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Dipentum

Generic Name: Olsalazine Sodium
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 on September 1, 2017

Introduction

Anti-inflammatory agent with GI tract activity; a 5-aminosalicylic acid derivative and a prodrug of mesalamine.1 2 4

Uses for Dipentum

Ulcerative Colitis

Used to maintain clinical remission in patients who are intolerant of sulfasalazine.1 2 3 4 5 6

Crohn’s Disease

May be beneficial in the management of Crohn’s disease involving the colon.4 40 41 42

Dipentum Dosage and Administration

Administration

Oral Administration

Administer orally1 2 3 4 twice daily1 2 with food.1 4

Dosage

Dosage of olsalazine sodium, which is commercially available as the disodium salt, is expressed in terms of olsalazine sodium.1

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

Adults

Ulcerative Colitis
Oral

500 mg twice daily.1 2 3 4

Cautions for Dipentum

Contraindications

  • Known hypersensitivity to salicylates, olsalazine or its metabolites, or any ingredient in the formulation.1 43

Warnings/Precautions

Major Toxicities

Diarrhea

Diarrhea (reported in about 17% of patients) 1 2 3 4 6 has required discontinuance in about 6% of patients.1 2 4

Diarrhea/loose stools, possibly dose-related,1 3 tend to occur within 1 week of initiating the drug or a dosage increase.2 4

Occasionally bloody2 and difficult to distinguish from underlying disease symptoms1 or may be distinguishable by its high water content and absence of blood.4 Possibly more severe and frequent in patients with extensive ulcerative colitis.2 4 5

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.3 4

May resolve without dosage reduction3 and once it has resolved, may not recur.4

General Precautions

GI effects

Exacerbation of preexisting symptoms of ulcerative colitis has been reported with other 5-aminosalicylic acid derivatives (e.g., mesalamine, sulfasalazine).1

Sodium Content

Each g of olsalazine sodium, which contains the disodium salt, provides approximately 5.78 mEq (133 mg) of sodium.1 43

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use caution.1

Pediatric Use

Safety and efficacy not established.1 43

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Renal Impairment

Use with caution in patients with renal impairment, since renal tubular damage has been reported in animals and rarely in postmarketing surveillance;1 perform urinalysis, monitor serum creatinine and BUN concentrations in such patients.1

Common Adverse Effects

Diarrhea/loose stools,1 2 3 4 6 abdominal pain or cramps,1 4 nausea,1 4 dyspepsia,1 heartburn,1 bloating,1 anorexia,1 vomiting,1 stomatitis,1 rectal bleeding,1 headache,1 2 4 fatigue,1 2 drowsiness,1 lethargy,1 depression,1 insomnia,1 vertigo,1 dizziness or lightheadedness,1 4 rash,1 2 4 pruritus,1 arthralgia or joint pain,1 4 upper respiratory infection.1

Interactions for Dipentum

Specific Drugs

Drug

Interaction

Warfarin

Potential interaction (increased prothrombin time).1

Dipentum Pharmacokinetics

Absorption

Bioavailability

Olsalazine (prodrug) has limited systemic bioavailability; about 2.4% of an oral dose may be absorbed.1 4

Most (98–99%) of an oral dose reaches the colon intact1 2 3 4 resulting in very high local concentrations of the active metabolite mesalamine.1

Distribution

Plasma Protein Binding

Olsalazine: >99%;1 Mesalamine: 74%;1 N-acetyl-5-acetylsalicylic acid (a metabolite): 81%.1

Crosses placenta in animals.1

Distributed into milk in rats; not known whether distributed into human milk.1

Elimination

Metabolism

Azo-linkage is cleaved in the colon by intestinal flora to form 2 molecules of mesalamine.1 2 3 4

Mesalamine is rapidly acetylated in colonic epithelium and liver to N-acetyl-5-acetylsalicylic acid.1 4 6

0.1% of olsalazine is metabolized in the liver to olsalazine-O-sulfate.1 4

Elimination Route

Mesalamine is excreted principally in feces as N-acetyl-5-acetylsalicylic acid,1 4 6 and to a lesser extent in urine (about 20%) mostly as N-acetyl-5-acetylsalicylic acid;7 9 25 <1% of olsalazine excreted in urine unchanged.1

Half-life

Olsalazine: approximately 0.9 hours.1 Olsalazine-O-sulfate: 7 days.1

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).1

Actions

  • Prodrug with little or no anti-inflammatory activity until cleaved to form mesalamine (active moiety).1 2 3 4 6

  • Exerts local (not systemic) anti-inflammatory effects in the GI tract.1 2 3 4 7 8 9 10 11 12 13 14 15 17 18 19 21 23 24 26 27 28 29 30 31 32 35 33 34 36 38

  • 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.1 4 7 8 9 11 12 13 14 15 16 18 19 20 21 23 32 35 38 39

Advice to Patients

  • Importance of taking with food.1

  • Importance of taking in equally divided doses.1

  • Importance of informing clinicians if diarrhea occurs.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • 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.

Olsalazine Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg

Dipentum

Celltech

AHFS DI Essentials. © Copyright 2018, Selected Revisions September 1, 2005. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Celltech. Dipentum (olsalazine) capsules prescribing information. Rochester, NY; 2002 Sep.

2. Sandberg-Gertzen H, Jarnerot G, Kraaz W. Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse prevention properties. Gastroenterol. 1986:90:1024-30. (IDIS 214428)

3. Ireland A, Mason CH, Jewell DP. Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis. Gut. 1988; 29:835-7. http://www.ncbi.nlm.nih.gov/pubmed/2898422?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1433723&blobtype=pdf

4. Wadworth AN, Fitton A. Olsalazine. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in inflammatory bowel disease. Drugs. 19911; 41:647-64.

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6. Sandborn WJ. Rational selection of oral 5-aminosalicylate formulations and prodrugs for the treatment of ulcerative colitis. Am J Gastroenterol. 2002; 97:2939-41. (IDIS 492059)

7. Salix Pharmaceuticals. Colazal (balsalazide disodium) capsules prescribing information. Raleigh, NC; 2000 Jul.

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43. Celltech, Rochester, NY: Personal communication.

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