#1 dispensed branded
combination glaucoma medication1
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COMBIGAN® was designed to deliver proven IOP-reducing power as adjunctive or replacement therapy for patients with open-angle glaucoma or ocular hypertension.2

IOP=intraocular pressure.

COMBlGAN® was designed to deliver proven IOP-reducing power
as adjunctive or replacement therapy for patients with open-angle glaucoma or ocular hypertension.2

IOP=intraocular pressure.

Efficacy

Designed to deliver the power of a combination2

COMBIGAN® as monotherapy delivered up to

7.6mm Hg

mean IOP reduction from baseline (10 AM, Month 3)3

  • 38% greater mean IOP reduction than brimonidine 0.2% and 36% greater mean IOP reduction than timolol (10 AM, Month 3; P<0.001)3
  • 62% of patients had mean follow-up IOP ≤17.5 mm Hg over 12 months with COMBIGAN®4

COMBIGAN® as adjunctive therapy delivered

8.3mm Hg

mean IOP reduction from treated baseline when added to latanoprost (10 AM, Week 12)5

  • Up to 35% mean IOP reduction from treated baseline
  • 47% of patients achieved ≥30% mean IOP reduction from treated baseline at both peak and trough with COMBIGAN® added to latanoprost (8 AMand 10 AM, Week 12)5
    More than twice as many patients vs timolol added to latanoprost (22% of patients); (P <0.001)

COMBIGAN® vs Cosopt,

7.7mm Hg

mean IOP reduction from baseline as monotherapy* vs 6.7 mm Hg with Cosopt (Month 3; P=0.04),

and

6.9mm Hg

mean IOP reduction from baseline when added to a PGA vs 5.2 mm Hg with Cosopt (Month 3; P=0.213)6

  • In two 3-month studies, mean IOP reductions from baseline were not significant vs Cosopt at Month 1 as monotherapy and at Months 1 and 3 as adjunctive therapy with a PGA6
  • Mean IOP <16 mm Hg as both monotherapy and adjunctive therapy with a PGA (Month 3)6
  • There was no significant difference in the overall incidence of treatment-related AEs between COMBIGAN® and Cosopt6

FULL EFFICACY DATA STUDY DESIGN AND LIMITATIONS

*15 patients (28%) in the COMBIGAN® group and 16 patients (34%) in the Cosopt group were naïve to IOP-lowering medication.
AE=adverse event; IOP=intraocular pressure; PGA=prostaglandin analog.

Proposed Dual Mechanism of Action

COMBIGAN®: Designed to offer a dual mechanism of action2

  • Thought to reduce IOP by reducing aqueous humor production and increasing uveoscleral overflow

Tolerability

Added power proven to be well tolerated3,4

  • The majority of AEs with COMBIGAN® were mild to moderate in severity3
  • The most common treatment-related AEs over 12 months were conjunctival hyperemia (14.5%; n=56), ocular stinging (6.2%; n=24), eye pruritus (5.5%; n=21), allergic conjunctivitis (5.2%; n=20), and conjunctival folliculosis (4.9%; n=19)4

AE=adverse event.

Discontinuations due to AEs were significantly lower with COMBIGAN® vs brimonidine 0.2%4,7

Discontinuations due to AEs were significantly lower with COMBIGAN® vs brimonidine 0.2% Discontinuations due to AEs were significantly lower with COMBIGAN® vs brimonidine 0.2%

P-values for comparisons to the COMBIGAN® group.4,7
AE=adverse event.



STUDY DESIGN

Dosing

Starting patients on COMBIGAN®2

COMBIGAN® dosing is 1 drop twice a day approximately 12 hours apart.

May be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure.

If more than 1 topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

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Instructions for applying eye drops

Step One Visual

Step 1

Wash your hands. Tilt your head back and look at the ceiling.

  • If you wear contact lenses, remove them first, then wait 15 minutes after using your eye drops to put them back into your eyes.
Step Two Visual

Step 2

Using your index finger, pull down your lower eyelid to form a pocket.

Step Three Visual

Step 3

Gently squeeze 1 drop into the pocket. Don’t let the bottle tip touch your eye, your fingers, or anything else.

Step Four Visual

Step 4

Gently close your eyes and lightly press on the inside corners of your eyes.

Step Five Visual

Step 5

Carefully blot away any excess liquid that may be on your skin.

Access and Savings

Eligible patients may pay as little as
$15 FOR A 30- OR 90-DAY SUPPLY*

That’s as little as $5 per month for a 90-day supply. Help patients start saving by prescribing a 90-day supply

Enroll your patient

Patients can also call 1-833-DIAL-AYS
(1-833-342-5297) or text SAVINGS to 72428

*Maximum savings limit applies; patient out-of-pocket expense may vary. Offer not valid for patients enrolled in Medicare, Medicaid, a Medicare drug benefit plan, TRICARE, or other federal or state health programs (such as medical assistance programs). Other limitations may apply.

This offer is valid for up to 12 prescription fills for a 30-day supply and 4 prescription fills for a 90-day supply of COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5%. Offer applies only to prescriptions filled before the program expires on 05/01/20. This offer cannot be combined with any other programs, offers, or discounts, and may not be redeemed for cash. Allergan reserves the right to rescind, revoke, or amend this offer without notice anytime.

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References

  1. Data on file, Allergan, 2018.

  2. COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5% Prescribing Information.

  3. Data on file, Allergan, 2002. 190342-012T/013T.

  4. Sherwood MB, et al. Twice-daily 0.2% brimonidine–0.5% timolol fixed-combination therapy vs monotherapy with timolol or brimonidine in patients with glaucoma or ocular hypertension. Arch Ophthalmol. 2006;124(9):1230-1238.

  5. Fechtner RD, et al. Twelve-week, randomized, multicenter study comparing a fixed combination of brimonidine/timolol with timolol as therapy adjunctive to latanoprost. Clin Ophthalmol. 2011;5:945-953.

  6. Nixon DR, et al. Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy. Curr Med Res Opin. 2009;25(7):1645-1653.

  7. Craven ER, et al. Brimonidine and timolol fixed-combination therapy versus monotherapy: a 3-month randomized trial in patients with glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2005;21(4):337-348.

INDICATIONS AND USAGE

COMBIGAN® (brimonidine tartrate/timolol maleate ophthalmic solution) 0.2%/0.5% is an
alpha-adrenergic receptor agonist with a beta-adrenergic receptor inhibitor indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP; the IOP-lowering of COMBIGAN® dosed twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol maleate ophthalmic solution dosed twice a day and 0.2% brimonidine tartrate ophthalmic solution dosed three times per day.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

COMBIGAN® is contraindicated in patients with reactive airway disease including bronchial asthma; a history of bronchial asthma; severe chronic obstructive pulmonary disease; in patients with sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure; cardiogenic shock; in neonates and infants (aged 2 years and younger); in patients with a hypersensitivity reaction to any component of COMBIGAN® in the past.

WARNINGS AND PRECAUTIONS

COMBIGAN® contains timolol maleate. COMBIGAN® is administered topically, but can be absorbed systemically. The adverse reactions with systemic administration of beta-adrenergic blocking agents may occur with topical use (eg, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with systemic or ophthalmic administration of timolol maleate). Ophthalmic beta-blockers may impair compensatory tachycardia and increase risk of hypotension.

Sympathetic stimulation may be essential to support the circulation in patients with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. In patients with no history of cardiac failure, continued depression of the myocardium with beta-blocking agents over time can lead to cardiac failure. Discontinue COMBIGAN® at the first sign or symptom of cardiac failure.

Patients with chronic obstructive pulmonary disease (eg, chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease should not receive beta-blocking agents, including COMBIGAN®.

COMBIGAN® may potentiate syndromes associated with vascular insufficiency. Use caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

Patients taking beta-blockers with a history of atopy or severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

Beta-adrenergic blockade can potentiate muscle weakness with myasthenic symptoms (eg, diplopia, ptosis, and generalized weakness). Although rare, timolol can increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.

Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia and clinical signs (eg, tachycardia) of hyperthyroidism. Use caution in patients subject to spontaneous hypoglycemia or in diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Carefully manage patients who may develop thyrotoxicosis to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate a thyroid storm.

Ocular hypersensitivity has occurred with brimonidine tartrate ophthalmic solutions 0.2% (eg, increase in IOP).

Some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents due to impairment of beta-adrenergically mediated reflexes during surgery. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists.

ADVERSE REACTIONS

The most frequent reactions with COMBIGAN® in about 5% to 15% of patients included: allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging.

DRUG INTERACTIONS

COMBIGAN® may reduce blood pressure. Use caution in patients on antihypertensives and/or cardiac glycosides.

Observe patients receiving a beta-adrenergic blocking agent either orally or intravenously and COMBIGAN® for additive effects of beta-blockade, both systemic and on intraocular pressure. Concomitant use of two topical beta-adrenergic blocking agents is not recommended.

Use caution in the co-administration of beta-adrenergic blocking agents (eg, COMBIGAN®) and oral or intravenous calcium antagonists due to possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. Avoid co-administration in patients with impaired cardiac function.

Observe patients closely when a beta-blocker is administered to patients receiving catecholamine-depleting drugs (eg, reserpine) due to possible additive effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.

Specific drug interaction studies have not been conducted with COMBlGAN®, but consider the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics).

Concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.

Potentiated systemic beta-blockade (eg, decreased heart rate, depression) has been reported with combined use of CYP2D6 inhibitors (eg, quinidine, SSRls) and timolol.

Tricyclic antidepressants (TCAs) can blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of TCAs with COMBIGAN® in humans can interfere with the IOP-lowering effect. Caution is advised in patients taking TCAs, which can affect the metabolism and uptake of circulating amines.

Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially increase systemic side effects such as hypotension. Use caution in patients taking MAO inhibitors, which can affect the metabolism and uptake of circulating amines.

Click here for full COMBIGAN® Prescribing Information.