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{{Short description|Chemical compound}}
{{Use dmy dates|date=March 2024}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Verifiedfields = changed
| verifiedrevid = 460764435
| Watchedfields = changed
| verifiedrevid = 408904051
| IUPAC_name = 2-hydroxy-5-phenyl}diazen-1-yl]benzoic acid
| image = Sulfasalazine.svg | image = Sulfasalazine.svg
| alt =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Azulfidine | tradename = Azulfidine, Salazopyrin, Sulazine, others
| Drugs.com = {{drugs.com|monograph|sulfasalazine}} | Drugs.com = {{drugs.com|monograph|sulfasalazine}}
| MedlinePlus = a682204 | MedlinePlus = a682204
| DailyMedID = Sulfasalazine
| pregnancy_category =
| legal_status = | pregnancy_AU = A
| pregnancy_AU_comment = <ref name="Drugs.com Pregnancy">{{cite web | title=Sulfasalazine Use During Pregnancy | website=Drugs.com | date=9 November 2018 | url=https://www.drugs.com/pregnancy/sulfasalazine.html | access-date=24 January 2020}}</ref>
| routes_of_administration = oral
| pregnancy_category=
| routes_of_administration = ]
| class = Sulfonamides
| ATC_prefix = A07
| ATC_suffix = EC01

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref name="UK sulfasalazine label">{{cite web | title=Sulfasalazine 250mg/5ml Oral Suspension - Summary of Product Characteristics (SmPC) | website=electronic medicines compendium (emc) | date=13 September 2019 | url=https://www.medicines.org.uk/emc/product/413/smpc | access-date=4 December 2019}}</ref><ref name=UKlabel2014 />
| legal_US = Rx-only
| legal_US_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = <!--For countries not listed above-->


<!--Pharmacokinetic data--> <!--Pharmacokinetic data-->
| bioavailability = <15%<references/> | bioavailability = <15%
| metabolism = | metabolism =
| elimination_half-life = 5-10 hours | elimination_half-life = 5-10 hours
| excretion = drug metabolites are excreted in urine and feces <ref name=Dav2014 />
| excretion =


<!--Identifiers--> <!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 599-79-1 | CAS_number = 599-79-1
| ATC_prefix = A07 | PubChem = 5339
| ATC_suffix = EC01
| PubChem = 5384001
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00795 | DrugBank = DB00795
Line 35: Line 57:
| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00448 | KEGG = D00448
| KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = C07316
| ChEBI = 9334
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = <!-- blanked - oldvalue: 421 --> | ChEMBL = 421
| synonyms = Sulphasalazine, SSZ
| C=18 | H=14 | N=4 | O=5 | S=1

| molecular_weight = 398.394 g/mol
<!--Chemical data-->
| smiles = O=S(=O)(Nc1ccccn1)c3ccc(/N=N/c2cc(C(O)=O)c(O)cc2)cc3
| IUPAC_name = 2-hydroxy-5-phenyl}diazen-1-yl]benzoic acid
| InChI = 1/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25)
| C=18 | H=14 | N=4 | O=5 | S=1
| InChIKey = NCEXYHBECQHGNR-UHFFFAOYAO
| SMILES = C1=CC=NC(=C1)NS(=O)(=O)C2=CC=C(C=C2)N=NC3=CC(=C(C=C3)O)C(=O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25) | StdInChI = 1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NCEXYHBECQHGNR-UHFFFAOYSA-N | StdInChIKey = NCEXYHBECQHGNR-UHFFFAOYSA-N
| melting_point = 240
| melting_high = 245
| melting_notes = (dec.)
}} }}


<!-- Definition and medical uses -->
'''Sulfasalazine''' (brand name '''Azulfidine''' in the ], '''Salazopyrin''' in ] and ]) is a ], a derivative of ] (also called 5-aminosalicylic acid, or 5-ASA), used primarily as an anti-inflammatory agent in the treatment of ] as well as for ] and enthesitis related arthritis like juvenile spondyloarthropathies. It may be abbreviated '''SSZ'''. It is not a pain killer, but a ] or a mutual prodrug of ] and 5-amino salicylic acid coupled with an azo linkage.
'''Sulfasalazine''', sold under the brand name '''Azulfidine''' among others, is a ] used to treat ], ], and ].<ref name=AHFS2016/> It is considered by some to be a first-line treatment in rheumatoid arthritis.<ref name=WHO2008/> It is taken ] or can be administered rectally.<ref name=AHFS2016/>


<!-- Side effects -->
==Indications==
Significant side effects occur in about 25% of people.<ref name=WHO2008/> Commonly these include loss of appetite, nausea, headache, and rash.<ref name=AHFS2016/> Severe side effects include ], ], ], and ].<ref name=WHO2008/><ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=464}}</ref><ref name=Dav2014>{{Cite book|title=Davis's drug guide for nurses| vauthors = Vallerand AH, Sanoski CA, Deglin JH |isbn=978-0-8036-4085-6|edition=Fourteenth|location=Philadelphia|oclc=881473728|date = 5 June 2014}}</ref> It should not be used in people allergic to ] or ].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | pages=41, 45 }}</ref> Use during ] appears to be safe for the baby.<ref name=AHFS2016/>
:''See also ]s for its role in ]''


<!-- Mechanism -->
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ] and ]. It is also indicated for use in ] and used in other types of inflammatory arthritis (e.g. ]) where it has a beneficial affect. It is often well tolerated compared to other ].
Sulfasalazine is in the ] (DMARDs) family of medications.<ref name=AHFS2016/> It is unclear exactly how it works.<ref name=AHFS2016/> One proposed mechanism is the inhibition of ]s, resulting in local ] effects in the colon.<ref name=Dav2014 /> The medication is broken down by ] into ] and ].<ref name="AHFS2016" />


<!-- Society and culture -->
In recent British research involving animal studies, and more recently, human trials for the treatment of chronic alcoholics, sulfasalazine has been found to reverse the scarring associated with cirrhosis of the liver. Cells called myofibroblasts, which contribute to scar tissue in a diseased liver, also appear to secrete proteins that prevent the breakdown of the scar tissue. Sulfasalazine appears to retard this secretion.
Sulfasalazine was approved for medical use in the United States in 1950.<ref name=AHFS2016>{{cite web|title=Sulfasalazine|url=https://www.drugs.com/monograph/sulfasalazine.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221012800/https://www.drugs.com/monograph/sulfasalazine.html|archive-date=21 December 2016}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Sulfasalazine is available as a ].<ref name=AHFS2016/> In 2020, it was the 284th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022}}</ref><ref>{{cite web | title = Sulfasalazine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Sulfasalazine | access-date = 7 October 2022}}</ref>


==Medical uses==
A study at ] found that the drug may also act to aid the healing of ].<ref name="urlBBC NEWS | Health | Drug may reverse liver disease">{{cite news |url=http://news.bbc.co.uk/1/hi/health/5382172.stm |title= Drug 'may reverse liver disease' |format= |work= BBC News|accessdate= 2010-05-24| date=2006-09-26}}</ref>
Sulfasalazine is used in the treatment of ], including ] and ]. It is also indicated for use in ] and used in other types of inflammatory arthritis (e.g. ] and ]).<ref name=USlabel2014>{{cite web | title=Azulfidine- sulfasalazine tablet | website=DailyMed | date=8 May 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddbe69f3-bd55-45f3-a64f-f60226c744c4 | archive-url=https://web.archive.org/web/20151029144549/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddbe69f3-bd55-45f3-a64f-f60226c744c4 | archive-date=29 October 2015 | url-status=live | access-date=24 January 2020 }}</ref><ref name=UKlabel2014>{{cite web|title=Salazopyrin Tablets - Summary of Product Characteristics|url=https://www.medicines.org.uk/emc/medicine/3344|publisher=electronic medicines compendium (emc) |date=February 2014|url-status=live|archive-url=https://web.archive.org/web/20170416220909/https://www.medicines.org.uk/emc/medicine/3344|archive-date=16 April 2017}}</ref><ref name="UK sulfasalazine label" />


It is usually not given to children under 2 years of age. It is usually not given to children under two years of age.<ref name=UKlabel2014/><ref name="UK sulfasalazine label" />


==Side effects==
The use of sulfasalazine in inflammatory bowel disease has declined due mainly to the fact that it yields the metabolite ] which gives rise to side-effects such as ] and ]. However, the other metabolite of sulfasalazine, ] (5-ASA) is attributed to the drug's therapeutic effect. Therefore, 5-ASA and other derivatives of 5-ASA, are now usually preferred and given alone (as ]), despite their increased cost, due to their more favourable side-effect profile.
Use of sulfasalazine is contraindicated in people with ] and in those with ]s, ], and severe ] or ].<ref name=Dav2014 />


Sulfasalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/L are associated with side effects. In rare cases, sulfasalazine can cause severe ] in young males. It can also cause oligospermia and temporary ]. Immune ] has been reported.<ref name="pmid17551063">{{cite journal | vauthors = Cantarini L, Tinazzi I, Biasi D, Fioravanti A, Galeazzi M | title = Sulfasalazine-induced immune thrombocytopenia | journal = Postgraduate Medical Journal | volume = 83 | issue = 980 | pages = e1 | date = June 2007 | pmid = 17551063 | pmc = 2600053 | doi = 10.1136/pgmj.2006.055194 }}</ref>
Sulfasalazine has also been used successfully to treat cases of idiopathic ] that do not respond to antihistamines.<ref name="pmid17043190">{{cite journal |author=McGirt LY, Vasagar K, Gober LM, Saini SS, Beck LA |title=Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine |journal=Arch Dermatol |volume=142 |issue=10 |pages=1337–1342 |year=2006 |month=Oct |pmid=17043190 |doi= 10.1001/archderm.142.10.1337|url=}}</ref>


Sulfasalazine inhibits ], and can cause ] and ].<ref>{{EMedicine|article|179037|Inflammatory Bowel Disease|workup}}</ref><ref>Women With Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine; {{cite web |url=http://www.medscape.org/viewarticle/720225_7 |title=Women with Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine |access-date=8 March 2012 |url-status=live |archive-url=https://web.archive.org/web/20111021082209/http://www.medscape.org/viewarticle/720225_7 |archive-date=21 October 2011 }}</ref><ref>{{cite journal | vauthors = Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA | title = Folic acid antagonists during pregnancy and the risk of birth defects | journal = The New England Journal of Medicine | volume = 343 | issue = 22 | pages = 1608–1614 | date = November 2000 | pmid = 11096168 | doi = 10.1056/NEJM200011303432204 | doi-access = free }}</ref> and various other undesirable effects.<ref>{{cite journal | vauthors = Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS, Stockwell BR | display-authors = 6 | title = Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis | journal = eLife | volume = 3 | pages = e02523 | date = May 2014 | pmid = 24844246 | pmc = 4054777 | doi = 10.7554/eLife.02523 | doi-access = free }}</ref>
==Mode of action==
Sulfasalazine, and its metabolite 5-ASA, are poorly absorbed from the gut. Its main mode of action is therefore believed to be inside the intestine.


Sulfasalazine can cause ] in people with ].<ref>{{cite web | url = https://www.merckmanuals.com/professional/appendixes/brand-names-of-some-commonly-used-drugs?search=sulfasalazine | title = SulfaSALAzine: Drug Information Provided by Lexi-Comp | access-date = 28 July 2012 | date = Jan 2012 | publisher = ] | url-status = unfit | archive-url = https://web.archive.org/web/20110829125852/http://www.merckmanuals.com/professional/lexicomp/sulfasalazine.html | archive-date = 29 August 2011 }}</ref>
===Bowel disease===
In Crohn's disease and ulcerative colitis, it is thought to be an antinflammatory drug that is essentially providing topical relief inside the intestine. It does this via a number of mechanisms such as reducing the synthesis of inflammatory mediators known as ] and inflammatory ]. However, unlike ] (another class of drug used in the treatment in ]), sulfasalazine has no ] action.


Sulfasalazine can cause kidney stones.<ref>{{cite journal | vauthors = De Koninck AS, Groen LA, Maes H, Verstraete AG, Stove V, Delanghe JR | title = An Unusual Type of Kidney Stone | journal = Clinical Laboratory | volume = 62 | issue = 1–2 | pages = 235–239 | date = 2016 | pmid = 27012055 | doi = 10.7754/Clin.Lab.2015.150605 | hdl-access = free | hdl = 1854/LU-6847821 | url = https://biblio.ugent.be/publication/6847821 }}</ref>
===Arthritis===
Sulfasalazine may cause stomach upset, ], vomiting, loss of ], headache, ], or unusual tiredness.<ref name=AHFS2016/> Skin and urine can become orange, with occasional allergic reactions.<ref>{{cite web|title=Sulfasalazine|url=http://www.webmd.com/drugs/2/drug-6260/sulfasalazine-oral/details|website=WebMD|url-status=live|archive-url=https://web.archive.org/web/20160126171655/http://www.webmd.com/drugs/2/drug-6260/sulfasalazine-oral/details|archive-date=26 January 2016}}</ref><ref name=AHFS2016/>
When treatment for arthritis is successful, pain, joint swelling and stiffness will be reduced and this may slow down or stop the development of joint damage. The precise reasons why sulfasalazine are effective in various forms of arthritis is not clearly understood.


Sulfasalazine may cause ].{{Citation needed|date=September 2019}}
Because sulfasalazine and its metabolite 5-ASA are poorly absorbed into the bloodstream, it is surprising that the drug is effective against symptoms outside of the intestine. One possible explanation is that, given that ulcerative colitis produces arthritic symptoms, the arthritic symptoms are actually a product of unrecognized ulcerative colitis, which is effectively treated with sulfazalazine.


==Pharmacology==
The other metabolite, sulfapyridine, is absorbed into the blood, and is believed to be the source of the side-effects discussed below. It is possible that the sulfapyridine is responsible for some of the anti-arthritic effects of sulfasalazine.
Around 90% of a dose of sulfasalazine reaches the colon, where most of it is metabolized by bacteria into ] and ] (also known as 5-aminosalicylic acid or 5-ASA). Both metabolites are active; most of the sulfapyridine is absorbed and then further metabolized, but most mesalazine is not, and remains in the colon.<ref name=UKlabel2014/>


A mix of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine, as is acetylated mesalazine and unmetabolized sulfasalazine.<ref name=UKlabel2014/><ref name="UK sulfasalazine label" />
==Side effects==
Refer to external links for a full listing of known side effects.
In rare cases, Sulfasalazine can cause severe ] in young males. It can also cause temporary ]. <ref>http://www.medic8.com/medicines/Azulfidine.html</ref>


The mechanism of action is not clear, but it appears that sulfasalazine and its metabolites have ], antibacterial, and anti-inflammatory effects.<ref name=USlabel2014/><ref name=UKlabel2014/> It also appears to inhibit the ]-] ],<ref>{{cite journal | vauthors = Bridges RJ, Natale NR, Patel SA | title = System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS | journal = British Journal of Pharmacology | volume = 165 | issue = 1 | pages = 20–34 | date = January 2012 | pmid = 21564084 | pmc = 3252963 | doi = 10.1111/j.1476-5381.2011.01480.x }}</ref> as well as ].<ref name="pmid22178186">{{cite journal | vauthors = Costigan M, Latremoliere A, Woolf CJ | title = Analgesia by inhibiting tetrahydrobiopterin synthesis | journal = Current Opinion in Pharmacology | volume = 12 | issue = 1 | pages = 92–99 | date = February 2012 | pmid = 22178186 | pmc = 3288148 | doi = 10.1016/j.coph.2011.10.019 }}</ref>
Sulfsalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/l are associated with side effects.


==Chemistry==
Immune ] has been reported.<ref name="pmid17551063">{{cite journal |author=Cantarini L, Tinazzi I, Biasi D, Fioravanti A, Galeazzi M |title=Sulfasalazine-induced immune thrombocytopenia |journal=Postgraduate medical journal |volume=83 |issue=980 |pages=e1 |year=2007 |month=June |pmid=17551063 |pmc=2600053 |doi=10.1136/pgmj.2006.055194 |url=}}</ref>
It is a ] which is a combination of ] and ] coupled with an azo linkage.


==References== ==Cost==
In people with rheumatoid arthritis, the ] of sulfasalazine is improved by combining it with other drugs.<ref>{{cite journal | vauthors = Benucci M, Saviola G, Manfredi M, Sarzi-Puttini P, Atzeni F | title = Cost effectiveness analysis of disease-modifying antirheumatic drugs in rheumatoid arthritis. A systematic review literature | journal = International Journal of Rheumatology | volume = 2011 | pages = 845496 | date = 2011 | pmid = 22162693 | pmc = 3228304 | doi = 10.1155/2011/845496 | doi-access = free }}</ref> It is commonly used in treating ] in part due to its cost effectiveness.<ref name="Bau2017">{{cite book| vauthors = Baumgart DC |url=https://books.google.com/books?id=zLE-DgAAQBAJ&dq=Sulfasalazine+cost&pg=PA395|title=Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach|date=2017|publisher=Springer|isbn=978-3-319-33703-6|page=395|language=en}}</ref>
{{reflist}}


==External links== ==Research==
Sulfasalazine has been studied in ],<ref name=Oakely2005>{{cite journal | vauthors = Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA | display-authors = 6 | title = Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis | journal = Gastroenterology | volume = 128 | issue = 1 | pages = 108–120 | date = January 2005 | pmid = 15633128 | doi = 10.1053/j.gastro.2004.10.003 | doi-access = free }}</ref> ],<ref name=Aditya1990>{{cite journal | vauthors = Gupta AK, Ellis CN, Siegel MT, Duell EA, Griffiths CE, Hamilton TA, Nickoloff BJ, Voorhees JJ | display-authors = 6 | title = Sulfasalazine improves psoriasis. A double-blind analysis | journal = Archives of Dermatology | volume = 126 | issue = 4 | pages = 487–493 | date = April 1990 | pmid = 1690970 | doi = 10.1001/archderm.1990.01670280071013 }}</ref> idiopathic ],<ref name="pmid17043190">{{cite journal | vauthors = McGirt LY, Vasagar K, Gober LM, Saini SS, Beck LA | title = Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine | journal = Archives of Dermatology | volume = 142 | issue = 10 | pages = 1337–1342 | date = October 2006 | pmid = 17043190 | doi = 10.1001/archderm.142.10.1337 | doi-access = }}</ref> and ].<ref name="pmid26576950">{{cite journal | vauthors = Brumshtein B, Esswein SR, Salwinski L, Phillips ML, Ly AT, Cascio D, Sawaya MR, Eisenberg DS | display-authors = 6 | title = Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain | journal = eLife | volume = 4 | pages = e10935 | date = November 2015 | pmid = 26576950 | pmc = 4758944 | doi = 10.7554/eLife.10935 | doi-access = free }}</ref>
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== References ==
* {{dead link|date=November 2011}}
{{Reflist}}


{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}} {{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
{{Antirheumatic products}} {{Antirheumatic products}}
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