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

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

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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.

Olsalazine Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

250 mg

Dipentum

Celltech

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Dipentum 250MG Capsules (MEDA PHARMACEUTICALS): 100/$625.01 or 300/$1,839.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions September 1, 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, 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. [IDIS 243681] [PubMed 2898422]

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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23. Kirsner JB, Shorter RG. Recent developments in ‘nonspecific’ inflammatory bowel disease: first of two parts. N Engl J Med. 1982; 306:775-85. [IDIS 146719] [PubMed 7038488]

24. Campieri M, Lanfranchi GA, Boschi S et al. Topical administration of 5- aminosalicylic acid enemas in patients with ulcerative colitis: studies on rectal absorption and excretion. Gut. 1985; 26:400-5. [IDIS 203829] [PubMed 3979912]

25. Dew MJ, Ebden P, Kidwai NS et al. Comparison of the absorption and metabolism of sulphasalazine and acrylic-coated 5-amino salicylic acid in normal subjects and patients with colitis. Br J Clin Pharmacol. 1984; 17:474-6. [IDIS 184171] [PubMed 6144318]

26. Klotz U. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet. 1985; 10:285-302. [IDIS 203379] [PubMed 2864155]

27. Campieri M, Lanfranchi GA, Brignola C et al. 5-ASA blood levels in topical treatment of ulcerative colitis: preliminary observations. Scand J Gastroenterol. 1982; 17:(Suppl)500.

28. Fischer C, Maier K, Stumpf E et al. al. Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man. Eur J Clin Pharmacol. 1983; 25:511-5. [IDIS 179570] [PubMed 6140167]

29. Dew MJ, Cardwell M, Kidwai NS. et. al. 5-Aminosalicylic acid in serum and urine after administration by enema to patients with colitis. J Pharm Pharmacol. 1983; 35:323-4. [IDIS 170825] [PubMed 6134804]

30. Pieniaszek HJ Jr, Bates TR. Capacity-limited gut wall metabolism of 5- aminosalicylic acid, a therapeutically active metabolite of sulfasalazine, in rats. J Pharm Sci. 1979; 68:1323-5. [PubMed 41931]

31. Klotz U, Maier K, Fischer C et al. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. N Engl J Med. 1980; 303:1499-1502. [IDIS 125198] [PubMed 6107853]

32. Cooper BT. Sulphasalazine in inflammatory bowel disease: recent advances. N Z Med J. 1986; 99:757-9. [IDIS 231591] [PubMed 2877428]

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34. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderatel active ulcerative colitis. N Engl J Med. 1987; 317:1625-9. [IDIS 236262] [PubMed 3317057]

35. Peskar BM, Dreyling KW, May B, et. al. Possible mode of action of 5-aminosalicylic acid. Dig Dis Sci. 1987; 32(Suppl)51-6S. (PubMed 2891468)

36. McPhee MS, Swan JT, Biddle WL et al. al. Proctocolitis unresponsive to conventional therapy. Dig Dis Sci. 1987; 32:(Suppl)76-81S. [IDIS 317556] [PubMed 3319462]

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38. Allgayer H, Stenson WF. A comparison of effects of sulfasalazine and its metabolites on the metabolism of endogenous vs. exogenous arachidonic acid. Immunopharmacology. 1988; 15:39-46. [PubMed 2896181]

39. Hoult JRS, Page H. 5-Aminosalicylic acid, a co-factor for colonic prostacyclin synthesis? Lancet. 1981; 2:255. Letter.

40. Blomqvist P, Feltelius N, Lofberg R et al. A 10-year survey of inflammatory bowel diseases-drug therapy, costs and adverse reactions. Aliment Pharmacol Ther. 2001; 15:475-81. [PubMed 11284775]

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43. Celltech, Rochester, NY: Personal communication.

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