Benzalkonium Chloride - Uses, Precautions, Side Effects, and Pharmacological Aspects

Overview

Benzalkonium chloride (BAC) is a broad-spectrum quaternary ammonium compound biocide. The term relates to a chemical class with a dimethyl benzyl ammonium chloride structure and a variable length (C8 to 18) alkyl chain.

BAC has a wide antimicrobial action against fungi, algae, bacteria, and viruses because of having long half-life and low toxicity. BAC is utilized at high concentrations (greater than 0.05 percent) in hospitals and households as surface disinfection and at lower doses (0.002 to 0.02 percent) as a preservative in medical formulations like eye drops and intranasal sprays.

Indication of Benzalkonium Chloride

• For Eye Drops - For the treatment of eye infections and conjunctivitis.

• For Nasal Sprays and Drops - To decrease nasal congestion in allergic rhinitis patients.

• For Cutaneous Use - For antiseptic cleansing of minor wounds.

Dosage

• Dosage Form and Strength: These are available as eye drops, nasal sprays and drops, and cutaneous sprays.

  • Benzalkonium chloride - 0.3 percent weight in volume (w/v) as eye drops.

  • 0.1 percent weight in volume (w/v) as nasal spray con solution contains 0.028 milligrams of Benzalkonium chloride per spray dose, equivalent to 0.2 grams per milliliter.

  • 0.1 percent nasal drops, the solution contains 0.2 milligrams of Benzalkonium chloride per milliliter.

  • Benzalkonium Chloride - 0.20 percent weight in weight (w/w) as a cutaneous spray.

Recommended Dose

• Benzalkonium Chloride - 0.3 Percent Eye Drops: The normal dose is one or two drops into the infected eye(s) every two to four hours for the first two days; the patient must take four times per day after that regularly to be effective. Should not take this medication for more than ten days.

• Benzalkonium Chloride - 0.1 Percent Nasal Spray: For adults and children aged six and above, take one spray in each nostril up to three times daily, as needed.

• Benzalkonium Chloride - 0.1 Percent Nasal Drops: For adults and children above six years, use one to two drops in each nostril up to three times per day, as needed.

• Benzalkonium Chloride - 0.20 Percent Cutaneous Spray:

  • For adults and children above six, apply a total dosage (one to two sprays) to each wound and leave for five minutes. Wipe away any extra liquid with a clean tissue or cotton wool if required.

  • For children aged one to six years old: Apply one spray over each wound (can treat a maximum of four wounds at once) and allow it to stay for five minutes. Wipe away any extra liquid with a clean tissue or cotton wool if required.

  • Adults and children over twelve months: Only for intermittent, localized, short-term usage. To be administered to small fresh wounds to destroy common bacteria linked to minor wound infection. The product should be sprayed over the whole wound and can be repeated if the wound becomes infected again.

Contraindication:

Do not use this if the patient is allergic to Benzalkonium chloride.

Warnings and Precautions

1. Benzalkonium Chloride - 0.3 Percent Eye Drops

• In individuals who are allergic to other quinolone antibacterial agents.

• Long-term usage may cause a new bacterial infection and resistance to Benzalkonium chloride.

• In individuals with an eye defect or ulceration near the eye's surface, Benzalkonium chloride should be used with caution.

• Patients should avoid direct exposure to sunlight or the sun because they are susceptible to sunlight while using this drug.

• Heart Problems: Use with caution if the patient was born with or possesses a family history of the prolonged QT interval (seen on ECG, electrical recording of the heart), has an imbalance of salts in the blood (particularly potassium or magnesium levels are low in the blood), have a prolonged heart rate (called bradycardia), have previous heart disease or with a history of heart attack (myocardial infarction).

• Children: There has been little evidence of using Benzalkonium chloride in youngsters.

• Breastfeeding and Pregnancy: If the patient is pregnant or breastfeeding, inform the doctor before taking Benzalkonium chloride.

2. Benzalkonium Chloride - 0.1 Percent Nasal Spray and 0.1 Percent Nasal Drops:

• Heart Problems: Do not take this drug if the patient has a history of prolonged QT syndrome.

• Following pituitary gland excision or nasal or oral procedures involving exposure of the dura mater.

• Long-term usage of nasal decongestant medications may result in persistent nasal congestion and mucosa atrophy of the nose.

• Breastfeeding and Pregnancy: Benzalkonium chloride nasal sprays or drops are to be avoided during pregnancy because of the possibility of systemic vasoconstriction unless otherwise prescribed by the physician. If patients are pregnant or breastfeeding or if they suspect they may be pregnant or planning for pregnancy.

3. Benzalkonium Chloride - 0.20 Percent Cutaneous Spray:

• Breastfeeding and Pregnancy: Because skin absorption is limited, used during pregnancy, and breastfeeding is unlikely to have adverse effects. Do not spray directly on the breasts during breastfeeding to prevent ingestion by the child.

• Allergic Reactions: This spray contains a mild pine aroma of D-Limonene and Lilial. D-Limonene and Lilial have the potential to produce allergic responses.

For Patients:

What Is Benzalkonium Chloride?

Benzalkonium chloride is a quaternary ammonium chloride antiseptic and disinfectant with properties and applications comparable to cationic surfactants. It is also utilized in medicinal formulations as an antibacterial preservative. Benzalkonium chloride is the preservative for most multidose aqueous nasal, ophthalmic, and otic medications.

What Are the General Uses of Benzalkonium Chloride?

• It is used to protect from skin infections.

• It is used as a disinfectant to clean wounds.

• It is used for the disinfection of the skin and eyes.

• It is used to maintain hand hygiene.

• It is used as a lubricant for the eyes.

What Are the Possible Side Effects?

1. Benzalkonium Chloride - 0.3 Percent Eye Drops:

• Allergic Reactions: The frequency of the allergic reactions is unclear.

  • Allergic reactions in the eye include eye in the eye and eyelid.

  • Skin inflammation caused by an allergy - such as rash, itching, or hives.

  • A severe life-threatening allergic reaction that is of sudden onsets, such as anaphylactic reaction characterized by swelling underneath the skin in regions like the face, lips, or other parts of the body, swelling of the mouth, tongue, or throat can obstruct the airways, resulting in wheezing, difficulty in swallowing, breathing, or shortness of breath.

  • Rashes on the skin could be fatal (Stevens-Johnson syndrome, toxic epidermal necrolysis).

• Usual Side Effects: Eye irritation and ocular discomfort (may affect one in 100 individuals).

• Side Effects Affecting the Eye:

  • Visual impairment.

  • Tearing of the skin around the skin,

  • Inflammation and redness.

  • Light sensitivity, eye irritation, edema, swelling around the eyes (particularly eyelid swelling).

  • Dryness and discomfort in the eyes (mild stinging or burning).

• Side Effects Affecting the Body:

  • Tiredness and nausea.

• Side Effects Affecting the Heart:

  • Abnormally rapid heartbeat.

  • A potentially fatal abnormal heartbeat.

  • Alteration in heart rhythm - prolonged QT interval on ECG electrical activity of the heart.

2. Benzalkonium Chloride - 0.1 Percent Nasal Spray and 0.1 Percent Nasal Drops:

• Rare Side Effects (Up to One in 100): Bleeding through the nose.

• Very Rare Adverse Effects (Less than One in 10,000): Burning sensation in the mucosa and dryness of the nose.

• Rebound Effect - Due to prolonged drug usage, rhinitis gets exacerbated.

3. Benzalkonium Chloride - 0.20 Percent Cutaneous Spray:

• Skin and Subcutaneous Tissue Disorders Are Very Rare: Dystrophy of the skin, acrodermatitis (rare disorder associated with zinc deficiency), exacerbation of eczema, contact dermatitis, alopecia, or rash.

• Very Rare Side Effects (Occur in Less than 1 User in 10,000): After local cleansing of minor wounds, skin itching of the skin, rashes, redness, burning, swelling, and discoloration. Consult the doctor immediately. Hair loss has also been observed.

How to Store Benzalkonium Chloride?

Keep it away from the access and sight of children. After the expiry date, do not use Benzalkonium Chloride. There are no particular storage specifications. Never throw away medicines in wastewater or household garbage.

For Doctors:

What Is Benzalkonium Chloride?

Benzalkonium chloride (BAC) is a chlorine-based chemical molecule having antibacterial, viral, and fungal activities. It is composed of a combination of alkyl benzyl dimethylammonium chloride with varying numbers of carbon atoms, most commonly n-C12H25 (dodecyl), n-C14H29 (tetradecyl), and n-C16H33 (hexadecyl) [2]. The length of the alkyl chain determines the antimicrobial action.

C12-homologs are efficient against fungi and molds, whereas C14 and C16 are effective against Gram-positive and Gram-negative bacteria. Alkyl benzyl dimethyl ammonium chlorides have three major applications: biocide, a cationic surfactant, and a phase transfer agent. The range of applications for benzalkonium chloride is broad, ranging from preservatives in medical products to skin antiseptics and active substances in surgical disinfection.

What Are the Indications of Benzalkonium Chloride?

When used as an active component in products such as antibacterial, antiseptic, or disinfectant soaps, topical sanitizers, or cleaning agents, Benzalkonium chloride is frequently the sole active ingredient. It is noted that the principal goal of topical washing is to reduce bacteria on the skin.

On the other hand, Benzalkonium chloride is employed as the antimicrobial preservative of choice in a range of multidose aqueous nose, eye, or ear solutions to promote efficient bactericidal and fungicidal effects to assist in the reduction of the growth of undesired microorganisms in the multidose containers.

What Are the Conditions Benzalkonium Chloride Is Used to Treat?

• Dermatitis of the diaper or diaper rash.

• Syndrome of the eye, such as dry eye syndrome (DES).

• Infections of the eyes and eyelids.

• Gingivitis.

• Infantile eczema.

• Hemorrhoids or piles.

• Irritation of the mouth.

• Pruritus (irritation of the skin)

• Tonsillitis and throat Inflammation.

Clinical Pharmacology:

Mechanism of Action

Although not completely understood, Benzalkonium chloride's bactericidal activity is thought to be linked to the breakdown of intermolecular connections. Such rupture can result in separating bacterial cellular membrane lipid bilayers, compromising the control of cellular permeability and allowing actual cellular contents to flow.

In addition, other critical molecular complexes, such as enzymes, which govern a wide variety of respiratory and metabolic functions of the cells, are also vulnerable to such deactivation.

As a result, cationic surfactants like Benzalkonium chloride may easily disrupt or deactivate a range of essential intermolecular interactions and tertiary structures in extremely particular biochemical systems that allow bacterial agents to operate correctly.

Pharmacodynamics

Benzalkonium chloride solutions are biocidal agents with relatively long durations of activity. Their antibacterial effectiveness has been established against bacteria, viruses, fungi, and protozoa, while bacterial spores are considered resistant to the agent. Furthermore, the drug is more effective against gram-positive bacteria than gram-negative bacteria.

Finally, depending on the concentration, benzalkonium chloride solutions are bacteriostatic (inhibits the growth of bacteria) or bactericidal (destroys the bacteria). In general, pH has little effect on the agent's action, although it does rise significantly at higher temperatures and over longer periods.

Pharmacokinetics

Absorption: Percutaneous absorption is regarded to be negligible.

• In one investigation, absorption of Benzalkonium chloride was assessed in women using agent-containing tampons. Venous blood samples were collected 15 minutes before tampon application and again 15 minutes, 1 hour, 3 hours, and 24 hours after. Benzalkonium chloride was not identified in any of the blood samples analyzed at any time.

• Likewise, Benzalkonium chloride absorption of Benzalkonium chloride was investigated in women using tampons that contained the agent in another investigation. Samples of venous blood and breast milk were collected 15 minutes before application and three and twenty-four hours afterward. Benzalkonium chloride was not discovered in any samples collected from the individuals.

• Furthermore, in a study where Benzalkonium chloride solution was applied to the corneal surface of rabbits, washed the rabbits' eyes with 1 milliliter of saline.

Remove the following tissues and fluids: bulbar and palpebral conjunctiva, aqueous humor, corneal epithelium, endothelium and stroma, iris-ciliary body, lens, vitreous, retina, and choroid.

Direct cardiac punctures were performed to acquire plasma samples. One drop of Benzalkonium chloride was discovered in the corneal epithelium, endothelium, and stroma, as well as the bulbar and palpebral conjunctivae. Benzalkonium chloride elimination from ocular tissues was such that after 24 hours, about one-third to two-thirds of its concentration (based on the tissue) was retained; detectable levels lasted as long as 120 minutes.

• Distribution:

  • When used as a topical antibacterial, antiseptic, disinfectant, or sanitizer, Benzalkonium chloride molecules are thought to be absorbed poorly, especially considering that specific topical applications are expected to retain their biocidal agents readily accessible for action at the topical level and not be absorbed substantially beyond its measure.

  • When Benzalkonium chloride is used as an excipient (as a medium for the drug) preservation component in the different eye, nose, and aqueous ear solutions, additional active pharmacological agents whose volume of distribution is more critical are also incorporated. In these circumstances, excipients will only be present at the bare minimum required to preserve the integrity.

• Metabolism and Elimination:

  • Because Benzalkonium chloride is a huge, positively charged molecule, it is expected to be poorly absorbed and excreted primarily in feces, just like other quaternary ammonium compounds.

Toxicity: In humans, an oral dosage of 100 to 400 milligrams per kilogram or a parenteral dose of five to fifteen milligrams per kilogram is considered hazardous to humans.

• A possible risk that higher concentrations of Benzalkonium chloride may cause ocular injury when used as an excipient in aqueous eye solutions. Because reduced regular blinking and tear generation in patients suffering from dry eyes due to a variety of eye conditions can lead to less dilution of applied eye drops comprising the Benzalkonium chloride preservative should be considered, alternative options such as Benzalkonium chloride-free products should be taken into account.

• When Benzalkonium chloride-containing ear drops are administered to the ear, there is a risk of ototoxicity.

• Benzalkonium chloride, used as a preservative in anti-asthmatic medicine nebulizers, has been linked to dose-related bronchoconstriction, particularly in asthmatic patients, and has been related to the precipitation of respiratory arrest.