Balsalazide Disodium
FDA Label NDC 64380-209

Balsalazide disodium tablets is indicated for the treatment of mildly to moderately active ulcerative colitis in male patients 18 years of age and older.

Limitations of Use:

• Effectiveness of balsalazide disodium tablets in the treatment of female patients was not demonstrated in clinical trials [seeClinical Trials (14)].
• Safety and effectiveness of balsalazide disodium tablets therapy beyond 8 weeks have not been established.

The recommended dosage is 3.3 g (three 1.1 g tablets) orally twice daily with or without food [see Clinical Pharmacology (12.3)] for up to 8 weeks.

Drink an adequate amount of fluids [see Warnings and Precautions (5.7)].

Balsalazide disodium tablets is available as yellow colored, oval shaped, biconvex, film-coated tablets debossed with "P" on one side and "840" on other side.

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

Renal impairment, including minimal change disease, acute and chronic interstitial nephritis and renal failure, has been reported in patients given products that release mesalamine in the gastrointestinal tract. Evaluate renal function prior to initiation of balsalazide disodium tablets and periodically while on therapy. Evaluate the risks and benefits of using balsalazide disodium tablets in patients with known renal impairment, a history of renal disease or taking nephrotoxic drugs [see Drug Interactions (7.2), Use in Specific Populations (8.6)].

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. In controlled clinical trials with balsalazide disodium tablets in adults with ulcerative colitis, 7% of male patients reported exacerbation of the symptoms of ulcerative colitis. 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 tablets.

Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to balsalazide disodium tablets 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 tablets if an alternative etiology for the signs and symptoms cannot be established.

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 balsalazide disodium tablets in patients with known liver impairment.

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) have been reported with the use of mesalamine, the active moiety of balsalazide disodium tablets [see Adverse Reactions (6.2)]. Discontinue balsalazide disodium tablets at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

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.

Cases of nephrolithiasis have been reported with the use of mesalamine, the active moiety of balsalazide disodium tablets, 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 tablets.

Each 1.1 g tablet of balsalazide disodium tablets contains 126 mg of sodium. The recommended dosage of balsalazide disodium tablets (6.6 g/day) provides about 756 mg of sodium per day. Take the sodium content of balsalazide disodium tablets into consideration when administering to patients on a sodium-restricted diet or those at risk for developing congestive heart failure.

Use of balsalazide disodium tablets, 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 mesalamine's main metabolite, N acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective assay for normetanephrine.

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

• Renal Impairment [ see Warnings and Precautions (5.1)]
• Mesalamine-Induced Acute Intolerance Syndrome [ seeWarnings and Precautions (5.2)]
• Hypersensitivity Reactions [seeWarnings and Precautions (5.3)]
• Hepatic Failure [seeWarnings and Precautions (5.4)]
• Severe Cutaneous Adverse Reactions [seeWarnings and Precautions (5.5)]
• Photosensitivity [ seeWarnings and Precautions (5.6)]
• Nephrolithiasis [seeWarnings and Precautions (5.7)]

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 data described below reflect exposure of balsalazide disodium in 565 ulcerative colitis patients with mildly to moderately active disease. Balsalazide disodium was evaluated in one placebo-controlled trial (168 treated with balsalazide disodium), one active-controlled trial (210 treated with balsalazide disodium); and a subset of these patients also participated in an uncontrolled, open-label, extension study (additional 187 treated with balsalazide disodium). The population studied had a mean age of 43.1 (range: 18-80) years; approximately 94% of patients were < 65 years old, 49% were male, and 84% were white.

In the placebo-controlled trial, the most common adverse reactions with balsalazide disodium in male patients were headache, nasopharyngitis, anemia, diarrhea, fatigue, pharyngolaryngeal pain, and urinary tract infection. 10% of patients in the balsalazide disodium group and 13% of patients in the placebo group discontinued treatment due to an adverse reaction. The majority of adverse reactions were mild to moderate in severity. The most common serious adverse reactions in both the placebo and balsalazide disodium groups were gastrointestinal disorders, which were mainly associated with symptoms of ulcerative colitis.

Adverse reactions occurring in at least 2% of male patients and at a rate numerically higher than placebo in the placebo-controlled trial are listed in Table 1.

Table 1: Adverse Reactions Experienced by at Least 2% of Balsalazide Disodium –Treated Male Patients and at a Rate Numerically Greater than Placebo in a Placebo-Controlled Trial

Data collected from all three trials (placebo-controlled, active-controlled, and open-label) showed that female patients reported adverse reactions more frequently than did male patients (76% and 66%, respectively).

The following adverse reactions, presented by body system, were reported by less than 1% of balsalazide disodium-treated ulcerative colitis patients in controlled trials.

Cardiovascular and Vascular: increased blood pressure, increased heart rate

Dermatological: erythema nodosum, rash

Respiratory, Thoracic and Mediastinal Disorders: dyspnea

Gastrointestinal Disorders: abdominal pain, constipation, defecation urgency, diarrhea, dry mouth, hard feces, flatulence, gastroesophageal reflux disease, vomiting

Hepatobiliary Disorders: increased aspartate aminotransferase

Infections and Infestations: gastroenteritis, upper respiratory infection

Musculoskeletal and Connective Tissue Disorders: arthralgia, back pain, myalgia

Nervous System Disorders: dizziness, lethargy

General Disorders and Administrative Site Disorders: face edema, fatigue, malaise, pain, pyrexia, swelling

The following adverse reactions have been identified during postapproval use of balsalazide, or other products which contain or are metabolized to mesalamine. 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.

Cardiovascular and Vascular: myocarditis, pericarditis, vasculitis [see Warnings and Precautions (5.3)]

Respiratory: alveolitis, pleural effusion, pneumonia (with and without eosinophilia), pleurisy/pleuritis

Gastrointestinal: pancreatitis

Renal: interstitial nephritis, renal failure, nephrolithiasis [see Warnings and Precautions (5.1, 5.7)]. Urine discoloration occurring ex-vivo caused by contact of mesalamine, including inactive metabolite, with surfaces or

water treated with hypochlorite containing bleach.

Hepatobiliary Disorders: elevated liver enzymes (AST, ALT, GGT, LDH, alkaline phosphatase), elevated bilirubin, jaundice, cholestatic jaundice, cirrhosis, hepatocellular damage including liver necrosis and liver failure, Kawasaki-like syndrome including hepatic dysfunction. Some of these cases were fatal [see Warnings and Precautions (5.4)]

Dermatological: alopecia, pruritus, SJS/TEN, DRESS, and AGEP [see Warnings and Precautions (5.5)]

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)].

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 and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.

Use of balsalazide disodium, 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.

Risk Summary

Published data from meta-analyses, cohort studies and case series on the use of mesalamine, the active moiety of balsalazide disodium, during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are adverse effects on maternal and fetal outcomes associated with ulcerative colitis in pregnancy (see Clinical Considerations). In animal reproduction studies, there were no adverse developmental effects observed after oral administration of balsalazide disodium in pregnant rats and rabbits during organogenesis at doses up to 2.4 and 4.7 times, respectively, the maximum recommended human dose (MRHD) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations

Disease-associated maternal and embryo/fetal risk

Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Data

Human Data

Published data from meta-analyses, cohort studies and case series on the use of mesalamine, the active moiety of balsalazide disodium, during early pregnancy (first trimester) and throughout pregnancy have not reliably informed an association of mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. There is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk in major congenital malformations, including cardiac malformations. Published epidemiologic studies have important methodological limitations which hinder interpretation of the data, including inability to control for confounders, such as underlying maternal disease, and maternal use of concomitant medications, and missing information on the dose and duration of use for mesalamine products.

Animal Data

Reproduction studies in rats and rabbits following administration of balsalazide disodium during organogenesis at oral doses up to 2 g/kg/day, equivalent to 2.5 and 4.9 times the recommended human dose, respectively, based on body surface area, revealed no evidence of no adverse embryofetal developmental effects due to balsalazide disodium.

Risk Summary

Data from published literature report the presence of mesalamine and its metabolite, N acetyl-5 aminosalicylic acid, in human milk in small amounts with relative infant doses (RID) of 0.1% or less for mesalamine (see Data). There are case reports of diarrhea in breastfed infants exposed to mesalamine (see Clinical Considerations). There is no information on the effects of the drug on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of balsalazide disodium to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for balsalazide disodium and any potential adverse effects on the breastfed child from balsalazide disodium or from the underlying maternal condition.

Clinical Considerations

Advise the caregiver to monitor breastfed infants for diarrhea.

Data

In published lactation studies, maternal mesalamine doses from various oral and rectal mesalamine formulations and products ranged from 500 mg to 4.8 g daily. The average concentration of mesalamine in milk ranged from non-detectable to 0.5 mg/L. The average concentration of N-acetyl-5 aminosalicylic acid in milk ranged from 0.2 to 9.3 mg/L. Based on these concentrations, estimated infant daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day (RID 0 to 0.1%) of mesalamine and 0.03 to 1.4 mg/kg/day of N-acetyl-5-aminosalicylic acid.

Safety and effectiveness of balsalazide disodium in pediatric patients have not been established.

Clinical trials of balsalazide disodium did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently than younger subjects. Reports from uncontrolled clinical studies and postmarketing reporting systems suggested a higher incidence of blood dyscrasias, i.e., neutropenia and pancytopenia, in patients who were 65 years or older compared to younger patients taking mesalamine-containing products. Balsalazide disodium is converted into mesalamine in the colon. Monitor complete blood cell counts and platelet counts in elderly patients during treatment with balsalazide disodium. In general, consider the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients when prescribing balsalazide disodium [see Use in Specific Populations (8.6)].

Mesalamine is known to be substantially excreted by the kidney, and the risk of adverse reactions to balsalazide disodium, which is converted to mesalamine, may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on balsalazide disodium therapy. Monitor patients with known renal impairment or history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions [see Warnings and Precautions (5.1), Adverse Reactions (6.2), Drug Interactions (7.1)].

Balsalazide Disodium 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 intoxication with salicylates may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) damage. There is no specific antidote for balsalazide overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption. Proper medical care should be sought immediately with appropriate supportive care, including the possible use of emesis, cathartics, and activated charcoal to prevent further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.

Each balsalazide disodium tablet contains 1.1 g of balsalazide disodium, an orally available prodrug that is enzymatically cleaved to produce mesalamine (5-aminosalicylic acid, 5-ASA), an anti-inflammatory drug. Balsalazide disodium has the chemical name (E)-5-[[-4-[[(2-carboxyethyl) amino]carbonyl] phenyl]azo]-2-hydroxybenzoic acid, disodium salt, dihydrate. Its structural formula is:

Balsalazide-struct.jpg (Cca5af28 Ed30 4158 804f B893e9a878b4 01)

Molecular Weight: 437.32

Molecular Formula: C₁₇H₁₃N₃O₆Na₂•2H₂O

Balsalazide disodium is a stable, odorless, yellow to orange crystalline powder. It is insoluble in acid, but soluble at a pH of at least 4.5. It is freely soluble in water and isotonic saline, sparingly soluble in methanol and ethanol, and practically insoluble in all other organic solvents.

Inactive Ingredients: Each tablet contains d&c yellow#10 aluminum lake, fd&c yellow#6/sunset yellow fcf aluminum lake, hypromellose, macrogol, magnesium stearate, polydextrose, titanium dioxide and triacetin. The sodium content of each tablet is approximately 126 mg

Balsalazide is a prodrug of mesalamine (5-aminosalicylic acid, 5-ASA). The mechanism of action of 5-ASA is not fully understood, but appears to be a local anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with ulcerative colitis, and it is possible that 5-ASA diminishes inflammation by blocking production of arachidonic acid metabolites in the colon.

Following oral administration, balsalazide is cleaved by azoreductases produced by anaerobic bacteria found in the gut, to release equimolar quantities of 5-ASA, the active moiety, and 4-aminobenzoyl-ß-alanine (4-ABA), a carrier moiety. Both of these moieties are N-acetylated to form N-Ac-5-ASA and N-Ac-4-ABA, respectively.

Absorption

After single-dose administration of 3.3 g balsalazide disodium tablets in 18 healthy subjects, the median time of peak plasma concentration (T_max) was 0.5 hr for balsalazide, while the median T_max was 12 hr for both 5-ASA and N-Ac-5-ASA (Table 2). Pharmacokinetic parameters exhibited high variability, with %CV ranging from 31% to 67% for AUC and from 27% to 68% for C_max.

Pharmacokinetics were also estimated in healthy subjects after repeated doses of 3.3 g balsalazide disodium tablets every 12 hours for 7 days. After multiple doses, steady-state was achieved after about 3 days for balsalazide and all metabolites. The AUC and C_max were the highest for N-Ac-5-ASA, followed by 5-ASA and balsalazide. There was minimal accumulation of balsalazide, as suggested by a 1.2-fold increase in AUC; however, a relatively larger increase in the systemic exposure to metabolites was observed at steady-state. The accumulation ratios based on AUC for the metabolites were 6.1 for 5-ASA, 3.6 for N-Ac-5-ASA, 4.8 for 4-ABA, and 3.6 for N-Ac-4-ABA.

Table 2: Pharmacokinetic Parameters for Balsalazide and Metabolites (5-ASA and N-Ac-5-ASA) Following Single-and Repeated-Doses (every 12 hours) of 3.3 g Balsalazide Disodium as Balsalazide Disodium Tablets (N=18)

a Expressed as median and range.

b N=17

Effect of food

After administration of single dose of 3.3 g (3 × 1.1 g tablets) of balsalazide disodium tablets with a high-fat meal in healthy subjects, the AUC of balsalazide was unaffected compared to fasted administration, but the presence of food reduced both peak concentrations and AUC of the metabolites 5-ASA and N-Ac-5-ASA. A high fat meal increased the median T_max for balsalazide from 0.5 to 2 hours; for 5-ASA from 12 to 24 hours; and for N-Ac-5-ASA from 12 to 24 hours. Under fed conditions, the mean C_max was reduced by 44% for balsalazide, 65% for 5-ASA, and 48% for N-Ac-5-ASA. No significant changes were observed for AUC_{0 to ∞} for balsalazide; however, AUC_{0 to ∞} was reduced for 5-ASA by 46% and for N-Ac-5-ASA by 17% [see Dosage and Administration (2)].

Distribution

The binding of balsalazide to human plasma proteins was ≥ 99%; 5-ASA and N-Ac-5-ASA were 43% and 78% bound, respectively, to plasma proteins.

Elimination

Metabolism

Following oral administration, balsalazide is cleaved by bacterial azoreduction to release equimolar quantities of 5-ASA, the active moiety, and 4-ABA, a carrier moiety. Mesalamine (5-ASA) and 4-ABA are further acetylated to N-Ac-5-ASA and N-Ac-4-ABA, respectively in the intestinal mucosa and liver. The terminal half-life was 1.9 h for balsalazide, 9.5 h for 5-ASA, and 10.5 h for N-Ac-5-ASA.

Excretion

At steady-state following administration of repeated doses of 3.3 g balsalazide disodium tablets every 12 hours in healthy volunteers, the combined % of dose excreted in urine for balsalazide and its metabolites over 12 hours was 23%. The mean % of dose excreted in urine over 12 hours was 0.16% for balsalazide, 4.6% for 5-ASA, 15.6% for N-Ac-5-ASA, 0.40% for 4-ABA, and 1.8% for N-Ac-4-ABA.

Drug Interaction Studies

Based on in vitro studies, balsalazide and its metabolites [5-aminosalicylic acid (5 ASA), N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), 4-aminobenzoyl-ß-alanine (4-ABA), and N-acetyl-4-aminobenzoyl ß-alanine (N-Ac-4-ABA)] are not expected to inhibit the metabolism of other drugs that are substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5.

In a 24-month rat (Sprague Dawley) carcinogenicity study, oral (dietary) balsalazide disodium at doses up to 2 g/kg/day was not tumorigenic. For a 50 kg person of average height this dose represents 2.5 times the recommended human dose on a body surface area basis. Balsalazide disodium was not genotoxic in the following in vitro or in vivo tests: Ames test, human lymphocyte chromosomal aberration test, and mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, or mouse micronucleus test. However, it was genotoxic in the in vitro Chinese hamster lung cell (CH V79/HGPRT) forward mutation test.

The compound 4-aminobenzoyl-ß-alanine, a metabolite of balsalazide disodium, was not genotoxic in the Ames test and the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test but was positive in the human lymphocyte chromosomal aberration test. N-acetyl-4-aminobenzoyl-ß-alanine, a conjugated metabolite of balsalazide disodium, was not genotoxic in Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, or the human lymphocyte chromosomal aberration test. Balsalazide disodium at oral doses up to 2 g/kg/day, 2.5 times the recommended human dose based on body surface area, was found to have no effect on fertility and reproductive performance in rats.

A double-blind, placebo-controlled, multi-center trial was conducted in 250 adult patients with mildly to moderately active ulcerative colitis. The trial population was primarily white (84%), had a mean age of 44 years (7% age 65 years or older), and 49% were men. Disease activity was assessed using a modified Mayo Disease Activity Index (MMDAI), which was a sum of four subscores (bowel frequency, rectal bleeding, endoscopic appearance, and physician's global assessment), each ranging from 0 to 3, with higher scores indicating worse disease. The median baseline MMDAI score was 8 and the median baseline rectal bleeding subscore was 2. Patients were randomized 2:1 to receive 8 weeks of treatment with either balsalazide disodium tablets 3.3 g twice daily or placebo.

The primary efficacy endpoint was the proportion of patients that achieved clinical improvement and improvement in the rectal bleeding subscale of the MMDAI at the end of 8 weeks of treatment. Clinical Improvement was defined as having both a ≥ 3 point improvement from baseline in the MMDAI score and a ≥ 1 point improvement from baseline in the rectal bleeding subscore. Two key secondary efficacy endpoints were the proportion of patients with Clinical Remission and Mucosal Healing at the end of 8 weeks of treatment. Clinical Remission was defined as a score of 0 for rectal bleeding and a combined score of ≤ 2 for bowel frequency and physician's assessment using the MMDAI subscale; the endoscopic sub-score was not considered in this definition. Mucosal Healing was defined as an endoscopy/sigmoidoscopy score of 0 or 1, where a score of 1 could include signs of erythema or decreased vascular pattern; by definition, the presence of friability indicated a score of 2 or 3.

After 8 weeks of treatment, the proportion of patients who met the definition of Clinical Improvement was greater for the balsalazide disodium tablets-treated group compared to the placebo group (Table 3).

Table 3: Proportion of Patients with Clinical Improvement* at Week 8 for the Total Population and by Gender Subgroups

* Clinical Improvement: ≥ 3 improvement in MMDAI score and ≥ 1 point improvement in rectal bleeding.

These differences were statistically significant in the overall population; however, these effects were entirely driven by the results in the male subpopulation. With adjustment for multiplicity, statistically significant differences were also seen in the male patients for Clinical Remission (35% with balsalazide disodium tablets vs. 13% for placebo) and for Mucosal Healing (52% with balsalazide disodium tablets vs. 20% for placebo). Effectiveness of balsalazide disodium tablets was not demonstrated in the female subpopulation in the clinical trial.

How Supplied

Balsalazide disodium tablets are available as yellow colored, oval shaped, biconvex, film-coated tablets debossed with "P" on one side and "840" on other side.

NDC 64380-209-01 Bottles of 180 tablets

NDC 64380-209-02 Bottles of 500 tablets

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° and 30°C (59° and 86°F). See USP Controlled Room Temperature.

Renal Impairment

Inform patients that balsalazide disodium tablets may decrease their renal function, especially if they have known renal impairment or are taking nephrotoxic drugs, including NSAIDs, and 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 [see Warnings and Precautions (5.1), Drug Interactions (7.1)].

Mesalamine-Induced Acute Intolerance Syndrome and Other Hypersensitivity Reactions

Inform patients of the signs and symptoms of hypersensitivity reactions. Instruct patients to stop taking balsalazide disodium tablets and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome (cramping, abdominal pain, bloody diarrhea, fever, headache, and rash) or other symptoms suggestive of mesalamine-induced hypersensitivity [see Warnings and Precautions (5.2, 5.3)].

Hepatic Failure

Inform patients with known liver disease of the signs and symptoms of worsening liver function and advise them to report to their healthcare provider if they experience such signs or symptoms [see Warnings and Precautions (5.4)].

Severe Cutaneous Adverse Reactions

Inform patients of the signs and symptoms of severe cutaneous adverse reactions. Instruct patients to stop taking balsalazide disodium tablets and report to their healthcare provider at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity [see Warnings and Precautions (5.5)].

Photosensitivity

Advise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors [see Warnings and Precautions (5.6)].

Nephrolithiasis

Instruct patients to drink an adequate amount of fluids during treatment in order to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone (e.g., severe side or back pain, blood in the urine) [see Warnings and Precautions (5.7)].

Sodium Content of Balsalazide Disodium Tablets

Inform patients on a sodium-restricted diet or patients at risk of developing congestive heart failure of the sodium content of balsalazide disodium tablets (126 mg per tablet) [see Warnings and Precautions (5.8)].

Blood Disorders

Inform elderly patients and those taking azathioprine or 6-mercaptopurine of the risk for blood disorders and the need for periodic monitoring of complete blood cell counts and platelet counts while on therapy. Advise patients to complete all blood tests ordered by their healthcare provider [see Drug Interactions (7.2), Use in Specific Populations (8.5)].

Administration

Instruct patients:

• Balsalazide disodium tablets can be taken with or without food [see Dosage and Administration (2)].
• Drink an adequate amount of fluids.

Urine Discoloration

Advise patients that urine may become discolored reddish-brown while taking balsalazide disodium tablets when it comes in contact with surfaces or water treated with hypochlorite-containing bleach. If discolored urine is observed, advise patients to observe their urine flow. Report to the healthcare provider only if urine is discolored on leaving the body, before contact with any surface or water (e.g., in the toilet).

Distributed by:

Strides Pharma Inc.

East Brunswick, NJ 08816

Revised: 10/2023