Dorzolamide hydrochloride and timolol maleate 20 mg/mL; 5 mg/mL Solution/ Drops
Other active recalls for Dorzolamide Hydrochloride And Timolol Maleate (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the beta-Adrenergic Blocker class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Dorzolamide and timolol is used to treat glaucoma and ocular hypertension (eye conditions that lead to increased intraocular pressure and can progress to vision loss). Dorzolamide is in a class of medications called topical carbonic anhydrase inhibitors. Timolol is in a class of medications called topical beta blockers. Dorzolamide and timolol lowers pressure in the eye by decreasing the production of natural fluids in the eye.
Read the full MedlinePlus article ↗- Your eye constantly produces a fluid called aqueous humor, and if too much builds up, the pressure inside your eye rises. That extra pressure can damage your optic nerve over time,...
- What exactly does this eye drop do — and why do I need two medications in one?
- Yes, and this is one of the most important things to know. Both ingredients are absorbed into your bloodstream through the tissues of your eye and tear duct. Timolol, in particular...
- I only put it in my eye — can it really affect my heart or lungs?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII S38J6RZN16
Hydroxyethyl cellulose is a plant-derived thickening agent made from cellulose. In medicines, it acts as a binder to hold ingredients together, a thickener to adjust product texture, and a film-former to create smooth coatings on tablets.
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A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.132 | $67.92 / 60 vials |
| Medicaid paysCMS SDUD · 12 mo | $1.60 | $95.92 / 60 vials |
| Medicare drug plans payPart D · Q2 2026 | $1.75 | $105.03 / 60 vials |
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🔁 Therapeutic equivalents
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 50742-0323-60 You're viewing this | 12 POUCH in 1 CARTON (50742-323-60) / 5 VIAL in 1 POUCH (50742-323-05) / .2 mL in 1 VIAL | 2023-05-02 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers (failed to achieve target IOP determined after multiple measurements over time). The IOP-lowering of dorzolamide hydrochloride and timolol maleate ophthalmic solution administered twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol administered twice a day and 2% dorzolamide administered three times a day [see Clinical Studies (14.1) ].
Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is a carbonic anhydrase inhibitor with a beta-adrenergic receptor blocking agent indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers. The IOP-lowering of dorzolamide hydrochloride and timolol maleate ophthalmic solution twice daily was slightly less than that seen with the concomitant administration of 0.5% timolol twice daily, and 2% dorzolamide three times daily.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The dose is one drop of dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) in the affected eye(s) two times daily. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart [see Drug Interactions (7.3) ]. The solution from one individual unit is to be used immediately after opening for administration to one or both eyes.
Since sterility cannot be maintained after the individual unit is opened, the remaining contents should be discarded immediately after administration. The dose is one drop of dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) in the affected eye(s) two times daily. ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Solution containing 20 mg/mL dorzolamide (22.26 mg of dorzolamide hydrochloride) and 5 mg/mL timolol (6.83 mg timolol maleate). Solution containing 20 mg/mL dorzolamide and 5 mg/mL timolol. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is contraindicated in patients with: Bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease. ( 4.1 ) Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock. ( 4.2 ) Hypersensitivity to any component of this product. ( 4.3 , 5.3 )
4.1Asthma, COPD Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is contraindicated in patients with bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease [see Warnings and Precautions (5.1) ].
4.2Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is contraindicated in patients with sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, and cardiogenic shock [see Warnings and Precautions (5.2) ].
4.3Hypersensitivity Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is contraindicated in patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.3) ] .
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Potentiation of Respiratory Reactions Including Asthma ( 5.1 ) Cardiac Failure ( 5.2 ) Sulfonamide Hypersensitivity ( 5.3 ) Obstructive Pulmonary Disease ( 5.4 ) Increased Reactivity to Allergens ( 5.5 ) Potentiation of Muscle Weakness ( 5.6 ) Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus ( 5.7 ) Masking of Thyrotoxicosis ( 5.8 ) Renal and Hepatic Impairment ( 5.9 ) Impairment of Beta-Adrenergically Mediated Reflexes During Surgery ( 5.10 )
5.1Potentiation of Respiratory Reactions Including Asthma Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) contains timolol maleate, a beta-adrenergic blocking agent; and although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported following systemic or ophthalmic administration of timolol maleate [see Contraindications (4.1) and Patient Counseling Information (17.1) ].
5.2Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. In patients without a history of cardiac failure continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) should be discontinued [see Contraindications (4.2) and Patient Counseling Information (17.2) ].
5.3Sulfonamide Hypersensitivity Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) contains dorzolamide, a sulfonamide; and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free). Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.
Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation [see Contraindications (4.3) and Patient Counseling Information (17.3) ] .
5.4Obstructive Pulmonary Disease Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma, in which dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is contraindicated) should, in general, not receive beta-blocking agents, including dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) [see Contraindications (4.1) and Patient Counseling Information (17.1) ].
5.5Increased Reactivity to Allergens While taking beta-blockers, patients with a history of atopy or a history of 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.
5.6Potentiation of Muscle Weakness Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic sy…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most frequently reported adverse reactions were taste perversion (bitter, sour, or unusual taste) or ocular burning and/or stinging in up to 30% of patients. Conjunctival hyperemia, blurred vision, superficial punctate keratitis or eye itching were reported between 5-15% of patients. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals, LLC at 1-877-748-1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution and Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution ( Preservative Free) Dorzolamide hydrochloride and timolol maleate ophthalmic solution and dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) were evaluated in patients with elevated intraocular pressure treated for open-angle glaucoma or ocular hypertension for up to 15 months.
Approximately 5% of all patients discontinued therapy because of adverse reactions. The most frequently reported adverse reactions occurring in up to 30% of patients were taste perversion (bitter, sour, or unusual taste) or ocular burning and/or stinging. The following adverse reactions were reported in 5-15% of patients: conjunctival hyperemia, blurred vision, superficial punctate keratitis or eye itching.
The following adverse reactions were reported in 1-5% of patients: abdominal pain, back pain, blepharitis, bronchitis, cloudy vision, conjunctival discharge, conjunctival edema, conjunctival follicles, conjunctival injection, conjunctivitis, corneal erosion, corneal staining, cortical lens opacity, cough, dizziness, dryness of eyes, dyspepsia, eye debris, eye discharge, eye pain, eye tearing, eyelid edema, eyelid erythema, eyelid exudate/scales, eyelid pain or discomfort, foreign body sensation, glaucomatous cupping, headache, hypertension, influenza, lens nucleus coloration, lens opacity, nausea, nuclear lens opacity, pharyngitis, post-subcapsular cataract, sinusitis, upper respiratory infection, urinary tract infection, visual field defect, vitreous detachment.
Other adverse reactions that have been reported with the individual components are listed below: Dorzolamide 2% Angioedema, asthenia/fatigue, bronchospasm, contact dermatitis, epistaxis, eyelid crusting, ocular discomfort, photophobia, signs and symptoms of ocular allergic reaction, transient myopia. Timolol (ocular administration) Body as a Whole : Asthenia/fatigue; Cardiovascular : Arrhythmia, syncope, cerebral ischemia, worsening of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud's phenomenon, and cold hands and feet ; Digestive : Anorexia; Immunologic: Systemic lupus erythematosus; Nervous System/Psychiatric : Increase in signs and symptoms of myasthenia gravis, somnolence, insomnia, nightmares, behavioral changes and psychic disturbances including confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss; Skin : Alopecia, psoriasiform rash or exacerbation of psoriasis; Hypersensitivity : Signs and symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and localized and generalized rash; Respiratory : Bronchospasm (predominantly in patients with pre-existing bronchospastic disease); Endocrine : Masked symptoms of hypoglycemia in diabetic patients; Special Senses : Ptosis, decreased corneal sensitivity, cystoid macular edema, visual disturbances including refractive changes and diplopia, pseudopemphigoid, and tinnitus; Urogenital : Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie's disease.
6.2 Post-Marketing Experience The following adverse reactions have been i…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Potential additive effect of oral carbonic anhydrase inhibitor with dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free). ( 7.1 ) Potential acid-base and electrolyte disturbances. ( 7.2 ) Concomitant use with systemic beta-blockers may potentiate systemic beta-blockade.
( 7.3 ) Oral or intravenous calcium antagonists may cause atrioventricular conduction disturbances, left ventricular failure, and hypotension. ( 7.4 ) Catecholamine-depleting drugs may have additive effects and produce hypotension and/or marked bradycardia. ( 7.5 ) Digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.
( 7.6 ) CYP2D6 inhibitors may potentiate systemic beta-blockade. ( 7.7 )
7.1Oral Carbonic Anhydrase Inhibitors There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free). The concomitant administration of dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) and oral carbonic anhydrase inhibitors is not recommended.
7.2High-Dose Salicylate Therapy Although acid-base and electrolyte disturbances were not reported in the clinical trials with dorzolamide hydrochloride ophthalmic solution, 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 hydrochloride and timolol maleate ophthalmic solution (preservative free).
7.3Beta-Adrenergic Blocking Agents Patients who are receiving a beta-adrenergic blocking agent orally and dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two topical beta-adrenergic blocking agents is not recommended.
7.4Calcium Antagonists Caution should be used in the coadministration of beta-adrenergic blocking agents, such as dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free), and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, coadministration should be avoided.
7.5Catecholamine-Depleting Drugs Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may result in vertigo, syncope, or postural hypotension.
7.6Digitalis and Calcium Antagonists The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.
7.7CYP2D6 Inhibitors 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.
7.8Clonidine Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. There have been no reports of exacerbation of rebound hypertension with ophthalmic timolol maleate.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Teratogenic Effects . Pregnancy Category C. Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥2.5 mg/kg/day (31 times the recommended human ophthalmic dose) revealed malformations of the vertebral bodies.
These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment-related malformations were seen at 1 mg/kg/day (13 times the recommended human ophthalmic dose). Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations.
Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity.
There are no adequate and well-controlled studies in pregnant women. Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.3Nursing Mothers It is not known whether dorzolamide is excreted in human milk. Timolol maleate has been detected in human milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions from dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4Pediatric Use The safety and effectiveness of dorzolamide hydrochloride ophthalmic solution and timolol maleate ophthalmic solution have been established when administered individually in pediatric patients aged 2 years and older. Use of these drug products in these children is supported by evidence from adequate and well-controlled studies in children and adults. Safety and efficacy in pediatric patients below the age of 2 years have not been established.
8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.
🤰 Pregnancy ▾
8.1Pregnancy Teratogenic Effects . Pregnancy Category C. Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥2.5 mg/kg/day (31 times the recommended human ophthalmic dose) revealed malformations of the vertebral bodies.
These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment-related malformations were seen at 1 mg/kg/day (13 times the recommended human ophthalmic dose). Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations.
Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity.
There are no adequate and well-controlled studies in pregnant women. Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of dorzolamide hydrochloride ophthalmic solution and timolol maleate ophthalmic solution have been established when administered individually in pediatric patients aged 2 years and older. Use of these drug products in these children is supported by evidence from adequate and well-controlled studies in children and adults. Safety and efficacy in pediatric patients below the age of 2 years have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.
🆘 Overdosage ▾
10 OVERDOSAGE Symptoms consistent with systemic administration of beta-blockers or carbonic anhydrase inhibitors may occur, including electrolyte imbalance, development of an acidotic state, dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest and possible central nervous system effects. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored [See Adverse Reactions (6) ] . A study of patients with renal failure showed that timolol did not dialyze readily.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is comprised of two components: dorzolamide hydrochloride and timolol maleate. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma, by reducing aqueous humor secretion. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Dorzolamide hydrochloride is an inhibitor of human carbonic anhydrase II. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.
Timolol maleate is a beta1 and beta2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. The combined effect of these two agents administered as dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) administered twice daily results in additional intraocular pressure reduction compared to either component administered alone, but the reduction is not as much as when dorzolamide administered three times daily and timolol twice daily are administered concomitantly [See Clinical Studies (14) ] .
12.3Pharmacokinetics Dorzolamide Hydrochloride 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 binding to CA-II.
The parent drug forms a single N-desethyl metabolite, which inhibits CA-II less potently than the parent drug but also inhibits CA-I. The metabolite also accumulates in RBCs where it binds primarily to CA-I. Plasma concentrations of dorzolamide and metabolite are generally below the assay limit of quantitation (15nM).
Dorzolamide binds moderately to plasma proteins (approximately 33%). Dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. After dosing is stopped, 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.
To simulate the systemic exposure after long-term topical ocular administration, dorzolamide was given orally to eight healthy subjects for up to 20 weeks. The oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of dorzolamide 2% three times daily. Steady state was reached within 8 weeks.
The inhibition of CA-II and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals. Timolol Maleate In a study of plasma drug concentrations 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.
🧬 Mechanism of Action ▾
12.1Mechanism of Action Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is comprised of two components: dorzolamide hydrochloride and timolol maleate. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma, by reducing aqueous humor secretion. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Dorzolamide hydrochloride is an inhibitor of human carbonic anhydrase II. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport.
Timolol maleate is a beta1 and beta2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. The combined effect of these two agents administered as dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) administered twice daily results in additional intraocular pressure reduction compared to either component administered alone, but the reduction is not as much as when dorzolamide administered three times daily and timolol twice daily are administered concomitantly [See Clinical Studies (14) ] .
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) is supplied in a foil pouch containing 5 low density polyethylene 0.2 mL single-use containers. Carton of 12 pouches NDC 50742-323-60, package of 60 single-use vials. Store dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) at 20° to 25°C (68° to 77°F) [See USP controlled room temperature].
Do not freeze. Store in the original pouch. After the pouch is opened, store the remaining single-use containers in the foil pouch to protect from light.
Write down the date you open the foil pouch in the space provided on the pouch. Discard any unused containers 15 days after first opening the pouch.
📋 Description ▾
11 DESCRIPTION Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) is the combination of a topical carbonic anhydrase inhibitor and a topical beta-adrenergic receptor blocking agent. Dorzolamide hydrochloride, USP is described chemically as: (4 S - trans )-4-(ethylamino)-5,6-dihydro-6methyl-4 H -thieno[2,3- b ]thiopyran-2-sulfonamide 7,7-dioxide monohydrochloride. Dorzolamide hydrochloride is optically active.
The specific rotation is: [α] 25°C 405 nm (C=1, water) = ~ - 17°. Its empirical formula is C 10 H 16 N 2 O 4 S 3 •HCl and its structural formula is: Dorzolamide hydrochloride, USP has a molecular weight of 360.91. It is a white or almost white crystalline powder, which is soluble in water and slightly soluble in methanol and very slightly soluble in anhydrous ethanol.
Timolol maleate, USP is described chemically as: (-)-1-( tert -butylamino)-3-[(4-morpholino-1,2,5thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt). Timolol maleate, USP possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer. The optical rotation of timolol maleate is: [α] 25°C 405 nm in 1N HCl (C=5) = -12.2° (-11.7° to -12.5°).
Its molecular formula is C 13 H 24 N 4 O 3 S•C 4 H 4 O 4 and its structural formula is: Timolol maleate, USP has a molecular weight of 432.50. It is a white, or practically white, odorless or practically odorless powder which is soluble in water, in alcohol, and in methanol; sparingly soluble in chloroform and in propylene glycol; insoluble in ether and in cyclohexane. Timolol maleate, USP is stable at room temperature.
Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) is supplied as a sterile, clear, colorless to nearly colorless, isotonic, buffered, slightly viscous, aqueous solution. The pH of the solution is approximately 5.65, and the osmolarity is 242 - 323 mOsM. Each mL of dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) contains 20 mg dorzolamide (22.26 mg of dorzolamide hydrochloride) and 5 mg timolol (6.83 mg timolol maleate).
Inactive ingredients are sodium citrate dihydrate, hydroxyethyl cellulose, sodium hydroxide, mannitol, and water for injection. Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) does not contain a preservative. Image Image
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling (Patient Information).
17.1Potential for Exacerbation of Asthma and COPD Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) may cause severe worsening of asthma and COPD symptoms including death due to bronchospasm. Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease should be advised not to take this product [See Contraindications (4.1) ].
17.2Potential of Cardiovascular Effects Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) may cause worsening of cardiac symptoms. Patients with sinus bradycardia, second or third degree atrioventricular block, or cardiac failure should be advised not to take this product [See Contraindications (4.2) ] .
17.3Sulfonamide Reactions Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) contains dorzolamide (which is a sulfonamide) and, although administered topically, is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration, including severe skin reactions. Patients should be advised that if serious or unusual reactions or signs of hypersensitivity occur, they should discontinue the use of the product and seek their physician's advice [See Warnings and Precautions (5.3) ] .
17.4Handling the Single-Use Container Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is a sterile solution that does not contain a preservative. The solution from one individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the individual unit is opened, the remaining contents should be discarded immediately after administration.
17.5Intercurrent Ocular Conditions Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of this product.
17.6Concomitant Topical Ocular Therapy If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. Manufactured for: Ingenus Pharmaceuticals, LLC Orlando, FL 32811-7193 Made in France Image
💬 Patient Medication Information ▾
PATIENT PACKAGE INSERT Patient Information Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, USP 2%/0.5% (Preservative Free) (dor zoe' la mide hye'' droe klor' ide and tim' oh lol mal' ee ate) Read this information before you start using dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.
What is dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free)? Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is a prescription sterile eye drop solution that contains 2 medicines, dorzolamide hydrochloride (a sulfonamide carbonic anhydrase inhibitor) and timolol maleate (a beta-adrenergic blocker). Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is used to lower the pressure in the eye (intraocular pressure) in people with open-angle glaucoma or ocular hypertension, when their eye pressure is too high and beta-adrenergic blocker medicines alone have not adequately lowered the pressure.
It is not known if dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is safe and effective in children under 2 years of age. Who should not use dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free)? Do not use dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) if you: ● have or have had asthma ● have or have had severe lung problems (chronic obstructive pulmonary disease) ● have heart problems, including slow or irregular heartbeat or heart failure ● are allergic to dorzolamide hydrochloride, timolol maleate, or any of the ingredients in dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free).
See the end of this leaflet for a complete list of ingredients in dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free). Talk to your healthcare provider before taking this medicine if you have any of these conditions. What should I tell my doctor before using dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free)?
Before you use dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free), tell your doctor if you: ● have problems with muscle weakness (myasthenia gravis) ● have diabetes or problems with low blood sugar (hypoglycemia) ● have thyroid, kidney, or liver problems ● are planning to have surgery ● are allergic to sulfa drugs ● have or have had eye problems, including any surgery on your eye or eyes, or are using any other eye medicines ● have any other medical problems ● are pregnant or plan to become pregnant.
It is not known if dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) will harm your unborn baby. If you become pregnant while using dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) talk to your doctor right away. ● are breastfeeding or plan to breastfeed. It is not known whether dorzolamide passes into your breast milk however, timolol has been detected in breast milk.
Talk to your doctor about the best way to feed your baby if you use dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free). Tell your doctor about all the medicines you take , including prescription and non-prescription medicines, vitamins, and herbal supplements. Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) and other medicines may affect each other causing side effects.
Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) may affect the way other medicines work, and other medicines may affect how dorzolamide hydrochloride and timolol maleate ophthalmic solution (pres…