Istalol Timolol Maleate 5 mg/mL Solution/ Drops — NDC 24208-004-03 (Billing 24208-0004-03)
This is a package of Istalol Timolol Maleate 5 mg/mL Solution/ Drops from Bausch & Lomb Incorporated, marketed since Aug 2004 and currently FDA-listed; retail pharmacies pay about $80.01 per mL (NADAC). It is the main listing for this product, which comes in 3 package sizes.
NDC database record
One package, one record: these facts belong to NDC 24208-004-03 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 24208 labeler · 004 product · 03 package
- Package marketed since
- Aug 2, 2004
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2026
- Barcode (UPC-A, from the NDC)
- 3 2420800403 6
- Medicaid fills, this package
- 580 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Other active recalls for Timolol Maleate (different manufacturers) — 6 · tap to view
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 059074
- GCN: 24615
- GPI-14 (Medi-Span): 86250030102060
- HICL (First Databank): 002105
- AHFS class code: 52:40.08.00
- RxCUI (RxNorm): 1992299
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 3, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the beta-Adrenergic Blocker class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Ophthalmic timolol is used to treat glaucoma, a condition in which increased pressure in the eye can lead to gradual loss of vision. Timolol is in a class of medications called beta-blockers. It works by decreasing the pressure in the eye.
Read the full MedlinePlus article ↗- It depends on the form. The eye drops lower high pressure in the eye from ocular hypertension or open-angle glaucoma. The tablets treat high blood pressure, lower the risk of death...
- Put the drop in the affected eye as directed, usually once or twice a day depending on your product. If yours is a gel-forming type, shake the closed bottle once first. Wait at lea...
- Burning or stinging right after the drops go in is the most common. Blurred vision, redness, itching and headache can also happen. Call your doctor if you notice wheezing, a very s...
- If your drops contain benzalkonium chloride, soft lenses can absorb it. Take your lenses out before using the drops and wait 15 minutes before putting them back in.
Patient education
Supplement & herbal interactions
Timolol may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 3, 2026
Ask a licensed pharmacist directly — free, answered by our team.
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 mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $80.015 | $400.07 / 5 ml |
| Medicaid paysCMS SDUD · 12 mo | $81.91 | $409.54 / 5 ml |
| Medicare drug plans payPart D · Q2 2026 | $81.59 | $407.94 / 5 ml |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 24208-0004-01 24208-004-01 | 1 BOTTLE, DROPPER in 1 CARTON / 2.5 mL in 1 BOTTLE, DROPPER | $79.76 / mL | $199.41 | 2004-08-02 | — | Active |
| 24208-0004-02 24208-004-02 | 1 BOTTLE, DROPPER in 1 CARTON / 2.5 mL in 1 BOTTLE, DROPPER | — | — | 2004-08-02 | — | Active |
| 24208-0004-03 You're viewing this Main listing | 1 BOTTLE, DROPPER in 1 CARTON / 5 mL in 1 BOTTLE, DROPPER | $80.01 / mL | $400.07 | 2004-08-02 | — | Active |
This pack effectively ties for the lowest per-mL cost of the 2 priced pack sizes ($80.01 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 74% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Istalol Timolol Maleate 5 mg/mL Solution/ Drops?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| timolol maleate 5 mg/mL 70756-0657-30 | Lifestar | 1 bottle | $0.720 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 64980-0514-01 | Rising | 1 bottle | $0.720 | AT1 | Availability likely | save 99% |
| Timolol maleate 5 mg/mL 70069-0707-01 | Somerset | 1 bottle | $0.720 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 65145-0153-01 | Caplin | 1 bottle | $0.720 | AT1 | Availability likely | save 99% |
| Timolol maleate 5 mg/mL 70069-0708-01 | Somerset | 1 bottle | $0.774 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 65145-0154-01 | Caplin | 1 bottle | $0.774 | AT1 | Availability likely | save 99% |
| timolol maleate 5 mg/mL 70756-0656-15 | Lifestar | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 65145-0152-01 | Caplin | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| Timolol maleate 5 mg/mL 70069-0706-01 | Somerset | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 61314-0227-05 | Sandoz | 5 ml | $1.046 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 69315-0325-05 | Leading | 5 ml | $1.046 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 60758-0801-05 | Pacific | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| Timolol Maleate 5 mg/mL 82260-0813-05 | Bausch | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| timolol maleate 5 mg/mL 72603-0540-01 | NorthStar | 1 bottle | $1.046 | AT1 | Availability likely | save 99% |
| Timoptic in Ocudose 5 mg/mL 69918-0601-60 | Nordic | 60 pouches | $1.255 | AT3 | Availability likely | save 98% |
| Timolol Maleate 5 mg/mL 82260-0819-05 | Bausch | 1 bottle | $8.302 | AB | Availability likely | save 90% |
| Timolol hemihydrate 5 mg/mL 70069-0516-01 | Somerset | 1 bottle | $21.806 | AT2 | Availability likely | save 73% |
| Timolol hemihydrate 5 mg/mL 70069-0517-01 | Somerset | 1 bottle | $22.290 | AT2 | Availability likely | save 72% |
| Timolol Maleate 5 mg/mL 82260-0045-05 | Bausch | 1 bottle | $22.290 | AT2 | Availability likely | save 72% |
| Timolol Maleate 5 mg/mL 68682-0045-25 | Oceanside | 1 bottle | $26.378 | AT2 | Discontinued | save 67% |
| Istalol 5 mg/mLthis 24208-0004-03 | Bausch | 1 bottle | $80.015 | AT2 | Availability likely | — |
| Timoptic 5 mg/mL 24208-0813-05 | Bausch | 1 bottle | — | AT1 | FDA listed | — |
| Timoptic-XE 5 mg/mL 24208-0816-05 | Bausch | 1 bottle | — | AB | FDA listed | — |
| Timolol Maleate 5 mg/mL 50090-7837-00 | A-S | 1 bottle | — | AT1 | FDA listed | — |
| Timolol Maleate 5 mg/mL 50090-3441-00 | A-S | 10 ml | — | AT1 | FDA listed | — |
| Timolol Maleate 5 mg/mL 59651-0313-05 | Aurobindo | 1 bottle | — | AB | FDA listed | — |
| Timolol Maleate 5 mg/mL 50090-5769-00 | A-S | 1 bottle | — | AT1 | FDA listed | — |
| timolol maleate 5 mg/mL 81469-0210-05 | First | 1 bottle | — | AT1 | FDA listed | — |
| Timolol Maleate 5 mg/mL 50090-1852-00 | A-S | 1 bottle | — | AT1 | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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0.05 mg / 1 mL
UNII F5UM2KM3W7
Benzalkonium chloride is a chemical compound that works as a preservative and antimicrobial agent in medications. It prevents bacterial and fungal growth in liquid formulations to keep the product safe during storage and use.
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UNII 1VPU26JZZ4
Potassium sorbate is a salt derived from sorbic acid, a naturally occurring preservative. It prevents growth of mold, yeast, and some bacteria, extending the medicine's shelf life.
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UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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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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UNII 593YOG76RN
A salt made from sodium and phosphate that helps regulate acidity and maintain proper pH balance in the medicine. It also acts as a buffer to keep the product stable.
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UNII 059QF0KO0R
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.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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.- FDA label on DailyMed · label index refreshed Oct 3, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Bausch & Lomb Incorporated labeler code 24208
- PURPOSE Octinoxate, Octisalate and Oxybenzone 7.5 g/100g; 5 g/100g; 3 g/100g Lotion NDC 24208-001-04
- Advanced Eye Relief Eye Wash water solution 99.05 mL/100mL Solution/ Drops NDC 24208-005-04
- Biotrue Hydration Boost Glycerin 5 mg/mL Solution/ Drops NDC 24208-006-05
- Methazolamide 25 mg Tablet NDC 24208-022-01
- Methazolamide 50 mg Tablet NDC 24208-023-01
- Xipere triamcinolone acetonide 40 mg/mL Injection, Suspension NDC 24208-040-01
- Tetracaine Hydrochloride 5 mg/mL Solution/ Drops NDC 24208-092-05
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ISTALOL ® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. ISTALOL is a beta adrenergic blocker indicated for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION One drop of ISTALOL should be administered in the affected eye(s) once a day in the morning (AM). If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. One drop in the affected eye(s) once a day in the morning. ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Ophthalmic solution containing 0.5% (5 mg/mL) of timolol (6.8 mg/mL of timolol maleate). Ophthalmic solution containing timolol 0.5% (5 mg/mL) ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease ( 4.1 , 5.1 , 5.3 ) Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock ( 4.2 , 5.2 ) Hypersensitivity to any component of this product ( 4.3 )
4.1Asthma, COPD ISTALOL is contraindicated in patients with bronchial asthma; a history of bronchial asthma; severe chronic obstructive pulmonary disease [see Warnings and Precautions ( 5.1 , 5.3 )] .
4.2Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock ISTALOL is contraindicated in patients with sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure; cardiogenic shock [see Warnings and Precautions ( 5.2 )] .
4.3Hypersensitivity Reactions ISTALOL is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this product in the past.
4.1Asthma, COPD ISTALOL is contraindicated in patients with bronchial asthma; a history of bronchial asthma; severe chronic obstructive pulmonary disease [see Warnings and Precautions ( 5.1 , 5.3 )] .
4.2Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock ISTALOL is contraindicated in patients with sinus bradycardia; second or third degree atrioventricular block; overt cardiac failure; cardiogenic shock [see Warnings and Precautions ( 5.2 )] .
4.3Hypersensitivity Reactions ISTALOL is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this product in the past.
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Potentiation of Respiratory Reactions Including Asthma ( 5.1 ) Cardiac Failure ( 5.2 ) Obstructive Pulmonary Disease ( 5.3 ) Increased Reactivity to Allergens ( 5.4 ) Potentiation of Muscle Weakness ( 5.5 ) Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus ( 5.6 ) Masking of Thyrotoxicosis ( 5.7 )
5.1Potentiation of Respiratory Reactions Including Asthma ISTALOL contains timolol maleate; and although administered topically, it can be absorbed systemically. Therefore, the same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported following systemic or ophthalmic administration of timolol maleate [see Contraindications ( 4.1 )].
5.2Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition of 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, ISTALOL should be discontinued [see Contraindications ( 4.2 )].
5.3Obstructive 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 ISTALOL is contraindicated] should, in general, not receive beta-blocking agents, including ISTALOL [see Contraindications ( 4.1 )].
5.4Increased 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.
5.5Potentiation of Muscle Weakness Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.
5.6Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.
5.7Masking of Thyrotoxicosis Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate a thyroid storm.
5.8Contamination of Topical Ophthalmic Products After Use There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information ( 17 )].
5.9Impairment of Beta-adrenergically Mediated Reflexes During Surgery The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to re… [Excerpted — this section continues on DailyMed.]
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most frequently reported adverse reactions have been burning and stinging upon instillation in 38% of patients treated with ISTALOL. Additional reactions reported with ISTALOL at a frequency of 4% to 10% include: blurred vision, cataract, conjunctival injection, headache, hypertension, infection, itching and decreased visual acuity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials 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. The most frequently reported adverse reactions have been burning and stinging upon instillation in 38% of patients treated with ISTALOL. Additional reactions reported with ISTALOL at a frequency of 4% to 10% include: blurred vision, cataract, conjunctival injection, headache, hypertension, infection, itching and decreased visual acuity.
The following additional adverse reactions have been reported less frequently with ocular administration of this or other timolol maleate formulations. Timolol (Ocular Administration) Body as a Whole: Asthenia/fatigue and chest pain; Cardiovascular: Bradycardia, arrhythmia, hypotension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure, worsening of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud’s phenomenon and cold hands and feet; Digestive: Nausea, diarrhea, dyspepsia, anorexia, and dry mouth; Immunologic: Systemic lupus erythematosus; Nervous System/Psychiatric: Dizziness, increase in signs and symptoms of myasthenia gravis, paresthesia, somnolence, insomnia, nightmares, behavioral changes and psychic disturbances including depression, confusion, hallucinations, anxiety, disorientation, nervousness and memory loss; Skin: Alopecia and psoriasiform rash or exacerbation of psoriasis; Hypersensitivity: Signs and symptoms of systemic allergic reactions, including angioedema, urticaria, and localized and generalized rash; Respiratory: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnea, nasal congestion, cough and upper respiratory infections; Endocrine: Masked symptoms of hypoglycemia in diabetic patients [see Warnings and Precautions ( 5.6 )]; Special Senses: Signs and symptoms of ocular irritation including conjunctivitis, blepharitis, keratitis, ocular pain, discharge (e.g., crusting), foreign body sensation, itching and tearing, and dry eyes; ptosis, decreased corneal sensitivity; cystoid macular edema; visual disturbances including refractive changes and diplopia; pseudopemphigoid; choroidal detachment following filtration surgery [see Warnings and Precautions ( 5.12 )]; Urogenital: Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie’s disease.
6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of ISTALOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Oral Timolol/Oral Beta-Blockers The following additional adverse effects have been reported in clinical experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Body as a Whole: Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular: Worsening of arterial insufficiency, vasodilatation; Digestive: Gastrointestinal pain, hepatomegaly, vomiting, mesenteric arterial thrombosis, ischemic… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Concomitant use with systemic beta-blockers may potentiate systemic beta-blockade. ( 7.1 ) Oral or intravenous calcium antagonists may cause atrioventricular conduction disturbances, left ventricular failure, and hypotension. ( 7.2 ) Catecholamine-depleting drugs may have additive effects and produce hypotension and/or marked bradycardia.
( 7.3 ) Digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time. ( 7.4 ) Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with quinidine and timolol. ( 7.5 )
7.1Beta-Adrenergic Blocking Agents Patients who are receiving a beta-adrenergic blocking agent orally and ISTALOL 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.
7.2Calcium Antagonists Caution should be used in the co-administration of beta-adrenergic blocking agents, such as ISTALOL, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, co-administration should be avoided.
7.3Catecholamine-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.
7.4Digitalis 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.
7.5CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine) and timolol.
7.6Clonidine 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.
7.1Beta-Adrenergic Blocking Agents Patients who are receiving a beta-adrenergic blocking agent orally and ISTALOL 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.
7.2Calcium Antagonists Caution should be used in the co-administration of beta-adrenergic blocking agents, such as ISTALOL, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, co-administration should be avoided.
7.3Catecholamine-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.
7.4Digitalis 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.
7.5CYP2D6 Inhibitors Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine) and timolol.
7.6Clonidine 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 Risk Summary There are no adequate and well-controlled studies in pregnant women with timolol maleate to inform a drug-associated risk. Administration of oral timolol maleate to pregnant mice, rats and rabbits did not produce teratogenicity at clinically relevant systemic exposures (see Data). Because animal reproductive studies are not always predictive of human response, ISTALOL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Teratogenicity studies with timolol in pregnant 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 1,000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternally toxic 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 without apparent maternal toxicity.
8.2Lactation Risk Summary Timolol has been detected in human milk following oral and ophthalmic drug administration. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ISTALOL and any potential adverse effects on the breastfed child from ISTALOL.
8.4Pediatric Use The safety and effectiveness of ISTALOL in pediatric patients 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 Risk Summary There are no adequate and well-controlled studies in pregnant women with timolol maleate to inform a drug-associated risk. Administration of oral timolol maleate to pregnant mice, rats and rabbits did not produce teratogenicity at clinically relevant systemic exposures (see Data). Because animal reproductive studies are not always predictive of human response, ISTALOL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Teratogenicity studies with timolol in pregnant 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 1,000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternally toxic 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 without apparent maternal toxicity.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ISTALOL in pediatric patients 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 There have been reports of inadvertent overdosage with ISTALOL resulting in systemic effects similar to those seen with systemic beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. An in vitro hemodialysis study, using 14 C timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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. Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous. ISTALOL ophthalmic solution, when applied topically on the eye, has the action of reducing elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma.
Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage. The onset of reduction in intraocular pressure following administration of ISTALOL can usually be detected within one-half hour after a single dose.
The maximum effect usually occurs in one to two hours and significant lowering of intraocular pressure can be maintained for periods as long as 24 hours with a single dose. Repeated observations over a period of one year indicate that the intraocular pressure lowering effect of ISTALOL is well maintained. The precise mechanism of the ocular hypotensive action of ISTALOL is not clearly established at this time.
Tonography and fluorophotometry studies in man suggest that its predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed.
12.3Pharmacokinetics In a study of plasma drug concentration in 12 healthy subjects, the systemic exposure to timolol was determined following twice daily administration of ISTALOL (exaggerated regimen) for eight days. With ISTALOL, mean plasma concentrations of timolol were 0.68 ng/mL and 0.88 ng/mL two hours after the first dose and the dose on the eighth day, respectively.
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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. Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.
Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous. ISTALOL ophthalmic solution, when applied topically on the eye, has the action of reducing elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma.
Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage. The onset of reduction in intraocular pressure following administration of ISTALOL can usually be detected within one-half hour after a single dose.
The maximum effect usually occurs in one to two hours and significant lowering of intraocular pressure can be maintained for periods as long as 24 hours with a single dose. Repeated observations over a period of one year indicate that the intraocular pressure lowering effect of ISTALOL is well maintained. The precise mechanism of the ocular hypotensive action of ISTALOL is not clearly established at this time.
Tonography and fluorophotometry studies in man suggest that its predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING ISTALOL (timolol maleate ophthalmic solution) 0.5% is supplied in white LDPE bottles with 15 mm PP yellow caps and 15 mm LLDPE white dropper tips as follows: NDC 24208-004-03 5 mL in 10 mL container NDC 24208-004-01 2.5 mL in 7.5 mL container Storage: Store at 15ºC to 25ºC (59ºF to 77ºF). After opening, ISTALOL can be used until the expiration date on the bottle.
📋 Description ▾
11 DESCRIPTION ISTALOL (timolol maleate ophthalmic solution) 0.5% is a non-selective beta-adrenergic receptor blocking agent for topical ophthalmic use. Its chemical name is (-)-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.
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 has a molecular weight of 432.49. It is a white, odorless, crystalline powder which is soluble in water, methanol, and alcohol. ISTALOL is stable at room temperature.
ISTALOL ophthalmic solution is supplied as a sterile, isotonic, buffered, aqueous solution of timolol maleate in a single strength. It has a pH of 6.5-7.5 and an osmolality of 275-330 mOsm/kg. Each mL of ISTALOL contains the active ingredient 5 mg of timolol (6.8 mg of timolol maleate) with the inactive ingredients benzalkonium chloride (0.05 mg/mL), monobasic sodium phosphate monohydrate, potassium sorbate 0.47%, sodium chloride, sodium hydroxide, and purified water. chemstructure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Asthma, COPD, Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease (COPD), sinus bradycardia, second or third degree atrioventricular block, or cardiac failure should be advised not to use ISTALOL [see Contraindications ( 4.1 , 4.2 )]. Avoiding Contamination of the Product Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections.
Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions ( 5.8 )]. When to Seek Physician Advice Advise patients 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 the present multiple-dose container. Concomitant Topical Ophthalmic Medications Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.
Contact Lens Use Advise patients that ISTALOL contains benzalkonium chloride, an anti-microbial preservative, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following ISTALOL administration.
Distributed by: Bausch & Lomb Americas Inc. Bridgewater, NJ 08807 USA Manufactured by: Bausch & Lomb Incorporated Tampa, FL 33637 USA Under License from: Senju Pharmaceutical Co., Ltd. Osaka, Japan 541-0046 ISTALOL is a trademark of Bausch & Lomb Incorporated or its affiliates. © 2024 Bausch & Lomb Incorporated or its affiliates 9733102 (Folded) 9733202 (Flat)
🧬 Pharmacokinetics ▾
12.3Pharmacokinetics In a study of plasma drug concentration in 12 healthy subjects, the systemic exposure to timolol was determined following twice daily administration of ISTALOL (exaggerated regimen) for eight days. With ISTALOL, mean plasma concentrations of timolol were 0.68 ng/mL and 0.88 ng/mL two hours after the first dose and the dose on the eighth day, respectively.
🔬 Clinical Studies ▾
14 CLINICAL STUDIES In a controlled, double-masked, parallel study in 332 patients with untreated intraocular pressures of 22 mm Hg or greater, ISTALOL 0.5% administered once daily (AM) was equivalent to timolol maleate ophthalmic solution 0.5% administered twice daily. In both groups, mean intraocular pressure decreased from 25 mm Hg at baseline to 18 mm Hg at peak and 19 mm Hg at trough. ISTALOL was generally well tolerated, and 3% of patients had treatment discontinued for adverse events judged related to treatment.
There was a slight decrease in cardiovascular function consistent with known systemic absorption of a β-adrenoceptor antagonist.
🧪 Nonclinical Toxicology ▾
13 NONCLINICAL TOXICOLOGY
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis 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 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.
Mutagenesis 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 positive Ames test. Impairment of Fertility Reproduction and fertility studies in rats demonstrated no adverse effect on male or female fertility at doses up to 21,000 times the systemic exposure following the maximum recommended human ophthalmic dose.
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis 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 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.
Mutagenesis 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 positive Ames test. Impairment of Fertility Reproduction and fertility studies in rats demonstrated no adverse effect on male or female fertility at doses up to 21,000 times the systemic exposure following the maximum recommended human ophthalmic dose.
📄 Package Label / Principal Display Panel ▾
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 24208-004-03 Rx only Istalol ® (timolol maleate ophthalmic solution) 0.5% For Topical Ophthalmic Use 5mL Sterile BAUSCH + LOMB Once Daily 9542005 AB44207 carton