Finding the Right Combination: The Art of Lowering IOP
By Leo Semes, OD, FAAO
The U.S. Food and Drug Administration (FDA) has approved a number of topical medications to reduce intraocular pressure (IOP). In fact, a 2002 editorial in Ophthalmology calculated that the combination of all concentrations in all combinations would exceed 50,000. More recently, a panel of glaucoma experts whittled the initial choice to one of the prostaglandin analogs (PGAs) (Singh et al, 2008).
While most of us who manage glaucoma see a PGA as the mainstay, the question of next steps always lurks. While it may be easy to forget about alternatives, other options such as beta-blockers (BBs), topical carbonic anhydrase inhibitors (tCAIs), alpha adrenergic agonists, and even the cholinergics may have their place. Let's explore some of these.
Occasionally, a PGA will be contraindicated or a patient will complain about the level of hyperemia and another first-line medication will have to be chosen. In this instance, considering mechanism of action becomes secondary.
While the PGAs are expected to lower IOP by about 30 percent, this may be more difficult to achieve with other classes of medication. Remember that BBs and tCAIs, while reducing aqueous formation, do not increase uveoscleral outflow. Also, remember dosing. The BBs are recommended for twice daily administration while as stand-alone drops, the tCAIs will have to be administered thrice daily. Not only are these less convenient dosing schedules compared to a once-daily PGA, the potential for systemic absorption of BB that may reduce perfusion pressure to the optic nerve must be considered.
Ocular perfusion pressure is an emerging issue. We know that BBs as a class are ineffective at lowering IOP at night; when we go to sleep so do our Beta receptors. Also, systemic absorption may lead to lower systemic blood pressure, which has the potential to reduce blood flow (perfusion pressure) to the optic nerve head. Finally, when one lies down to sleep, IOP increases. So, there is a double whammy for optic nerve damage risk—lower perfusion and higher IOP at night.
More exact information will be forthcoming but currently, diastolic ocular perfusion pressure (DOPP = systolic BP − IOP) should probably have a value greater than 50 or 55. Remember, we are still trying to get our arms around this. In the meantime, measure blood pressure and IOP.
A Look at tCAIs
The tCAIs may be best employed in combination formats but are effective additives, also. The current tCAI combination approved by the FDA includes timolol 0.5% plus dorzolamide 2% (CoSopot, Merck and generics). In addition, timolol 0.5% plus brimonidine 0.2% (Combigan, Allergan) couples timolol with an alpha-adrenergic agonist.
Aside from frequent dosing, the tCAIs present some other challenges, most notably allergic reactions. We are aware of the apparent risk in those sensitive to sulfonamide antibiotics. Another contraindication has emerged that may be more significant, and that is in those who have penicillin sensitivities.
Other Options Coming
This month (March 26, 2011), Xalatan (latanoprost 0.005%, Pfizer) goes off patent. The FDA has issued tentative approval for Abbreviated New Drug Application (ANDAs) for Par Pharmaceuticals and Apotex, Inc. as well as for Bausch + Lomb and Alcon. Pay particular attention to the concentration and remember that 99.995% is not latanoprost. Stay tuned. CLS
For references, please visit www.clspectrum.com/references.asp and click on document #184.
Dr. Semes is a professor of optometry at the UAB School of Optometry. He is also a consultant or advisor to Alcon, Allergan, Optovue, and Zeiss.