Rifaximin

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H51N3O11
Molecular Weight	785.8785
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C2=O)C4=C(C(O)=C3C)C(O)=C(NC(=O)C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C5=C4N=C6C=C(C)C=CN56

InChI

InChIKey=NZCRJKRKKOLAOJ-XRCRFVBUSA-N

InChI=1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/cdi/rifaximin.html http://www.rxlist.com/xifaxan-drug.htm http://www.wikidoc.org/index.php/Special:Search?search=RIFAXIMIN

Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. It is FDA approved for the treatment of travelers’ diarrhea, reduction in risk of overt hepatic encephalopathy (HE) recurrence and treatment of irritable bowel syndrome with diarrhea. More common side effects are: black, tarry stools; dizziness or lightheadedness; muscle spasm; rapid breathing; shortness of breath; trouble sleeping. Co-administration of cyclosporine, with XIFAXAN resulted in 83-fold and 124-fold increases in rifaximin mean Cmax in healthy subjects.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf	Inhibitor 8504	25.0 µM [IC50]
Pregnane X receptor 36 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17442842	Activator 1447
DNA-directed RNA polymerase subunit beta 5 Target ID: P0A8V2 Gene ID: 948488.0 Gene Symbol: rpoB Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16096056	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Travelers’ diarrhea 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf	Curative	Approved 8583	XIFAXAN Approved Use To reduce the development of drug-resistant bacteria and maintain the effectiveness of XIFAXAN and other antibacterial drugs, XIFAXAN when used to treat infection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. XIFAXAN is a rifamycin antibacterial indicated for: The treatment of patients (≥ 12 years of age) with travelers’ diarrhea (TD) caused by noninvasive strains of ( ) Escherichia coli 1.1 Reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥ 18 years of age ( ) 1.2 Limitations of Use TD: Do not use in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than ( ) Escherichia coli 1.1 1.1 Travelers’ Diarrhea XIFAXAN 200 mg is indicated for the treatment of patients (≥ 12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli [see Warnings and Precautions ( ), Clinical Pharmacology ( ) and Clinical Studies ( ) Launch Date 2004
Overt hepatic encephalopathy recurrence 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf	Preventing	Approved 8583	XIFAXAN Approved Use To reduce the development of drug-resistant bacteria and maintain the effectiveness of XIFAXAN and other antibacterial drugs, XIFAXAN when used to treat infection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. XIFAXAN is a rifamycin antibacterial indicated for: The treatment of patients (≥ 12 years of age) with travelers’ diarrhea (TD) caused by noninvasive strains of ( ) Escherichia coli 1.1 Reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥ 18 years of age ( ) 1.2 Limitations of Use TD: Do not use in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than ( ) Escherichia coli 1.1 1.1 Travelers’ Diarrhea XIFAXAN 200 mg is indicated for the treatment of patients (≥ 12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli [see Warnings and Precautions ( ), Clinical Pharmacology ( ) and Clinical Studies ( ) Launch Date 2004
Irritable bowel syndrome with diarrhea 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf	Primary	Approved 8583	XIFAXAN Approved Use To reduce the development of drug-resistant bacteria and maintain the effectiveness of XIFAXAN and other antibacterial drugs, XIFAXAN when used to treat infection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. XIFAXAN is a rifamycin antibacterial indicated for: The treatment of patients (≥ 12 years of age) with travelers’ diarrhea (TD) caused by noninvasive strains of ( ) Escherichia coli 1.1 Reduction in risk of overt hepatic encephalopathy (HE) recurrence in patients ≥ 18 years of age ( ) 1.2 Limitations of Use TD: Do not use in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than ( ) Escherichia coli 1.1 1.1 Travelers’ Diarrhea XIFAXAN 200 mg is indicated for the treatment of patients (≥ 12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli [see Warnings and Precautions ( ), Clinical Pharmacology ( ) and Clinical Studies ( ) Launch Date 2004

C_max

Value	Dose	Analyte	Population
3.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg 2 times / day steady-state, oral dose: 550 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.8 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

AUC

Value	Dose	Analyte	Population
12.3 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg 2 times / day steady-state, oral dose: 550 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
11.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
22.5 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:	RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4.8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
32.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	550 mg single, oral dose: 550 mg route of administration: Oral experiment type: SINGLE co-administered:		RIFAXIMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	Disc. AE: Taste loss, Dysentery... AEs leading to discontinuation/dose reduction: Taste loss Dysentery Weight decrease Anorexia Nausea Nasal passage irritation Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
1200 mg 2 times / day multiple, oral Highest studied dose Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22155172	unhealthy, 18–73 Health Status: unhealthy Age Group: 18–73 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/22155172	Sources: https://pubmed.ncbi.nlm.nih.gov/22155172
800 mg 3 times / day multiple, oral Highest studied dose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10741936	unhealthy, 32-82 Health Status: unhealthy Age Group: 32-82 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10741936	Sources: https://pubmed.ncbi.nlm.nih.gov/10741936
550 mg 3 times / day multiple, oral Studied dose Dose: 550 mg, 3 times / day Route: oral Route: multiple Dose: 550 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27528177	unhealthy, 46.4 Health Status: unhealthy Age Group: 46.4 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27528177	Sources: https://pubmed.ncbi.nlm.nih.gov/27528177

AEs

AE	Significance	Dose	Population
Anorexia	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
Dysentery	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
Nasal passage irritation	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
Nausea	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
Taste loss	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf
Weight decrease	Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf	unhealthy, 18-79 Health Status: unhealthy Age Group: 18-79 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021361s013lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C19 2057 CYP2E1 1060	P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=23 Page: 23,30	likely
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0	yes	weak (co-administration study) Comment: Mean AUC of midazolam was 3.8% and 8.8% lower, respectively, after rifaximin was administered 3x a day for 7 days and 14 days, respectively. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=30 Page: 30.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000ClinPharmR.pdf#page=23 Page: 23,30	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022554Orig1s000PharmR.pdf#page=9 Page: 9.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75246	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75246
ChemicalBook	CB5244184	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5244184
eMolecules	26943529	https://www.emolecules.com/cgi-bin/more?vid=26943529
eMolecules	29781310	https://www.emolecules.com/cgi-bin/more?vid=29781310
eMolecules	30154455	https://www.emolecules.com/cgi-bin/more?vid=30154455
eMolecules	31590059	https://www.emolecules.com/cgi-bin/more?vid=31590059
eMolecules	32278142	https://www.emolecules.com/cgi-bin/more?vid=32278142
MolPort	MolPort-003-850-182	https://www.molport.com/shop/molecule-link/MolPort-003-850-182
MolPort	MolPort-046-416-955	https://www.molport.com/shop/molecule-link/MolPort-046-416-955
Selleck Chemicals	Rifaximin(Xifaxan)	http://www.selleckchem.com/products/Rifaximin(Xifaxan).html
ZINC	ZINC000169621200	http://zinc15.docking.org/substances/ZINC000169621200

PubMed

Title	Date	PubMed
Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria.	1995 Mar	7774516
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Rifaximin: a new treatment for travelers' diarrhea.	2005 Feb	15598963
Pharmacotherapy of hepatic encephalopathy in cirrhosis.	2010 Jun	20384539
Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoea.	2010 Jun	20331580
Solomonsterols A and B from Theonella swinhoei. The first example of C-24 and C-23 sulfated sterols from a marine source endowed with a PXR agonistic activity.	2011 Jan 13	21141967
Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity.	2011 Jul 14	21599020
Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis.	2012	22291955
Chronic exposure to rifaximin causes hepatic steatosis in pregnane X receptor-humanized mice.	2012 Oct	22790967

Patents

Sample Use Guides

In Vivo Use Guide

Travelers’ Diarrhea: The recommended dose is one 200 mg tablet taken orally three times a day for 3 days. Hepatic Encephalopathy: The recommended dose is one 550 mg tablet taken orally two times a day. Irritable Bowel Syndrome with Diarrhea: The recommended dose is one 550 mg tablet taken orally three times a day for 14 days. It can be taken with or without food.

Route of Administration: Oral

In Vitro Use Guide

The activities of rifaximin against enteropathogens were found to be as follows: a MIC50 of 4 to 8 μg/ml and a MIC90 of >8 μg/ml.

Name

Type

Language

XIFAXSAN

Preferred Name

English

Rifaximin

Official Name

English

(2S,16Z,18E,20S,21S,22R,23R,24R,25S,26R,27S,28E)-25-(ACETYLOXY)-5,6,21,23-TETRAHYDROXY-27-METHOXY-2,4,11,16,20,22,24,26-OCTAMETHYL-2,7-(EPOXYPENTADECA(1,11,13)TRIENIMINO)BENZOFURO(4,5-E)PYRIDO(1,2-A)BENZIMIDAZOLE-1,15(2H)-DIONE

Common Name

English

RIFAXIMIN [USAN]

Common Name

English

rifaximin [INN]

Common Name

English

NSC-758957

Code

English

RIFAXIMIN [VANDF]

Common Name

English

RIFAXIMIN [EP IMPURITY]

Common Name

English

RIFAXIMIN [ORANGE BOOK]

Common Name

English

RIFAMYCIN L 105

Common Name

English

RIFAXIDIN

Common Name

English

L-105

Common Name

English

RIFAXIMIN [EP MONOGRAPH]

Common Name

English

Rifaximin [WHO-DD]

Common Name

English

RIFAXIMIN [MART.]

Common Name

English

RIFAXIMIN [MI]

Common Name

English

2,7-(EPOXYPENTADECA(1,11,13)TRIENIMINO)BENZOFURO(4,5-E)PYRIDO(1,2-A)BENZIMIDAZOLE-1,15(2H)-DIONE, 25-(ACETYLOXY)-5,6,21,23-TETRAHYDROXY-27-METHOXY-2,4,11,16,20,22,24,26-OCTAMETHYL-, (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26R,27S,28E)-

Systematic Name

English

RIFAXIMIN [JAN]

Common Name

English

4-DEOXY-4'-METHYLPYRIDO(1',2'-1,2)IMIDAZO(5,4-C)RIFAMYCIN SV

Common Name

English

Classification Tree Code System Code

WHO-ATC

D06AX11