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PRESCRIBING ALERT®

Dear Healthcare Professional,

At MPR we strive to bring you important drug information in a concise and timely fashion. In keeping with this goal, we are pleased to bring you this PRESCRIBING ALERT® about GIAZO® (balsalazide disodium), a product of Salix Pharmaceuticals, Inc.GIAZO is a new product that is the only twice daily, 5-aminosalicylic acid (5-ASA) ulcerative colitis (UC) therapy for men that works independently of pH levels to treat mild to moderate UC and help induce remission. GIAZO’s active ingredient, balsalazide, is a prodrug of mesalamine. Activation begins in the gut, where it is cleaved by bacterial azo-reduction and then works to diminish inflammation in the colon.1

GIAZO is indicated for the treatment of mildly to moderately active UC in male patients 18 years of age and older.1 In the clinical trial, significantly more male patients achieved clinical improvement, clinical remission, and mucosal healing compared to placebo. Also, fewer GIAZO patients discontinued due to an adverse reaction compared to those on placebo. GIAZO tablets are contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or their metabolites or to any of the components of GIAZO tablets.1 The most common adverse reactions occurring in at least 2% of male patients and at a rate greater than placebo in the clinical trial were anemia, diarrhea, pharyngolaryngeal pain, urinary tract infection, arthralgia, insomnia, and musculoskeletal pain.1

With its proven efficacy, tolerability profile, and pH-independent mechanism of action, GIAZO is an alternative route to remission for indicated male ulcerative colitis patients.More information about the use of GIAZO is available in the current edition of MPR.For your reference, please see the Important Safety Information on the next page and the complete Prescribing Information for GIAZO.

Sincerely,

Madonna Krawczyk, PharmD Director of Clinical Communications MPR Custom Programs

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REFERENCE

1. GIAZO [prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc.; 2012.

IMPORTANT SAFETY INFORMATION ABOUT GIAZOGIAZO® (balsalazide disodium) tablets are contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or their metabolites or to any of the components of GIAZO tablets.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. Symptoms include cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache, and rash. Observe patients closely for worsening of their ulcerative colitis symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with GIAZO.It is recommended that patients have an evaluation of renal function prior to initiation of GIAZO therapy and periodically while on therapy. Exercise caution when using GIAZO in patients with known renal dysfunction or a history of renal disease.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, use caution and consider liver function testing when administering GIAZO to patients with liver disease.Effectiveness of GIAZO in female patients was not demonstrated in clinical trials. Safety and effectiveness of GIAZO beyond 8 weeks have not been established.Advise patients who need to control sodium intake that the recommended dosing of GIAZO (6.6 g/day) provides about 756 mg of sodium per day.The most common adverse reactions occurring in at least 2% of male patients and at a rate greater than placebo in the clinical study were anemia, diarrhea, pharyngolaryngeal pain, urinary tract infection, arthralgia, insomnia, and musculoskeletal pain.Please see the complete Prescribing Information for GIAZO.

BZ 13/24 2/13

√ MPR PRESCRIBING ALERT

[√] �Twice�daily�GIAZO�is�the�only�pH-independent�UC�therapy�for�male�patients1

■ Targeted delivery to the gut

■ Activation begins in the gut, where GIAZO is cleaved by bacterial azo-reduction

■ Works to diminish inflammation in the colon

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

GIAZO tablets are contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or their metabolites or to any of the components of GIAZO tablets.

(continued on next page)

Please see the Important Safety Information and the complete Prescribing Information.

GIAZO®(balsalazide disodium) tablets℞

Company: Salix Pharmaceuticals, Inc.Pharmacologic class: Aminosalicylate.Active Ingredients: Balsalazide disodium (prodrug of mesalamine) 1.1 g tablets.Indications: ≥18yrs: Mildly to moderately active ulcerative colitis (UC) in male patients.Adults: Three tablets twice daily (6.6 g/day) with or without food for 8 weeks.Children: <18yrs: not recommended.Contraindications: Hypersensitivity to salicylates, aminosalicylates or their metabolites, or any component of GIAZO tablets

Warnings & Precautions: Observe patients closely for worsening of UC symptoms; discontinue in acute intolerance syndrome. Renal dysfunction or history of renal disease; assess renal function at the beginning and periodically during treatment. Patients with liver disease; consider liver function testing.Special Populations: Pregnancy (Cat.B). Nursing mothers: use caution. Elderly (monitor CBCs).Adverse reactions: Anemia, diarrhea, pharyngolaryngeal pain, urinary tract infection.How Supplied: Tablets—180/bottle

MPR PRESCRIBING ALERT

[√] �GIAZO®�(balsalazide�disodium)�achieved�its�primary�efficacy�endpoint

■ Significantly more male patients on GIAZO achieved clinical improvement1

[√] �GIAZO�achieved�statistically�significant�results�in�clinical�remission

■ 35% of male patients on GIAZO achieved clinical remission vs 13% on placebo at 8 weeks1

[√] �GIAZO�achieved�statistically�significant�results�in�mucosal�healing

■ 52% of male patients on GIAZO achieved mucosal healing vs 20% on placebo at 8 weeks1

It is recommended that patients have an evaluation of renal function prior to initiation of GIAZO therapy and periodically while on therapy. Exercise caution when using GIAZO in patients with known renal dysfunction or a history of renal disease.

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, use caution and consider liver function testing when administering GIAZO to patients with liver disease.

(continued on next page)

Please see the Important Safety Information and the complete Prescribing Information.

PROPORTION OF MALE PATIENTS WITH CLINICAL IMPROVEMENT AT WEEK 8

Study Design: Based on an 8-week, randomized, double-blind, placebo-controlled, multicenter trial in 250 adults with mildly to moderately active ulcerative colitis, of which 121 were male. Disease activity was assessed using a modified Mayo Disease Activity Index (MMDAI),1 which was a sum of 4 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 2.1

Source: GIAZO [prescribing information].1

Clinical improvement

vsNEARLY 6 out of 10

MALE PATIENTS ON GIAZO ACHIEVED

CLINICAL IMPROVEMENT

57%

P=0.0001

ONLY 2 out of 10 MALE PATIENTS ON

PLACEBO ACHIEVED CLINICAL IMPROVEMENT

20%

[√] �GIAZO®�(balsalazide�disodium)�has�twice�daily�dosing

■ Male patients should take three tablets with or without food, for up to 8 weeks1

[√] �Clinical�trials�demonstrated�proven�tolerability�with�GIAZO

■ When used as directed, the majority of adverse reactions were mild to moderate in severity1

[√] �Low�discontinuation�rate�in�GIAZO�patients

■ In the clinical trial, fewer GIAZO patients (10%) discontinued due to an adverse reaction compared to those on placebo (13%)1

Advise patients who need to control sodium intake that the recommended dosing of GIAZO (6.6 g/day) provides about 756 mg of sodium per day.

The most common adverse reactions occurring in at least 2% of male patients and at a rate greater than placebo in the clinical study were anemia, diarrhea, pharyngolaryngeal pain, urinary tract infection, arthralgia, insomnia, and musculoskeletal pain.

(continued on next page)

Please see the Important Safety Information and the complete Prescribing Information.

DOSAGE AND ADMINISTRATION

Source: GIAZO [prescribing information].1

MOST COMMON ADVERSE EVENTS COMPARED WITH PLACEBO

Adverse ReactionsGIAZO 6.6 g/day

(N=82)Placebo (N=37)

Anemia 3.7% 0%

Diarrhea 3.7% 0%

Pharyngolaryngeal Pain 3.7% 0%

Urinary Tract Infection 3.7% 0%

Arthralgia 2.4% 0%

Insomnia 2.4% 0%

Musculoskeletal Pain 2.4% 0%

Rates above are reflective of adverse reactions experienced by at least 2% of GIAZO-treated male patients and at a rate greater than placebo.1

Source: GIAZO [prescribing information].1

twice-daily dosingTHREE TABLETS TAKEN WITH OR WITHOUT FOOD1 BID AM & PM

MPR PRESCRIBING ALERT

REFERENCE 1. GIAZO [prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc.; 2012

GIAZO® (balsalazide disodium) is indicated for the treatment of mildly to moderately active ulcerative colitis in male patients 18 years of age and older.

IMPORTANT�SAFETY�INFORMATION�ABOUT�GIAZOGIAZO tablets are contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or their metabolites or to any of the components of GIAZO tablets.

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. Symptoms include cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache, and rash. Observe patients closely for worsening of their ulcerative colitis symptoms while on treat-ment. If acute intolerance syndrome is suspected, promptly discontinue treatment with GIAZO.

It is recommended that patients have an evaluation of renal function prior to initiation of GIAZO therapy and periodically while on therapy. Exercise caution when using GIAZO in patients with known renal dysfunction or a history of renal disease.

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, use caution and con-sider liver function testing when administering GIAZO to patients with liver disease.

Effectiveness of GIAZO in female patients was not demonstrated in clinical trials. Safety and effectiveness of GIAZO beyond 8 weeks have not been established.

Advise patients who need to control sodium intake that the recommended dosing of GIAZO (6.6 g/day) provides about 756 mg of sodium per day.

The most common adverse reactions occurring in at least 2% of male patients and at a rate greater than placebo in the clinical study were anemia, diarrhea, pharyngolaryngeal pain, urinary tract infection, arthralgia, insomnia, and musculoskeletal pain.

Please see the complete Prescribing Information.

BZ 13/24 2/13