PHENACETIN

US Previously Marketed

First marketed in 1887

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H13NO2
Molecular Weight	179.2157
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=CC=C(NC(C)=O)C=C1

InChI

InChIKey=CPJSUEIXXCENMM-UHFFFAOYSA-N

InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)

HIDE SMILES / InChI

Molecular Formula	C10H13NO2
Molecular Weight	179.2157
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18140117 | https://www.ncbi.nlm.nih.gov/pubmed/3552585 | https://www.ncbi.nlm.nih.gov/pubmed/12242329 | https://www.ncbi.nlm.nih.gov/pubmed/14592552

Phenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol, it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite, paracetamol, whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite, p-phenetidine. Phenacetin was shown to inhibit cyclooxygenase (COX)-3, a cyclooxygenase-1 variant while p-phenetidine potently inhibits both COX-1 and COX-2. There is sufficient evidence in humans for the carcinogenicity of analgesic mixtures containing phenacetin. Analgesic mixtures containing phenacetin cause cancer of the renal pelvis, and of the ureter. Phenacetin was withdrawn from many analgesic mixtures long before the legal ban in several countries.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Prostaglandin G/H synthase 1 30 Target ID: Q8HZR1 Gene ID: 403544.0 Gene Symbol: PTGS1 Target Organism: Canis lupus familiaris (Dog) (Canis familiaris) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12242329	Inhibitor 8504	102.0 µM [IC50]
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552	Inhibitor 8504
Cyclooxygenase-2 201 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337 https://www.ncbi.nlm.nih.gov/pubmed/3552585	Primary		Withdrawn	Phenacetin Approved Use Phenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Launch Date 1886

C_max

Value	Dose	Analyte	Population
13.5 μg/mL EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.5 μg/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.9 μg/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.84 μg/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.48 μg/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
20.72 μg × h/mL EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.3 μg × h/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
40.4 μg × h/mL EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.84 μg × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.58 μg × h/mL EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
0.6 h EXPERIMENT https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/j.1552-4604.1974.tb02323.x	1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.9 h EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.6 h EXPERIMENT https://journals.lww.com/drug-monitoring/Abstract/1998/08000/Effect_of_Active_and_Passive_Cigarette_Smoking_on.2.aspx	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	ACETAMINOPHEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.1 h EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.98 h EXPERIMENT https://www.jstage.jst.go.jp/article/jscpt1970/19/4/19_4_767/_pdf	900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENACETIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23607050/			PHENACETIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	unhealthy, 34 years Health Status: unhealthy Age Group: 34 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	Other AEs: Nephropathy... Other AEs: Nephropathy Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/
250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	unhealthy, 54 years Health Status: unhealthy Age Group: 54 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	Other AEs: Nephropathy... Other AEs: Nephropathy Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/
1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	unhealthy, 56 years Health Status: unhealthy Age Group: 56 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	Other AEs: Transitional cell carcinoma... Other AEs: Transitional cell carcinoma Sources: https://pubmed.ncbi.nlm.nih.gov/831357/
625 mg 1 times / day multiple, oral Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	unhealthy, 85 years Health Status: unhealthy Age Group: 85 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	Other AEs: Urothelial carcinoma... Other AEs: Urothelial carcinoma Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/
0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	healthy, age 18 to 44 years Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	Other AEs: Nephritis NEC... Other AEs: Nephritis NEC (20%) Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/

AEs

AE	Significance	Dose	Population
Nephropathy		1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/	unhealthy, 34 years Health Status: unhealthy Age Group: 34 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/6025701/
Nephropathy		250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/	unhealthy, 54 years Health Status: unhealthy Age Group: 54 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/5915057/
Transitional cell carcinoma		1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/831357/	unhealthy, 56 years Health Status: unhealthy Age Group: 56 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/831357/
Urothelial carcinoma		625 mg 1 times / day multiple, oral Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/	unhealthy, 85 years Health Status: unhealthy Age Group: 85 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/21318943/
Nephritis NEC	20%	0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/	healthy, age 18 to 44 years Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/5327673/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197 CYP2E1 729 CYP1A1 389 CYP2C19 1119

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	inconclusive
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC298137/pdf/pnas00287-0044.pdf#page=1 Page: 1.0	major	yes (co-administration study) Comment: cigarette smoking induced CYP1A2 and increased O-deethylase activity Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC298137/pdf/pnas00287-0044.pdf#page=1 Page: 1.0
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10627170/ Page: 1.0	minor
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0	minor

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8050	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8050
ChemicalBook	CB44796969	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB44796969
ChemicalBook	CB6141828	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6141828
eMolecules	490668	https://www.emolecules.com/cgi-bin/more?vid=490668
MolPort	MolPort-000-626-710	https://www.molport.com/shop/molecule-link/MolPort-000-626-710
Selleck Chemicals	phenacetin	http://www.selleckchem.com/products/phenacetin.html
ZINC	ZINC000000000602	http://zinc15.docking.org/substances/ZINC000000000602

PubMed

Title	Date	PubMed
IS PHENACETIN A NEPHROTOXIN?A REPORT ON TWENTY-THREE USERS OF THE DRUG.	1964 Aug	14180501
Analgesic abuse, ureteric obstruction, and retroperitoneal fibrosis.	1975 Apr 12	1131554
Letter: The clinical course of patients with analgesic nephropathy.	1975 Aug 9	1139519
The induction of renal papillary necrosis in Gunn rats by analgesics and analgesic mixtures.	1975 Feb	1203171
The radiological diagnosis of analgesic nephropathy.	1975 Jul	1201638
Epidemiology and etiology of premalignant and malignant urothelial changes.	2000	11144890
A population approach to enzyme characterization and identification: application to phenacetin O-deethylation.	2000 Dec	11303964
[Determination of three components in compound chlorophenamine tablet by iterative target transformation factor analysis].	2001 Apr	12947639
Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis.	2001 Apr 10	11284709
Polymer particle erosion controlling drug release. I. Factors influencing drug release and characterization of the release mechanism.	2001 Apr 17	11292550
[Simultaneous determination of aspirin, phenacetin and caffeine in compound APC by derivative ratio UV adsorption spectrum method].	2001 Aug	12945285
"No, Duke. No divorce".	2001 Aug 20	11550441
Analysis of the phase solubility diagram of a phenacetin/competitor/beta-cyclodextrin ternary system, involving competitive inclusion complexation.	2001 Jan	11201230
Relationship between nonphenacetin-combined analgesics and nephropathy.	2001 Jun	11409383
Relationship between nonphenacetin-combined analgesics and nephropathy.	2001 Jun	11409382
Relationship between nonphenacetin-combined analgesics and nephropathy.	2001 Jun	11409381
Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.	2001 Mar	11465391
Trends of analgesic nephropathy in two high-endemic regions with different legislation.	2001 Mar	11181803
Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium citrate concentration on the suppression of particle agglomeration and the physical properties of HPMC film.	2001 Mar 14	11250087
[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary].	2001 May 13	11419294
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Drug-induced hepatitis with hepatic granuloma due to saridon.	2002	12522541
Comparison of vasoconstrictor responses to selected NSAIDs in rabbit renal and femoral arteries.	2002	12061021
The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/ caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis).	2002	11999141
A straightforward means of coupling preparative high-performance liquid chromatography and mass spectrometry.	2002	11870892
Phenacetin O-deethylation in extrahepatic tissues of rats.	2002 Apr-Jun	12064368
Validated HPLC method for determination of chlorzoxazone in human serum and its application in a clinical pharmacokinetic study.	2002 Dec	12561241
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions.	2002 Dec	12433797
Method development and validation of a high-performance liquid chromatographic method for tramadol in human plasma using liquid-liquid extraction.	2002 May 25	12016023
Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules.	2002 Nov	12458672
Renal papillary necrosis.	2002 Nov-Dec	12512867
COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression.	2002 Oct 15	12242329
Analgesics and renal disease in the postphenacetin era.	2003 Aug	12900824
'Open access' generic method for continuous determination of major human CYP450 probe substrates/metabolites and its application in drug metabolism studies.	2003 Dec	14742145
Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A.	2003 Feb 14	12586202
High-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.	2003 Jan 1	12467917
HPLC analyses and pharmacokinetic studies of baicalin and oxymatrine in rabbits.	2003 Sep	14531454
Assessment of tableting properties using infinitesimal quantities of powdered medicine.	2003 Sep 16	12954193
Induction of diphenytriazol on cytochrome CYP1A.	2004 Apr	15066225
Analgesic nephropathy in Hungary: the HANS study.	2004 Apr	15031338
Phenacetin and cocaine in a body packer.	2004 Apr 20	15066715
Interaction of cyclooxygenase isoenzymes, nitric oxide, and afferent neurons in gastric mucosal defense in rats.	2004 Jan	14569068
Validated assays for human cytochrome P450 activities.	2004 Jun	15155557
Evaluation of the patient with hematuria.	2004 Mar	15049581
In vitro metabolism and inductive or inhibitive effect of DL111 on rat cytochrome P4501A enzyme.	2004 Mar 15	15013813
Evaluation of the Xpa-deficient transgenic mouse model for short-term carcinogenicity testing: 9-month studies with haloperidol, reserpine, phenacetin, and D-mannitol.	2004 Mar-Apr	15200157
[Prevention of bladder cancer].	2004 May	15150694

Patents

Sample Use Guides

In Vivo Use Guide

Analgesic mixtures containing phenacetin were previously marketed as tablets or capsules containing between 150 and 300 mg phenacetin. Common combinations were: 150 mg phenacetin, 230 mg aspirin, and 15 or 30 mg caffeine; or 150 mg phenacetin, 230 mg aspirin, 30 mg caffeine, and 8, 15, 30, or 60 mg codeine phosphate. Phenacetin alone was also available in 250 and 300 mg doses as tablets, and up to 500 mg doses as powder. The usual dose was 300 mg 4–6 times per day, and the daily dose was not to exceed 2 g

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:46:06 GMT 2025` Edited by `admin` on `Mon Mar 31 17:46:06 GMT 2025`
Record UNII	ER0CTH01H9
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PHENACETIN

Official Name

English

PHENACETINUM

Preferred Name

English

PHENACETIN [VANDF]

Common Name

English

4-ETHOXY-1-ACETYLAMINOBENZENE

Systematic Name

English

FENIDINA

Common Name

English

NSC-7651

Code

English

PHENACETIN [MART.]

Common Name

English

ACETAMIDE, N-(4-ETHOXYPHENOL)-

Common Name

English

PHENACETIN [JAN]

Common Name

English

ACETPHENETIDIN

Common Name

English

KALMIN

Common Name

English

PHENACETIN MELTING POINT STANDARD

Common Name

English

PHENACETIN [MI]

Common Name

English

PHENACETINUM [HPUS]

Common Name

English

PHENACETIN [USP-RS]

Common Name

English

PHENACETIN [IARC]

Common Name

English

PHENAZETIN

Common Name

English

phenacetin [INN]

Common Name

English

P-ACETOPHENETIDIDE

Common Name

English

Phenacetin [WHO-DD]

Common Name

English

PHENACETIN [HSDB]

Common Name

English

ACETOPHENETIDIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

N02BE53