Cosopt/Cosopt-S

Dorzolamide hydrochloride, timolol maleate.

Each mL of ophthalmic solution contains dorzolamide HCl equivalent to dorzolamide 20 mg and timolol maleate equivalent to timolol 5 mg.

ATC Code: S01ED51.
Cosopt/Cosopt-S ophthalmic solution (dorzolamide HCl and timolol maleate) is the first combination of a topical carbonic anhydrase inhibitor and a topical β-adrenergic receptor-blocking agent.

Treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension, open-angle glaucoma, pseudoexfoliative glaucoma or other secondary open-angle glaucomas when concomitant therapy is appropriate.

The dose is one drop of COSOPT/COSOPT-S in the affected eye(s) two times daily.
When substituting COSOPT/COSOPT-S for another ophthalmic antiglaucoma agent(s), discontinue the other agent(s) after proper dosing on one day, and start COSOPT/COSOPT-S on the next day.
If another topical ophthalmic agent is being used, COSOPT/COSOPT-S and the other agent should be administered at least ten minutes apart.
Safety and efficacy in pediatric patients below the age of 2 years have not been established (For information regarding use in pediatric patients ≥2 years of age see section VIII).
When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in an increase in local activity.

No data are available with regard to human overdosage by accidental or deliberate ingestion of Cosopt/Cosopt-S.
There have been reports of inadvertent overdosage with timolol maleate ophthalmic solution resulting in systemic effects similar to those seen with systemic beta-adrenergic-blocking agents eg, dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest. The most common signs and symptoms to be expected with overdosage of dorzolamide are electrolyte imbalance, development of an acidotic state and possibly central nervous system effects.
Treatment should be symptomatic and supportive. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Studies have shown that timolol does not dialyze readily.

COSOPT/COSOPT-S is contraindicated in patients with: Reactive airway disease, bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease; sinus bradycardia, sino-atrial block, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock; hypersensitivity to any component of this product.
The previously mentioned are based on the components and are not unique to the combination.

As with other topically-applied ophthalmic agents, this drug may be absorbed systemically. The timolol component is a beta-blocker. Therefore, the same types of adverse reactions found with systemic administration of beta-blockers may occur with topical administration.
Cardio-respiratory Reactions: Because of the timolol maleate component, cardiac failure should be adequately controlled before beginning therapy with COSOPT/COSOPT-S. Patients with a history of cardiovascular disease, including cardiac failure should be watched for signs of deterioration of these diseases, and pulse rates should be checked.
Due to its negative effect on conduction time, beta-blockers should be given with caution to patients with first degree heart block.
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 following administration of timolol maleate ophthalmic solution.
In patients with mild/moderate chronic obstructive pulmonary disease (COPD), COSOPT/COSOPT-S should be used with caution, and only if the potential benefit outweighs the potential risk.
Vascular Disorders: Patients with severe peripheral circulatory disturbance/disorders (e.g. severe forms of Raynaud's disease or Raynaud's syndrome) should be treated with caution.
Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic blocking agents may mask the signs and symptoms of acute hypoglycemia.
Masking of Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs of hyperthyroidism (e.g., tachycardia). Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.
Surgical Anesthesia: The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists.
Renal and Hepatic Impairment: COSOPT/COSOPT-S has not been studied in patients with severe renal impairment (CrCl <30 milliliter/min). Because dorzolamide hydrochloride and its metabolite are excreted predominantly by the kidney, COSOPT/COSOPT-S is not recommended in such patients.
COSOPT/COSOPT-S has not been studied in patients with hepatic impairment and therefore should be used with caution in such patients.
Immunology and Hypersensitivity: As with other topically-applied ophthalmic agents, this drug may be absorbed systemically. The dorzolamide component is a sulfonamide. Therefore, the same types of adverse reactions found with systemic administration of sulfonamides may occur with topical administration, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. If signs of serious reactions or hypersensitivity occur, discontinue use of this preparation.
In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of dorzolamide hydrochloride ophthalmic solution. Some of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of drug therapy. Similar reactions have been reported with COSOPT/COSOPT-S. If such reactions are observed, discontinuation of treatment with COSOPT/COSOPT-S should be considered.
While taking β-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to accidental, diagnostic, or therapeutic repeated challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.
Concomitant Therapy: There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving oral and topical carbonic anhydrase inhibitors concomitantly. The concomitant administration of COSOPT/COSOPT-S and oral carbonic anhydrase inhibitors has not been studied and is not recommended.
Patients who are already receiving a beta-adrenergic blocking agent systemically and who are given COSOPT/COSOPT-S should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta-blockade. The use of two topical beta-adrenergic blocking agents is not recommended.
Other: The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. COSOPT/COSOPT-S has not been studied in patients with acute angle-closure glaucoma.
Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g., timolol, acetazolamide, dorzolamide) after filtration procedures.
There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Precautions should be used when prescribing COSOPT/COSOPT-S to this group of patients.
Contact Lens Use: COSOPT/COSOPT-S contains the preservative benzalkonium chloride, which may be deposited in soft contact lenses; therefore, COSOPT/COSOPT-S should not be administered while wearing these lenses. The lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use.
Use in Children: The safety and efficacy of 2% dorzolamide hydrochloride ophthalmic solution has been established in a clinical study of children under the age of 6 years. In this study patients under 6 and greater than 2 years of age whose IOP was not controlled with monotherapy received COSOPT/COSOPT-S. In those patients COSOPT/COSOPT-S was generally well tolerated.

Use in Pregnancy: There are no adequate and well-controlled studies in pregnant women. Cosopt/Cosopt-S should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Use in Lactation: It is not known whether dorzolamide HCl is excreted in human milk. Timolol maleate does appear in human milk. Because of the potential for serious adverse reactions on the nursing infant, a decision should be made whether to discontinue nursing or discontinue Cosopt/Cosopt-S, taking into account the importance of the drug to the mother.

In clinical studies, Cosopt/Cosopt-S was generally well tolerated; no adverse experiences peculiar to this combination drug have been observed. Adverse experiences have been limited to those that were reported previously with dorzolamide HCl and/or timolol maleate. In general, common adverse experiences were mild and did not cause discontinuation.
During clinical studies, 1035 patients were treated with Cosopt/Cosopt-S. Approximately 2.4% of all patients discontinued therapy with Cosopt/Cosopt-S because of local ocular adverse reactions. Approximately 1.2% of all patients discontinued because of local adverse reactions suggestive of allergy or hypersensitivity. The most frequently reported drug-related adverse effects were: Ocular burning and stinging, taste perversion, corneal erosion, conjunctival infection, blurred vision, tearing and ocular itching. Urolithiasis was reported rarely.
The following adverse reactions have been reported in post-marketing experience: Dyspnea, respiratory failure, contact dermatitis, bradycardia, heart block, choroidal detachment following filtration surgery, nausea, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Specific drug interaction studies have not been performed with Cosopt/Cosopt-S.
In clinical studies, Cosopt/Cosopt-S was used concomitantly with the following systemic medications without evidence of adverse interactions: ACE inhibitors, calcium-channel blockers, diuretics, nonsteroidal anti-inflammatory drugs including aspirin and hormones (eg, estrogen, insulin, thyroxine).
However, the potential exists for additive effects and production of hypotension and/or marked bradycardia when timolol maleate ophthalmic solution is administered together with oral calcium-channel blockers, catecholamine-depleting drugs or β-adrenergic-blocking agents.
Potentiated systemic β-blockade (eg, decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (eg, quinidine, selective serotonin reuptake inhibitors) and timolol.
The dorzolamide component of Cosopt/Cosopt-S is a carbonic-anhydrase inhibitor and although administered topically, is absorbed systemically. In clinical studies, dorzolamide HCl ophthalmic solution was not associated with acid-base disturbances. However, these disturbances have been reported with oral carbonic anhydrase inhibitors and have in some instances, resulted in drug interactions (eg, toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving Cosopt/Cosopt-S.
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

Store at 15-30°C (59-86°F). Protect from light.

Antiglaucoma Preparations

S01ED51 - timolol, combinations ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.

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