Olsalazine (Monograph)

Brand name: Dipentum
Drug class: Anti-inflammatory Agents
VA class: GA900
Chemical name: 3,3′-azobis[6-hydroxybenzoic acid disodium salt
Molecular formula: C₁₄H₈N₂Na₂O₆
CAS number: 6054-98-4

Medically reviewed by Drugs.com on Aug 22, 2023. Written by ASHP.

Introduction

Anti-inflammatory agent with GI tract activity; a 5-aminosalicylic acid derivative and a prodrug of mesalamine.

Uses for Olsalazine

Ulcerative Colitis

Used to maintain clinical remission in patients who are intolerant of sulfasalazine.

Crohn’s Disease

May be beneficial in the management of Crohn’s disease^{† [off-label]} involving the colon.

Olsalazine Dosage and Administration

Administration

Oral Administration

Administer orally twice daily with food.

Dosage

Dosage of olsalazine sodium, which is commercially available as the disodium salt, is expressed in terms of olsalazine sodium.

Daily dosage of 1g usually provides >0.9 g of mesalamine in the colon.

Adults

Ulcerative Colitis

Oral

500 mg twice daily.

Cautions for Olsalazine

Contraindications

Known hypersensitivity to salicylates, olsalazine or its metabolites, or any ingredient in the formulation.

Warnings/Precautions

Major Toxicities

Diarrhea

Diarrhea (reported in about 17% of patients) has required discontinuance in about 6% of patients.

Diarrhea/loose stools, possibly dose-related, tend to occur within 1 week of initiating the drug or a dosage increase.

Occasionally bloody and difficult to distinguish from underlying disease symptoms or may be distinguishable by its high water content and absence of blood. Possibly more severe and frequent in patients with extensive ulcerative colitis.

Usually transient and dosage reduction or increased frequency of dosing of the drug and concomitant administration of food or an antidiarrhea agent (e.g., loperamide) may reduce severity.

May resolve without dosage reduction and once it has resolved, may not recur.

General Precautions

GI effects

Exacerbation of preexisting symptoms of ulcerative colitis has been reported with other 5-aminosalicylic acid derivatives (e.g., mesalamine, sulfasalazine).

Sodium Content

Each g of olsalazine sodium, which contains the disodium salt, provides approximately 5.78 mEq (133 mg) of sodium.

Specific Populations

Pregnancy

Category C.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Use caution.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Renal Impairment

Use with caution in patients with renal impairment, since renal tubular damage has been reported in animals and rarely in postmarketing surveillance; perform urinalysis, monitor serum creatinine and BUN concentrations in such patients.

Common Adverse Effects

Diarrhea/loose stools, abdominal pain or cramps, nausea, dyspepsia, heartburn, bloating, anorexia, vomiting, stomatitis, rectal bleeding, headache, fatigue, drowsiness, lethargy, depression, insomnia, vertigo, dizziness or lightheadedness, rash, pruritus, arthralgia or joint pain, upper respiratory infection.

Drug Interactions

Specific Drugs

Drug	Interaction
Warfarin	Potential interaction (increased prothrombin time).

Olsalazine Pharmacokinetics

Absorption

Bioavailability

Olsalazine (prodrug) has limited systemic bioavailability; about 2.4% of an oral dose may be absorbed.

Most (98–99%) of an oral dose reaches the colon intact resulting in very high local concentrations of the active metabolite mesalamine.

Distribution

Plasma Protein Binding

Olsalazine: >99%; Mesalamine: 74%; N-acetyl-5-acetylsalicylic acid (a metabolite): 81%.

Crosses placenta in animals.

Distributed into milk in rats; not known whether distributed into human milk.

Elimination

Metabolism

Azo-linkage is cleaved in the colon by intestinal flora to form 2 molecules of mesalamine.

Mesalamine is rapidly acetylated in colonic epithelium and liver to N-acetyl-5-acetylsalicylic acid.

0.1% of olsalazine is metabolized in the liver to olsalazine-O-sulfate.

Elimination Route

Mesalamine is excreted principally in feces as N-acetyl-5-acetylsalicylic acid, and to a lesser extent in urine (about 20%) mostly as N-acetyl-5-acetylsalicylic acid; <1% of olsalazine excreted in urine unchanged.

Half-life

Olsalazine: approximately 0.9 hours. Olsalazine-O-sulfate: 7 days.

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).

Actions

Prodrug with little or no anti-inflammatory activity until cleaved to form mesalamine (active moiety).
Exerts local (not systemic) anti-inflammatory effects in the GI tract.
May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase, which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.

Importance of taking with food.
Importance of taking in equally divided doses.
Importance of informing clinicians if diarrhea occurs.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.