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  • Benzalkonium chloride interferes with effectiveness of ocular allergy medications

    http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

    Graefes Archive for Clinical Experimental Ophthalmology. 2006 Aug 10; [Epub ahead of print]

    Comparative study of topical anti-allergic eye drops on human conjunctiva-derived cells: responses to histamine and IFNgamma and toxicological profiles.

    * Pauly A,
    * Brignole-Baudouin F,
    * Guenoun JM,
    * Riancho L,
    * Rat P,
    * Warnet JM,
    * Baudouin C.

    U598, INSERM, Cordeliers Biomedical Institute, 15 rue de l'ecole de medecine, 75006, Paris, France.

    BACKGROUND: The purpose of the study was to compare toxic effects and responses to histamine and IFNgamma associated with the use of some widely used anti-allergic eye drops commercially available today. METHODS: For dynamic studies, the Wong-Kilbourne cell line was stimulated for 24 h with histamine or IFNgamma in the presence or absence of anti-allergic eye drops. Supernatants of histamine-stimulated cells were evaluated for the production of IL-6 and IL-8 by ELISA, while the expression of ICAM-1 was evaluated by flow cytometry on IFNgamma-stimulated cells. Toxicological assays were performed using cold light cytofluorometry: viability and apoptosis as well as reactive oxygen species (ROS) and O2(.)- production were assessed using neutral red, Hoechst/propidium iodide, H(2)-DCFDA and hydroethidine tests, respectively. RESULTS: Antihistamines reduced IL-6 release and presented dose-dependent inhibitory effects on IL-8 production. None of the eye drops decreased the basal or IFNgamma-stimulated expression of ICAM-1. Conversely, eye drops preserved with benzalkonium chloride (BAC) induced even higher ICAM-1 expression levels on IFNgamma-stimulated cells than did IFNgamma alone, whereas unpreserved drugs had no effect. Toxicological assays confirmed the pivotal role of BAC in proportionally reducing cell viability while increasing apoptosis and oxidative stress. CONCLUSIONS: The ability of topical ocular anti-H(1) drugs to significantly reduce the production of IL-6 and IL-8 argues that they may help treat the inflammatory processes occurring in allergic ocular surface disorders. Nevertheless, preserved ophthalmic formulations may enhance epithelial conjunctival expression of ICAM-1 in the presence of a low inflammatory stimulus, such as IFNgamma, and displayed toxic as well as pro-oxidative effects on these cells. Therefore, BAC used as preservative might in part interfere with the potential anti-inflammatory properties of the active compound by modulating the immuno-inflammatory response of epithelial conjunctival cells.

    PMID: 16900358 [PubMed - as supplied by publisher]

  • #2
    excellent post

    Hi Scout,

    did you write to them about Patanol lately? if not please consider sending them this article with it your request...

    In layman's term, an anti-allergic drops is less effective if it contains BAC (Benzalkonium) ... besides the toxic effects (as if these weren't enough!).

    I'll do that as well, They'll have to listen to "informed" patients someday... too bad for them, they won't make million selling us their crap.

    take care
    K

    Comment


    • #3
      not good enough for our noses but good enough for our damaged eyes

      Saline - Additives, Preservatives, Antibacterial Agents, Antifungal Agents

      + Intro: Problems Due To Additives
      + Thimerosal
      + Benzalkonium
      + An Additive-Free And Better Saline Solution
      + Problems with Hypertonic Saline
      + Pediatric Use of Saline Nasal Sprays
      + References



      The Additives May Be The Problem

      Saline nose drops are often prescribed for nasal and sinus conditions. These are recommended for dryness, crusting, and as an aid to normal nasal function. Saline sprays can also be used to treat nose bleeds.

      The nose is supposed to moisten inhaled air, helping to maintain a moist environment for the cilia in the sinuses. These cilia are the body's first line of defense against infection. The moist, mucous environment also forms a pathway for the good white cells to reach the bad bacteria that may attempt to infect the body through inhalation.

      Any dryness, itching, or crusting in the nose means that a moisturizer is needed for the nose to do it's job. Saline is the most common, safe, and simple such moisturizer. When I first heard patients complain that saline burned or made their nose worse, I was very puzzled. Then I figured out that the troubles might be the result of the additives. Here is a partial list of the additives found in saline nasal sprays:
      Nasal Spray Additives:

      Benzalkonium

      Benzyl Alcohol
      Thimerosal (Merthiolate)

      Edetate Disodium
      MonoBasic Sodium Phosphate

      Providone
      DiBasic Sodium Phosphate

      Disodium ETA
      Potassium Phosphate Monobasic

      Iodine
      Phenylcarbinol

      Sodium Silicoaluminate

      To avoid additives, I had patients make saline themselves, using Kosher or Pickling salt - a simple, pure salt. This cleared up the burning problem, and made kids more likely to take to regular use of the spray.

      Some patients did not respond, however, even to the saline made without preservatives. The explanation came only recently from Professor Wilbert M Boek of University Hospital, Utrecht. He found that certain solutions containing potassium chloride, calcium chloride, sodium bicarbonate, and salt were much better for restoring nasal/sinus cilia than those without these ingredients. My clinical experience has borne this out.
      Thimerosal

      There is yet more complexity to the business of additives. Thimerosal (merthiolate) is a preservative that contains ethyl mercury. It has been used in small amounts to reduce the chance of bacterial growth since the 1930s. On July 9, 1999, however, the US Public Health Service (USPHS) and the American Academy of Pediatrics (AAP) officially called for the elimination of such preservatives from some drugs, suggesting serious questions about the safety of such additives.
      Benzalkonium

      The preservative Benzalkonium Sodium causes problems with nasal sprays. Around 1985, it was noted that the number and severity of cases of rhinitis medicamentosum was increasing with increased use of benzalkonium, an antibacterial preservative found in most over-the-counter prepared saline nasal spray products. Rhinitis medicamentosum means that the nose gets stuffy and congested after use of nose drops such as oxymetazoline (Afrin™). The more the nose drops are used, the more "rebound" when the drug wears off, that is, the worse the patient gets after the drops wear off, requiring more and more use of the drops. The drops become effectively addictive, and worse, the nose is always stuffy anytime the drug is not active in the nose.

      Next, it was discovered that you could get rhinitis medicamentosum just form the Benzalkonium alone, as well as saline with Benzalkonium. So, it wasn't the nasal medication oxymetazoline that was responsible, but the Benzalkonium. The oxymetazoline did shrink the nose nicely, but the benzalkonim caused a rebound congestion.

      These additive problems are so important that the Dannemiller Memorial Educational Foundation gives special training to doctors on this subject. This training emphasizes that if you are allergic or have an infection, the additives can be more irritating than when you are "normal".

      Recent articles on the negative effects of Benzalkonium include:

      Berg: Mucosa exposed to benzalkonium chloride showed squamus cell metaplasia ( the normal cells changed to undesirable cells). Benzalkonium chloride appears to be potentially toxic to the mucosa.

      Steinsvag: benzalkonium chloride has toxic effects on human respiratory mucosa and human neutrophils. It destroyed mucosa and inhibited human neutrophil action.Benzalkonium chloride induces mucosal swelling, which explains why the presence of this preservative in a decongestant spray aggravates rhinitis medicamentosa.

      Hoffman An irreversible cessation of ciliary movement was observed in ciliary cells exposed to nasal sprays containing Benzalkonium chloride As benzalkonium chloride can cause complete standstill of ciliary beat frequency in vitro in human nasal mucosa, we recommend that this preservative should not be used anymore in topical nasal medications.


      An Additive-Free And Better Saline Solution

      You can find solutions, enhanced nasal/sinus moisturizing formulas, which contain the same constituents as Boek's Locke-Ringer's Solution, including Soda Bicarbonate, Potassium and Calcium Chloride, and Salt. It doesn't contain any of the additives or preservatives now known to be harmful to the nose/ sinuses. By using a product free of irritating additives, in a more "friendly" mix, patients can benefit by use of moisturizing solutions.
      Warm Saline
      Saline solutions can also be used for pulsatile irrigation of the nasal passages and sinuses . Every doctor tells you to irrigate with warm saline. Warm solution helps bring more circulation to the area, and besides, it feels good. Yet, some solutions with additives allow use only at room temperature!
      Hypertonic Saline

      Hypertonic saline has been studied recently. There is evidence that it can "dry out" swollen tissues. By pulling liquid out of the tissue, this can thin the mucus according to some authors. It acts like sea water. Excessive hypertonic solution has been shown to impair movement of cilia. Many of the commercial preparations also contain additives that can irritate. Not everyone can use such a strong product in the nose. In one study to determine the use of hypertonic saline for acute common cold, no difference was found between this and regular saline. However, many patients complained of the burning from the hypertonic saline and wouldn't use it again.
      Pediatric Use

      Many children might have prevented chronic nasal/sinus problems by regular use of moisturizing spray. As a parent, I know how difficult it is to get a child to do "healthful habits".

      First, an enhanced nasal/sinus moisturizing formula that is additive-free is more likely to be used by children because it doesn't burn. Using a spray bottle that is child size, and a solution that doesn't burn or cause other discomfort, I feel we can significantly reduce children's nasal problems. Find arefillable spray bottle thatis easy for the child to handle; the one I use has an oval surface that is ideal for the parent to put on a child's favorite stickers, (e.g. "Mickey Mouse¨", "Pokeman¨", etc.).



      If you find that the saline nasal preparation you use burns or makes your condition worse, check the additives and preservatives. They may be the problem. Some of the preparations warn that they must be used at room temperature only. Check the label carefully as this too may be a problem - hot or cold may affect the additives / preservatives.

      ©2000, 2003 Dr. Murray Grossan

      References:

      Physiologic and hypertonic saline solutions impair ciliary activity in vitro. Boek WM. Laryngoscope, 109(3):396-9 1999 Mar
      Physiological salt solution (0.9%) was found to slow cilia movement. Locke-Ringers solution with soda bicarbonate, potassium and calcium chloride, and salt was found best for cilia. "This solution is more appropriate than saline for nasal irrigator and nebulazation or sinus lavage." He reported complete ciliastasis with some hypertonic solutions, often within 5 minutes of exposure.

      Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers. Clin Exp Allergy.1995; 25:957-965
      Benzalkonium chloride induces mucosal swelling, which explains why the presence of this preservative in a decongestant spray aggravates nasal/sinus symptoms

      Effects of topical nasal steroids on human respiratory mucosa and human granulocytes in vitro. Steinsv¡ag S. Acta Otolaryngol (Stockh), 116(6):868-75 1996
      "It is concluded that benzalkonium chloride has toxic effects on human respiratory mucosa and human neutrophils in vitro."

      Effect of topical corticosteroids and topical antihistaminics on ciliary epithelium of human nasal mucosa in vitro. Hofmann T. HNO, 46(2):146-51 1998 Feb
      "An irreversible cessation of ciliary movement was observed in all cells exposed to nasal sprays containing benzalconium chloride....." "we recommend that this preservative should not be used anymore in topical nasal medications."

      The effects of topical nasal steroids on rat respiratory mucosa in vivo, with special reference to benzalkonium chloride. Berg OH. Allergy, 52(6):627-32 1997 Jun
      "In conclusion, benzalkonium chloride appears to be potentially toxic to the nasal mucosa."

      A clinical trial of hypertonic saline nasal spray in subjects with the common cold or rhinosinusitis. Adam P. Arch Fam Med, 7(1):39-43 1998 Jan-Feb
      Hypertonic saline does not improve nasal symptoms or illness duration in patients with the common cold or rhinosinusitis. Thirty two percent of users noted burning and wouldn't use the product again.

      ©2000, 2003 Dr. Murray Grossan

      Comment


      • #4
        Physical & Theoretical Chemistry Lab. Safety home page

        Safety (MSDS) data for benzalkonium chloride
        Hazard: harmful Hazard: corrosive

        General

        Synonyms: parasterol, alkyl benzyl dimethylammonium chloride, alkyl dimethyl benzylammonium chloride, benirol, cequartryl, drapolene, enuclene, germitol, gesminol, rodalon, ammonyx, zephiran chloride, various further trade names
        Use: medical disinfectant
        Molecular formula: (mixture)
        CAS No: 8001-54-5
        EC No:

        Physical data

        Appearance: white or light yellow/grey solid, or colourless aqueous solution
        Melting point:
        Boiling point:
        Vapour density:
        Vapour pressure:
        Specific gravity: 0.98
        Flash point: 250 C
        Explosion limits:
        Autoignition temperature:

        Stability

        Stable. Incompatible with strong oxidizing agents, moisture. Hygroscopic.

        Toxicology

        Corrosive, toxic - causes burns. Harmful by inhalation, ingestion and through skin contact. May cause reproductive defects. May act as a mutagen.

        Toxicity data
        (The meaning of any abbreviations which appear in this section is given here.)
        ORL-RAT LD50 240 mg kg-1
        ORL-WMN lowest published toxic dose 266 mg kg-1
        IPN-RAT LD50 14.5 mg kg-1

        Risk phrases
        (The meaning of any risk phrases which appear in this section is given here.)
        R20 R21 R22 R34.

        Transport information

        (The meaning of any UN hazard codes which appear in this section is given here.)
        Hazard class 8. Packing group III

        Personal protection

        Safety glasses, adequate ventilation, gloves.

        Safety phrases
        (The meaning of any safety phrases which appear in this section is given here.)
        S26 S28b S36 S37 S39

        [Return to Physical & Theoretical Chemistry Lab. Safety home page.]

        This information was last updated on February 22, 2005. We have tried to make it as accurate and useful as possible, but can take no responsibility for its use, misuse, or accuracy. We have not verified this information, and cannot guarantee that it is up-to-date.

        Comment


        • #5
          what's worse, they know it

          Don't read the whole post just have a look at the highlighted bits...

          AZOPTIC Eye Drops is a sterile, aqueous suspension containing 10 mg brinzolamide per mL with benzalkonium chloride 0.01% (m/v) as preservative. It is formulated to be readily suspended with slow settling following shaking, with a pH of approximately 7.5 and an osmolality of 300 mOsm/kg. Inactive ingredients are mannitol, carbomer 974P, tyloxapol, edetate disodium, sodium chloride, hydrochloric acid and/or sodium hydroxide (to adjust pH), and purified water.

          PHARMACOLOGICAL ACTION
          Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyses the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. It exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II), found primarily in red blood cells, but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure.

          I removed some of it too long

          INDICATIONS
          AZOPTIC is indicated as monotherapy, or as adjunctive therapy to beta-blockers in the treatment of elevated intraocular pressure in ocular hypertension, or open-angle glaucoma.

          WARNINGS
          Brinzolamide is a sulphonamide and although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulphonamides may occur with AZOPTIC. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.
          There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and AZOPTIC. The concomitant administration of AZOPTIC and oral carbonic anhydrase inhibitors is not recommended.
          AZOPTIC has not been studied in patients with hepatic impairment and is therefore not recommended in such patients.
          There is limited experience with AZOPTIC in the treatment of patients with pseudoexfoliative glaucoma or pigmentary glaucoma.
          AZOPTIC was primarily evaluated in concomitant administration with timolol during adjunctive glaucoma therapy. Therefore, there are limited data regarding the administration of brinzolamide with other antiglaucomatous agents.
          AZOPTIC has not been studied in patients with narrow-angle glaucoma.
          The possible role of brinzolamide on corneal endothelial function has not been investigated in patients with compromised corneas (particularly in patients with low endothelial cell count). Specifically, patients wearing contact lenses have not been studied and careful monitoring of these patients when using brinzolamide is recommended, since carbonic anhydrase inhibitors may affect corneal hydration and wearing contact lenses might increase the risk for the cornea. Likewise, in other cases of compromised corneas such as patients with diabetes mellitus, careful monitoring is recommended.
          Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since AZOPTIC contains benzalkonium chloride, close monitoring is required with frequent or prolonged use in dry eye patients, or in conditions where the cornea is compromised.
          AZOPTIC has not been studied in patients wearing contact lenses. AZOPTIC contains the preservative benzalkonium chloride, which may be adsorbed by soft contact lenses. Therefore, patients must be instructed to wait 15 minutes after instillation of AZOPTIC before inserting contact lenses. AZOPTIC must not be administered while wearing contact lenses.
          Potential rebound effects following cessation of treatment with AZOPTIC have not been studied; the IOP-lowering effect is expected to last for 5-7 days.
          Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination in elderly patients. AZOPTIC is absorbed systemically and therefore this may occur with topical administration.
          Paediatric Use:
          The safety and effectiveness of AZOPTIC in paediatric patients have not been established.
          Effects on Ability to Drive and to Use Machines
          Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If transient blurring of vision occurs upon instillation, the patient should wait until the vision clears before driving or operating machinery.
          Interactions with Other Medicines and Other Forms of Interaction
          Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors and have resulted in drug interactions (e.g., toxicity associated with high-dose salicylate therapy). Brinzolamide is a carbonic anhydrase inhibitor and although administered topically, is absorbed systemically. Therefore, the potential for such drug interactions should be considered in patients receiving AZOPTIC.

          idem

          Specific interaction studies with other medicinal products have not been performed with AZOPTIC. AZOPTIC was used with ophthalmic timolol preparations without evidence of adverse reactions. An association between AZOPTIC and miotics or adrenergic agonists or other antiglaucoma agents than timolol has not been evaluated.

          idem

          Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures or with other surfaces.
          Nasolacrimal occlusion or gently closing the eyelids after instillation is recommended. This may reduce the systemic absorption of medication administered via the ocular route and result in a decrease in systemic side-effects.
          Contact Lenses
          The preservative in AZOPTIC, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of AZOPTIC but may be reinserted 15 minutes after instillation.
          Elderly Use:
          The probability of having a side-effect with AZOPTIC is independent of age. No dosage alteration in elderly patients is therefore necessary.

          SIDE-EFFECTS AND SPECIAL PRECAUTIONS
          The most frequent treatment related side-effects and local symptoms that may be experienced are taste perversion (bitter, sour or unusual taste) (5.4%) and temporary blurred vision upon instillation, lasting from a few seconds to a few minutes (5.0%) (see alsoEffects on ability to drive or use machinery).
          The following adverse reactions that were definitely, probably or possibly related to treatment have been reported. Their incidence was either common (less than 10%), uncommon (less than 1%) or rare (less than 0.1%).
          Ocular Effects
          Common: blurred vision (temporary blurring upon instillation, lasting from a few seconds to a few minutes), ocular discomfort (transient burning or stinging upon instillation), foreign body sensation, ocular hyperaemia and dry eye.
          Uncommon: ocular pain, ocular discharge, ocular pruritis, keratitis, blepharitis, conjunctivitis, lid margin crusting, sticky sensation, tearing, eye fatigue, keratopathy, and abnormal vision.
          Rare: keratoconjunctivitis, corneal staining, eye disorder, photophobia, meibomitis, vision change, irritation, glare, lid disorder, decreased vision and corneal erosion.
          Systemic Effects
          Brinzolamide is a sulphonamide and although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulphonamides may occur with AZOPTIC (class effect) (see also Warnings section).
          Taste perversion (bitter or unusual taste in the mouth following instillation) is the most frequently reported systemic side-effect reported with the use of AZOPTIC. It is likely caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal. Nasolacrimal occlusion or closing the eyelid for 3 minutes may help to reduce the incidence of this effect.
          Body as a whole: Uncommon: chest pain, alopecia. Rare: pain.
          Gastrointestinal Effects: Common: taste perversion. Uncommon: dry mouth, nausea and dyspepsia. Rare: diarrhoea and gastrointestinal disorder.
          Hypersensitivity Reactions: Uncommon: dermatitis. Rare: urticaria, pruritus.
          Nervous System Effects: Common: headache. Uncommon: paraesthesia characterised as numbness and a tingling sensation of the extremities, depression and dizziness. Rare: dream abnormality, hypertonia, agitation, amnesia, depersonalisation, nervousness, asthenia, insomnia, and tinnitus.
          Respiratory Effects: Uncommon: rhinitis, dyspnoea, pharyngitis, and bronchitis. Rare: dry nose, epistaxis, and increased cough.
          Urogenital Effects: Rare: kidney pain and impotence.
          The following additional adverse reactions have been rarely reported from post-marketing experience with AZOPTIC. They are generally known adverse effects as related to the use of oral carbonic anhydrase inhibitors: abnormal liver function, malaise, somnolence, vomiting and increased urinary frequency.

          KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
          Electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Treatment should be symptomatic and supportive.

          idem

          REGISTRATION NUMBER
          34/15.4/0382

          NAME AND BUSINESS ADDRESS OF THE APPLICANT
          Alcon Laboratories (SA) (Pty) Ltd
          261 Surrey Avenue
          Randburg, 2194

          DATE OF PUBLICATION OF THIS PACKAGE INSERT
          19 July 2001

          Updated on this site: October 2003
          Source: Pharmaceutical Industry

          Comment


          • #6
            bad for the mucin layer, and guess what...

            Bad for the individual's eye behind it
            Take care
            K

            Impact of short-term exposure of commercial eyedrops preserved with benzalkonium chloride on precorneal mucin

            So-Hyang Chung,1 Su Kyung Lee,1 Stephen M. Cristol,2 Eun Suk Lee,3 Dong Wook Lee,4 Kyoung Yul Seo,1 Eung Kweon Kim1,5

            1Institute of Vision Research, Department of Ophthalmology and 5Brain Korea 21, Division of Medical Sciences, Yonsei University College of Medicine, Seoul, Korea; 2Department of Ophthalmology, Emory Eye Center, Emory University, Atlanta, GA; 3Department of Ophthalmology, Inha University College of Medicine, Inchon, Korea; 4Mokdong Yonsei Eye Clinic, Seoul, Korea

            Correspondence to: Eung Kweon Kim, MD, PhD, Institute of Vision Research, Department of Ophthalmology and Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, CPO Box 8044, Seoul, Korea, 120-752; Phone: 822-2228-3577; FAX: 822-312-0541; email: eungkkim@yumc.yonsei.ac.kr

            Abstract

            Purpose: The aim of this study is to investigate the short-term effects of benzalkonium chloride (BAC), a preservative used in many ophthalmic topical solutions, on precorneal mucin in humans.

            Methods: Immortalized human corneal-limbal epithelial (HCLE) cells were exposed to eyedrops containing BAC solutions at 0.0025% and 0.01% concentrations for a period of 15 min. Human corneal epithelium was acquired with consent, as a byproduct of elective excimer photorefractive keratectomy procedures after application of Ocuflox® eyedrops (0.3% ofloxacin with 0.0025% BAC) for 1 week before surgery. The relative expression of the MUC1 and MUC16 mucin gene was determined by conventional and real-time reverse transcription-polymerase chain reaction (RT-PCR). Monoclonal antibodies for MUC1 (HMFG-1) and MUC16 (OC125) were used in western blot analysis to detect MUC1 and MUC16. Human corneas exposed to 0.01% BAC solutions were examined by transmission electron microscopy.

            Results: The expression of MUC1 and MUC16 gene transcripts was not changed after exposure to BAC in HCLE cells and human corneal epithelium. However, MUC1 and MUC16 were reduced after exposure to BAC in HCLE cells and human corneal epithelium. Transmission electron microscopy of the anterior corneal surface revealed fixation of the mucous layer after exposure to 0.01% BAC for 5 or 15 min; prolonged exposure (60 min) to 0.01% BAC destroys the mucous layer.

            Conclusions: This study demonstrates that short-term exposure to BAC can alter the precorneal mucin.

            Comment


            • #7
              Good article about BAK in glaucoma meds. Has a summary of all the bad things that BAK is proven to cause. Also has a bit about a new preservative in trial for a glaucoma med.

              http://www.optometric.com/article.aspx?article=71748

              Comment


              • #8
                Preservatives' Role in Topical Ocular Drugs

                Pretty in-depth article.

                http://www.revophth.com/index.asp?page=1_1012.htm



                Also, an article about Travatan Z, the new glaucoma medication that is BAK-free.

                http://www.eyeworld.org/article.php?sid=3583

                Comment


                • #9
                  a reversible logic

                  Hi

                  Here are a few excerpts:

                  "To some—even Dr. Mah—it has been considered a force for good in some regards.
                  Because of its abrasive nature on the epithelium, BAK has been thought to provide for better drug penetration.
                  But Travatan Z “is shockingly similar [to Travatan] in terms of efficacy,” Dr. Mah said.

                  A second opinion

                  Indeed, glaucoma specialists generally recognize BAK as problematic “both in terms of allergy rates and for its effects on the ocular surface,” said Ike K. Ahmed, M.D., assistant professor of ophthalmology, University of Toronto, Ontario, Canada.
                  Dr. Ahmed confided he has a heavy suspicion that it could negatively influence patients who might require future filtration surgery.
                  “There’s some indirect evidence that patients on [BAK] drops for multiple years and on multiple drops have more fibrosis and conjunctival problems,” Dr. Ahmed said. “I welcome manufacturers trying to go away from BAK.”

                  Editors’ note: Dr. Mah is a consultant for Alcon and Allergan. Dr. Ahmed has no financial interests related to his comments.

                  One speaks for ALCon and Allergan the other is independent...
                  pick your own.

                  People with DE and annual or long seasonal allergies - (many people then) do use MORE BAK-containing drops than the usual glaucoma treatment... therefore it's not just an issue for glaucoma but for all of us here.
                  Obviously Alcon is now offering a PF glaucoma drug and therefore security considerations arise to meet their available market in this particular sector.
                  So the logic they applied to glaucoma (frequent BAK use = problem) they didn't apply to all chronic surface ocular disease.

                  I spoke to Pr. Baudouin yesterday and he welcomes PF version for antibiotics and steroids for instance.
                  The good news for France is that we may have a solution soon.
                  Of course, Pr. Baudouin is an independent researcher and head of hospital dealing the most severe OSD cases in France, so directly dealing with patients (not just clinical healthy subjects)... who cares about his patients and I can tell you, isn't just critising BAK just to bother big pharmas.

                  I really tired of hearing about the penetrating effect of BAK, penetrating effect just means making the epithelium more fragile to let the active part of the drug work there... so this is not the way to go (a needle scrape would be more effective then!),... and why not use cationic emulsions instead.
                  BAK drops sting for some reason, BAK drops do cause KPS for some reason...

                  Moreover, many infections don't require such aggresive treatments (so no need to enhance further penetration for most minor infections) anyway, in case you had such an "incurable" and rare infection, in which the bacteria is antiobitic-resistant, then you would have to get special antibiotics from the hospital (certainly not those in the market for regular use). At least that's what happens here. So it's certainly not a reason to put BAK in every drop on the market...

                  Take care
                  and beware of sources when reading...
                  K

                  Comment


                  • #10
                    Hi Kakinda,
                    I don’t know if you have been up on this latest news: by spring of this year, Baush & Lomb will market an over-the-counter allergy medication with the same formula as prescription Zaditor, called Alaway OTC. I have not been able to find out the preservative used in the 10 ml bottles, but I am assuming it is benzalkonium chloride. Can anyone find this out? http://www.alimerasciences.com/news-pressrel.asp
                    Alimera Sciences Inc., an ophthalmic pharmaceutical company founded just three years ago, today announced that the U. S. Food and Drug Administration (FDA) has approved its ophthalmic solution Rx–to-OTC-switch new drug application (NDA) for Alaway™ (ketotifen fumarate ophthalmic solution 0.025%). Alaway™, a multiple action eye anti-allergic, is Alimera’s first NDA submission and the first to win approval. Indicated for the temporary relief of itchy eyes, Alaway™ will be marketed over-the-counter with the prescription strength active ingredient found in a prescription allergy eye drop.
                    Alimera Sciences, a privately-held company headquartered in Atlanta, GA and Bausch & Lomb (NYSE:BOL) today announced that Bausch & Lomb has purchased Alimera’s OTC allergy franchise, including Alaway (ketotifen fumarate ophthalmic solution 0.025%), which was recently approved by the U.S. Food and Drug Administration.
                    Scout

                    Comment


                    • #11
                      That's great!

                      Seems like the same concentration 0.25%... so one more option (check prices... play the competition!).

                      In fact we already have Zaditen (same thing, but European more gentle name... Zaditor, Terminator, etc) in PF drops for a few years. By the way, i use them all the time... rather than ALMIDE which is less effective but the only other PF anti-histaminic drop available here.
                      So it can effectively be done... in the States as well. Great... same logic for B&L on both sides of the Atlantic as far as BAK is concerned... we must be doing some progress !

                      Take care
                      K

                      Comment


                      • #12
                        Originally posted by kakinda
                        That's great!
                        I'm not so sure about that, Kakinda. The prescription brand Zaditor is not available in a PF formula in the U.S., so I am almost certain an over-the-counter formula in 10 ml bottles would have to have a preservative as well. I am assuming this is not great news, in fact, is fairly bad news. If indeed, the formula does have a preservative, there will be no doctor to advise the patient of the dangers of overuse. Maybe there will be a warning on the label?
                        If anyone can research this, it would be very helpful to us. So far, the chemical formula has not been listed anywhere I have searched.

                        Scout

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                        • #13
                          This is all speculation until the actual preservative is known. I checked the FDA site - labelling info is not available. But...

                          Originally posted by Scout
                          I am assuming this is not great news, in fact, is fairly bad news. If indeed, the formula does have a preservative, there will be no doctor to advise the patient of the dangers of overuse.
                          IF it has BAK specifically, I would agree that an OTC drop like this is not good news for those with predisposition to dry eye. - Just like all those other drops on the shelves (tears, vasoconstrictors, itchy eye drops) with BAK in fact. Few people would bother getting a prescription if they could get an effective OTC, and many people - uh, like the ones who buy vasoconstrictors and allergy drops - experience dry eye symptoms without knowing that's what they're experiencing let alone knowing that BAK could make it worse.
                          Rebecca Petris
                          The Dry Eye Zone

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                          • #14
                            I e-mailed Alimera Sciences:

                            I would like to know if there is a preservative in Alaway OTC and if so, which one?
                            Thank you for your attention to this.

                            Here is the reply:

                            The preservative is 0.01% BAK (benzalkonium chloride).

                            Best regards,

                            Yvonne Johnson
                            Alimera Sciences
                            6120 Windward Parkway
                            Alpharetta, GA 30005
                            Ph: 678-527-1751
                            FAX: 678-527-1335

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