14)] .

Balsalazide Disodium Capsules, USP are available as light orange opaque capsules containing 750 mg balsalazide disodium, USP and "54 795" printed in black ink on the cap and body, containing a yellow-orange powder.

• Nephrotoxic Agents including NSAIDs

: Increased risk of nephrotoxicity; monitor for changes in renal function and mesalamine-related adverse reactions. (7.1)

• Azathioprine or 6-Mercaptopurine

: Increased risk of blood disorders; monitor complete blood cell counts and platelet counts. (7.2) 7.1 Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs

The concurrent use of mesalamine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs), may increase the risk of renal reactions. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions [see Warnings and Precautions (5.1)]. 7.2 Azathioprine or 6-Mercaptopurine

The concurrent use of mesalamine with azathioprine or 6-mercaptopurine and/or any other drugs known to cause myelotoxicity may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of balsalazide disodium capsules and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts. 7.3 Interference With Urinary Normetanephrine Measurements

Use of balsalazide disodium capsules, which is converted to mesalamine, may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection [see Warnings and Precautions (5.9)]. Consider an alternative, selective assay for normetanephrine.