Alkyl Gallates/Benzalkonium Chloride 1629

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Alkyl Gallates/Benzalkonium Chloride 1629
Fr.: Strepsils; Strepsils Lidocaine; Strepsils Miel-Citron; Strepsils Vitamine C;
Strepsilspray Lidocaine; Ger.: Dobendan Synergie; Neo-Angin; Gr.: Strepsils; Hong Kong: Strepsils; Strepsils Dual Action; Hung.: Neo-Angin; Strepsils; Strepsils Menthol and Eucalyptus; Strepsils Plus; Strepsils Vitamin C; India: Cof Q; Cofsils†; Irl.: Strepsils; Strepsils +Plus Anaesthetic; Strepsils
Dual Action; Strepsils Vitamin C; Israel: Strepsils; Strepsils Plus; Strepsils
with Menthol and Eucalyptus; Strepsils with Vitamin C; Ital.: Benagol;
Benagol Mentolo-Eucaliptolo; Benagol Vitamina C; Malaysia: Chericof;
Strepsils; Strepsils Dual Action; Neth.: Strepsils; Strepsils Menthol en Eucalyptus; Strepsils Sinaasappel en Vitamine C; NZ: Strepsils; Strepsils Plus Anaesthetic; Strepsils with Vitamin C; Philipp.: Strepsils; Pol.: Neo-Angin;
Strepsils; Rus.: Astrasept (Астрасепт); Coldact Lorpils (Колдакт
Лорпилс)†; Rinza Lorsept (Ринза Лорсепт); Strepsils (Стрепсилс); Strepsils Plus (Стрепсилс Плюс); Suprima-Lor (Суприма-Лор); S.Afr.: Strepsils;
Strepsils Eucalyptus Menthol; Strepsils Orange-C; Strepsils Plus; Strepsils
Soothing Honey & Lemon; Singapore: Strepsils; Strepsils Dual Action;
Spain: Strepsils; Strepsils con Vitamina C; Strepsils Lidocaina; Swed.: Strepsils; Switz.: Neo-Angin au miel et citron; Neo-Angin avec vitamin C sans
sucre; Neo-Angin sans sucre; Thai.: Strepsils Butter Menthol Capsicum;
Strepsils Plus Anaesthetic; Strepsils Plus Vit C; Strepsils Sugar Free; Throatsil;
Turk.: Strepsils; Strepsils C; Strepsils Mentollu; UK: Strepsils; Strepsils with
Vitamin C.
Ascorbyl Palmitate
Ascorbilo, palmitato de; Ascorbyle, palmitate d’; Ascorbylis
palmitas; Askorbilo palmitatas; Askorbylpalmitat; Askorbylpalmitát; Askorbylu palmitynian; Askorbyylipalmitaatti; Aszkorbilpalmitát; Vitamin C Palmitate. L-Ascorbic acid 6-hexadecanoate;
L-Ascorbic acid 6-palmitate; 3-Oxo-L-gulofuranolactone 6-palmitate.
C 22 H 38O 7 = 414.5.
C AS — 137-66-6.
NOTE. The code E304 is used for fatty acid esters of ascorbic acid,
which include ascorbyl palmitate.
Pharmacopoeias. In Eur. (see p.vii). Also in USNF.
Ph. Eur. 6.2 (Ascorbyl Palmitate). A white or yellowish-white
powder. Practically insoluble in water; freely soluble in alcohol
and in methyl alcohol; practically insoluble in dichloromethane
and in fatty oils. Store in airtight containers. Protect from light.
USNF 26 (Ascorbyl Palmitate). A white to yellowish-white
powder with a characteristic odour. Very slightly soluble in water, in chloroform, in ether, and in vegetable oils; soluble 1 in 125
of alcohol. Store at 8° to 15° in airtight containers.
Ascorbyl palmitate is an antoxidant used as a preservative in
pharmaceutical products and foods. It is often used with alpha
tocopherol (p.1992), and this combination shows marked synergy. As it is a fat-soluble derivative of vitamin C (ascorbic acid,
p.1983), ascorbyl palmitate is sometimes used as a source of vitamin C in nutritional supplements.
Proprietary Preparations (details are given in Part 3)
Chile: Neolucid-C.
Multi-ingredient: Hong Kong: Proflavanol†; Malaysia: Proflavanol;
Port.: Thiospot; Singapore: Proflavanol.
Benzalkonium Chloride (BAN, rINN)
Bensalkoniumklorid; Bentsalkoniumkloridi; Benzalconio Cloruro;
Benzalkonii chloridum; Benzalkonio chloridas; Benzalkoniowy
chlorek; Benzalkonium Chloratum; Benzalkonium, chlorure de;
Benzalkonium-chlorid; Benzalkónium-klorid; Benzalkonyum Klorür; Cloreto de Benzalconio; Cloruro de benzalconio.
Бензалкония Хлорид
C AS — 8001-54-5.
ATC — D08AJ01; D09AA11; R02AA16.
ATC Vet — QD08AJ01; QD09AA11; QR02AA16.
H 3C
R = C8H17 to C18H37
Pharmacopoeias. In Chin., Eur. (see p.vii), Int., and Jpn. Also
in USNF. Some pharmacopoeias also have a monograph for a solution.
Chin. also includes benzalkonium bromide.
Ph. Eur. 6.2 (Benzalkonium Chloride). A mixture of alkylbenzyldimethylammonium chlorides, the alkyl groups having chain
lengths of C8 to C18. It contains not less than 95% and not more
than 104% of alkylbenzyldimethylammonium chlorides, calculated as C22H40ClN with reference to the anhydrous substance.
A white or yellowish-white powder, or gelatinous yellowishwhite pieces, hygroscopic and soapy to the touch. It forms a clear
molten mass on heating. It contains not more than 10% of water.
Very soluble in water and in alcohol. An aqueous solution froths
copiously when shaken.
USNF 26 (Benzalkonium Chloride). A mixture of alkylbenzyldimethylammonium chlorides of the general formula
[C6H5.CH2.N(CH3)2.R]Cl, in which R represents a mixture of
the alkyls having chain lengths from C8 to C16. It contains not
less than 40% of the C12H25 compound, calculated on the anhydrous substance, not less than 20% of the C14H29 compound, and
not less than 70% of the 2 compounds together.
A white or yellowish-white, thick gel, or gelatinous pieces with
a mild aromatic odour. It contains not more than 15% of water.
Very soluble in water and in alcohol; the anhydrous form is soluble 1 in 100 of ether and 1 in 6 of benzene. A solution in water
is usually slightly alkaline and foams strongly when shaken.
Store in airtight containers.
and irritation of the eyes and throat lasting 48 hours.1 A review2
of 18 studies (14 in vivo, 4 in vitro) where benzalkonium chloride
was used as the preservative in multidose nasal products found
that 8 studies (all in vivo) found no toxic effects, while 10 reported degenerative changes to the nasal epithelia or exacerbation of
rhinitis medicamentosa. However, in only 2 of these 10 studies
were the differences between benzalkonium chloride and control
groups found to be significant, and both of these included the use
of oxymetazoline, which is known to cause rhinitis medicamentosa.
Benzalkonium chloride used as a preservative in nebulised solutions of anti-asthma drugs has been reported to cause dose-related bronchoconstriction especially in asthmatic patients,3 and has
been associated with the precipitation of respiratory arrest.4
Incompatibility. Benzalkonium chloride is incompatible with
soaps and other anionic surfactants, citrates, iodides, nitrates,
permanganates, salicylates, silver salts, tartrates, and zinc oxide
and sulfate. Incompatibilities have been demonstrated with ingredients of some commercial rubber mixes or plastics. Incompatibilities have also been reported with other substances including aluminium, cotton dressings, fluorescein sodium, hydrogen
peroxide, hypromellose, kaolin, hydrous wool fat, and some sulfonamides.
Benzalkonium chloride is not suitable for use in eye
drops containing local anaesthetics (see Effects on the
Eyes, above).
Adverse Effects, Treatment, and Precautions
As for Cetrimide, p.1634. Because some rubbers are
incompatible with benzalkonium chloride silicone rubber teats should be used on eye drop containers unless
the suitability has been established.
Catheters and cannulas. For reference to benzalkonium
chloride used in the manufacturing process of heparin-bonded
catheters interfering with determination of serum concentrations
of sodium and potassium, see under Precautions for Heparin,
Effects on the eyes. Benzalkonium chloride is one of the most
disruptive ophthalmic additives to the stability of the lipid film
and to corneal epithelial membranes;1 toxicity studies have tended to be carried out using relatively high concentrations of benzalkonium chloride2 but damage to the tear film and corneoconjunctival surface have been noted in patients receiving regular
long-term treatment for glaucoma with eye drops preserved with
benzalkonium chloride in usual concentrations.3,4
Corneal toxicity has also been reported in patients inadvertently
exposed to benzalkonium chloride as a preservative in viscoelastic material during cataract surgery.5 The use of preservatives in
eye drops should generally be avoided and the formulation of
such preparations in single-dose containers is desirable.1,2 Benzalkonium chloride is not suitable for use in solutions for storing
and washing hydrophilic soft contact lenses, as it can bind to the
lenses and may later produce ocular toxicity when the lenses are
worn.6 Similarly, benzalkonium chloride use in anaesthetic eye
drops is discouraged, as the anaesthetic component reduces the
blink reflex and increases the contact time with the eye drops
which may consequently result in increased toxicity due to the
preservative. Patients with dry eye syndrome are also at increased risk of toxicity as the corneal epithelium is exposed to the
full strength of the eye drops, in addition to which these patients
do not produce enough tears to dilute the preservative in the eye
1. Burstein NL. The effects of topical drugs and preservatives on
the tears and corneal epithelium in dry eye. Trans Ophthalmol
Soc U K 1985; 104: 402–9.
2. Burstein NL. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Surv Ophthalmol 1980; 25: 15–30.
3. Herreras JM, et al. Ocular surface alteration after long-term
treatment with an antiglaucomatous drug. Ophthalmology 1992;
99: 1082–8.
4. Kuppens EVMJ, et al. Effect of timolol with and without preservative on the basal tear turnover in glaucoma. Br J Ophthalmol 1995; 79: 339–42.
5. Eleftheriadis H, et al. Corneal toxicity secondary to inadvertent
use of benzalkonium chloride preserved viscoelastic material in
cataract surgery. Br J Ophthalmol 2002; 86: 299–305.
6. Gasset AR. Benzalkonium chloride toxicity to the human cornea.
Am J Ophthalmol 1977; 84: 169–71.
Effects on the respiratory tract. Hypersensitivity to benzalkonium chloride, used as a preservative in nasal drops, was confirmed in a patient by a challenge that produced nasal congestion
The symbol † denotes a preparation no longer actively marketed
1. Hillerdal G. Adverse reaction to locally applied preservatives in
nose drops. ORL J Otorhinolaryngol Relat Spec 1985; 47:
2. Marple B, et al. Safety review of benzalkonium chloride used as
a preservative in intranasal solutions: an overview of conflicting
data and opinions. Otolaryngol Head Neck Surg 2004; 130:
3. Committee on Drugs, American Academy of Pediatrics. "Inactive" ingredients in pharmaceutical products: update. Pediatrics
1997; 99: 268–78.
4. Boucher M, et al. Possible association of benzalkonium chloride
in nebulizer solutions with respiratory arrest. Ann Pharmacother
1992; 26: 772–4.
Uses and Administration
Benzalkonium chloride is a quaternary ammonium antiseptic and disinfectant with actions and uses similar
to those of the other cationic surfactants (see Cetrimide, p.1634). It is also used as an antimicrobial preservative for pharmaceutical products. Benzalkonium bromide and benzalkonium saccharinate have also been
Solutions of benzalkonium chloride 0.01 to 0.1% are
used for cleansing skin, mucous membranes, and
wounds. More dilute solutions of 0.005% are suitable
for irrigation of deep wounds. A 0.02 to 0.05% solution
has been used as a vaginal douche. An aqueous solution containing 0.005 to 0.02% has been used for irrigation of the bladder and urethra and a 0.0025 to
0.005% solution for retention lavage of the bladder.
Creams containing benzalkonium chloride are used in
the treatment of napkin rash and other dermatoses.
A 0.2 to 0.5% solution has been used as a shampoo in
seborrhoeic dermatitis.
Lozenges containing benzalkonium chloride are used
for the treatment of superficial infections of the mouth
and throat.
Benzalkonium chloride is used as a preservative in
ophthalmic solutions at a concentration of 0.01 to
0.02%, and in nasal and otic solutions at a concentration of 0.002 to 0.02%. Benzalkonium chloride is used
for disinfecting rigid contact lenses (p.1622) but is
unsuitable as a preservative in solutions for washing
and storing hydrophilic soft contact lenses (see also Effects on the Eyes, above).
Benzalkonium chloride is also used as a spermicide.
Solutions of 0.13% are used for disinfection and storage of surgical instruments, sometimes with the addition of sodium nitrite to inhibit rust.
Action. The antibacterial effect of benzalkonium chloride
0.003% was enhanced by 0.175% of benzyl alcohol, phenylpropanol, or phenethyl alcohol.1 For the use of phenethyl alcohol
with benzalkonium chloride as a preservative for ophthalmic solutions, see Antimicrobial Action, under Phenethyl Alcohol,
1. Richards RME, McBride RJ. Enhancement of benzalkonium
chloride and chlorhexidine acetate activity against Pseudomonas
aeruginosa by aromatic alcohols. J Pharm Sci 1973; 62: 2035–7.
Catheter-related sepsis. Benzalkonium chloride has been
investigated1,2 for incorporation into catheters to reduce catheterrelated sepsis (p.1624).
1. Tebbs SE, Elliott TSJ. A novel, antimicrobial central venous
catheter impregnated with benzalkonium chloride. J Antimicrob
Chemother 1993; 31: 261–71.
2. Moss HA, et al. A central venous catheter coated with benzalkonium chloride for the prevention of catheter-related microbial
colonization. Eur J Anaesthesiol 2000; 17: 680–7.
The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)
1630 Disinfectants and Preservatives
USP 31 (Benzethonium Chloride). White crystals with a mild
odour. Soluble 1 in less than 1 of water, of alcohol, and of chloroform, and 1 in 6000 of ether. A 1% solution in water is slightly
alkaline to litmus. Store in airtight containers. Protect from light.
USNF 26: Benzalkonium Chloride Solution.
Proprietary Preparations (details are given in Part 3)
Arg.: Benzalcream†; Hidratant; Pharmatex; Usnicon†; Austral.: Bepanthen;
Dettol Fresh; Belg.: Cedium; Braz.: Bacterian†; Fluimucil Solucao Nasal;
Canad.: Antiseptic Skin Cream†; Chile: Germosept; Cz.: Pharmatex; Fr.:
Humex; Pharmatex; Sparaplaie; Ger.: Baktonium†; Killavon; Laudamonium;
Lysoform Killavon†; Hong Kong: Pharmatex; Hung.: Pharmatex; Irl.: Dettol Fresh; Israel: Pharmatex†; Ital.: Alfa C; Amuclean; Benalcon; Bergagyn;
Bluesteril; Citrosil; Citrosteril Ambiente; Citrosteril Deterferri; Detergil; Dimanin R†; DiMill; Diseptil; Disigien; Disintyl; Display; Distasil; Disteril; Eso
Deterferri; Eso Ferri; Esosan Casa; Esosan Soap; Germicidin; Germozero
Clean; Helis; Hygienist Pavimenti e Piastrelle†; Iridina Light; Lacribase; Lozione Vittoria; Maxisteril; Neo-Desogen; Norica†; Polisan; Sanaform; Sangen†; SaniSteril Deterferri; Saquat; Sguardi; Sirigen; Steramin†; Steramina G;
Stilla Delicato; Streptosil L PMC; Ten-Quat; Video-Light; Mex.: Derman
Talco; Lubrizal†; Merthiolate†; NZ: Dettol; Dettol Fresh; Virasolve; Port.:
Pharmatex; Rus.: Pharmatex (Фарматекс); Spermatex (Сперматекс);
Spain: Armil†; Crema Contracepti Lanzas; Mini Ovulo Lanzas; Switz.: Benzaltex†; Thai.: Pose-Bac; Turk.: Zefan; Zefiran; Zefol; Zefort; Zefsolin; Zenfektol; Zentan; UK: Bradosol; Dermax Therapeutic Shampoo; Dettol Antiseptic Wash; Dettol Fresh; USA: Bacti-Cleanse; Benza; Mycocide NS; OnyClear†; Zephiran; Venez.: Decomed.
Multi-ingredient: Arg.: Antisepthic Plus; Crema de Ordene; Eurocoal;
Hexil Antiseptico; Merthiolate NF; Muelita; Neo Coltirot; Oilalfo; Polviderm
NF; Soquette; Austral.: Animine; Clean Skin Face Wash; Gum-Ese†; Mycil
Healthy Feet†; Oilatum Plus; Paxyl; Solyptol†; TAGG†; Virasolve; Austria:
Aleot; Dequonal; Dermaspray; Dorithricin; Limexx; Tyrothricin comp;
Belg.: Akinspray; Dermaspray†; Braz.: Belagin; Cetrilan; Colpatrin; Colpist;
Colpistar; Colpistatin; Dermol†; Dinill; Donnagel; Drapolene; Ginestatin;
Higicler; Nasolin; Oxizinco; Pomada Minancora; Rinotil†; Tricomax; Vagi Biotic; Visolon; Canad.: Bactine; Family Medic First Aid Treatment; MediDan; Protectaid; Tanac; Chile: Dermobarrina; Dexagin; Medisept†; Orajel
Compuesto†; Cz.: Coldrex Laryplus; Dr Rentschler Halstabletten†; Oilatum Plus; Septolete; Fr.: Acarcid†; Biseptine; Dermaspraid Antiseptique;
Dermobacter ; Humex†; Kenalcol; Mercryl; Mercrylsoins; Pharmatex;
Rhinofluimucil; Ger.: Baccalin†; Bacillocid rasant†; Cutasept; Dequonal;
Dorithricin Original; Dynexan Mundgel; Freka-Derm; Freka-Sept 80; Gingicain D; Hexaquart L†; Hexaquart S; Incidin; Incidin extra N; Incidin Extra†;
Incidin perfekt; Incidur Spray†; Inova†; Kohrsolin FF; Korsolex Extra; Korsolex FF; Lysetol Med†; Mikrobac; Quatohex; Sekusept Extra N; Sekusept
forte†; Septolit†; Skinman Soft; Ultrasol-F; Gr.: Beta Opthiole; Cutasept;
Olamyc; Hong Kong: Dermobacter; Dermojela; Drapolene†; Mycil; Oilatum Plus; Protectaid; Virasolve†; Hung.: Coldrex Laryplus†; Dorithricin; India: Rashfree; Indon.: Mexochrome; Oilatum Plus; Irl.: Conotrane†; Drapolene; Emulsiderm; Mycil; Oilatum Junior Flare-Up; Oilatum Plus; Torbetol;
Israel: Aphtagone; Aptha-X; Emulsiderm; Garonsept; Ital.: Agipiu†; AZ 15;
Barrycidal; Bemonalcool; Cerosteril; Cerox†; Citromed 80 and 85; Citromed Chirurgico; Citromedics Pronto; Citrosil Alcolico Azzuro; Citrosil
Alcolico Bruno; Citrosil Alcolico Incolore; Citrosil Nubesan; Citrosteril Impronte; Citrosteril Pronto; Citrosteril Strumenti; Collyria†; Eso Ferri Alcolico; Eso Ferri Alcolico Plus; Eso S 80; Esoalcolico Incolore; Esoform 92; Esoform Alcolico; Esosan Pronto; Germozero Dermo; Germozero Plus;
Hamamilla†; Herbe†; Incidin Spezial; Incidur Spray; Indulfan; Ipragocce†; Linea F; Lycia Luminique; Mediplus; Neo Emocicatrol; Neomedil; Norica;
Odongi; Pupilla Light; Rexichlor; Sangen Casa; SaniSteril Strumenti Alcolico†; Sekusept Extra N†; Sicura3 Medical; Simp; Simpottantacinque; Sterosan; Tirs; Zincometil; Malaysia: Drapolene; Oilatum Plus Antibacterial; QV
Flare Up; Mex.: Dermacid; Glossderm; Novageon; Sutin†; NZ: Oilatum
Plus; Philipp.: Drapolene; Oilatum Plus; Pol.: Coldrex; Oilatum Plus; Septolete; Rus.: Drapolene (Драполен); Septogal (Септогал); Septolete
(Септолете); S.Afr.: Oilatum Plus; Singapore: Dorithricin; Drapolene;
Napitol†; Oilatum Plus; QV Flare Up; Spain: Aftajuventus; Alcohol Benzalconio; Alcohol CL Benz; Alcohol Potenciado; Avril; Curine†; Dermo Halibut; Desinvag; Egarone†; Ginejuvent; Gradin Del D Andreu†; Lindemil;
Mercryl Plus; Odamida; Otogen Calmante; Pental Forte†; Phonal; Pomada
Heridas†; Resorborina; Sebumselen; Tulgrasum Cicatrizante; Vaselatum;
Switz.: Cutasept; Dequonal; Frekaderm†; Leucen; Parapic; Thai.: Drapolene; Gynecon; Gynecon-T; Gynoco; Gynova; Gyracon; Napilene; Nystin;
Oilatum Plus; Sanaco†; Turk.: Drapolene; Kortos; UK: Beechams Max
Strength Sore Throat Relief; Beechams Throat-Plus; Cetanorm; Conotrane;
Dermol; Dettol; Drapolene; Emulsiderm; Germolene†; Germoloids†; Mycil;
Neo Baby Cream; Oilatum Junior Flare-Up†; Oilatum Plus; Protectaid;
USA: Bactine Antiseptic; Bactine Pain Relieving Cleansing; Cetylcide II; Cortic ND; Medi-Quik; Mediotic-HC; Orajel Mouth Aid; Oxyzal; Pedi-Pro; Tanac; Tanac Dual Core; Vagi-Gard Medicated Cream; Vi Rid-Ready; Zonite;
Venez.: Gynovit; Pedi-Lotion.
Benzethonium Chloride (BAN, rINN)
Bensetoniumklorid; Bentsetoniumkloridi; Benzethonii chloridum;
Benzéthonium, chlorure de; Benzethonium-chlorid; Benzetonio
chloridas; Benzetoniowy chlorek; Benzetónium-klorid; Cloruro
de bencetonio; Diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride. Benzyldimethyl(2-{2-[4-(1,1,3,3-tetramethylbutyl)phenoxy]ethoxy}ethyl)ammonium chloride.
Бензетония Хлорид
C 27 H 42 ClNO 2 = 448.1.
C AS — 121-54-0.
ATC — R02AA09.
ATC Vet — QR02AA09.
Pharmacopoeias. In Eur. (see p.vii), Jpn, and US.
Ph. Eur. 6.2 (Benzethonium Chloride). A white or yellowishwhite powder. Very soluble in water and in alcohol; freely soluble in dichloromethane. An aqueous solution froths copiously
when shaken. Protect from light.
Incompatibility. Benzethonium chloride is incompatible with
soaps and other anionic surfactants.
Benzethonium chloride is a quaternary ammonium antiseptic
with actions and uses similar to those of other cationic surfactants (see Cetrimide, p.1634). It is used as a preservative in
pharmaceutical and cosmetic products. It has also been used as a
vaginal spermicide.
◊ Benzethonium chloride, which produced mild skin irritation at
a concentration of 5% but not lower, was not considered to be a
sensitiser, and was considered to be safe at a concentration of
0.5% in cosmetics applied to the skin and at a maximum concentration of 0.02% in cosmetics used in the eye area.1
1. The Expert Panel of the American College of Toxicology. Final
report on the safety assessment of benzethonium chloride and
methylbenzethonium chloride. J Am Coll Toxicol 1985; 4:
USP 31: Benzethonium Chloride Concentrate; Benzethonium Chloride
Tincture; Benzethonium Chloride Topical Solution.
Proprietary Preparations (details are given in Part 3)
Canad.: Clearskin Antibacterial; Neutrogena Antiseptic Cleanser†; Skin
Cleanser & Deodorizer†; S.Afr.: Johnson’s Antiseptic Powder; USA: Antiseptic Wound & Skin Cleanser.
Multi-ingredient: Arg.: Butimerin; Solumerin; Austral.: Summers Eve
Feminine; Belg.: Neo-Golaseptine; Braz.: Andolba; Hipodex; Solemil†;
Spray Anti-Septico; Canad.: Antiseptic Skin Cream†; Lipsorex Plus; Lipsorex†; MRX†; Protecto†; VoSoL HC†; Chile: Aucusik; Dermaglos Plus†; Lerfimin; Molca; Cz.: Cemaquin†; Ger.: Brand- u. Wundgel-Medice N; Hong
Kong: Cemaquin†; Ital.: Barrycidal; Sangen Casa; NZ: VoSoL; S.Afr.: Dry
& Clear Medicated Skin Cleanser; Spain: Alcohol Poten; Eupnol; Halibut;
Halibut Hidrocortisona; Isdinex†; Switz.: Angidine; Cemaquin; Rhinocure;
Rhinocure simplex; Tyrocombine; Tyrothricine + Gramicidine; Thai.:
Iwazin; Sigatricin; USA: Acetasol; Acetasol HC; Aerocaine†; Americaine
First Aid†; Dermoplast Antibacterial; Skin Shield; Vagisil; VoSoL HC†;
Benzoic Acid
Acide benzoïque; Acidum benzoicum; Bensoesyra; Bentsoehap_
po; Benzoesäure; Benzoesav; Benzoico, ácido; Benzoinė ru gštis;
Dracylic Acid; E210; Kwas benzoesowy; Kyselina benzoová.
C 6 H 5 .CO 2 H = 122.1.
C AS — 65-85-0.
Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, US, and
Ph. Eur. 6.2 (Benzoic Acid). A white or almost white, crystalline
powder or colourless crystals, odourless or with a very slight
characteristic odour. Slightly soluble in water; soluble in boiling
water; freely soluble in alcohol and in fatty oils. M.p. 121° to
USP 31 (Benzoic Acid). White crystals, scales, or needles, with
a slight characteristic odour. Soluble 1 in 300 of water, 1 in 3 of
alcohol, 1 in 5 of chloroform, and 1 in 3 of ether; freely volatile
in steam. Congealing range 121° to 123°.
Incompatibility. The incompatibilities of benzoic acid are described under Sodium Benzoate, below.
Sodium Benzoate
Benzoan sodný; Benzoato sódico; E211; Natrii benzoas; Natrio
benzoatas; Natrium Benzoicum; Natriumbensoat; Natriumbentsoaatti; Nátrium-benzoát; Sodii Benzoas; Sodium, benzoate de;
Sodu benzoesan; Sodyum Benzoat.
C 6 H 5 .CO 2 Na = 144.1.
C AS — 532-32-1.
Pharmacopoeias. In Chin., Eur. (see p.vii), Jpn, and Viet. Also
in USNF.
Ph. Eur. 6.2 (Sodium Benzoate). A white or almost white,
slightly hygroscopic, crystalline or granular powder or flakes.
Freely soluble in water; sparingly soluble in alcohol (90% v/v).
USNF 26 (Sodium Benzoate). A white, odourless or practically
odourless, granular or crystalline powder. Soluble 1 in 2 of water,
1 in 75 of alcohol, and 1 in 50 of alcohol 90%.
Incompatibility. Benzoic acid and its salts are incompatible
with quaternary compounds, calcium salts, ferric salts, and salts
of heavy metals. Their activity is also diminished by nonionic
surfactants or due to absorption by kaolin. They are relatively
inactive above a pH of about 5.
Adverse Effects and Precautions
The benzoates can cause hypersensitivity reactions,
but there have also been reports of non-immunological
contact urticaria. The acid can be irritant to skin, eyes,
and mucous membranes.
Infants given large doses of sodium benzoate have suffered vomiting. Symptoms of overdosage reported in
this group have included vomiting, irritability and, in
more severe cases, renal tubular dysfunction, hypokalaemia, hypocalcaemia, and metabolic acidosis.
Premature infants have been reported to be at risk of
metabolic acidosis and kernicterus.
Hypersensitivity. Respiratory reactions to benzoates may occur, especially in patients susceptible to aspirin-induced asthma.1,2 Urticarial reactions have also been associated with these
compounds,3,4 though at a lower incidence5 and they can be nonimmunological.6 However, these reports have to be balanced
against a controlled study7 that showed no difference in the incidence of urticaria or atopic symptoms between patients given
benzoic acid and those given lactose placebo. A retrospective
study8 of 47 patients who had previously shown a hypersensitivity reaction after ingesting food or products containing benzoate
sodium found that the incidence of a repeat episode of acute urticaria or angioedema on re-challenge was very low (2%).
Anaphylactoid reactions have been reported in 2 patients.9,10
Erythema multiforme has been observed in several patients.11
1. Rosenhall L. Evaluation of intolerance to analgesics, preservatives and food colorants with challenge tests. Eur J Respir Dis
1982; 63: 410–19.
2. Settipane GA. Aspirin and allergic diseases: a review. Am J Med
1983; 74 (suppl): 102–9.
3. Michaëlsson G, Juhlin L. Urticaria induced by preservatives and
dye additives in food and drugs. Br J Dermatol 1973; 88:
4. Warin RP, Smith RJ. Challenge test battery in chronic urticaria.
Br J Dermatol 1976; 94: 401–6.
5. Wüthrich B, Fabro L. Acetysalicylsäure-und lebensmitteladditiva-intoleranz bei urtikaria, asthma bronchiale und chronischer
rhinopathie. Schweiz Med Wochenschr 1981; III: 1445–50.
6. Nethercott JR, et al. Airborne contact urticaria due to sodium
benzoate in a pharmaceutical manufacturing plant. J Occup Med
1984; 26: 734–6.
7. Lahti A, Hannuksela M. Is Benzoic acid really harmful in cases
of atopy and urticaria? Lancet 1981; ii: 1055.
8. Nettis E, et al. Sodium benzoate-induced repeated episodes of
acute urticaria/angio-oedema: randomized controlled trial. Br J
Dermatol 2004; 151: 898–902.
9. Moneret-Vautrin DA, et al. Anaphylactoid reaction to general
anaesthesia: a case of intolerance to sodium benzoate. Anaesth
Intensive Care 1982; 10: 156–7.
10. Michils A, et al. Anaphylaxis with sodium benzoate. Lancet
1991; 337: 1424–5.
11. Lewis MAO, et al. Recurrent erythema multiforme: a possible
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Neonates. Serious metabolic disturbances in premature neonates given intravenous fluids with benzyl alcohol as a preservative have been attributed to the accumulation of benzoic acid, a
metabolite of benzyl alcohol (see p.1632). This risk led to the
recommendation that Caffeine and Sodium Benzoate Injection
(USP), which has been given as a respiratory stimulant, should
not be used in neonates.1
Sodium benzoate has been tried in the treatment of some neonatal metabolic disorders (see Uses and Administration, below).
However, benzoates can also displace bound bilirubin from albumin putting neonates at risk of kernicterus.2 Three cases of toxicity have been reported after accidental high doses of intravenous sodium benzoate and sodium phenylacetate were given to
children with hyperammonaemia.3 All the children initially became agitated and confused, had Kussmaul respiration (rapid,
deep breathing) and developed a partial metabolic acidosis with
an increased anion gap. Two patients subsequently developed
cerebral oedema and hypotension and died while the third survived after haemodialysis.
1. Edwards RC, Voegeli CJ. Inadvisability of using caffeine and sodium benzoate in neonates. Am J Hosp Pharm 1984; 41: 658.
2. Schiff D, et al. Fixed drug combinations and the displacement of
bilirubin from albumin. Pediatrics 1971: 48: 139–41.
3. Praphanphoj V, et al. Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia. J Inherit Metab Dis 2000; 23:
The benzoates are absorbed from the gastrointestinal
tract and conjugated with glycine in the liver to form
hippuric acid, which is rapidly excreted in the urine.
Neonates. References.
1. Green TP, et al. Disposition of sodium benzoate in newborn infants with hyperammonemia. J Pediatr 1983; 102: 785–90.

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