Home › NDC Lookup › Ingredients › Dorzolamide Hydrochloride And Timolol Ma... › 64950-0390-60
👁️image loading
(from DailyMed)

Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL Solution, 60 vials — NDC 64950-390-60 (Billing 64950-0390-60)

by Genus Lifesciences · 60 VIAL, SINGLE-DOSE in 1 CARTON / .2 mL in 1 VIAL, SINGLE-DOSE

This is a package of 60 vials of Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL Solution from Genus Lifesciences, no longer marketed (first marketed Aug 2025), no longer in the FDA NDC Directory. It is this product's only package size.

NDC 64950-0390-60
🏷️ FDA NDC (as labeled) 64950-390-60 billing pads the product segment with a zero
Rx only Generic Discontinued Non-controlled ⚠ Discontinued by firm ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

⚠️
Other active recalls for Dorzolamide Hydrochloride And Timolol Maleate (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Jul 22, 2026 — Defective Container: Firm received multiple complaints of broken cap spikes and undeliverable drops. (MICRO LABS USA INC) · FDA recall D-0730-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗
⚠️
Excluded from the active FDA NDC Directory. The labeler reported this product as discontinued, so it is excluded from the active NDC Directory. The listing was last certified through Aug 2025. A label may still appear on DailyMed, but the NDC is no longer in the current FDA NDC Directory. Search the FDA NDC Directory ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 64950-390-60
Product NDC 64950-390
11-digit billing NDC 64950039060
RxCUI 1923432
UNII QZO5366EW7, P8Y54F701R
Application # ANDA216308
SPL Set ID 3b3a4716-1082-4a7a-bf5a-2e2bac38dfbc
Established class (EPC) Carbonic Anhydrase Inhibitor; beta-Adrenergic Blocker
Mechanism of action Adrenergic beta-Antagonists; Carbonic Anhydrase Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status Discontinued
FDA listing status Discontinued by firm (certified through Aug 2025)
Marketing start 2025-08-01
Route OPHTHALMIC
Dosage form SOLUTION
Substance DORZOLAMIDE HYDROCHLORIDE; TIMOLOL MALEATE
TE code (Orange Book) AT2 · RLD · RS
Quick answers
  • RxCUI (RxNorm): 1923432
Why two NDCs? The FDA registers this code as 64950-390-60 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 64950-0390-60. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the beta-Adrenergic Blocker class.

Pharmacologic class beta-Adrenergic Blocker
Drug family (ATC) Beta blocking agents, non-selective, Beta blocking agents
How it works Adrenergic beta-Antagonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It lowers high pressure inside the eye in open-angle glaucoma or ocular hypertension. It's used when beta-blockers alone haven't brought the pressure down enough. Lowering eye pres...
  • You put one drop in the affected eye(s) twice a day. If you use other eye drops, wait at least five minutes between them. If yours is a preservative-free single-use unit, use it ri...
  • The most common are a bitter or unusual taste, plus eye burning or stinging. Redness, blurry vision and itching can also happen. These are usually manageable, but tell me if they b...
  • Call for wheezing, trouble breathing, swelling or signs of heart failure, a very slow heartbeat, fainting, or a severe rash or allergic reaction. Stop the drops and get help if the...
📖 Read our full Dorzolamide / Timolol guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $1.23 $14.80 / 12 ml
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
64950-0390-60 You're viewing this Main listing 60 VIAL, SINGLE-DOSE in 1 CARTON / .2 mL in 1 VIAL, SINGLE-DOSE 2025-08-01 — Discontinued by firm

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Dorzolamide Hydrochloride and Timolol Maleate ophthalmic Solution 22.3 mg/mL; 6.8 mg/mL 42571-0147-26 Micro 1 bottle $0.893 AT1 Availability likely —
Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution 20 mg/mL; 5 mg/mL 62332-0553-10 Alembic 1 bottle $0.893 AT1 Availability likely —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 65862-0946-01 Aurobindo 1 bottle $0.893 AT1 Availability likely —
Dorzolamide Hydrochloride Timolol Maleate 20 mg/mL; 5 mg/mL 71921-0226-10 Florida 1 bottle $0.893 AT1 Availability likely —
Dorzolamide hydrochloride and timolol maleate 20 mg/mL; 5 mg/mL 50742-0323-60 Ingenus 12 pouches $1.094 AT2 Availability likely —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 50383-0261-61 Akorn 4 pouches $1.751 AT2 Discontinued —
Cosopt Pf 20 mg/mL; 5 mg/mL 82584-0604-30 Thea 4 pouches $3.300 AT2 Availability likely —
Cosopt 20 mg/mL; 5 mg/mL 82584-0605-10 Thea 1 bottle $23.162 AT1 Availability likely —
Dorzolamide Hydrochloride Timolol Maletae 20 mg/mL; 5 mg/mL 14445-0405-10 Indoco 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 24208-0486-05 Bausch 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution 20 mg/mL; 5 mg/mL 46708-0553-10 Alembic 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 50090-6371-00 A-S 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 61314-0030-01 Sandoz 5 ml — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mLthis 64950-0390-60 Genus 60 vials — AT2 Discontinued —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 68083-0490-01 Gland 1 bottle — AT1 FDA listed —
Dorzolamide and Timolol 20 mg/mL; 5 mg/mL 69315-0305-05 Leading 1 bottle — AT1 FDA listed —
DORZOLAMIDE HYDROCHLORIDE and TIMOLOL MALEATE 20 mg/mL; 5 mg/mL 70069-0051-12 Somerset 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 72162-2166-02 Bryant 1 bottle — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate 20 mg/mL; 5 mg/mL 72162-2184-02 Bryant 10 ml — AT1 FDA listed —
Dorzolamide Hydrochloride and Timolol Maleate ophthalmic Solution 22.3 mg/mL; 6.8 mg/mL 72162-2381-02 Bryant 1 bottle — AT1 FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2025
On the market since
Aug 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerGenus Lifesciences
Application holderALEMBIC THERAPEUTICS LLC
FDA applicationANDA216308 (ANDA)
Labeler code64950
First marketedAug 2025
Product typeHuman Prescription Drug
Portfolio25 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 167 words ▾

1 INDICATIONS AND USAGE Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (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 COSOPT 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 118 words ▾

2 DOSAGE AND ADMINISTRATION The dose is one drop of Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (preservative free) in the affected eye(s) two times daily. ( 2 )

💊 Dosage Forms and Strengths 45 words ▾

3 DOSAGE FORMS AND STRENGTHS Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) containing 20 mg/mL dorzolamide (22.26 mg of dorzolamide hydrochloride USP) and 5 mg/mL timolol (6.83 mg timolol maleate USP). Solution containing 20 mg/mL Dorzolamide and 5 mg/mL timolol.( 3 )

⛔ Contraindications 173 words ▾

4 CONTRAINDICATIONS Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (preservative free) is contraindicated in patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.3) ].

⚠️ Warnings and Cautions ~2 min read ▾

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, 2%/0.5% (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 betablocking 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, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (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 wea… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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 Allucent at 1-866-511-6754 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. COSOPT and Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) COSOPT and Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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 to 15% of patients: conjunctival hyperemia, blurred vision, superficial punctate keratitis or eye itching.

The following adverse reactions were reported in 1 to 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.

6.2Post-Marketing Experience The following adverse reactions have been identified during post-approval use of COSOPT or Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (pre… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Potential additive effect of oral carbonic anhydrase inhibitor with Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (preservative free) should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two topical betaadrenergic 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, 2%/0.5% (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 ~2 min read ▾

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, 2%/0.5% (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, 2%/0.5% (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 219 words ▾

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, 2%/0.5% (preservative free) should be used during pregnancy, only if the potential benefit justifies the potential risk to the fetus.

🧒 Pediatric Use 68 words ▾

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 18 words ▾

8.5Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.

🆘 Overdosage 69 words ▾

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 ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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 beta 1 and beta 2 (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 211 words ▾

12.1Mechanism of Action Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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 beta 1 and beta 2 (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 129 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, USP (preservative free) is a clear, colorless to nearly colorless, slightly viscous solution packed in natural LDPE BFS container and supplied in a foil pouch containing 15 low density polyethylene 0.2 mL fill single-use containers. Carton of 4 pouches NDC 64950-390-60 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.

📦 Storage and Handling 76 words ▾

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 ~1 min read ▾

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: (4S, 6S)-4-(Ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulphonamide 7,7-dioxide monohydrochloride. Dorzolamide hydrochloride is optically active.

The specific rotation is: [α] 25°C (C=1, water) = ~ -17°. 405 nm Its molecular formula is C 10 H 16 N 2 O 4 S 3 ∙ HCl and its structural formula is: Chemical Structure Dorzolamide hydrochloride USP has a molecular weight of 360.91. It is a white to off-white, crystalline powder, which is soluble in water and slightly soluble in methanol and ethanol.

Timolol maleate USP is described chemically as: (-)-1-(tert-Butylamino)-3- [(4-morpholino-1,2,5 thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt). Timolol maleate 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 in 1N HCl (C=5) = -12.2° (-11.7° to -12.5°) 405 nm 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 432.49.

It is a white to practically white powder which is soluble in water, methanol, and alcohol. Timolol maleate 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 osmolality is 242 to 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 USP) and 5 mg timolol (6.83 mg timolol maleate USP). Inactive ingredients are hydroxyethyl cellulose, mannitol, sodium citrate dihydrate, sodium hydroxide, and water for injection.

Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP (preservative free) does not contain a preservative. Chemical Structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling ( Patient Information ).

17.1Potential for Exacerbation of As thma and COPD Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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 Cardiovas cular Effects Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (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.

🍼 Nursing Mothers 75 words ▾

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, 2%/0.5% (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.

🧬 Pharmacokinetics ~1 min read ▾

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.

🔬 Clinical Studies 193 words ▾

14 CLINICAL STUDIES

14.1COSOPT Efficacy Clinical studies of 3 to 15 months duration were conducted to compare the IOP-lowering effect over the course of the day of COSOPT twice daily (dosed morning and bedtime) to individually- and concomitantly-administered 0.5% timolol twice daily and 2.0% dorzolamide twice and three times daily. The IOP-lowering effect of COSOPT twice daily was greater (1 to 3 mmHg) than that of monotherapy with either 2.0% dorzolamide three times daily or 0.5% timolol twice daily. The IOP lowering effect of COSOPT twice daily was approximately 1 mmHg less than that of concomitant therapy with 2.0% dorzolamide three times daily and 0.5% timolol twice daily.

Open-label extensions of two studies were conducted for up to 12 months. During this period, the IOP lowering effect of COSOPT twice daily was consistent during the 12 month follow-up period.

14.2Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) Equivalence Study In an active-treatment controlled, parallel, double-masked study in 261 patients with elevated intraocular pressure ≥22 mmHg in one or both eyes, Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) had an IOP-lowering effect equivalent to that of COSOPT.

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year study of dorzolamide hydrochloride administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day (250 times the recommended human ophthalmic dose). Papillomas were not seen in rats given oral doses equivalent to approximately 12 times the recommended human ophthalmic dose. No treatment-related tumors were seen in a 21-month study in female and male mice given oral doses up to 75 mg/kg/day (~900 times the recommended human ophthalmic dose).

The increased incidence of urinary bladder papillomas seen in the high-dose male rats is a class-effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria, and diverse sodium salts. No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for one year at 2 mg/kg/day (25 times the recommended human ophthalmic dose) or monkeys dosed topically to the eye at 0.4 mg/kg/day (~5 times the recommended human ophthalmic dose) for one year.

In a two-year study of timolol maleate administered orally to rats, there was a statistically significant increase in the incidence of adrenal pheochromocytomas in male rats administered 300 mg/kg/day (approximately 42,000 times the systemic exposure following the maximum recommended human ophthalmic dose). Similar differences were not observed in rats administered oral doses equivalent to approximately 14,000 times the maximum recommended human ophthalmic dose. In a lifetime oral study of timolol maleate in mice, there were statistically significant increases in the incidence of benign and malignant pulmonary tumors, benign uterine polyps and mammary adenocarcinomas in female mice at 500 mg/kg/day, (approximately 71,000 times the systemic exposure following the maximum recommended human ophthalmic dose), but not at 5 or 50 mg/kg/day (approximately 700 or 7,000, respectively, times the systemic exposure following the maximum recommended human ophthalmic dose).

In a subsequent study in female mice, in which post-mortem examinations were limited to the uterus and the lungs, a statistically significant increase in the incidence of pulmonary tumors was again observed at 500 mg/kg/day. The increased occurrence of mammary adenocarcinomas was associated with elevations in serum prolactin which occurred in female mice administered oral timolol at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence of mammary adenocarcinomas in rodents has been associated with administration of several other therapeutic agents that elevate serum prolactin, but no correlation between serum prolactin levels and mammary tumors has been established in humans.

Furthermore, in adult human female subjects who received oral dosages of up to 60 mg of timolol maleate (the maximum recommended human oral dosage), there were no clinically meaningful changes in serum prolactin. The following tests for mutagenic potential were negative for dorzolamide: (1) in vivo (mouse) cytogenetic assay; (2) in vitro chromosomal aberration assay; (3) alkaline elution assay; (4) V-79 assay; and (5) Ames test. Timolol maleate was devoid of mutagenic potential when tested in vivo (mouse) in the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in a neoplastic cell transformation assay (up to 100 mcg/mL).

In Ames tests the highest concentrations of timolol employed, 5,000 or 10,000 mcg/plate, were associated with statistically significant elevations of revertants observed with tester strain TA100 (in seven replicate assays), but not in the remaining three strains. In the assays with tester strain TA100, no consistent dose response relationship was observed, and the ratio of test to control revertants did not reach 2. A ratio of 2 is usually considered… [Excerpted — this section continues on DailyMed.]

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~3 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year study of dorzolamide hydrochloride administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day (250 times the recommended human ophthalmic dose). Papillomas were not seen in rats given oral doses equivalent to approximately 12 times the recommended human ophthalmic dose. No treatment-related tumors were seen in a 21-month study in female and male mice given oral doses up to 75 mg/kg/day (~900 times the recommended human ophthalmic dose).

The increased incidence of urinary bladder papillomas seen in the high-dose male rats is a class-effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria, and diverse sodium salts. No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for one year at 2 mg/kg/day (25 times the recommended human ophthalmic dose) or monkeys dosed topically to the eye at 0.4 mg/kg/day (~5 times the recommended human ophthalmic dose) for one year.

In a two-year study of timolol maleate administered orally to rats, there was a statistically significant increase in the incidence of adrenal pheochromocytomas in male rats administered 300 mg/kg/day (approximately 42,000 times the systemic exposure following the maximum recommended human ophthalmic dose). Similar differences were not observed in rats administered oral doses equivalent to approximately 14,000 times the maximum recommended human ophthalmic dose. In a lifetime oral study of timolol maleate in mice, there were statistically significant increases in the incidence of benign and malignant pulmonary tumors, benign uterine polyps and mammary adenocarcinomas in female mice at 500 mg/kg/day, (approximately 71,000 times the systemic exposure following the maximum recommended human ophthalmic dose), but not at 5 or 50 mg/kg/day (approximately 700 or 7,000, respectively, times the systemic exposure following the maximum recommended human ophthalmic dose).

In a subsequent study in female mice, in which post-mortem examinations were limited to the uterus and the lungs, a statistically significant increase in the incidence of pulmonary tumors was again observed at 500 mg/kg/day. The increased occurrence of mammary adenocarcinomas was associated with elevations in serum prolactin which occurred in female mice administered oral timolol at 500 mg/kg/day, but not at doses of 5 or 50 mg/kg/day. An increased incidence of mammary adenocarcinomas in rodents has been associated with administration of several other therapeutic agents that elevate serum prolactin, but no correlation between serum prolactin levels and mammary tumors has been established in humans.

Furthermore, in adult human female subjects who received oral dosages of up to 60 mg of timolol maleate (the maximum recommended human oral dosage), there were no clinically meaningful changes in serum prolactin. The following tests for mutagenic potential were negative for dorzolamide: (1) in vivo (mouse) cytogenetic assay; (2) in vitro chromosomal aberration assay; (3) alkaline elution assay; (4) V-79 assay; and (5) Ames test. Timolol maleate was devoid of mutagenic potential when tested in vivo (mouse) in the micronucleus test and cytogenetic assay (doses up to 800 mg/kg) and in vitro in a neoplastic cell transformation assay (up to 100 mcg/mL).

In Ames tests the highest concentrations of timolol employed, 5,000 or 10,000 mcg/plate, were associated with statistically significant elevations of revertants observed with tester strain TA100 (in seven replicate assays), but not in the remaining three strains. In the assays with tester strain TA100, no consistent dose response relationship was observed, and the ratio of test to control revertants did not reach 2. A ratio of 2 is usually considered the criterion for a positi… [Excerpted — this section continues on DailyMed.]

📄 Patient Package Insert ~3 min read ▾

Patient Information Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution 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, 2%/0.5% (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, 2%/0.5% (preservative free)? Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (preservative free) is safe and effective in children under 2 years of age. Who should not use Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free)? Do not use Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (preservative free).

See the end of this leaflet for a complete list of ingredients in Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (preservative free)?

Before you use Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (preservative free) will harm your unborn baby. If you become pregnant while using Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (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, 2%/0.5% (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, 2%/0.5% (preservative free) and other medicines may affect each other causing side effects.

Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) may affect the way other medicines work, and other medicines may affec… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~2 min read ▾

Instructions for Use Read these instructions before using your Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

Important: Dorzolamide hydrochloride and timolol maleate ophthalmic solution (preservative free) is for the eye only. Do not swallow Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free). Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) single-use containers are packaged in a foil pouch.

Write down the date you open the foil pouch in the space provided on the pouch. Every time you use Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free): Step 1. Wash your hands.

Step 2. Take the strip of single-use containers from the pouch. Step 3.

Pull off 1 single-use container from the strip. Step 4. Put the remaining strip of single-use containers back in the pouch and fold the edge to close the pouch.

Step 5. Hold the single-use container upright. Make sure that the solution is in the bottom part of the single-use container (See Figure A ).

(Figure A) Step 6. Open the single-use container by twisting off the tab (See Figure B ). (Figure B) Step 7.

Tilt your head backwards. If you are unable to tilt your head, lie down. Step 8.

Place the tip of the single-use container close to your eye. Be careful not to touch your eye with the tip of the single-use container (See Figure C ). (Figure C) Step 9.

Pull the lower eyelid downwards and look up. Step 10. Gently squeeze the container and let 1 drop of Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) fall into the space between your lower eyelid and your eye.

If a drop misses your eye, try again (See Figure D ). (Figure D) Step 11. Blot any excess solution from the skin around the eye with a tissue.

If your doctor has told you to use drops in both eyes, repeat steps 7 to 11 for your other eye. There is enough Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) in 1 single-use container for 1 or both of your eyes. Throw away the opened single-use container with any remaining Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, 2%/0.5% (preservative free) right away.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration. Distributed by: Genus Lifesciences Inc.

Allentown, PA 18102 Manufactured by: Rommelag CDMO GmbH, Bahnhofstrasse 18, 74429 Sulzbach-Laufen, Deutschland Rev 07/25 Figure A Figure B Figure C Figure D

📄 Package Label / Principal Display Panel 56 words ▾

PRINCIPAL DISPLAY PANEL - 0.2 mL Vial Carton NDC 64950-390-60 Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution, USP 2% / 0.5% For eye use only Preservative Free Rx only 60 Single-Use Containers: 4 pouches x 15 Single-Use Containers [0.2 mL in each single-use container] Sterile Genus Lifesciences Inc. PRINCIPAL DISPLAY PANEL - 0.2 mL Vial Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Dorzolamide Hydrochloride and Timolol Maleate — the ingredient across all brands.

Top reported reactions

Eye Irritation806
Ocular Hyperaemia656
Treatment Failure564
Eye Pain500
Eye Pruritus395
Intraocular Pressure Increased376
Death343

Age at onset

Neonate1
Infant1
Child9
Adolescent3
Adult181
Elderly567

Reporter sex

8,520 reports
Male · 40%
Female · 59%
Unknown · 1%

Serious outcomes

Hospitalization1,762
Disabling285
Life-threatening229
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,322 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product No longer marketed (per FDA listing data)
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
What does the discontinued status mean for this NDC?
The labeler reported a marketing end date (or the listing was delisted), so this specific package is no longer actively marketed. Remaining stock may still be dispensed for a time, and the NDC stays valid for historical records and claims — but data feeds (pricing, labeling) typically stop updating for it. Other package sizes or other manufacturers' versions of the same medication may still be marketed — see the equivalents section where available.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Who lists this product with the FDA?
Genus Lifesciences is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 64950-0381-14 · Genus 64950-0550-01 · Genus →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.