Istalol

Timolol is a beta-blocker that also reduces pressure inside the eye.

Timolol ophthalmic (for the eyes) is used to treat open-angle glaucoma and other causes of high pressure inside the eye.

Timolol ophthalmic may also be used for other purposes not listed in this medication guide.

Do not allow the dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

Do not use any other eye medication unless your doctor has prescribed it for you. If you use another eye medication, use it at least 10 minutes before or after using timolol ophthalmic. Do not use the medications at the same time.

Timolol ophthalmic can cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

Do not use this medication if you are allergic to timolol, or if you have:

• asthma or severe chronic obstructive pulmonary disease (COPD);
• certain serious heart conditions, especially "AV block"; or
• severe or uncontrolled congestive heart failure.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:

• breathing problems such as bronchitis or emphysema;
• a history of heart disease or congestive heart failure;
• diabetes;
• history of stroke, blood clot, or circulation problems;
• a thyroid disorder;
• a muscle disorder such as myasthenia gravis;
• kidney disease; or
• liver disease.

FDA pregnancy category C. It is not known whether timolol ophthalmic is harmful to an unborn baby. Before using this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

Timolol ophthalmic passes into breast milk and could cause harm to a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not use this medicine for a child younger than 2 years old.

Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block, or cardiac failure should be advised not to take this product (see CONTRAINDICATIONS).

Patients should also be instructed 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).

Patients should also 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 the present multidose container. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

Patients should be advised that Istalol® contains benzalkonium chloride 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.

Clinical 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.

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); 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); Urogenital: Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie's disease.

Postmarketing Experience

The following additional adverse reactions 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 colitis; Hematologic: Nonthrombocytopenic purpura; thrombocytopenic purpura, agranulocytosis; Endocrine: Hyperglycemia, hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local weakness, diminished concentration, reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, emotional lability, slightly clouded sensorium and decreased performance on neuropsychometrics; Respiratory: Rales, bronchial obstruction; Urogenital: Urination difficulties.

Read the entire FDA prescribing information for Istalol (Timolol Maleate Ophthalmic Solution)

This section provides information on the proper use of a number of products that contain timolol. It may not be specific to Istalol. Please read with care.

Use this medicine exactly as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Shake the regular eye drops well just before each use. If you are using the gel-forming eye drops, turn the bottle upside down and shake it once. You do not need to shake the gel-forming eye drops more than once.

To use the eye drops (solution and gel):

• First, wash your hands. Tilt the head back and, pressing your finger gently on the skin just beneath the lower eyelid, pull the lower eyelid away from the eye to make a space. Drop the medicine into this space. Let go of the eyelid and gently close the eyes. Do not blink. Keep the eyes closed and apply pressure to the inner corner of the eye with your finger for 1 or 2 minutes to allow the medicine to be absorbed by the eye.
• Immediately after using the medicine, wash your hands to remove any medicine that may be on them.
• To keep the medicine as germ-free as possible, do not touch the applicator tip to any surface (including the eye). Also, keep the container tightly closed. Serious damage to the eye and possible loss of vision may result from using contaminated eye medicines.

If your doctor ordered two different eye medicines to be used together, wait at least 10 minutes after the regular eye drops before using the second medicine. This will help prevent the second medicine from “washing out” the first one. The gel-forming eye drops should always be the last medicine used if two medicines are ordered. Wait 10 minutes before using the gel-forming eye drops.

You should not use the regular eye drops if you have contact lenses in your eyes. Remove your contact lenses before you use this medicine. Wait at least 15 minutes after you use the medicine before putting the contact lenses back in.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For glaucoma or ocular hypertension:
  • For ophthalmic gel-forming solution dosage form (eye drops):
    • Adults—Use 1 drop in the affected eye once a day.
    • Children—Use and dose must be determined by your doctor. .
  • For ophthalmic solution dosage form (eye drops):
    • Adults and children 2 years of age and older—Use 1 drop in the affected eye two times a day. Your doctor may need to adjust your dose as needed.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

If you are using Timoptic®, use the medicine immediately after opening and throw away any unused medicine after use.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects.

Do not use this medicine if you are also using a beta-blocker medicine that is taken by the mouth.

If itching, redness, swelling, or other signs of eye or eyelid irritation occur, stop using this medicine and check with your doctor. These signs may mean that you are allergic to this medicine.

Timolol may cause heart failure in some patients. Check with your doctor right away if you are having chest pain or discomfort, dilated neck veins, extreme fatigue, irregular breathing, an irregular heartbeat, swelling of the face, fingers, feet, or lower legs, weight gain, or trouble breathing.

This medicine may cause changes in your blood sugar levels. Also, this medicine may cover up signs of low blood sugar, such as a rapid pulse rate. Check with your doctor if you have these problems or if you notice a change in the results of your blood or urine sugar tests.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery.

The gel-forming eye drops may cause blurred vision or other vision problems that last about 30 seconds to 5 minutes after you put them in your eye. If any of these occur, do not drive, use machines, or do anything else that could be dangerous if you are not able to see well. If these eye changes are bothersome, check with your doctor.

• It is used to treat glaucoma.
• It is used to lower high eye pressure.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• For the eye only.
• Use as you have been told, even if your signs get better.
• Use Istalol at the same time of day.
• Take out contact lenses before using this medicine. Lenses may be put back in 15 minutes after Istalol is given. Do not put contacts back in if your eyes are irritated or infected.
• Do not touch the container tip to the eye, lid, or other skin.
• Tilt your head back and drop drug into the eye.
• After use, keep your eyes closed. Put pressure on the inside corner of the eye. Do this for 1 to 2 minutes. This keeps the drug in your eye.
• Blot extra solution from the eyelid.
• If more than 1 drug is being used in the same eye, use each drug at least 5 minutes apart.
• Some products are for use in the morning if using once a day. For some products it does not matter. Check with the pharmacist about how to use this medicine.

What do I do if I miss a dose?

• Use a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not use 2 doses or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Change in eyesight, eye pain, or very bad eye irritation.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Very bad dizziness or passing out.
• Very bad headache.
• Slow heartbeat.
• A heartbeat that does not feel normal.
• Chest pain.
• Trouble breathing.
• Muscle weakness.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

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.

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.

You should not use Istalol if you have asthma or severe COPD, or a serious heart condition (such as "sick sinus syndrome," 2nd or 3rd degree "AV block," severe heart failure, or very slow heartbeats).

Side effects may occur if timolol is absorbed into your bloodstream. Call your doctor right away if you have: chest pain, trouble breathing, slow heartbeats, muscle weakness, numbness or coldness in your hands or feet, unusual mood or behavior changes, or severe dizziness.

Do not allow the Istalol dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

Istalol can cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

Applies to timolol ophthalmic: ophthalmic gel forming solution, ophthalmic solution

General

The most commonly reported side effects were burning/stinging sensation, blurred vision, and abnormal vision.[Ref]

Ocular

Very common (10% or more): Burning/stinging sensation (up to 38%), blurred/abnormal vision (up to 25%)
Common (1% to 10%): Conjunctival hyperemia, foreign body sensation, keratitis, conjunctivitis, cataract, decreased visual acuity
Frequency not reported: Itching, tearing, redness, blepharitis, dry eyes, decreased corneal sensitivity, corneal erosion, refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis and choroidal detachment following filtration surgery, discharge (e.g., crusting), foreign body sensation, cystoid macular edema, pseudopemphigoid[Ref]

Cardiovascular

Common (1% to 10%): Hypertension
Frequency not reported: Bradycardia, chest pain, arrhythmia, heart block, congestive heart failure, palpitations, cardiac arrest, atrioventricular block, cardiac failure, edema; AV block (second- or third-degree), sino-atrial block, worsening of arterial insufficiency, worsening of angina pectoris, vasodilation, claudication, hypotension, syncope, Raynaud's phenomenon, cold hands and feet[Ref]

Respiratory

Frequency not reported: Pulmonary edema, bronchospasm (predominantly in patients with pre-existing bronchospastic disease), respiratory failure, dyspnea, cough, rales, sore throat, laryngospasm, respiratory distress
Postmarketing reports: Bronchial obstruction[Ref]

Nervous system

Common (1% to 10%): Headache
Frequency not reported: Tinnitus, memory loss, diminished concentration, increased dreaming, cerebrovascular accident, cerebral ischemia, dizziness, increase in signs and symptoms of myasthenia gravis, paresthesia, vertigo, local weakness[Ref]

Psychiatric

Frequency not reported: Depression, insomnia, nightmares, catatonia[Ref]

Dermatologic

Frequency not reported: Alopecia, psoriasiform rash or exacerbation of psoriasis, skin rash, sweating, exfoliative dermatitis[Ref]

Gastrointestinal

Frequency not reported: Nausea, diarrhea, dyspepsia, dry mouth, dysgeusia, abdominal pain, vomiting, mesenteric artery thrombosis, ischemic colitis[Ref]

Immunologic

Frequency not reported: Systemic lupus erythematosus[Ref]

Hypersensitivity

Frequency not reported: Anaphylaxis, angioedema, urticaria, localized/generalized rash, anaphylactic reaction
Postmarketing reports: Erythematous rash[Ref]

Genitourinary

Frequency not reported: Decreased libido, Peyronie's disease, impotence, micturition difficulties, retroperitoneal fibrosis[Ref]

Other

Frequency not reported: Asthenia, fatigue, extremity pain, decreased exercise tolerance, fever[Ref]

Hematologic

Frequency not reported: Non-thrombocytopenic purpura, thrombocytopenic purpura, agranulocytosis[Ref]

Musculoskeletal

Frequency not reported: Myalgia, arthralgia[Ref]

Hepatic

Postmarketing reports: Hepatomegaly[Ref]

Metabolic

Frequency not reported: Hypoglycemia, hyperglycemia, anorexia[Ref]

Some side effects of Istalol may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Timolol ophthalmic can cause blurred vision. Be careful if you drive or do anything that requires you to be able to see clearly.

You may need to use other glaucoma medications in addition to timolol ophthalmic. Do not use other eye medications unless your doctor tells you to.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• any other beta-blocker eye medication--betaxolol, carteolol, levobunolol, or metipranolol;

• any other beta-blocker heart or blood pressure medicine--atenolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, propranolol, sotalol, and others; or

• other heart or blood pressure medications--amiodarone, clonidine, digoxin, diltiazem, disopyramide, nicardipine, nifedipine, reserpine, verapamil, and others.

This list is not complete. Other drugs may interact with timolol ophthalmic, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.