CLASSES

Antiinfectives and Antiseptics for Local Oral Treatment
Antiseptics and Disinfectants, Excluding Hand Products

DEA CLASS

Rx, OTC

DESCRIPTION

Topical antimicrobial agent
Bacterial spectrum includes both gram-positive and gram-negative organisms, some viruses including HIV, and fungi; sporicidal only at elevated temperatures
Used as an oral rinse, topical skin cleanser, and is incorporated into several types of medical devices

COMMON BRAND NAMES

Betasept, Chlorostat, Hibiclens, Oro Clense, Peridex, Periogard, PerioRx, Perisol

HOW SUPPLIED

Betasept/Hibiclens Topical Sol: 4%
Chlorhexidine/Chlorhexidine Gluconate/Oro Clense/Peridex/Periogard/PerioRx/Perisol Oral Sol: 0.12%
Chlorhexidine/Chlorhexidine Gluconate/Oro Clense/Peridex/Periogard/PerioRx/Perisol Periodontal Sol: 0.12%
Peridex Buccal Liq: 0.12%

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

Maximum dosage information not available.

Maximum dosage information not available.

Maximum dosage information not available.

Maximum dosage information not available.

Maximum dosage information not available.

Maximum dosage information not available.

DOSING CONSIDERATIONS

Chlorhexidine is poorly absorbed from the GI tract following inadvertent ingestion; excretion is primarily through the feces. Therefore, no dosage adjustments are necessary.

Chlorhexidine is poorly absorbed from the GI tract following inadvertent ingestion; excretion is primarily through the feces with < 1% excreted in urine. Therefore, no dosage adjustments are necessary.

ADMINISTRATION

For external use only. Keep out of eyes, ears, and mouth; if accidental exposure occurs, rinse promptly and thoroughly with water. Serious and permanent eye injury has occurred during surgery when chlorhexidine enters and remains in the eye.
Do not heat solution.
Apply solution in a well ventilated area to clean, completely dry, residue-free, intact skin.
Avoid getting the solution into areas with excess hair as the solution may take longer to dry or may not dry completely. When necessary, remove hair using surgical clippers on the morning of surgery. If a wet shave is used, thoroughly remove all soap residues.
When applying to skin folds, toes, or fingers, use a sterile-gloved hand to hold skin apart until completely dry. Otherwise, skin may adhere to itself.
To reduce the risk of fire, wait to drape or use ignition sources (e.g., cautery, laser) until solution is completely dry (minimum of 3 minutes on hairless skin; up to 1 hour in hair).
Tinted solution will slowly fade from skin over time. After the procedure, alcohol may be used to remove tint if desired.
 
Betasept:
Surgical hand scrub:
Wet hands and forearms with warm water.
Scrub for 3 minutes with approximately 5 mL of product and a wet sponge. Pay close attention to nails, cuticles, and interdigital spaces. A separate nail cleaner may be used.
Rinse thoroughly.
Wash for an additional 3 minutes with approximately 5 mL of product and rinse under running water.
Dry thoroughly.
Health care personnel hand wash:
Wet hands with water.
Dispense approximately 5 mL of product into cupped hands and wash in a vigorous manner for 15 seconds.
Rinse and dry thoroughly.
Patient preoperative skin preparation:
Apply liberally to surgical site and swab for at least 2 minutes.
Dry with a sterile towel.
Repeat swabbing process for an additional 2 minutes, and dry with a sterile towel.
Skin wound and general skin cleansing:
Thoroughly rinse area to be cleansed with water.
Apply the minimum amount of product necessary to cover the skin or wound area and wash gently.
Rinse again thoroughly.
 
Bactoshield sponge:
Wet hands and forearms with warm water.
Clean under nails with nail pick provided. Nails should be maintained with a 1 mm free edge.
Wet sponge and squeeze to work up lather.
Scrub for 3 minutes. Pay close attention to nails, cuticles, and interdigital spaces. Use the brush side to clean the interdigital spaces, and the sponge side to scrub the hands and forearms.
Rinse thoroughly with warm water.
Scrub for an additional 3 minutes using the sponge side, then rinse hands.
Dry thoroughly. Discard brush-sponge.
 
Hibiclens:
Surgical hand scrub:
Wet hands and forearms with warm water.
Scrub for 3 minutes with approximately 5 mL of product and a brush.
Rinse thoroughly under running water.
Wash for an additional 3 minutes with approximately 5 mL of product and rinse under running water.
Dry thoroughly.
Healthcare personnel hand wash:
Wet hands with water.
Dispense approximately 5 mL of product into cupped hands and wash in a vigorous manner for 15 seconds.
Rinse and dry thoroughly.
Patient preoperative skin preparation:
Apply liberally to surgical site and swab for at least 2 minutes.
Dry with a sterile towel.
Repeat swabbing process for an additional 2 minutes, and dry with a sterile towel.
Skin wound and general skin cleansing:
Thoroughly rinse area to be cleansed with water.
Apply the minimum amount of product necessary to cover the skin or wound area and wash gently.
Rinse again thoroughly.

Oral Rinse
May be dispensed in the original container, which includes a measuring cup, or in an amber bottle with a device to measure 15 ml.
 
Dental Implantation
Assure the periodontal pocket and surrounding area are dry prior to implant insertion.
Grasp the implant with forceps such that the rounded end points are away from the forceps.
Insert the implant into the periodontal pocket to its maximum depth; may be maneuvered into position using the tips of the forceps or a flat instrument.
The implants are biodegradable and do not need to be removed.
If the implant becomes dislodged <= 48 hours after insertion, place a new implant. If the implant becomes dislodged 7 or more days after insertion, no replacement is needed. If the implant becomes dislodged > 48 hours after insertion, do not replace the implant, reevaluate the patient at 3 months and insert a new implant if the pocket depth is not < 5 mm.

STORAGE

Betasept:
- Avoid excessive heat (above 104 degrees F)
- Store between 68 to 77 degrees F
Chlorostat:
- Avoid excessive heat (above 104 degrees F)
- Store between 68 to 77 degrees F
Hibiclens:
- Avoid excessive heat (above 104 degrees F)
- Store between 68 to 77 degrees F
Oro Clense :
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Peridex:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Periogard:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
PerioRx :
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Perisol:
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

It is not known if chlorhexidine is excreted into breast milk. However, chlorhexidine is poorly absorbed from the gastrointestinal tract even after oral use. In studies using chlorhexidine vaginally prior to delivery to prevent mother-to-child transmission of HIV, no adverse events were reported in any breast-fed infant. In a case report, a woman who was breast-feeding sprayed chlorhexidine on her breasts to prevent mastitis. Her 2-day old infant developed bradycardia following breast feeding. The bradycardia episodes resolved when the chlorhexidine was discontinued. However, in a study of 200 nursing mothers who sprayed their breasts with chlorhexidine in alcohol before and after each feeding, there were no reported side effects in any breast-fed infant. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Patients with dental work such as anterior tooth restorations (front-tooth fillings) or dentures may develop excessive and permanent discoloration of these areas after using chlorhexidine oral rinse. Replacement of fillings and appliances may be needed for cosmetic reasons. If natural stain cannot be removed from these appliances, consider avoiding treatment with chlorhexidine oral rinse due to increased risk of permanent staining. Anterior tooth restorations with rough surfaces or margins are at increased risk for staining and discretion should be used in these patients.

The use of chlorhexidine in the management of patients with some types of periodontal disease should be carefully considered. For patients having coexisting gingivitis and periodontitis, the presence or absence of gingival inflammation following treatment with chlorhexidine oral rinse (e.g., Peridex) should not be used as a major indicator of underlying periodontitis; the effect of the oral rinse on periodontitis has not been determined. Chlorhexidine dental inserts (e.g., PerioChip) have not been studied in the treatment of acute abscessed periodontal pockets and are not recommended. Rarely, infections including abscesses and cellulitis, have been reported with the adjunctive use of PerioChip after scaling and root planing. Infection has been reported after scaling and root planing alone. Management of patients with periodontal disease should include consideration of potentially contributing medical disorders, such as cancer, diabetes, and immunocompromised status. Patients should notify the dentist promptly if pain, swelling, or other problems occur.

When using topical solutions containing alcohol, including chlorhexidine, prior to surgery, be aware that the solution gives off flammable vapors. Do not drape or use ignition source such as cautery or laser until solution is completely dry (minimum of 3 minutes on hairless skin). Avoid applying solution into hairy areas because the solution may take much longer to dry or may not dry completely. Do not allow the solution to pool and remove wet materials from prep area.

Following ocular exposure of chlorhexidine topical antiseptic, serious and permanent eye injury has occurred during surgery when chlorhexidine enters and remains in the eye. Ocular effects include corneal edema, severe corneal endothelium damage requiring penetrating keratoplasty, iris atrophy, anterior chamber applanation (or flattening), and increased intraocular pressure. Inadvertent ocular exposure of chlorhexidine is characterized by streak formation in the anterior chamber.

Chlorhexidine oral rise is pregnancy category B. However, adequate, well-controlled studies in pregnant women have not been done. Safety for use of topical chlorhexidine during pregnancy has not been established. Use only if clearly indicated and when the potential benefits are greater than the potential risks to the fetus.

In the presence of tympanic membrane perforation, take precautions to prevent exposure of inner ear tissues to chlorhexidine. Hearing loss and deafness may occur when chlorhexidine becomes in contact with the middle ear.

Chlorhexidine topical antiseptic should not be used in patients with skin disease or wounds involving more than the superficial layers of skin, or for repeated cleansing of large body areas except when it is necessary to reduce the bacteria population of the skin. Do not use under an occlusive dressing. Additionally, chlorhexidine should not be used to cleanse the skin prior to lumbar puncture; contact with the meninges should be avoided.

Topically administered chlorhexidine should be used with caution in premature infants, neonates and in infants less than 2 months of age because of the potential for irritation or chemical burns. The safety and efficacy of chlorhexidine oral rinse have not been established in neonates, infants, children, and adolescents.

The rare risk of serious hypersensitivity reactions or anaphylaxis has been reported with the use of prescription and OTC products that contain chlorhexidine gluconate, including skin antiseptic products, dental products, and medical devices such as dressing and intravenous lines. Reactions can occur within minutes of exposure, and may include the following symptoms: wheezing or difficulty breathing, shock, facial swelling, hives, and rash. Allergic reactions may require emergency department visits or hospitalizations and have rarely resulted in death. PerioChip, is contraindicated in patients with a known sensitivity to chlorhexidine. Consider the use of alternative products in patients in which allergy to chlorhexidine is documented or suspected.

Some chlorhexidine gluconate products are flammable. Avoid heat, flame, and tobacco smoking during and immediately following topical application.

ADVERSE REACTIONS

angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

gingival hyperplasia / Delayed / 2.3-3.6
hypertension / Early / 2.2-2.7
stomatitis / Delayed / 0-2.2
oral ulceration / Delayed / 0-1.0
erythema / Early / 0-1.0
edema / Delayed / 0-1.0
glossitis / Early / 0-1.0
parotitis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
wheezing / Rapid / Incidence not known

tooth discoloration / Delayed / 0-56.0
dental pain / Delayed / 0-50.7
infection / Delayed / 0-28.4
headache / Early / 27.1-27.5
sinusitis / Delayed / 13.1-13.8
back pain / Delayed / 6.7-11.3
influenza / Delayed / 7.6-9.5
arthralgia / Delayed / 3.1-5.9
myalgia / Early / 4.0-4.1
pharyngitis / Delayed / 2.3-3.6
rhinitis / Early / 2.7-3.2
cough / Delayed / 2.7-3.2
dyspepsia / Early / 2.7-3.1
paresthesias / Delayed / 0-1.0
hypoesthesia / Delayed / 0-1.0
xerostomia / Early / 0-1.0
gingivitis / Delayed / 0-1.0
metallic taste / Early / Incidence not known
calculus (tartar) formation / Delayed / Incidence not known
skin irritation / Early / Incidence not known
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

DRUG INTERACTIONS

Disulfiram: (Minor) Some chlorhexidine oral rinses contain ethanol in significant percentages. Although chlorhexidine is poorly absorbed from the GI tract and the products are intended for oral topical rinse and not for systemic ingestion, there is a potential for interaction with disulfiram when such products are swallowed.
Keratinocytes; Fibroblasts; Collagen: (Major) Avoid the use of chlorhexidine gluconate solution on the wound following application of keratinocytes and dermal fibroblast collagen. Administering these drugs together may reduce wound repair and regeneration. Chlorhexidine gluconate has been shown to be toxic to keratinocytes and human dermal fibroblasts.

PREGNANCY AND LACTATION

Chlorhexidine oral rise is pregnancy category B. However, adequate, well-controlled studies in pregnant women have not been done. Safety for use of topical chlorhexidine during pregnancy has not been established. Use only if clearly indicated and when the potential benefits are greater than the potential risks to the fetus.

It is not known if chlorhexidine is excreted into breast milk. However, chlorhexidine is poorly absorbed from the gastrointestinal tract even after oral use. In studies using chlorhexidine vaginally prior to delivery to prevent mother-to-child transmission of HIV, no adverse events were reported in any breast-fed infant. In a case report, a woman who was breast-feeding sprayed chlorhexidine on her breasts to prevent mastitis. Her 2-day old infant developed bradycardia following breast feeding. The bradycardia episodes resolved when the chlorhexidine was discontinued. However, in a study of 200 nursing mothers who sprayed their breasts with chlorhexidine in alcohol before and after each feeding, there were no reported side effects in any breast-fed infant. Consider the benefits of breast-feeding, the risk of potential drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding baby experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

MECHANISM OF ACTION

Chlorhexidine destabilizes and penetrates bacterial cell membranes. Chlorhexidine precipitates the cytoplasm and interferes with membrane function by inhibiting oxygen utilization leading to a decrease in cellular ATP levels and cell death. In gram-negative bacteria, chlorhexidine affects the outer membrane allowing the release of periplasmic enzymes. The inner membrane of these organisms is not ruptured but the uptake of small molecules is impaired. At low concentrations chlorhexidine exhibits a bacteriostatic effect while at high concentrations it is bactericidal. The following organisms have a high susceptibility to chlorhexidine: some staphylococci, Streptococcus mutans, Streptococcus salivarius, Candida albicans, Escherichia coli, Selenomonas, and anaerobic propinionic bacteria. Streptococcus sanguis has moderate sensitivity to chlorhexidine. Proteus strains, Pseudomonas, Klebsiella, and gram-negative cocci resembling Veillonella have a low sensitivity to chlorhexidine. Chlorhexidine dental implants have shown a reduction in the numbers of Porphyromonas (Bacteriodes) gingivalis, Prevotella (Bacteriodes) intermedia, Bacteriodes forsythus, and Campylobacter rectus (Wolinella recta) after implant placement. During 6-month use of chlorhexidine oral rinse, dental plaque samples showed a 54—97% reduction in certain aerobic and anaerobic bacteria. Clinical studies have not shown any significant changes in bacterial resistance or overgrowth of opportunistic infections during treatment with chlorhexidine oral rinse or after placement of chlorhexidine implants. Chlorhexidine 5% (Hibitane(R) Concentrate - not available in the US) has been shown to be effective against rubella-, measles-, mumps- and HIV viruses and ineffective against roto-, polio-, rhino- and adeno-viruses. In addition, chlorhexidine is effective against cytomegalovirus and influenza virus.

PHARMACOKINETICS

Chlorhexidine is applied topically to the skin or is used as an oral rinse; it should never be ingested or used in the eye. Excretion is primarily via the feces and <1% is excreted in the urine.