Dorzolamide/timolol

Dorzolamide/timolol eye drops (trade name Cosopt) are used to lower intraocular pressure in the eye to normal pressure and as a treatment for glaucoma.^[1] This medication is a combination of two active ingredients: dorzolamide hydrochloride and timolol maleate. Both compounds work by decreasing the production of aqueous humor, which works to lower intraocular pressure. It gained Food and Drug Administration (FDA) approval in April 1998, and is supplied by Merck.^[2]

Pharmacology

Dorzolamide is a human carboanydrase II inhibitor.^[3] Inhibition of carboanhydrase in the ciliary processes of the eye decreases aqueous humor secretion supposedly by decreasing the formation rate of bicarbonate ions.^[1] This results in reduction in both sodium and fluid transport.

Timolol is a non-selective beta-adrenergic antagonist.^[4]

Adverse effects

Common adverse effects include temporarily blurred vision, cloudy vision, double vision, temporary burning/stinging/itching of the eye, watery eyes, feeling as if something is in the eye, drooping eyelid, sensitivity to light, cough, flu symptoms, nausea, and stomach pain.^[5]

More serious adverse effects include dizziness, slow or irregular heartbeat, muscle weakness, mental/mood changes, and coldness/numbness/pain in the hands or feet.^[5]

Comparison to other products

Despite each of the active ingredients being availed in their own respective formulations, combination formulations are typically more convenient for the patient without sacrificing any quality in therapy. In the case of Cosopt, the combination formulation dosed twice daily provides equivalent treatment to both dorzolamide 2% dosed two times daily and timolol 0.5% dosed three times daily.^[6] Specifically, the mean reduction in intraocular pressure was 27.4% for the combination product, 15.5% for dorzolamide 2%, and 22.2% for timolol 0.5%.

Compared to other products such as latanoprost, both are equally efficacious with regard to lowering intraocular pressure and getting patients to reach their target intraocular pressure.^[6] Cosopt, though, is typically less well tolerated than other treatments due to a well documented feeling of ocular burning upon administration.

History

Cosopt gained Food and Drug Administration (FDA) approval in April 1998 and was supplied initially by Merck.^[2] In 2016, Merck & Co. had $95.3 billion in total assets, $40.3 billion in total equity, $24.3 billion in long term debt, and $13.4 billion in working capital.^[7] This same year Merck & Co spent $20 billion total split virtually evenly between research and development (R&D) and marketing efforts.  Cosopt had annual sales of $342 million during the 12 months before June 2008.^[8] In September 2013,  Merck & Co. sold the U.S. rights to their ophthalmic product line (including Cosopt) to Akorn Inc. for $52.8 million cash.^[9]

Upon the original patent expiration, Hi-Tech Pharma was the first of many generic competitors to submit an abbreviated new drug application (ANDA) for dorzolamide hydrochloride/timolol maleate eye drops.^[10] Hi-Tech Pharma’s ANDA was approved on October 28, 2008.  At the time, controversy surrounded the approval of this first ANDA.  Hi-Tech sued the FDA for their right to 180 market exclusivity as laid out in the Hatch-Waxman Act. Apotex, another firm seeking an ANDA approval for generic Cosopt, argued that Hi-Tech “forfeited its rights to market exclusivity because it has failed to market the drug within 30 months of its ANDA submission or within 75 days after Merck withdrew its patent information.”^[10] The FDA upheld their previous exclusivity decisions on acarbose and granisetron, allowing both Hi-Tech and Apotex to make a generic version of Cosopt.^[8] Soon after, ANDAs from Sandoz, Bausch & Laumb, TEVA and others were also approved.^[11]

Just over a year before Merck sold their ophthalmic line to Akorn, Akorn developed a new formulation of dorzolamide hydrochloride/timolol maleate called Cosopt PF, which is simply a preservative free formulation of Cosopt.^[12] It gained FDA approval in July 2012 and is currently protected by market exclusivity.

Legality

In the United States, Cosopt, as well as its generics, is only available to patients with a valid prescription.^[11]

Cost

The brand name Cosopt currently costs upwards of $200 after discounts^[13] while the generic formulation costs around $70 cash.^[14] The more recent preservative free formulation can be purchased for less than the original brand name formulation at around $160^[15]

References

External links

• The drug's web site
• The drug's label