Brimonidine-Dorzolamide

Drug overview for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Generic name: brimonidine tartrate/dorzolamide HCl/PF
Drug class: Ophthalmic Carbonic Anhydrase Inhibitors
Therapeutic class: Ophthalmic Agents

Brimonidine tartrate is a relatively selective alpha2-adrenergic agonist. Dorzolamide is a carbonic anhydrase inhibitor.

No enhanced Uses information available for this drug.

DRUG IMAGES

No Image Available

The following indications for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf) have been approved by the FDA:

Indications:
None.

Professional Synonyms:
None.

The following dosing information is available for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Dosing
Administration
Dosing Information
Generic

Dosage and concentration of dorzolamide hydrochloride are expressed in terms of dorzolamide.

For the treatment of open-angle glaucoma or ocular hypertension in adults and pediatric patients, the usual dosage of dorzolamide is 1 drop of a 2% ophthalmic solution in the affected eye(s) 3 times daily.

If the target intraocular pressure (IOP) is not achieved, alternative or additional ocular hypotensive agents may be required. (See Uses: Ocular Hypertension and Glaucoma.) When dorzolamide is used in fixed combination with timolol for the treatment of open-angle glaucoma or ocular hypertension in adults and pediatric patients 2 years of age or older, the usual dosage is 1 drop of an ophthalmic solution containing dorzolamide 2% and timolol 0.5% in the affected eye(s) twice daily.

Because of the potential for additive systemic effects, combined use of topical dorzolamide and an oral carbonic anhydrase inhibitor (e.g., acetazolamide, dichlorphenamide, methazolamide) is not recommended by the manufacturer.

Topical dorzolamide has not been evaluated in patients with severe renal impairment (i.e., creatinine clearance less than 30 mL/minute). Because dorzolamide and N-desethyldorzolamide are eliminated principally via renal excretion, the manufacturer states that topical ocular use of the drug in patients with severe renal impairment is not recommended.

Topical dorzolamide has not been evaluated in patients with hepatic impairment, and the manufacturer states that the drug should be used with caution in such patients.

Dorzolamide hydrochloride is applied topically to the eye as an ophthalmic solution. Dorzolamide hydrochloride also is commercially available in fixed combination with timolol maleate for topical application to the eye as an ophthalmic solution. Care should be taken to avoid contamination of the solution container.

(See Cautions: Precautions and Contraindications.) Dorzolamide ophthalmic solution and some formulations of dorzolamide and timolol ophthalmic solution contain benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to topical application of each dose of these preparations, but may be reinserted 15 minutes after the dose. Preservative-free dorzolamide and timolol ophthalmic solution in single-use containers should be administered topically to one or both eyes immediately after the container is opened; since sterility cannot be maintained after the individual unit is opened, any remaining contents should be discarded immediately after administration.

If the patient is receiving more than one ophthalmic preparation, the preparations should be administered at least 5 minutes apart. Brimonidine tartrate is applied topically to the eye as an ophthalmic solution. Brimonidine tartrate also is commercially available in fixed combination with brinzolamide (as an ophthalmic suspension) and in fixed combination with timolol (as an ophthalmic solution) for topical application to the eye.

Although topical brimonidine has been administered twice daily as an ocular hypotensive agent in certain clinical studies, reductions in intraocular pressure (IOP) induced by the drug appear to diminish 8 hours following administration. Therefore, the manufacturers recommend administering brimonidine tartrate 0.1, 0.15,

or 0.2% ophthalmic solution 3 times daily at intervals of approximately 8 hours. The fixed-combination ophthalmic suspension containing brinzolamide and brimonidine tartrate also is administered 3 times daily.

However, when used in fixed combination with timolol, brimonidine is administered twice daily at intervals of approximately 12 hours. For self-medication for temporary relief of ocular redness, brimonidine tartrate 0.025% may be administered up to 4 times daily.

The fixed-combination ophthalmic suspension containing brinzolamide and brimonidine tartrate should be shaken well prior to use. Care should be taken to avoid contamination of the dispensing container. (See Bacterial Keratitis under Cautions: Warnings/Precautions.) Some brimonidine ophthalmic preparations contain benzalkonium chloride, which may be absorbed by soft contact lenses.

Contact lenses should be removed prior to administration of each dose of these preparations, but may be reinserted 15 minutes after the dose. The manufacturer of brimonidine tartrate 0.025% ophthalmic solution states that contact lenses may be reinserted 10 minutes after the dose. If the patient is receiving more than one topical ophthalmic preparation, the preparations should be administered at least 5 minutes apart.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 0 severe interactions.

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Dorzolamide/Carbonic Anhydrase Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dorzolamide and other carbonic anhydrase inhibitors cause a decrease in aqueous humor secretion by slowing the formation of bicarbonate ions with a subsequent reduction of sodium and fluid transport which results in a reduction of intraocular pressure.(1) CLINICAL EFFECTS: If dorzolamide is given with other carbonic anhydrase inhibitors it may cause electrolyte disturbances, because dorzolamide can be absorbed systemically.(1) PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors. PATIENT MANAGEMENT: The manufacturer of dorzolamide states that concurrent use with oral carbonic anhydrase inhibitors is not recommended.(1) DISCUSSION: Although no human data is available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following administration of dorzolamide and oral carbonic anhydrase inhibitors.(1)	ACETAZOLAMIDE, ACETAZOLAMIDE ER, DICHLORPHENAMIDE, KEVEYIS, METHAZOLAMIDE, ORMALVI

Drug Interaction

Drug Names

Dorzolamide/Carbonic Anhydrase Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Dorzolamide and other carbonic anhydrase inhibitors cause a decrease in aqueous humor secretion by slowing the formation of bicarbonate ions with a subsequent reduction of sodium and fluid transport which results in a reduction of intraocular pressure.(1)

CLINICAL EFFECTS: If dorzolamide is given with other carbonic anhydrase inhibitors it may cause electrolyte disturbances, because dorzolamide can be absorbed systemically.(1)

PREDISPOSING FACTORS: Patients with conditions that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, and being on a ketogenic diet) may be at increased risk of experiencing adverse effects from concurrent carbonic anhydrase inhibitors.

PATIENT MANAGEMENT: The manufacturer of dorzolamide states that concurrent use with oral carbonic anhydrase inhibitors is not recommended.(1)

DISCUSSION: Although no human data is available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following administration of dorzolamide and oral carbonic anhydrase inhibitors.(1)

ACETAZOLAMIDE, ACETAZOLAMIDE ER, DICHLORPHENAMIDE, KEVEYIS, METHAZOLAMIDE, ORMALVI

The following contraindication information is available for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Brimonidine is contraindicated in neonates and infants younger than 2 years of age. (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.) Brimonidine also is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.

There are 0 contraindications.

There are 0 severe contraindications.

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Buerger's disease
Cerebrovascular disorder
Depression
No disease contraindications
Orthostatic hypotension
Raynaud's phenomenon

The following adverse reaction information is available for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in approximately 10-30% of patients receiving brimonidine tartrate 0.1-0.2% ophthalmic solution include oral dryness, ocular or conjunctival hyperemia, burning and stinging, allergic conjunctivitis, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus.

In addition, corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, GI symptoms, hypertension, asthenia, conjunctival blanching, abnormal vision, visual disturbances, and muscular pain have been reported in approximately 3-9% of patients receiving brimonidine tartrate 0.1-0.2% ophthalmic solution.

Adverse effects reported in approximately 1-4% of patients receiving brimonidine tartrate 0.025% ophthalmic solution include decreased visual acuity, conjunctival or ocular hyperemia, dry eye, instillation site pain, and headache.

There are 46 severe adverse reactions.

More Frequent	Less Frequent
Conjunctival hyperemia Follicular conjunctivitis Headache disorder Ocular itching Ocular redness	Blepharitis Blurred vision Chemosis Conjunctival hemorrhage Conjunctivitis Corneal erosion Depression Dizziness Eyelid edema Gastrointestinal irritation Hypertension Mucopurulent conjunctivitis Myalgia Nasal congestion Nausea Ocular discomfort Ocular pain Rhinitis Sneezing Syncope Visual changes Vomiting

Rare/Very Rare
Agranulocytosis Angioedema Aplastic anemia Bradycardia Bronchospastic pulmonary disease Choroidal detachment Contact dermatitis Dyspnea Epistaxis Hepatic necrosis Iridocyclitis Myopia Ocular pain Paresthesia Skin rash Sore throat Stevens-johnson syndrome Toxic epidermal necrolysis Urolithiasis

There are 28 less severe adverse reactions.

More Frequent	Less Frequent
Allergic conjunctivitis Drowsy Dysgeusia Eye tearing Fatigue Ocular irritation Punctate keratitis Xerostomia	Blurred vision Conjunctival blanching Corneal staining Dry eye Dysgeusia Eye tearing Eyelid crusting Insomnia Muscle weakness Ocular redness Palpitations Photophobia Symptoms of anxiety

Rare/Very Rare
Dizziness Eyelid crusting General weakness Headache disorder Iritis Nausea Xerostomia

The following precautions are available for BRIMONIDINE-DORZOLAMIDE (brimonidine tartrate/dorzolamide hcl/pf):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of topical brimonidine tartrate for the treatment of open-angle glaucoma or ocular hypertension in pediatric patients younger than 2 years of age have not been established. Because potentially serious adverse effects, including apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence, have been reported in infants treated with topical brimonidine tartrate, use of the drug is contraindicated in infants younger than 2 years of age. In a well-controlled clinical study in children 2-7 years of age with glaucoma who received brimonidine tartrate 0.2%

ophthalmic solution 3 times daily, the most commonly observed adverse effects were somnolence and decreased mental alertness; approximately 16% of these children discontinued therapy because of somnolence. The incidence of somnolence generally appeared to be age and weight related, occurring in 50-83% of children 2-6 years of age and 25% of those 7 years of age who weighed more than 20 kg. The individual components of brinzolamide and brimonidine tartrate fixed-combination ophthalmic suspension have been studied in pediatric patients 4 weeks to 5 years of age (brinzolamide) and 2-7 years of age (brimonidine).

Safety and efficacy of brimonidine tartrate and timolol fixed-combination ophthalmic solution in pediatric patients 2-16 years of age have been established based on evidence from adequate and well-controlled studies of the fixed combination in adults and additional data from a study evaluating the individually administered drugs (brimonidine tartrate 0.2% administered 3 times daily as an adjunct to timolol therapy) in children 2-7 years of age with glaucoma. Safety and efficacy of brimonidine tartrate 0.025% ophthalmic solution for self-medication for relief of ocular redness due to minor irritation have not been established in children younger than 5 years of age. Safety and efficacy in pediatric patients 5 years of age or older are supported by evidence from controlled clinical trials in adults and additional data from a safety study that included both adults and pediatric patients 5 years of age or older.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Reproduction studies in rabbits using oral dorzolamide at dosages that resulted in estimated peak plasma concentrations that were 37 times higher than the lower limit of detection in human plasma following ocular administration revealed malformations of the vertebral bodies. These malformations occurred at dosages that caused metabolic acidosis and decreased body weight gain in dams and decreased fetal weight. Reproductive studies in rabbits using oral dorzolamide at dosages that resulted in estimated peak plasma concentrations that were 15 times higher than the lower limit of detection in human plasma following ocular administration did not reveal evidence of teratogenic effects or embryotoxicity.

There are no adequate and controlled studies to date using dorzolamide in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. In studies in animals, brimonidine crossed the placenta and entered the fetal circulation to a limited extent; no evidence of teratogenicity was observed. There are no adequate and well-controlled studies of brimonidine to date in pregnant women. Brimonidine should be used during pregnancy only if potential benefits to the woman justify the potential risk to the fetus.

In lactating rats given oral dorzolamide at dosages that resulted in estimated peak plasma concentrations that were 52 times higher than the lower limit of detection in human plasma following ocular administration, decreases of 5-7% in body weight gain in offspring and developmental delay (i.e., incisor eruption, vaginal canalization, eye opening) secondary to lower fetal body weight have been reported. It is not known whether dorzolamide is distributed into human milk. Because of the potential for serious adverse reactions to dorzolamide in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Brimonidine is distributed into milk in animals. It is not known whether brimonidine is distributed into human milk following topical application to the eye. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No substantial differences in safety and efficacy have been observed between geriatric patients and younger adults.