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BAK: Boon or Bane?

Submitted by winter.lauder on Fri, 11/25/2011 - 11:51am

Preservatives found in pharmaceutical products are a group of chemical substances added in multidose solutions to primarily reduce the risk of microbial contamination. Benzalkonium chloride, Polyquad, SofZia, and Purite are the common preservatives especially used in anti glaucoma agents. While SofZia and Purite are new preservatives that have been called vanishing preservatives, because they convert to nontoxic substances once in the eye, Benzalkonium chloride, on the other hand is the most common ophthalmic preservative. Although this chemical detergent ultimately helps in preserving the solutions most of the eye doctors prescribe, the hazards it poses on our eyes' health significantly affect our decision on the kind of medications to use. Research has shown that long-term use of preserved antiglaucoma medications may cause problems. One study revealed that preservative agent like BAK has toxic effects, compromising tear film stability and causing damage to corneal, conjunctival, and trabecular cells. These ocular side effects can translate into symptoms such as stinging, burning, and dryness.

An article by John R. Samples, MD, professor of ophthalmology at the Oregon Health & Science University in Portland, helps strengthen the above claim as he said, “BAK is bad for the conjunctiva, the cornea and perhaps even the trabecular meshwork. It is a toxic detergent. It attracts monocytes and lymphocytes into the conjunctiva and it makes the tissue thicken up.” Dr. Samples contends that BAK can have negative consequences that extend from the ocular surface all the way to the posterior pole. “BAK makes dry eye worse in some patients; it is toxic to corneal epithelial cells and, according to our laboratory work, it is toxic to corneal endothelial cells and trabecular cells when it enters the anterior chamber; it gives us a dysfunctional conjunctiva when it comes time to consider filtration; it has a complex role in setting up allergic reactions in the eye. It has even been implicated in the occurrence of cystoid macular edema,” he noted.

Because of these drawbacks, preservative free medications have been developed to additionally minimize side effects like ocular surface disease. A number of studies have been done to investigate the efficacy of preserved versus preservative free anti glaucoma solutions and their potential effects on our eyes' health.

Below are the different preservative free anti glaucoma medications and their related study results.

1. Preservative Free Prostaglandin Analogues. Saflutan (Tafluprost) is a new preservative-free prostaglandin for the reduction of intra ocular pressure in open-angle glaucoma and ocular hypertension and one research results demonstrate that preservative-free tafluprost 0.0015% was effective, generally well tolerated, and safe in a broad and heterogeneous patient population. Meanwhile, Travatan Z (travoprost ophthalmic solution) uses SofZia as its preservative. SofZia is a proprietary, ionic, buffered solution consisting of zinc, borate, propylene glycol, and sorbitol— substances that are not significantly toxic to the ocular surface but maintain an antimicrobial environment in the container. One study results demonstrate that the substitution of the preservative BAK from topical ophthalmic drugs results in greater in vitro viability of trabecullar meshwork cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic BAK effects. BAK treatment appeared to cause elevated levels of MMP-9, a matrix metalloproteinase implicated in the pathogenesis of glaucoma.

In an article “The Cytotoxic Effects of Preserved and Preservative-Free Prostaglandin Analogs on Human Corneal and Conjunctival Epithelium”, the cytotoxic effects of latanoprost, travoprost, and bimatoprost were dependent on the BAK concentration in their formulations. BAKmix was cytotoxic at the concentrations above those corresponding to 0.001% BAK in ophthalmic medications. Preservative free tafluprost was the least toxic of the drugs tested.

2. Preservative Free Beta Blockers. Timoptic (timolol maleate) in Ocudose (dispenser) is the only topical glaucoma medication completely free of preservatives that is available in the United States . Timoptic in Ocudose is available in two dosage strengths, 0.25% and 0.5%. The fixed combination of travoprost/timolol with 0.001% Polyquad had decreased ocular surface toxicity relative to the BAK-containing solutions. Also, one research suggests that the use of preservatives in timolol 0.5% eyedrops leads to tear film instability and ocular surface inflammatory changes documented by a reduction of breakup time and an increase of IL-1beta tear concentrations. Preservative-free beta-blockers are preferable for long-term hypotensive therapy to prevent ocular surface inflammation.

3. Preservative free Carbonic Anhydrase Inhibitors. Trusopt is a preservative free antiglaucoma medications under Carbonic Anhydrase Inhibitors. Trusopt is indicated as adjunctive tharapy to beta blockers or as monotherapy in patients as responsive to beta blockers or in whom beta blockers are contraindicated. Dorzolamide 1.0%/timolol 0.5% fixed combination therapy added to prostaglandin analogs as glaucoma monotherapy is effective in patients with normal tension glaucoma. Cosopt (fixed-combination timolol 2%-dorzolamide 0.5%) is also available outside the United States.

4. Preservative free Adrenergic Agonists. Brimonidine (Alphagan) preserved with Purite. Purite is a stabilized oxychloro complex (sodium chlorite) with a long history of use in water purification systems; it degrades to chloride ions and water upon exposure to ultraviolet light. This proprietary preservative is used in Alphagan P, a brimonidine tartrate preparation for glaucoma. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride formulations due better tolerability while maintaining similar efficacy.

5. Preservative free Miotics. Pilocarpine nitrate 2% eye drops 0.5ml unit dose is also available outside the United States.

These studies show that topical glaucoma medications that contain alternative preservatives or that are free of preservatives offer the potential to preserve the health of the ocular surface as the therapy advances. This consideration is particularly valuable when patients are sensitive to preservatives or have concomitant ocular surface disease. Several studies also suggest that switching from a preserved to a preservative-free medication can benefit the tear film, conjunctiva, cornea, and eyelids.


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