COSOPT Dorzolamide / Timolol 20mg / 5mg per mL Ophthalmic Solution 5mL
RXDRUG-DR-XY27310
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Features
Brand
Cosopt
Full Details
Dosage Strength
20 mg / 5 mg per mL
Drug Ingredients
- Dorzolamide
- Timolol
Drug Packaging
Ophthalmic Solution 5ml
Generic Name
Dorzolamide Hydrochloride / Timolol Maleate
Dosage Form
Ophthalmic Solution
Registration Number
DR-XY27310
Drug Classification
Prescription Drug (RX)
Description
Indications/Uses
DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) is indicated in the 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.
Dosage/Direction for Use
The dose is one drop of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) in the affected eye(s) two times daily.
When substituting DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) for another ophthalmic antiglaucoma agent(s), discontinue the other agent(s) after proper dosing on one day, and start DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) on the next day.
If another topical ophthalmic agent is being used, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 Use in Children under Precautions.)
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.
Mode of Administration: The dose is one drop of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) in the affected eye(s) two times daily.
When substituting DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) for another ophthalmic antiglaucoma agent(s), discontinue the other agent(s) after proper dosing on one day, and start DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) on the next day.
If another topical ophthalmic agent is being used, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 Use in Children under Precautions.)
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.
Mode of Administration: The dose is one drop of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) in the affected eye(s) two times daily.
Overdosage
No data are available with regard to human overdosage by accidental or deliberate ingestion of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT).
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 such as 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.
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 such as 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.
Contraindications
DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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.
The previously mentioned are based on the components and are not unique to the combination.
Special Precautions
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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). 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), DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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: DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) is not recommended in such patients.
DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). If such reactions are observed, discontinuation of treatment with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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. DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) to this group of patients.
Contact Lens Use: DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) contains the preservative benzalkonium chloride, which may be deposited in soft contact lenses; therefore, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). In those patients DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) was generally well tolerated.
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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). 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), DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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: DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) is not recommended in such patients.
DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). If such reactions are observed, discontinuation of treatment with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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. DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) to this group of patients.
Contact Lens Use: DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) contains the preservative benzalkonium chloride, which may be deposited in soft contact lenses; therefore, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). In those patients DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) was generally well tolerated.
Use In Pregnancy & Lactation
There are no adequate and well-controlled studies in pregnant women. DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether dorzolamide hydrochloride 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 the drug, taking into account the importance of the drug to the mother.
It is not known whether dorzolamide hydrochloride 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 the drug, taking into account the importance of the drug to the mother.
Adverse Reactions
In clinical studies, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 hydrochloride and/or timolol maleate. In general, common adverse experiences were mild and did not cause discontinuation.
During clinical studies, 1035 patients were treated with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). Approximately 2.4% of all patients discontinued therapy with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 injection, 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.
During clinical studies, 1035 patients were treated with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT). Approximately 2.4% of all patients discontinued therapy with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) 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 injection, 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.
Drug Interactions
Specific drug interaction studies have not been performed with DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT).
In clinical studies, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) was used concomitantly with the following systemic medications without evidence of adverse interactions: ACE-inhibitors, calcium channel blockers, diuretics, non-steroidal anti-inflammatory drugs including aspirin, and hormones (e.g., 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, antiarrhythmics, parasympathomimetics or beta-adrenergic blocking agents.
Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, SSRIs) and timolol.
The dorzolamide component of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) is a carbonic anhydrase inhibitor and although administered topically, is absorbed systemically. In clinical studies, dorzolamide hydrochloride 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 (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT).
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.
In clinical studies, DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) was used concomitantly with the following systemic medications without evidence of adverse interactions: ACE-inhibitors, calcium channel blockers, diuretics, non-steroidal anti-inflammatory drugs including aspirin, and hormones (e.g., 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, antiarrhythmics, parasympathomimetics or beta-adrenergic blocking agents.
Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine, SSRIs) and timolol.
The dorzolamide component of DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT) is a carbonic anhydrase inhibitor and although administered topically, is absorbed systemically. In clinical studies, dorzolamide hydrochloride 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 (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving DORZOLAMIDE HCl + TIMOLOL MALEATE (COSOPT).
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.
Storage
Store at temperatures not exceeding 25°C. Protect from light.
Action
Pharmacology: Pharmacodynamics/Pharmacokinetics: Dorzolamide Hydrochloride: Unlike oral carbonic anhydrase inhibitors, topical administration of dorzolamide hydrochloride allows for the drug to exert its effects directly in the eye at substantially lower doses and therefore with less systemic exposure. In clinical trials, this resulted in a reduction in IOP without the acid-base disturbances or alterations in electrolytes characteristic of oral carbonic anhydrase inhibitors.
When topically applied, dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of selective binding to CA-II while extremely low concentrations of free drug in plasma are maintained. The parent drug forms a single N-desethyl metabolite that inhibits CA-II less potently than the parent drug but also inhibits a less active isoenzyme (CA-I). The metabolite also accumulates in RBCs where it binds primarily to CA-I. Dorzolamide binds moderately to plasma proteins (approximately 33%). Dorzolamide is primarily excreted unchanged in the urine; the metabolite is also excreted in urine. After dosing ends, dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months.
When dorzolamide was given orally to simulate the maximum systemic exposure after long term topical ocular administration, steady state was reached within 13 weeks. At steady state, there was virtually no free drug or metabolite in plasma; CA inhibition in RBCs was less than that anticipated to be necessary for a pharmacological effect on renal function or respiration. Similar pharmacokinetic results were observed after chronic, topical administration of dorzolamide hydrochloride. However, some elderly patients with renal impairment (estimated CrCl 30-60 milliliter/min) had higher metabolite concentrations in RBCs, but no meaningful differences in carbonic anhydrase inhibition and no clinically significant systemic side effects were directly attributable to this finding.
Timolol Maleate: In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following twice daily topical administration of timolol maleate ophthalmic solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL and following afternoon dosing was 0.35 ng/mL.
When topically applied, dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of selective binding to CA-II while extremely low concentrations of free drug in plasma are maintained. The parent drug forms a single N-desethyl metabolite that inhibits CA-II less potently than the parent drug but also inhibits a less active isoenzyme (CA-I). The metabolite also accumulates in RBCs where it binds primarily to CA-I. Dorzolamide binds moderately to plasma proteins (approximately 33%). Dorzolamide is primarily excreted unchanged in the urine; the metabolite is also excreted in urine. After dosing ends, dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months.
When dorzolamide was given orally to simulate the maximum systemic exposure after long term topical ocular administration, steady state was reached within 13 weeks. At steady state, there was virtually no free drug or metabolite in plasma; CA inhibition in RBCs was less than that anticipated to be necessary for a pharmacological effect on renal function or respiration. Similar pharmacokinetic results were observed after chronic, topical administration of dorzolamide hydrochloride. However, some elderly patients with renal impairment (estimated CrCl 30-60 milliliter/min) had higher metabolite concentrations in RBCs, but no meaningful differences in carbonic anhydrase inhibition and no clinically significant systemic side effects were directly attributable to this finding.
Timolol Maleate: In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following twice daily topical administration of timolol maleate ophthalmic solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL and following afternoon dosing was 0.35 ng/mL.
MedsGo Class
Antiglaucoma Preparations
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