VA Class:DE400
ATC Class:D08AE01
Hexachlorophene, a polychlorinated biphenol compound, is a topical antiseptic.
Hexachlorophene is used as a surgical hand scrub and a bacteriostatic skin cleanser. Topical preparations containing hexachlorophene have been used by physicians, dentists, food handlers, pediatric nurses, and other individuals who are in a position to spread contaminants from their hands. Efficacy of hexachlorophene as a topical antiseptic depends on residual amounts of the drug being adsorbed onto the skin. Hexachlorophene is most effective after repeated daily application and may be ineffective in reducing cutaneous flora if used in a single, brief application.
Hexachlorophene also is used topically to control outbreaks of gram-positive infections when other infection control procedures have been unsuccessful; hexachlorophene should be used for infection control no longer than necessary. Although hexachlorophene was used in the past for routine, daily bathing of neonates as a prophylactic measure against staphylococcal infections, the drug should not be used routinely for bathing infants because serious adverse effects have been reported. (See Cautions: Pediatric Precautions.)
Hexachlorophene has been used topically to suppress staphylococcal infections in patients with acne vulgaris. However, hexachlorophene is not active against Propionibacterium acnes and is of no additional benefit in individuals using topical benzoyl peroxide or topical tetracycline, clindamycin, or erythromycin.
Hexachlorophene is applied topically to the skin in a concentration of 3%. Hexachlorophene should not be applied to mucous membranes.
For use as a surgical scrub, an emulsion containing 3% hexachlorophene is used. The hands and forearms should be wetted with water. Then, approximately 5 mL of the emulsion containing hexachlorophene should be applied onto the hands and rubbed into a copious lather by adding small amounts of water. The suds should be spread over the hands and forearms and scrubbed well with a wet brush for 3 minutes. Particular attention should be paid to the nails and interdigital spaces; a separate nail cleaner may be used. The hands and forearms should then be rinsed thoroughly under running water. A second application of 5 mL of emulsion should be made and the hands and forearms scrubbed for an additional 3 minutes. The hands and forearms should be rinsed thoroughy with running water and dried. For additional surgical scrubs during the same day, the same procedure should be followed using the same amount of emulsion for 3 minutes only.
For use as a bacteriostatic cleansing agent, the hands should be wetted with water and approximately 5 mL of emulsion containing 3% hexachlorophene dispensed into the palm. A lather should be worked up with water and then applied to the area to be cleansed. The area should be rinsed thoroughly after each washing.
Dermatitis and photosensitivity have been reported following topical use of hexachlorophene. Topical use of hexachlorophene in individuals with highly sensitive skin may produce a reaction characterized by redness and/or mild scaling and dryness, especially when use of the drug is combined with mechanical factors such as excessive rubbing or exposure to heat or cold. Although sensitivity to hexachlorophene is rare, individuals who have developed photoallergy to similar compounds may also become sensitive to hexachlorophene.
Topical application of hexachlorophene can result in systemic toxicity including adverse CNS effects. Signs of stimulation (irritation) of the CNS, sometimes with seizures, have occurred following topical use of the drug. Dermatitis, irritability, generalized clonic muscular contractions, and decerebrate rigidity occurred in several infants following topical use of a powder containing 6% hexachlorophene; many of these infants died. Histologic examination of the brainstems of these infants revealed vacuolization resembling that which can be produced in newborn animals following repeated topical application of 3% hexachlorophene. A positive correlation has been established between topical use of hexachlorophene and brain lesions in the white matter of infants. (See Cautions: Pediatric Precautions.)
Precautions and Contraindications
Use of hexachlorophene should be discontinued immediately if signs or symptoms of cerebral irritability occur.
Hexachlorophene should not be used in individuals sensitive to the drug or any ingredient in the formulation. Because of the possibility of cross-sensitivity, hexachlorophene should not be used in individuals who have demonstrated primary light sensitivity to halogenated phenol derivatives.
Because of the possibility of rapid and extensive absorption of hexachlorophene, preparations containing the drug should not be used on burned or denuded skin or mucous membranes and should not be used as and/or with occlusive dressings, wet packs, lotions, vaginal packs, or tampons. In addition, hexachlorophene preparations should not be applied to generalized dermatologic conditions (e.g., lesions of ichthyosis congenita, dermatitis of Letterer-Siwe's syndrome).
Hexachlorophene should not be used routinely for prophylactic total body bathing. After use of hexachlorophene, the area, especially sensitive areas such as the scrotum and perineum, should be rinsed thoroughly. If hexachlorophene inadvertently gets into the eyes, the eyes should be flushed promptly and thoroughly with water.
Infants, especially premature infants or those with dermatoses, are particularly susceptible to hexachlorophene absorption following topical application. Preparations containing hexachlorophene should be used with caution on infants, especially premature and low-birthweight infants, and only when necessary for the control of outbreaks of staphyloccocal infections when other infection control procedures are ineffective. Hexachlorophene should not be used routinely for bathing infants.
A study of histologic sections of premature infants who died of unrelated causes has shown a positive correlation between hexachlorophene baths and brain lesions of the white matter. Diffuse status spongiosis of the brain, especially in the brain stem reticular formation, has occurred in infants following multiple exposures to topical hexachlorophene. Similar lesions, considered characteristic of hexachlorophene toxicity, have been induced experimentally in animals by toxic exposure to the drug.
Hexachlorophene is for external use only and, if swallowed, is especially harmful to infants and children. Hexachlorophene preparations should not be poured into measuring cups, medicine bottles, or similar containers since they may be mistaken for baby formula or other medications.
Pregnancy, Fertility, and Lactation
Hexachlorophene has been shown to be embryotoxic and teratogenic in rats following oral or intravaginal administration of large dosages. There are no adequate and well-controlled studies to date using hexachlorophene in pregnant women. Although one retrospective study reported an increased incidence of fetal malformations and minor deformities in children of nurses who used hexachlorophene preparations to wash their hands 10-60 times daily, other studies have failed to confirm this. Hexachlorophene should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.
Topical exposure of neonatal rats to 3% hexachlorophene solution (no longer commercially available in the US) caused decreased fertility at 7 months of age in male rats as a result of inability to ejaculate.
It is not known whether hexachlorophene distributes into milk in humans, but the drug distributes into milk in rats. Because of the potential for serious adverse reactions to hexachlorophene in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
The oral LD50 of hexachlorophene is 66 mg/kg in male rats, 56 mg/kg in female rats, 120 mg/kg in weanling rats, and 9 mg/kg in suckling rats 10 days old.
Accidental ingestion of 30-120 mL of pHisoHex® has caused anorexia, vomiting, abdominal cramps, diarrhea, dehydration, seizures, hypotension and shock, and has been fatal. Acute toxicity manifested by CNS and GI symptoms has also occurred following ingestion of large doses of hexachlorophene used in the investigational treatment of chlonorchiasis.
Following accidental ingestion of hexachlorophene, the stomach should be emptied immediately by inducing emesis or by gastric lavage. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. Approximately 60 mL of olive oil or vegetable oil may be administered orally to delay absorption of hexachlorophene, followed by a saline cathartic to hasten removal. Treatment is symptomatic and supportive. IV fluids (5% dextrose in 0.9% sodium chloride injection) may be given to treat dehydration, and electrolyte disturbances should be corrected. If marked hypotension occurs, vasopressor agents should be administered. Use of opiates may be considered if GI symptoms such as cramping or diarrhea are severe.
Hexachlorophene is a topical antibacterial agent and exhibits potent bacteriostatic activity against staphylococci. Although the exact mechanism(s) of action has not been determined, at low concentrations, hexachlorophene appears to interrupt bacterial electron transport and to inhibit other membrane-bound enzymes. Higher concentrations rupture bacterial membranes.
The effectiveness of hexachlorophene as a topical antibacterial agent depends on residual amounts of the drug being adsorbed onto skin. The antibacterial effect of topically applied hexachlorophene is slower than that of topically applied iodophors. The bacterial population of the skin may be reduced by only 30-50% immediately following a hand scrub with 3% w/w hexachlorophene compared with 99% immediately following a hand scrub with an iodophor; however, the surviving population may be reduced to about 4 or 16% of normal 1 hour later with hexachlorophene or an iodophor, respectively. Repeated daily application over a period of several days is necessary to create a residual of drug that will maintain the bacterial population of the skin at about 1-5% of normal; removal of the hexachlorophene residual results in prompt regrowth of normal flora. A rebound effect, in which surviving cutaneous bacteria undergo temporary excessive regeneration, reportedly occurs following discontinuance of hexachlorophene.
Hexachlorophene is active against gram-positive bacteria including Staphylococcus aureus .
Most gram-negative organisms are resistant to hexachlorophene. Suprainfections with gram-negative organisms or Candida may occur during prolonged use of hexachlorophene; when hexachlorophene is the only topical antibacterial agent in a preparation, an excess number of gram-negative organisms appears in the cutaneous flora within about a week of regular use. Resistance in susceptible staphylococci does not appear to occur. Changes in the susceptibility of S. aureus to hexachlorophene have not been reported to date.
Hexachlorophene is absorbed from the GI tract and from intact and denuded skin. Rapid absorption of hexachlorophene may occur following topical application to burned or inflamed skin.
Following topical application to intact skin, hexachlorophene is adsorbed onto the outer layers of skin. Repeated daily application of hexachlorophene results in a residual of the drug being retained on the skin for several days. One study using radiolabeled hexachlorophene indicated that the drug accumulates on the skin during the first 3 or 4 days of repeated use, but the concentration on skin remains relatively constant thereafter. Residual hexachlorophene is retained on the skin for several days after discontinuance of the drug or may be removed by cleansing with non-hexachlorophene-containing soaps or detergents or ethanol or isopropyl alcohol.
Hexachlorophene is absorbed systemically (percutaneously) following topical application to the skin. In one study, approximately 3% of a dose of hexachlorophene (in acetone) applied to the skin was absorbed systemically. Serum concentrations of hexachlorophene ranging from 0.009-4.35 mcg/mL have been reported in neonates bathed daily in hexachlorophene preparations for 1-56 days; highest concentrations occurred in low birthweight infants and infants with abraded or erythematous skin. In adults, 3-4 weeks of daily total body bathing with a 3% hexachlorophene preparation reportedly results in serum concentrations of the drug as high as 1.42 mcg/mL. Hexachlorophene serum concentrations of 0.5 mcg/mL or higher have been reported following use of a 3% hexachlorophene preparation as a surgical scrub for hands and forearms 5 times daily for 10 days. In animals, characteristic changes in the CNS associated with hexachlorophene toxicity occur at serum drug concentrations of about 1 mcg/mL or greater.
Hexachlorophene crosses the placenta. It is not known whether hexachlorophene is distributed into milk in humans; the drug is distributed into milk in rats.
In one study in 6 infants, hexachlorophene reportedly had a half-life of 6.1-44.2 hours.
Hexachlorophene, a polychlorinated biphenol compound, is a topical antiseptic. Hexachlorophene occurs as a white to light tan, crystalline powder that is odorless or has only a slight, phenolic odor. The drug is insoluble in water, freely soluble in alcohol and in acetone, and soluble in dilute solutions of fixed alkali hydroxides. Hexachlorophene may be incorporated in soaps, detergents, and other vehicles for topical use.
Hexachlorophene cleansing emulsion contains the drug in a suitable aqueous vehicle. The cleansing emulsion has a pH of 5-6. pHisoHex®, a typical detergent lotion of the drug, is a colloidal dispersion of hexachlorophene (3% w/w) in a stable cleansing emulsion of entsufon sodium, petrolatum, lanolin cholesterols, methylcellulose, polyethylene glycol, polyethylene glycol monostearate, a mixture of lauryl and myristyl diethanolamides, sodium benzoate, and water.
Unlike many antiseptics, the presence of soap does not substantially decrease the antibacterial activity of hexachlorophene; therefore, hexachlorophene is a suitable antiseptic for combination with soaps and detergents. Concentrations of nonionic detergents greater than 8% w/w may decrease the bacteriostatic activity of hexachlorophene when combined with the liquid soap. In soaps, one hydroxyl group of hexachlorophene is neutralized, which moderately decreases activity. The antibacterial activity of topically applied hexachlorophene depends on residual amounts of the drug being adsorbed onto the skin; removal of the hexachlorophene residual and subsequent decrease in antibacterial activity occur following cleansing with non-hexachlorophene-containing soaps or detergents, alcohol (ethanol), or isopropyl alcohol. The antibacterial activity of hexachlorophene is decreased by polysorbate (Tween®) 80.
Prolonged exposure of hexachlorophene cleansing emulsion (e.g., pHisoHex®) to strong, direct light may cause brownish discoloration on the surface of the emulsion; this discoloration does not affect the antibacterial or detergent properties of the emulsion and can be dispersed by shaking. Discoloration of porous surfaces may occur when hexachlorophene cleansing emulsion is spilled or splashed onto the surface; to avoid discoloration, the surface should be immediately rinsed. Hexachlorophene cleansing emulsion is incompatible with many metals. A special type of stainless steel must be used for storage and dispensing of the emulsion, or undesirable discoloration of the emulsion or oxidation of the metal may occur. Specially designed dispensers are available from the manufacturers.
Preparations containing hexachlorophene should be stored in tight, light-resistant containers; hexachlorophene cleansing emulsion should be stored in nonmetallic containers. The cleansing emulsion should not be dispensed from, or stored in, containers with ordinary metal parts.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Emulsion (Hexachlorophene Cleansing Emulsion) | 3% w/w |