balsalazide (Rx)

>10%

Headache (15% peds)

Abdominal pain (13% peds )

Vomiting (10% peds)

1-10% (Adults)

Headache (8%)

Abdominal pain (6%)

Nausea (5%)

Diarrhea (5%)

Respiratory infection (4%)

Arthralgia (4%)

Vomiting (4%)

Fatigue (2%)

Insomnia (2%)

Cough (2%)

Pharyngitis (2%)

Rhinitis (2%)

Dyspepsia (2%)

Anorexia (2%)

Flatulence (2%)

Fever (2%)

Constipation (1%)

Cramps (1%)

Ulcerative colitis exacerbation (1%)

Flu like syndrome (1%)

Myalgia (1%)

UTI (1%)

Xerostomia (1%)

1-10% (Pediatrics)

Diarrhea (9%)

Fever (6%)

Ulcerative colitis exacerbation (6%)

Pharyngitis (6%)

Fatigue (4%)

Flu like syndrome (4%)

Nausea (4%)

Hematochezia (4%)

Cough (3%)

Dysmenorrhea (3%)

Stomatitis (3%)

Postmarketing Reports

Cardiovascular and vascular: Myocarditis, pericarditis, vasculitis

Respiratory: Alveolitis, pleural effusion, pneumonia (with and without eosinophilia)

Gastrointestinal: Pancreatitis

Renal: Interstitial nephritis, renal failure, nephrolithiasis

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

Contraindications

Hypersensitivity to salicylates, balsalazide, mesalamine

Cautions

Risk of exacerbation of ulcerative colitis

Assess renal function at beginning of treatment and periodically during treatment; evaluate risks and benefits in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function.

Mesalamine-induced acute intolerance syndrome symptoms may be difficult to distinguish from exacerbation of ulcerative colitis; monitor for worsening symptoms; discontinue treatment if acute intolerance syndrome suspected

Hypersensitivity reactions, including myocarditis and pericarditis, reported; evaluate patients immediately and discontinue if hypersensitivity reaction is suspected

Hepatic failure reported; evaluate risks and benefits in patients with known liver impairment

Photosensitivity reported; advice patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors

Nephrolithiasis reported; stones containing mesalamine, the active moiety, are undetectable by standard radiography or computed tomography (CT). ensure adequate fluid intake during treatment

Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection

Pregnancy

Published data from meta-analyses, cohort studies and case series on use of mesalamine, the active moiety of the drug, during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes

Published data suggest that increased disease activity is associated with 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

Animal data

• There are adverse effects on maternal and fetal outcomes associated with ulcerative colitis in pregnancy; in animal reproduction studies, there were no adverse developmental effects observed after oral administration in pregnant rats and rabbits during organogenesis at doses up to 2.4 and 4.7 times, respectively, the maximum recommended human dose (MRHD)

Lactation

Data from published literature report presence of mesalamine and metabolite, N acetyl-5 aminosalicylic acid, in human milk in small amounts with relative infant doses (RID) of 0.1% or less for mesalamine; there are case reports of diarrhea in breastfed infants exposed to mesalamine; there is no information on effects of drug on milk production

Lack of clinical data during lactation precludes a clear determination of risk of drug to an infant during lactation; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Metabolized to mesalamine by intestinal flora

Mesalamine (5-aminosalicylic acid) has anti-inflammatory effect; active component of sulfasalazine, specific MOA unknown; probably inhibits prostaglandin & leukotrienes synthesis & release in colon

Absorption

Bioavailability: Low absorption

Onset: 10 days to 2 wk

Peak plasma time: 1-2 hr

Distribution

Protein bound: 99%

Vd: mesalamine: 0.2 L/kg

Metabolism

Following oral administration, balsalazide passes intact into colon where it is cleaved by intestinal flora to form mesalamine and 4-aminobenzoyl-b-alanine

Mesalamine is rapidly acetylated in colon wall and liver, independent of pt. acetylator status, into N-acetyl-5-aminosalycylic acid

Metabolites: mesalamine (active), N-acetyl-5-aminosalycylic acid (inactive), 4-aminobenzoyl-b-alanine (inactive)

Elimination

Half-life: Undetermined due to large intersubjective variability

Excretion: Feces (as metabolites) >65%; urine (as metabolites) >25%