Mesalamine

Class: Anti-inflammatory Agents
VA Class: GA900
Chemical Name: 5-Amino-2-hydroxybenzoic acid
Molecular Formula: C₇H₇NO₃
CAS Number: 89-57-6
Brands: Asacol, Canasa, Lialda, Pentasa, Rowasa

Introduction

The 5-amino derivative of salicylic acid; a GI anti-inflammatory agent.^{1 3 4 6 15}

Uses for Mesalamine

Ulcerative Colitis

Used for management of ulcerative colitis (as oral delayed-release tablets or extended-release capsules)^{228 229 231 232 233 236} and to induce (as extended-release capsules and as 1.2-g delayed-release tablets)^{229 236 448} and maintain (as 400-mg delayed-release tablets)^{228 234 235} clinical remission in adults with mildly to moderately active disease.

Management of mildly to moderately active distal ulcerative colitis (as rectal suspension) ^{1 2 3 7 71 72 74 78 93 94 104 154 175 176 177 203 204 205} including ulcerative proctosigmoiditis ^{1 2 7 15 97 99 100 102 120 122 153 154 173 175} and ulcerative proctitis.^{1 2 7 71 72 97 98 122 154}

Management of active ulcerative proctitis (as rectal suppositories).^{217 227 230 237}

Oral preparations of the drug may be preferable to rectal preparations in patients with extensive inflammatory bowel disease, since efficacy of rectal preparations may be limited to disease distal to the splenic flexure.^{86 156}

Crohn’s Disease

Has been used (as extended-release oral preparations) for the management of active Crohn’s disease†^{106 261 339 341 342 343 344 345} and to induce^{300 339 341} and maintain clinical remission^{241 245 248 250 339 348 349 350 351 352 353 354 355 356 357} in adults with mildly to moderately active disease.

Has been used (as rectal preparations) in a limited number of patients for the management of active Crohn’s disease†,⁷⁰ but the role of such therapy in this condition is not as well defined as in the management of ulcerative colitis.^{88 199 200}

Mesalamine Dosage and Administration

Administration

Administer orally^{66 73 80 81 83 85 90 91 96 136 156 164 172 174 228 229 231 233 234 235 236 448} or rectally.^{1 2 7 71 72 74 86 93 94 99 100 102 103 104 105 1 227}

Oral Administration

Administer orally as delayed-release tablets (Asacol, Lialda)^{228 231 233 234 448} or extended-release capsules (Pentasa).^{229 235 236}

Delayed-release tablets should be swallowed whole without breaking the outer coating, since the coating is designed to maintain the integrity of the tablets prior to entering the colon, where the drug is released.^{228 448} Intact or partially intact tablets may be present in stools; if this occurs repeatedly, patients should notify their clinician.²²⁸

1.2-g delayed-release tablets (Lialda): Administer orally with food.⁴⁴⁸

Rectal Administration

Administer rectally as a suspension retention enema^{1 2 7 71 72 74 86 93 94 99 100 102 103 104 105} or suppositories.^{227 230}

Administer rectal suspension preferably at bedtime and retain for about 8 hours.¹ Best results are achieved if the bowel is emptied just prior to enema administration.² Administer according to manufacturer’s instructions.¹

Retain rectal suppositories for ≥1–3 hours, if possible, to achieve maximum benefit.^{70 217 227 230}

Dosage

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Delayed-release tablets have been given in an initial dosage of 20–30 mg/kg daily and then increased up to 60 mg/kg daily.^{333 335}

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets: Usually, 2.4 g daily (given as two 400-mg delayed-release tablets 3 times daily) for 6 weeks.²²⁸

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Usually, 4 g daily in equally divided doses (given as four 250-mg extended-release capsules or two 500-mg extended-release capsules 4 times daily) for up to 8 weeks.²²⁹ Lower dosages (e.g., 2–4 g daily [in divided doses]) have been used†.²⁵⁰

Delayed-release tablets: 2.4 or 4.8 g once daily (given as two or four 1.2-g delayed-release tablets).⁴⁴⁸ Safety and efficacy beyond 8 weeks of treatment have not been established.⁴⁴⁸

Maintenance of Remission

Oral

Delayed-release tablets: Usually, 1.6 g daily (four 400-mg delayed-release tablets) given in divided doses for 6 months.²²⁸ Dosages of 800 mg to 4.8 g daily (in divided doses) also have been used.²⁵⁰

Extended-release capsules: Dosages of 1.5–3 g daily (in divided doses) have been used.²⁵⁰

Advise patients that ulcerative colitis rarely remits completely, and continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.²²⁸

Distal Ulcerative Colitis

Rectal

Suppositories: 1 g (using 1-g suppositories) once daily at bedtime.^{227 230}

Enema suspension: Usually, 4 g once daily (preferably at bedtime).^{1 2 72 78 86 93 94 205}

Although clinical response may be apparent within 3–21 days, therapy with rectal mesalamine usually is continued for 3–6 weeks or until clinical and/or sigmoidoscopic remission is achieved.^{1 227 230}

Efficacy of rectal therapy (in terms of modification of relapse rates) beyond 6 weeks has not been established,^{1 227} but mesalamine has been used rectally for prolonged periods (e.g., >1 year) in some patients.⁹³

Lower dosages^{7 71 99 100 102 104 105 176 203 204 208} or less frequent administration^{93 204} of the rectal drug has been used in some patients†, particularly after initial remission is achieved.

In some patients with distal ulcerative colitis in whom clinical remission occurred following daily administration of 4-g doses of the rectal suspension, dosage was reduced to 4 g every 2 or 3 nights or, occasionally, to less frequent administration.^{93 204} If clinical relapse occurred with such administration, dosage was increased to more frequent use.⁹³ In some patients with distal ulcerative colitis or ulcerative proctosigmoiditis, the rectal suspension also has been used in dosages of 1–3 g daily.^{7 71 99 100 102 104 105 176 203 204 208}

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease†

Oral

Adults have received dosages of 3.2–4.8 g daily (as delayed-release tablets)^{241 243 248 250 339 340 342} or 4 g daily (as extended-release capsules), generally in divided doses.^{300 339} Lower dosages do not appear to be effective.^{106 300 339 367 341}

Prescribing Limits

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Maximum 60 mg/kg daily.^{333 335}

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.^{229 250}

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Maximum 4 g daily in divided doses.²²⁹

Delayed-release tablets (1.2 g; Lialda): Safety and efficacy beyond 8 weeks of therapy not established.⁴⁴⁸

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily, in divided doses.²⁵⁰

Extended-release capsules†: Maximum 3 g daily in divided doses.²⁵⁰

Distal Ulcerative Colitis

Rectal

Enema suspension: Maximum 4 g once daily.^{1 2 72 78 86 93 94 205}

The drug has been used rectally for >1 year.⁹³

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.²⁵⁰

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses. ²⁵⁰

Extended-release capsules: Maximum 3 g daily in divided doses.²⁵⁰

Special Populations

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{228 230 448}

Cautions for Mesalamine

Contraindications

• 
  

  Extended-release capsules (Pentasa), delayed-release tablets (1.2-g; Lialda), rectal suppositories (Canasa): Known hypersensitivity to salicylates (including aspirin, mesalamine)^{229 230 448} or any ingredient in the respective formulation.^{1 227 228 229 230 448}

  
  

Warnings/Precautions

Sensitivity Reactions

Possible acute intolerance (sensitivity reaction) syndrome (e.g., cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, pruritus, rash); may require prompt discontinuance.^{1 2 78 112 114 121 156 180 198 213 227 228 229 230 448} A history of sulfasalazine intolerance, if any, should be reevaluated.^{1 2 198 227 228 230}

Use with caution in patients with a history of hypersensitivity to sulfasalazine.^{1 227 228 230 448}

Sulfite Sensitivity

Rectal suspension contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹

General Precautions

Renal Impairment

Renal impairment (e.g., minimal change nephropathy, acute and chronic interstitial nephritis, renal failure) and increases in BUN and S_cr reported.^{228 229}

Use with caution and only if the benefits outweigh the risks⁴⁴⁸ in patients with renal impairment.^{1 228 229 230 448}

Renal function should be evaluated prior to initiation of therapy and periodically thereafter.^{1 228 448}

GI Effects

Pancolitis reported rarely in patients receiving rectal mesalamine.^{1 2 227 230}

Possible worsening colitis or symptoms of inflammatory bowel disease (e.g., melena, hematochezia) in patients receiving rectal mesalamine.¹

Potential for prolonged gastric retention of oral delayed-release tablets in patients with pyloric stenosis.^{228 448}

The possibility of acute pancreatitis should be considered in any patient who develops new abdominal complaints while receiving mesalamine therapy.²²⁰

Cardiac Effects

Use with caution in patients with conditions predisposing them to the development of myocarditis or pericarditis.⁴⁴⁸ The possibility of pericarditis should be considered in any patient who develops chest pain or dyspnea during mesalamine therapy.¹ Discontinuance may be needed.²²⁷

Specific Populations

Pregnancy

Category B.^{1 228 229 230 448}

Lactation

Distributed into milk following oral administration.^{228 229} Use with caution.^{228 229 448}

Not known whether the rectal drug is distributed into milk.^{1 227 230} Use of rectal mesalamine usually not recommended,^{1 227} although one manufacturer of rectal suppositories states the preparation may be used with caution.²³⁰

Pediatric Use

Safety and efficacy not established in children.^{1 228 229 230 448}

Has been used (as oral delayed-release tablets) for the management of inflammatory bowel disease (i.e., mild ileal, ileocecal, ileocolonic, or colonic disease) and (as rectal mesalamine suspension) in those with left-sided colitis in a limited number of pediatric patients†.^{59 199 200 333 335} (See Pediatric Patients under Dosage.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.^{228 230 448} Response does not appear to differ from that in younger adults; however, drug dosage should be selected cautiously.^{230 448}

Possibility of increased incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, pancytopenia); CBCs should be monitored closely.²²⁸

Because mesalamine is substantially eliminated by kidneys, assess renal function prior to initiation of therapy and periodically thereafter since geriatric patients more likely to have decreased renal function.²²⁸

Hepatic Impairment

Use with caution in patients with hepatic impairment.^{229 448}

Renal Impairment

Use with caution in patients with renal impairment.^{1 228 229 230}

Common Adverse Effects

Oral therapy: Headache, rash, vomiting, diarrhea, flatulence, constipation, nausea, dyspepsia, abdominal pain, fever, arthralgia, flu syndrome.^{228 229 448}

Rectal therapy: Headache, abdominal pain, nausea, diarrhea, gas/flatulence, fever, dizziness, rectal pain, rash, leg/joint pain, flu syndrome.^{1 227 230}

Interactions for Mesalamine

No known drug interactions.^{228 229}

Specific Drugs

Drug	Interaction
Azathioprine	Possible increased risk of hematologic toxicity448
Digoxin	Decreased GI absorption of digoxin with concomitant sulfasalazine or aminosalicylic acid;115 143 195 not known whether mesalamine alters digoxin absorption199 200
Mercaptopurine	Possible increased risk of hematologic toxicity448
Nephrotoxic drugs (e.g., NSAIAs)	Possible increased nephrotoxicity448

Mesalamine Pharmacokinetics

Absorption

Bioavailability

Following oral administration of the 400-mg delayed-release tablets (Asacol), approximately 28% of mesalamine is absorbed and the remainder of the dose is available for topical activity and fecal excretion.²²⁸

Following oral administration of extended-release capsules (Pentasa), about 20–30% of the drug is absorbed.²²⁹

Following oral administration of the 1.2-g delayed-release tablets (Lialda), about 21–22% of the drug is absorbed.⁴⁴⁸

Rectally administered suspension is poorly absorbed from the GI tract (about 15% [range: 5–35%]).^{1 2 15 43 47 49 65 68 210 227} The rectal suspension usually is retained for about 3.5–12 hours after administration as an enema;^{1 2 42 47} prolonged retention may increase absorption of the drug.^{199 200}

Variably absorbed following rectal administration of the suppositories.²³⁰ Rectal suppositories usually are retained for 1–3 hours after administration.²²⁷

Food

Food does not appear to affect absorption of the 400-mg delayed-release tablets (Asacol).²²⁸

Food decreases rate of absorption and increases extent of absorption of the 1.2-g delayed-release tablets (Lialda).⁴⁴⁸

Distribution

Extent

Following oral or IV (IV preparation currently not available in the US) administration, the drug may be distributed into kidneys.^{1 199}

Rectal suspension distributes from the rectum into the colon, generally reaching the splenic flexure^{7 42 95 207} and possibly the ascending colon.²⁰⁷ Rectal suppositories distribute to some extent in rectal tissues.²³⁰

Oral mesalamine crosses the placenta;^{3 47 108 229 448} serum concentrations of mesalamine in umbilical cord and amniotic fluid are very low.¹⁰⁸

Not known whether rectal mesalamine crosses the placenta.³

Oral mesalamine is distributed into milk.^{228 229}

Not known whether rectal mesalamine is distributed into milk.^{1 2 6}

Plasma Protein Binding

Approximately 44–55% (as unchanged drug).^{3 54 60}

Approximately 43% at a concentration of 2.5 mcg/mL.⁴⁴⁸

Elimination

Metabolism

Rapidly metabolized, principally in the liver to form N-acetyl-5-aminosalicylic acid.^{3 47 63 70 228 448}

Elimination Route

Following oral administration, excreted in urine (about 20%) mainly as metabolites^{46 228 229} and in feces.²²⁹

Following rectal administration, principally excreted in feces (about 50%),^{47 71} as unchanged drug and metabolites,^{1 6} and in urine^{1 2 3 6 42} (about 10–35%).^{1 2 3 6 42 68 71}

Half-life

400-mg delayed-release tablets (Asacol): 12 hours (range: 2–15 hours).²²⁸

1.2-g delayed-release tablets (Lialda): 7–9 hours (for mesalamine) and 8–12 hours (for N-acetyl-5-aminosalicylic acid metabolite).⁴⁴⁸

Rectal suspension: 0.5–1.5 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).^{1 3 47 56 60 63}

Rectal suppositories: 0.5–7 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).^{227 230}

Stability

Storage

Oral

Extended-release Capsules

25°C (may be exposed to 15–30°C).²²⁹

Delayed-release Tablets

400-mg tablets: 20–25°C.²²⁸

1.2-g tablets: 15–25°C (may be exposed to 30°C).⁴⁴⁸

Rectal

Suppositories

<25°C.²³⁰ Do not freeze; keep out of reach of children.²³⁰

Suspension

20–25°C (may be exposed to 15–30°C); keep out of reach of children.^{1 6} May darken with time once the container has been removed from the foil wrap;¹ dark brown suspensions should be discarded.^{1 199}

ActionsActions

• 
  

  Exerts local (rather than systemic)^{1 2 3 5 7 42 47 49 65 68 69 70 95 156 173 228 229 230 448} anti-inflammatory effects in the GI tract.^{1 2 3 4 5 7 9 10 13 26 76 168 183}

  
  


• 
  

  May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase,^{1 2 3 10 12 13 14 168 228 229} which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes^{1 2 3 5 9 10 12 13 26 39 76 168 183 210} and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.^{5 10 13 210}

  
  

Advice to Patients

• 
  

  Importance of swallowing delayed-release tablets whole without breaking the outer coating.^{228 448}

  
  


• 
  

  Importance of taking 1.2-g delayed-release tablets with food.⁴⁴⁸

  
  


• 
  

  Importance of informing patients that intact or partially intact tablets may be present in stools and if this occurs repeatedly, they should notify their clinician.²²⁸

  
  


• 
  

  Importance of informing patients that the rectal suspension and suppositories will cause staining of direct contact surfaces, including, but not limited to, fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel¹ and therefore, they should carefully choose a suitable location for administration of the rectal suspension.^{1 230}

  
  


• 
  

  Importance of informing patients with sulfasalazine sensitivity^{1 2 78 87 121 180 228 230} to discontinue mesalamine therapy and contact their clinician if signs of sensitivity (e.g., rash, fever) develop^{1 2 198 230} or increased diarrhea or rectal bleeding occurs.²⁰⁰

  
  


• 
  

  Importance of informing clinicians of existing pancreatitis.²³⁰

  
  


• 
  

  Importance informing patients that ulcerative colitis rarely remits completely and that continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.²²⁸

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

  Importance of informing 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.

Mesalamine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release	250 mg	Pentasa	Shire
		500 mg	Pentasa	Shire
	Tablets, delayed-release	400 mg	Asacol	Procter & Gamble
		1.2 g	Lialda	Shire
Rectal	Suppositories	1 g	Canasa	Axcan
	Suspension	4 g/60 mL	Mesalamine Suspension Enema
			Rowasa Suspension Enema	Alaven

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Apriso 0.375GM 24-hr Capsules (SALIX PHARMACEUTICALS INC.): 120/$271.38 or 360/$781.93

Asacol 400MG Enteric-coated Tablets (WARNER CHILCOTT PHARMA): 30/$70.6 or 90/$180.72

Asacol HD 800MG Enteric-coated Tablets (WARNER CHILCOTT PHARMA): 90/$338.85 or 180/$656.48

Canasa 1000MG Suppositories (AXCAN PHARMA US): 30/$488.34 or 90/$1437.86

Lialda 1.2GM Enteric-coated Tablets (SHIRE US INC.): 120/$725.99 or 360/$2089.94

Mesalamine 4GM Enema (TEVA PHARMACEUTICALS USA): 60/$35.99 or 120/$59.98

Pentasa 250MG Controlled-release Capsules (SHIRE US INC.): 240/$290.98 or 720/$835.97

Pentasa 500MG Controlled-release Capsules (SHIRE US INC.): 30/$82.07 or 90/$222.45

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, 1959-2011, Selected Revisions August 2009. 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

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2. Reid-Rowell. Rowasa (mesalamine): a product profile. Marietta, GA; 1988 Mar.

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4. Weintraub M, Evans P. 5-Aminosalicylic acid: an old, ″new″ treatment for inflammatory bowel disease. Hosp Formul. 1987; 22:528-33.

5. Peppercorn MA. Sulfasalazine and related new drugs. J Clin Pharmacol. 1987; 260-5. (IDIS 228622)

6. Reid-Rowell. Rowasa (mesalamine) product information form for the American Hospital Formulary Service. Marietta, GA; 1988 Apr.

7. Anon. Mesalamine for ulcerative colitis. Med Lett Drugs Ther. 1988; 30:53-6. [PubMed 3283508]

8. Allgayer H, Sonnenbichler J, Kruis W et al. Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites. Arzneimittelforschung. 1985; 35:1457-9. [PubMed 2867770]

9. Ligumsky M, Karmeli F, Sharon P et al. Enhanced thromboxane A₂ and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine. Gastroenterology. 1981; 81:444-9. [IDIS 139848] [PubMed 6114012]

10. Sharon P, Ligumsky M, Rachmilewitz D et al. Role of prostaglandins in ulcerative colitis. Gastroenterology. 1978; 75:638-40. [PubMed 30669]

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12. Lauritsen K, Laursen LS, Bukhave K et al. Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E₂ and leukotriene B₄ levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis. Gastroenterology. 1986; 91:837-44. [IDIS 221448] [PubMed 3017804]

13. Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease: update requiring addition of a pathway. Gastroenterology. 1985; 88:580-7. [IDIS 196055] [PubMed 2856909]

14. Isselbacher KJ. The role of arachidonic acid metabolites in gastrointestinal homeostasis: biochemical, histological and clinical gastrointestinal effects. Drugs. 1987; 33(Suppl 1):38-46. [IDIS 230964] [PubMed 2885170]

15. Lewis JH. Summary of the 31st meeting of the Food and Drug Administration Gastrointestinal Drugs Advisory Committee December 8-9, 1986. Am J Gastroenterol. 1987; 82:443-7.

16. Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rats. Gastroenterology. 1985; 88:55-63. [PubMed 3917261]

17. Dull BJ, Salata K, van Langenhove A et al. 5-Aminosalicylate: oxidation by activated leukocytes and protection of cultured cells from oxidative damage. Biochem Pharmacol. 1987; 36:2467-72. [PubMed 3038125]

18. Molin L, Stendahl O. The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med Scand. 1979; 206:451-7. [IDIS 108764] [PubMed 43662]

19. Hillier K, Mason PI, Pacheco S et al. Ulcerative colitis: effect of sulphasalazine, its metabolites and indomethacin on the ability of human colonic mucosa to metabolize prostaglandins in vitro. Br J Pharmacol. 1982; 76:157-61. [IDIS 150404] [PubMed 6123357]

20. Rhodes JM, Jewell DP. Inhibition of leucocyte motility by drugs used in inflammatory bowel disease. Gut. 1980; 21:A452-3. [PubMed 6450718]

21. Hoult JRS, Page H. 5-Aminosalicylic acid, a co-factor for colonic prostacyclin synthesis? Lancet. 1981; 2:255. Letter. (IDIS 136287)

22. Holdstock G, Chastenay BF, Krawitt EL. Increased prostaglandin producing suppressor cells in inflammatory bowel disease not sensitive to sulfasalazine. Gastroenterology. 1981; 80:1177.

23. Das K, Zapp B, Rubinstein A. In vivo and in vitro effect of sulfasalazine on lymphocyte in inflammatory bowel disease (IBD): systemic immunological parameters in idiopathic proctitis (IP). Gastroenterology. 1976; 70:A17.

24. Smith PR, Dawson DJ, Swan CHJ. Prostaglandins and sulphasalazine. Lancet. 1978; 2:260.

25. Sharon P, Stenson WF. Enhanced synthesis of leukotriene B₄ by colonic mucosa in inflammatory bowel disease. Gastroenterology. 1984; 86:453-60. [PubMed 6319219]

26. 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]

27. Anon. Sulphasalazine: