Article Date: 1/1/2001

NEW DRUGS
New Drugs for 2001
Pharmacology expert Dr. Jimmy Bartlett highlights the newest drugs to make their way into  practice.
Jimmy D. Bartlett, O.D., F.A.A.O., Birmingham, Ala.

Last year seemed to be the year of allergy medications, but this year brings us a different trend. This year, we'll see a handful of new glaucoma drugs.

Overall, a trend I see becoming more apparent is the step toward improving our patients' compliance by moving to once- or twice-daily dosing. I think this will become a long-term trend.

Whenever a new drug makes its way into the ophthalmic market, we should learn as much about it as possible so that we use it safely and correctly. Of course, doing so only benefits our patients and us.

To help familiarize yourselves with some of the newcomers to our practice, we'll look at some of the important drugs that have either recently been approved or are scheduled for approval this year. We'll also review some promising drugs in the pipeline.

Anti-allergy

Three new anti-allergy medications became available to us last year. Here's a look at each:

• ALAMAST (pemirolast potassium ophthalmic solution 0.1%) by Santen Inc.
  • Approval status. Santen Inc. received approval for its New Drug Application (NDA) submitted in March 1999 from the FDA. Alamast was launched in the United States in July 2000.
  • Indications. For the prevention of itching due to allergic conjunctivitis.
  • How it works. It's a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction. In vitro and in vivo studies have demonstrated that pemirolast potassium inhibits the antigen-induced release of inflammatory mediators from human mast cells.
    It also inhibits the chemotaxis of eosinophils into ocular tissue and blocks the release of mediators from human eosinophils.
  • Dosing. One to two drops in each affected eye q.i.d.
  • Contraindications. Patients with previously demonstrated hypersensitivity to any of the ingredients in this product.
• ALOCRIL (nedocromil sodium ophthalmic solution 2%) by Allergan, Inc.
  • Approval status. Approved by the FDA in March 2000..
  • Indications. Primarily a mast cell inhibitor, Alocril also has other cellular mechanisms that are potentially beneficial to allergy patients. It's indicated for the treatment of itch associated with allergic conjunctivitis in patients age 3 and over.
  • How it works. Alocril is a mast cell stabilizer that inhibits the release of mediators from cells involved in hypersensitivity reactions.
  • Dosing. Twice daily instead of four times, which helps with compliance because it's more convenient for the patient. Therefore, it's hoped that the condition will resolve quicker.
  • Contraindications. Patients who show hypersensitivity.
• OPTIVAR (azelastine hydrochloride ophthalmic solution 0.05%) by ASTA Medica.
  • Approval status. Launched in September 2000.
  • Indications. For the treatment of itchy eyes associated with allergic conjunctivitis.
  • How it works. Azelastine hydrochloride is a relatively selective histamine. It's an H₁ antagonist and an inhibitor of the release of histamine and other mediators from cells involved in the allergic response. Evidence for mast cell stabilization and inhibition of other inflammatory mediators exists.
  • Dosing. One drop in affected eye(s) twice daily.
  • Contraindications. Patients with known or suspected hypersensitivity to any of this drug's components.

Anti-infectives

Of all the fluoroquinolone anti-infectives available, this one is better against gram-positive organisms such as streptococcus.

• QUIXIN (levofloxacin ophthalmic solution 0.5%), manufactured by Santen Inc.
  • Approval status. The FDA approved the company's NDA in August 2000. Santen launched the drug in the United States in November 2000.
  • Indications. For the treatment of bacterial conjunctivitis caused by susceptible strains of a broad spectrum of aerobic gram-positive and gram-negative ocular pathogens.
  • How it works. Levofloxacin is the L-isomer of the racemate ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves the inhibition of bacterial topoisomerase IV and DNA gyrase, enzymes required for DNA replication, transcription, repair and recombination.
  • Dosing. Days 1 and 2, one to two drops in the affected eye(s) every 2 hours, up to eight times per day. Days 3 to 7, one to two drops in the affected eye(s) every 4 hours, up to four times per day.
  • Contraindications. Patients with a history of hypersensitivity to levofloxacin, to other quinolones or to any of the components in this medication.

Steroid anti-inflammatories

I expect that FDA approval of this next drug will occur some time this year.

• RESTASIS (cyclosporine ophthalmic emulsion 0.05%), a new topical anti-inflammatory manufactured by Allergan, Inc.
  • Approval status. An NDA has been filed and designated "approvable" by the FDA. Final clearance awaits additional information from the manufacturer and further FDA review because the company needs to conduct another confirmatory study.
  • Indications. For the topical treatment of moderate to severe dry eye.
  • How it works. According to results from the Phase III clinical trials, it improves the signs and symptoms of chronic dry eye disease and reduces the ocular inflammation and immune reactivity associated with it.
  • Dosing. In the Phase III study, the recommended dosage was one drop twice daily.
  • Contraindications. Any contraindications will depend on the results of the new study.

Glaucoma medications

As mentioned earlier, this category holds the most new developments in ocular drugs.

• BETAXON (levobetaxolol hydrochloride ophthalmic suspension .5%) manufactured by Alcon Laboratories.
  • Approval status. Approved by the FDA in February 2000. Alcon expects to launch Betaxon later this year.
  • Indications. Lowers intraocular pressure (IOP) in patients with chronic open-angle glaucoma or ocular hypertension.
  • How it works. Betaxon reduces IOP by decreasing aqueous production. It's a more potent selective beta-blocker than its earlier-introduced brother, Betoptic.
  • Dosing. One drop in affected eye(s) twice daily.
  • Contraindications. Patients with hypersensitivity to any component of the product.
• LUMIGAN 0.03% (AGN 192024), Allergan Inc.'s new prostamide.
  • Approval status. Phase III clinical trials are completed, and the company filed an NDA in September 2000.
  • Indications. Allergan is seeking an indication for the treatment of glaucoma and ocular hypertension.
  • How it works. Prostamides are naturally occurring substances found in ocular tissues that have intrinsic factors for IOP regulation. Lumigan mimics these prostamides and increases outflow, although the precise receptor binding site is unknown.
  • Dosing. Once-daily dosages in the evening were most effective in the Phase III clinical trials.
  • Contraindications. Contraindications are dependent on the FDA's review.
• RESCULA (unoprostone isopropyl ophthalmic solution 0.15%), manufactured by CIBA Vision, is a docosanoid derivative, which is developed to minimize side effects of prostaglandin analogs.
  • Approval status. Approved by the FDA in August 2000.
  • Indications. For use in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure-lowering medications or insufficiently responsive over time to another IOP-lowering medication.
  • How it works. Rescula reduces IOP by increasing aqueous outflow, probably by enhancing uveoscleral outflow. It has no effect on conventional aqueous outflow or aqueous humor flow. Rescula is absorbed through the conjunctiva and corneal epithelium, where it's hydrolyzed by esterases to unoprostone-free acid.
  • Dosing. One drop in affected eye(s) b.i.d.
  • Contraindications. Use caution with patients who have diabetes or dry eyes. Monitor the corneal epithelium when Rescula is used with beta-blockers.
• TRAVATAN (travoprost) is Alcon Laboratories' soon-to-be released prostaglandin analog.
  • Approval status. Alcon anticipates approval for this product early this year.
  • Indications. For use in patients with open-angle glaucoma or ocular hypertension who are intolerant of other intraocular pressure-lowering medications or insufficiently responsive over time to another IOP-lowering medication.
  • How it works. It's believed to reduce IOP by increasing uveoscleral outflow.
  • Dosing. One drop in affected eye(s) in the evening.
  • Contraindications. Patients with known hypersensitivity to travoprost.
• XALCOM, a fixed combination of Xalatan (latanoprost ophthalmic solution) and timolol maleate 0.5%, manufactured by Pharmacia Corporation.
  • Approval status. Pharmacia just received its second approvable letter from the FDA in October 2000 regarding its NDA.
  • Indications. Pharmacia is seeking an indication to reduce IOP in patients who have open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta blockers, prostaglandins or other IOP-lowering medications.
  • How it works. It combines latanoprost's increased uveoscleral outflow with the aqueous suppression action of timolol.
  • Dosing. One drop per day.
  • Contraindications. Same as contraindications to either latanoprost or timolol.

Be cautious and wise

Many new drugs are now available to help us take even better care of our patients' ocular needs.

Use them carefully with your full consideration given to their uses, potential side effects and contraindications.

Dr. Bartlett is interim chair at the University of Alabama at Birmingham (UAB) Department of Optometry. He's also a professor of optometry at UAB School of Optometry and is a professor of pharmacology at the UAB School of Medicine.

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Optometric Management, Issue: January 2001