Hexachlorophene

(BAN, rINN)
Hexachlorophene Chemical formula
Synonyms: G-11; Heksaklorofeeni; Hexachlorofen; Hexachlorophane; Hexachlorophène; Hexachlorophenum; Hexaclorofeno; Hexaklorofen. 2,2′-Methylenebis(3,4,6-trichlorophenol).
Cyrillic synonym: Гексахлорофен.

💊 Chemical information

Chemical formula: C13H6Cl6O2 = 406.9.
CAS — 70-30-4.
ATC — D08 AE01.
ATC Vet — QD08AE01; QP52AG02.

Pharmacopoeias.

In Br. and US.

BP 2008

(Hexachlorophene). A white or pale buff, odourless or almost odourless, crystalline powder. Practically insoluble in water; freely soluble in alcohol; very soluble in acetone and in ether. It dissolves in dilute solutions of alkali hydroxides. Protect from light.

USP 31

(Hexachlorophene). A white or light tan, crystalline powder which is odourless or has a slight phenolic odour. Insoluble in water; freely soluble in alcohol, in acetone, and in ether; soluble in chloroform and in dilute solutions of fixed alkali hydroxides. Store in airtight containers. Protect from light.

Incompatibility.

The activity of hexachlorophene may be reduced in the presence of blood or other organic material. It retains some activity in the presence of soap. The activity has been reported 1 to be reduced by alkaline media and by nonionic surfactants such as polysorbate 80. It is extremely sensitive to iron, and to avoid discoloration due to traces of this metal in hexachlorophene detergent solutions, it is advisable to incorporate a sequestrant such as disodium edetate. 2 1. Walter G, Gump W. Effect of pH on hexachlorophene. Soap Chem Spec 1963; 39: 55–6. 2. Bell M. Hexachlorophene-based skin cleansers. Specialities 1965; 1: 16–18.

💊 Adverse Effects and Treatment

After ingestion, anorexia, nausea, vomiting, diarrhoea, abdominal cramps, dehydration, shock, and confusion may occur. Convulsions and death may follow. CNS stimulation, convulsions, and death have also occurred after absorption of hexachlorophene from burns and damaged skin. There have been reports showing that hexachlorophene can be absorbed through the skin of infants in amounts sufficient to produce spongy lesions of the brain, sometimes fatal. Photosensitivity and skin sensitisation have occasionally occurred after repeated use of hexachlorophene. Treatment of adverse effects is as for Phenol.

Effects on the respiratory system.

Asthma developed in a 43-year-old nurse after long-term exposure to hexachlorophene powder.1
1. Nagy L, Orosz M. Occupational asthma due to hexachlorophene. Thorax 1984; 39: 630–1.

💊 Precautions

Hexachlorophene should not be applied to mucous membranes, large areas of skin, or to burnt, damaged, or denuded skin and should not be used vaginally, applied under occlusive dressings, or applied to areas affected by dermatoses. It should be used with caution on infants, especially premature and low birth-weight neonates. Its use is not advised in pregnancy. Preparations of hexachlorophene are liable to contamination, especially with Gram-negative bacteria.

Breast feeding.

The American Academy of Pediatrics1 considers that, while no effects on the infant have been reported, there is a possibility of contamination of breast milk with hexachlorophene used by breast-feeding mothers for nipple washing.
1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: http://aappolicy.aappublications.org/cgi/content/full/ pediatrics%3b108/3/776 (accessed 15/03/06)

Neonates.

Spongiform encephalopathy has occurred in neonates who were treated topically with hexachlorophene.1 Neonates with a birth-weight of 1.4 kg or less appeared to be most susceptible, whereas those weighing over 2 kg were not considered to be at risk.1,2 Also most of the reports involved hexachlorophene applied in a concentration of 3%.
1. Anonymous. Hexachlorophene today. Lancet 1982; i: 87–8
2. Plueckhahn VD, Collins RB. Hexachlorophene emulsions and antiseptic skin care of newborn infants. Med J Aust 1976; 1: 815–19.

Pregnancy.

Hexachlorophene is absorbed from the skin and crosses the placenta, but whether it has produced teratogenic effects is subject to debate.1,2 However, it is considered best to avoid its use during pregnancy.
1. Halling H. Suspected link between exposure to hexachlorophene and malformed infants. Ann N Y Acad Sci 1979; 320: 426–35
2. Baltzar B, et al. Pregnancy outcome among women working in Swedish hospitals. N Engl J Med 1979; 300: 627–8.

💊 Pharmacokinetics

Hexachlorophene is absorbed from the gastrointestinal tract after accidental ingestion, and through intact and denuded skin. Percutaneous absorption may be significant in premature infants and through damaged skin. Hexachlorophene crosses the placenta.

💊 Uses and Administration

Hexachlorophene is a chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is most active at pH 5 to 6. Hexachlorophene is mainly used in soaps and creams in a concentration of 0.23 to 3% and is an ingredient of various preparations used for skin disorders. After repeated use of these preparations for several days there is a marked diminution of the bacterial flora due to accumulation of hexachlorophene in the skin. This residual effect is rapidly lost after washing with unmedicated soap or alcohol. A preparation containing 3% is used for the disinfection of the hands of surgeons and other health-care personnel. Thorough rinsing is recommended before drying. Hexachlorophene has been applied as a 0.33% dusting powder to the umbilical cord stump for the control of staphylococcal infection in the newborn. However, care is necessary when using hexachlorophene in neonates (see above). Hexachlorophene sodium has also been used.

Disinfection.

Eradication of an outbreak of infection with meticillin-resistant Staphylococcus aureus in a neonatal intensive care unit was achieved by use of hexachlorophene soap for hand washing. Previous infection-control measures including the use of chlorhexidine had failed.1 For a discussion of staphylococcal infections and their treatment.
1. Reboli AC, et al. Epidemic methicillin-gentamicin-resistant Staphylococcus aureus in a neonatal intensive care unit. Am J Dis Child 1989; 143: 34–9.

💊 Preparations

BP 2008: Hexachlorophene Dusting Powder; USP 31: Hexachlorophene Cleansing Emulsion; Hexachlorophene Liquid Soap.

Proprietary Preparations

Cz.: Aknefug-Simplex†; Ger.: Aknefug simplex†; Indon.: Dermisan; Switz.: Acne-Med Wolff Simplex†; UK: Ster-Zac†; USA: Septisol†; Venez.: Solu-Hex. Multi-ingredient: Braz.: Micosan†; Canad.: pHisoHex; Cz.: Aknefug†; Hexadecyl†; Septonex; Ger.: Aknefug-Emulsion†; Hung.: Phlogosol; Indon.: Topicide; Irl.: To r b e t o l ; Israel: Acnex†; Port.: Anacal; Spain: Cresophene; Switz.: Acerbine†; Thai.: Cibis; USA: pHisoHex; Venez.: Permucal.
Published January 06, 2019.