FIXED DRUG COMBINATIONS IN GLAUCOMA

Guest author 

Rubeena Khatoon

Ajmal Khan Tibiyya College

Aligarh, India

Introduction

In about 50% of the patients initial monotherapy for glaucoma is unable to control intra-ocular pressure (IOP).

This either requires addition of anti-glaucoma medications or change of the initial drug.

Fixed drug combinations (FDCs) are being increasingly available where two drugs are combined in one bottle.

FDCs have a number of advantages, compared to prescribing the same drugs in two separate bottles.

Advantages of FDCs include:

Increased compliance by reducing the time required to administer the drops, frequency of instillation and the total number of bottles.

Prescribing a single bottle is cheaper in the long term.

FDCs reduce the preservative load in the eye. The more the number of bottles used, the more the preservative entering the eye.

Addition of drugs (e.g. prostaglandin analogues or beta blockers) may have additive IOP lowering effects.

Disadvantages of FDCs Include:

Dosing of concomitant medications cannot be alerted within the concomitant product.

FDCs for twice daily use may contain too little or too much of one drug for a given patient.

Morning dosing may not be ideal for a PGA while beta blockers have little effects on IOP lowering during sleep.

FDCs may have components which are allergic to the patient. However, it may become difficult to identify the causative agent.

Available FDCs:

(1) Latanoprost/Timolol

The first FDC marketed commercially was a combination of Latanoprost 0.005%+Timolol 0.5%, used once daily.

Mean diurnal IOP reduction from baseline was 33.5% achieved in 73.5% patients.

Mean IOP reduction from baseline was -9.4 mmHg. This combination can be used in POAG and OHT Patients to decrease adverse effects improve compliance and tolerability.

(2) Travoprost/Timolol

Travoprost 0.004% + Timolol 0.5% combination is marketed by Alcon as "Duotrav" eyedrops. This combo achieved mean IOP decrease from 32-38%. Comparison of Travoprost/Timolol vs. Dorzolamide/Timolol found the mean reduction in IOP by the former combo was 8.96 mmHg (36.28%) vs. 8.07 mmHg (35.66%) for the latter. This combo can be used in patients not tolerating other drugs due to BAK toxicity. Duotrav contains polyquaternium (polyquad) as preservative. Studies have found morning and evening once daily dosing to be equally efficacious.

(3) Bimatoprost/Timolol

Bimatoprost 0.03% + Timolol 0.5% FDC can be used when there is any requirement for alternative/replacement therapy. Average reduction in IOP is 35%. Once daily dosing is more advantageous compared to separate medications.

(4) Dorzolamide/Timolol

Dorzolamide (a carbonic anhydrase inhibitor) is frequently used as adjunctive therapy to Timolol (a beta blocker). Both these agents reduce Aqueous humor production and thus lower IOP. An FDC of Dorzolamide 2% + Timolol 0.5%, when used twice daily, lowered IOP more than either of its individuals components and comparable in efficacy to the concomitant administration of the two medications when used as initial therapy in POAG and OHT it reduced IOP by 34.4-34.67%.

(5) Brinzolamide/Timolol

A FDCs of Brinzolamide 1% + Timolol 0.5% was found to have less adverse effects, better compliance, high tolerability and comfort compared to Dorzolamide+Timolol combo. In a study, IOP reduction from baseline was 28.4-34.9% in Brinzolamide/Timolol group vs 29.2-33.9% in Dorzolamide/Timolol group.

This FDC has a twice daily regimen and efficacious in POAG and OHT.

(6) Brinzolamide/Brimonidine

The newest FDC is Brinzolamide 1% + Brimonidine 2%. It is the only FDC which doesn't rely on the action of betablockers. The two components decrease aqueous humor production with an additional improvement in uveoscleral outflow by Brimonidine. An average reduction of IOP from 21.4-34.9% higher than either of its individual components is seen with this combo. This FDC is prescribed three times daily.

Conclusion

FDCs are useful in POAG/OHT Patients as first or second line therapy.

They offer advantages in terms of convenience, cost effectiveness, safety and compliance.