PPT on Mesalamine Group of Drugs Dr. Subhojit Ray PG Resident Dermatology

1. MESALAMINE GROUP OF
DRUGS
Presenter: Dr Subhojit Ray

2. CHEMISTRY
• The chemical structure of Mesalamine is 5 Amino Salicylic Acid ( 5-ASA)
• The archetype of this class of medication is Sulfasalazine
• In Sulfasalazine, 5- ASA is linked to Saulfapyridine by an azo bond.
• The other drugs of this group are Olsalazine and Balsalazide
• In Olsalazine , 2 molecules of 5-ASA are linked by azo bonds.
• In Balsalazide , 1 Molecule of 5-ASA is linked to an inert compound

3. GROUP OF DRUG
• Mesalamine/ Mesalazine is a Salicylate
• This group of drugs is considered to be under class DISEASE
MODIFYING ANTIRHEUMATIC DRUGS (DMARDS).
• Sulfasalazine was developed originally as therapy of rheumatoid
arthritis by Dr Nana Svartz, a Scandanavian rheumatologist in 1941.
• Later in clinical trials it showed beneficilal effect on the GI symptoms
of subjects with concomitant ulcerative colitis.

4. PHARMACOKINETICS
• Given orally both 5-ASA and Sulfapyridine gets absorbed in the upper
GI tract.
• The AZO BOND in Sulfasalazine prevents both this compounds to be
released in upper GI tract. This bond is broken down by enzymes
secreted by intestinal flora in the distal GI.
• Bioavailability: Immediate release preparations of Mesalamine are
extremely and rapidly absorbed; Extended release preparations are
20-30% absorbed.

5. • METABOLISM: Mesalamine gets rapidly acetylated in colon wall and
liver independent of patients’ acetylation status into compound N
acetyl 5 Aminosalicylic acid which is inactive .
• EXCRETION: by feces 72%, in Urine 19-30%

7. MECHANISM OF ACTION
• MESALAMINE is a salicylate but its therapeutic effect does not appear
to be related to cyclo-oxygenase inhibition.
• Specific Mechanism of action has not been identified.
• Many potential sites of actions has been demonstrated in vitro as
potential site of actions. They are:
1. Inhibition of IL-1 Production
2. Inhibition of TNF-alpha
3. Inhibition of Lipoxygenase pathway
4. Free radicals and oxidants scavenging
5. Inhibition of NF-kB.

8. USES IN DERMATOLOGY
• Mesalamine is an inexpensive drug that has immunomodulatory,
anti-inflammatory, and antiproliferative properties with relatively few
side effects.
• It can be especially useful in patients who fail to respond to standard
therapy or in those for whom standard therapy is contraindicated.

9. PSORIASIS AND PSORIATIC ARTHRITIS
• SSZ has been tried successfully alone and in combination with pentoxyphylline in patients
with:
- psoriasis[Bharti and Girgla,19961; El-Mofty et al.,20112; Gupta 19903;]
- psoriatic arthritis[ Marguerie et al.,20024]
The prescribed dose range - 1500 mg/day to 3 g/day.
• SSZ was also found to be effective in a case of acrodermatitis continua of Hallopeau.[Li et
al,2018a]
1.R. Bharti and S. Girgla, Sulfasalazine in treatment of psoriasis,Indian J Dermatol Venereol Leprol, 62 (2) (1996), pp. 87-88
2. M. El-Mofty, M. El-Darouti, H. Rasheed, D.A. Bassiouny, M. Abdel-Halim, N.S. Zaki et al., Sulfasalazine and Pentoxyphylline in posriais: A possible safe
alternative, J Dermatology Treat, 22 (2011), pp. 31-37
3.A.K.Gupta, Sulfasalazine improves psoriasis; Arch Dermatol, 126 (4) (1990), p. 487
4. L. Marguerie, R.M. Flipo, B. Grardel, D. Beaurain, B. Duquesnoy and B. Delcambre; Use of disease modifying antirheumatic drugs in patients with psoriatic
arthritis , Joint Bone Spine, 69 (3) (2002), pp. 275-281
5. M. Li, Y. Zhang, H. Xu, Z.Q. Chen and Y.M. Li; A case of acrodermatitis continua of Hallopeau (ACH) successfully treated with sulfasalazine, Dermatol
Ther, 31 (2018)

10. PSORIASIS AND PSORIATIC ARTHRITIS
• Mesalazine was tried in an open trial on 20 psoriatics.1
Results:
- 50% patients (10) had complete clearance in 4 weeks,
- 85% (17) patients had good response by 12 weeks
- 15% (3) patients had no relief at all.
No side effects were observed.
1. R. Bharti, Indian J Dermatol Venereol Leprol. Jul-Aug 1996;62(4):231-2]

11. ALOPECIA AREATA
SSZ in a dose of 500 mg twice daily for 1 month, 1 g twice daily for 1 month, and then 1.5 g
twice daily for a maximum of 3 months was used in recalcitrant cases of alopecia areata with
good response in 27% of cases (Aghaei, 2008)1.
Ellis et al. (2002) reported a 23% response in severe cases of alopecia areata with SSZ. (Ellis et
al. 2002)2
Mesalazine may be considered as effective as azathioprine in Alopecia Areata with lesser side
effects.(Maghoob RAS et al.)3
1. S. Aghaei, An uncontrolled open label study of sulfasalazine in severe Alopecia Areata, Indian J Dermatol Venereol Leprol, 74 (6) (2008), pp. 611-6.
2. C.N. Ellis, M.F. Brown and J.J. Voorhees; Sulfasalazine for Alopecia Areata; J Am Acad Dermatol, 46 (4) (2002), pp. 541-544
3. Mahgoob RAS, Elgamal EE, Elshahat OM, Almetwaly SA. Comparative study between the efficacies of azathioprine and mesalazine in the treatment of severe alopecia areata. J Cosmet Dermatol. 2021
Dec 16. doi: 10.1111/jocd.14687. Epub ahead of print. PMID: 34918459.

12. LICHEN PLANUS
• In a Randomized controlled longitudinal investigation [Sardella A et al]1, 25 OPD patients of Oral
Lichen Planus were randomly allocated into 2 groups for treatment with topical 5% Mesalamine and
0.05% Clobetasol Propionate for 4 weeks.
• Results: - Both obtained partial and complete loss of symptoms
- For Mesalazine: 57% Complete loss of symptoms
21.3% Partial Response
9% No response
No Statisical Relevant difference between 2 regimens
• However, 2 Case reports by Alstead E M et al2. showed typical oral and cutaneous lichen planus on
sulfasalazine and their skin lesions recurred when they were subsequently changed to mesalazine.
1. Sardella A, Demarosi F, Oltolina A, Rimondini L, Carrassi A. Efficacy of topical mesalazine compared with clobetasol propionate in treatment of symptomatic oral lichen
planus. Oral Dis. 1998 Dec;4(4):255-9. doi: 10.1111/j.1601-0825.1998.tb00289.x. PMID: 10200704.
2. Alstead EM, Wilson AG, Farthing MJ. Lichen planus and mesalazine. J Clin Gastroenterol. 1991 Jun;13(3):335-7. doi: 10.1097/00004836-199106000-00018. PMID:
1676716.

13. URTICARIA AND ANGIOEDEMA
• Sulfasalazine has been effectively tried in antihistamine resistant cases of chronic
idiopathic urticaria and angioedema (McGirt et al.’20061; Orden et al.,20142)
• Mesalazine induced a statistically significant decrease in DLQI in 22 (66%) of 33
patients. It is also effective in reducing symptom score in at least half of the
patients(Dastgheib L et al.)3
• 1. L.Y. McGirt, K. Vasagar, L.M. Gober, S.S. Saini and L.A. Beck; Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine; Arch
Dermatol, 142 (2006), pp. 1337-1342
• 2. R.A. Orden, H. Timble and S.S. Saini,Efficacy and safety of Sulfasalazine in patients with Chronic Idiopathic Urticaria; Ann Allergy Asthma
Immunol, 112 (1) (2014), pp. 64-70
• 3.Dastgheib L, Jowkar F, Abdollahee A, Namaz M R ; Mesalazine as a new therapeutic option for chronic idiopathic urticaria; J DermatologY Treat. 2012 Oct

14. PYODERMA GANGRENOSUM
• Anecdotal cases has been reported on the successful use of SSZ in pyoderma
gangrenosum.(Bhat 20121, Miranda 2002)2
• Mesalamine has been reported to improve Pyoderma Gangrenosum associated with
ulcerative Colitis (Lee et al)
1. R.M. Bhat; Pyoderma Gangrenosum: an update ; Indian Dermatol Online J, 3 (1) (2012 Jan), pp. 7-13
2. M.F.M. Miranda; Pyoderma gangrenosum treated with sulfasalazine and dapsone; Indian J Dermatol Venereol Leprol, 68 (3) (2002), pp. 160-161
3. Lee JI, Park HJ, Lee JY, Cho BK. A case of pyoderma gangrenosum with ulcerative colitis treated with mesalazine. Ann Dermatol. 2010 Nov;22(4):422-5. doi: 10.5021/ad.2010.22.4.422.
Epub 2010 Nov 5. PMID: 21165212; PMCID: PMC2991719.

15. REACTIVE ARTHRITIS
A Case Report study done by Thomson et al1. in a patient with Chronic
Reiter’s Syndrome non-reactive to NSAIDS showed response to mesalamine
therapy :
- Improvement in joint pain
- Improvement in morning stiffness and
- Improvement in fatigue
- Symptoms returned after cessation of therapy.
- His disease again went into remission after reintroduction
of mesalamine.
1. Thomson G T, McKibbon C, Inman R D; Mesalamine therapy in Reiter's syndrome; J Rheumatol. 1994 Mar.

16. ADVERSE EFFECTS
• SULFASALAZINE:
GI: Nausea, Vomiting, Dyspepsia, Anorexia, Abdominal Pain and
Diarrhrea
Haematologic : Leucopenia( Most common), Macrocytic anemia,
Haemolysis in G6PD Deficiency
Dermatologic : Maculopapular,pruritic, generalized rashes; Steven
Johnson Syndrome, Toxic Epedermal Necrolysis; Erythema Multiforme,
Lichenoid Eruptions, Phototoxicity
Fertility: Oligospermia( reversible) [No effect in female fertility]
Respiratory: Eosinophilic Pneumonia, Peripheral Eosinophilia, Interstitial
inflammation with or without fibrosis.

17. • MESALAZINE:
Headache
Dyspepsia
Skin Rash
Nephrotoxic : Interstitial Nephritis
• OLSALAZINE:
Diarrhea: due to stimulation of Chloride Channel in small intestine

18. DRUG INTERACTIONS
• SULFASALAZINE:
1. SSZ inhibits thio-purine methyl transferase enzyme activity and
thus may potentiate azathioprine toxicity.
2. SSZ reduces the absorption of folic acid and digoxin.
3. SSZ can increase the effects of oral hypoglycemic drugs and the
anticoagulant effect of warfarin.
• MESALAMINE:
1. PPIs: decreases Mesalamine effects by increasing gastric pH
2. Live Vaccines[Measles, Mumps, Rubella, Varicella]: may precipitate
Reye’s syndrome
3. NSAIDS: increases toxicity by pharmacokinetic synergism
4. Thiazide Diuretics: increases renal tubular reabsorption

19. CONTRAINDICATIONS
• Hypersensitivity
• Thrombocytopenia ( Platelet count less than 50,000/cmm)
• Hepatic diseases : Liver transaminases more than 2 folds of normal,
acute Hepatitis B or C , Chronic Hepatitis B
• Significant Renal Impairment
• Porphyria
• G6PD Deficiency

20. MESALAMINE AVAILABLE IN MARKET
BRAND NAME FORMULATIONS COMPANIES COST
ETIASA 500mg Sachet Packet of 1 gm sachet NOVARTIS INDIA LTD Rs 9.3
ELMES 500mg Powder Box of 1 gm powder ELDER PHARMACEUTICALS
LTD
Rs. 13
ROWASA 500mg Pellets Sachet of 1gm Granules ABBOTT Rs. 29.24
ASACUS Sachet Sachet of 1gm Granules GALACUS HEALTHCARE PVT
LTD
Rs. 32
MESACOL CR 1gm Granules Packet of 1 sachet SUN PHARMACEUTICAL
INDUSTRIES LTD
Rs. 39
VEGAZ OD 1gm Sachet Sachet of 1.66 gm grains DR. REDDY’S LABORATORIES
LTD
Rs. 40
PANTESA Tablet Strip of 10 Tablets MOTHOR REMEDIES Rs. 41
MESLATAJ 500mg pellets Bottle of 1 pellets TAJ PHARMA INDIA LTD Rs. 55
TIDOCOL 400mg Tablet Strip of 10 tablets TORRENT
PHARMACEUTICALS LTD
Rs. 57.9
MOSART TABLET DR Strip of 10 Tablets DR CADILA PHARMACEUTICALS
LTD
Rs. 58.6

21. REFERENCES
• Sabha Mushtaq MD, Rashmi Sarkar MD, Sulfasalazine in dermatology: a lesser explored drug with broad therapeutic
potential, International Journal of Women’s Dermatology.
• R. Bharti and S. Girgla, Sulfasalazine in treatment of psoriasis,Indian J Dermatol Venereol Leprol, 62 (2) (1996), pp. 87-88
• M. El-Mofty, M. El-Darouti, H. Rasheed, D.A. Bassiouny, M. Abdel-Halim, N.S. Zaki et al., Sulfasalazine and Pentoxyphylline
in posriais: A possible safe alternative, J Dermatology Treat, 22 (2011), pp. 31-37
• .A.K.Gupta, Sulfasalazine improves psoriasis; Arch Dermatol, 126 (4) (1990), p. 487.
• L. Marguerie, R.M. Flipo, B. Grardel, D. Beaurain, B. Duquesnoy and B. Delcambre; Use of disease modifying antirheumatic
drugs in patients with psoriatic arthritis , Joint Bone Spine, 69 (3) (2002), pp. 275-281
• . M. Li, Y. Zhang, H. Xu, Z.Q. Chen and Y.M. Li; A case of acrodermatitis continua of Hallopeau (ACH) successfully treated
with sulfasalazine, Dermatol Ther, 31 (2018)
• R. Bharti, Indian J Dermatol Venereol Leprol. Jul-Aug 1996;62(4):231-2]
• S. Aghaei, An uncontrolled open label study of sulfasalazine in severe Alopecia Areata, Indian J Dermatol Venereol
Leprol, 74 (6) (2008), pp. 611-6
• C.N. Ellis, M.F. Brown and J.J. Voorhees; Sulfasalazine for Alopecia Areata; J Am Acad Dermatol, 46 (4) (2002), pp. 541-544
• Mahgoob RAS, Elgamal EE, Elshahat OM, Almetwaly SA. Comparative study between the efficacies of azathioprine and
mesalazine in the treatment of severe alopecia areata. J Cosmet Dermatol. 2021 Dec 16. doi: 10.1111/jocd.14687. Epub
ahead of print. PMID: 34918459.
• Sardella A, Demarosi F, Oltolina A, Rimondini L, Carrassi A. Efficacy of topical mesalazine compared with clobetasol
propionate in treatment of symptomatic oral lichen planus. Oral Dis. 1998 Dec;4(4):255-9. doi: 10.1111/j.1601-
0825.1998.tb00289.x. PMID: 10200704.

22. REFERENCES
• Alstead EM, Wilson AG, Farthing MJ. Lichen planus and mesalazine. J Clin Gastroenterol. 1991 Jun;13(3):335-7. doi:
10.1097/00004836-199106000-00018. PMID: 1676716.
• L.Y. McGirt, K. Vasagar, L.M. Gober, S.S. Saini and L.A. Beck; Successful treatment of recalcitrant chronic idiopathic urticaria with
sulfasalazine; Arch Dermatol, 142 (2006), pp. 1337-1342
• R.A. Orden, H. Timble and S.S. Saini,Efficacy and safety of Sulfasalazine in patients with Chronic Idiopathic Urticaria; Ann Allergy
Asthma Immunol, 112 (1) (2014), pp. 64-70
• Jowkar F, Abdollahee A, Namaz M R ; Mesalazine as a new therapeutic option for chronic idiopathic urticaria; J Dermatolog Treat. 2012
Oct
• R.A. Orden, H. Timble and S.S. Saini,Efficacy and safety of Sulfasalazine in patients with Chronic Idiopathic Urticaria; Ann Allergy
Asthma Immunol, 112 (1) (2014), pp. 64-70
• Jowkar F, Abdollahee A, Namaz M R ; Mesalazine as a new therapeutic option for chronic idiopathic urticaria; J Dermatolog Treat. 2012
Oct
• R.M. Bhat; Pyoderma Gangrenosum: an update ; Indian Dermatol Online J, 3 (1) (2012 Jan), pp. 7-13
• Lee JI, Park HJ, Lee JY, Cho BK. A case of pyoderma gangrenosum with ulcerative colitis treated with mesalazine. Ann Dermatol. 2010
Nov;22(4):422-5. doi: 10.5021/ad.2010.22.4.422. Epub 2010 Nov 5. PMID: 21165212; PMCID: PMC2991719
• Thomson G T, McKibbon C, Inman R D; Mesalamine therapy in Reiter's syndrome; J Rheumatol. 1994 Mar.
• Stephen E. Wolvorten, MD; Jashin J. Wu,MD; Comprehensive Dermatologic Drug Therapy; 4TH Edition
• Goodman & Gilman’s The Pharmacological Basics of Therapeutics, 12TH Edition.