Timolol Ophthalmic

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 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.

Before using timolol ophthalmic, tell your doctor if you are using any of the following drugs:

• clonidine (Catapres);
• quinidine (Cardioquin, Quinadex, Quinaglute);
• reserpine;
• digitalis (digoxin, Lanoxin, Lanoxicaps);
• acetazolamide (Diamox), dichlorphenamide (Daranide), or methazolamide (Neptazane);
• oral timolol (Blocadren);
• any other beta-blocker such as atenolol (Tenormin), bisoprolol (Zebeta), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), penbutolol (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;
• a calcium channel blocker such as diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nifedipine (Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan), and others; or
• antidepressants such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), or sertraline (Zoloft).

This list is not complete and there may be other drugs that can interact with timolol ophthalmic. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

(TIM oh lol)

• Betimol
• Istalol
• Timoptic
• Timoptic Ocudose
• Timoptic-XE

Elevated intraocular pressure: Treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma

>10%: Ophthalmic: Burning sensation of eyes, stinging of eyes

Frequency not defined:

Cardiovascular: Angina pectoris, bradycardia, cardiac arrhythmia, cardiac failure, cerebral ischemia, cerebrovascular accident, claudication, cold extremities, edema, heart block, hypertension, hypotension, palpitations, Raynaud's phenomenon

Central nervous system: Amnesia, anxiety, confusion, depression, disorientation, dizziness, drowsiness, exacerbation of myasthenia gravis, hallucination, headache, insomnia, nervousness, nightmares, paresthesia

Dermatologic: Alopecia, exacerbation of psoriasis, pemphigoid-like lesion, psoriasiform eruption, skin rash, urticaria

Endocrine & metabolic: Hypoglycemia (masked), decreased libido

Gastrointestinal: Anorexia, diarrhea, dyspepsia, nausea, xerostomia

Genitourinary: Impotence, Peyronie’s disease, retroperitoneal fibrosis

Hypersensitivity: Angioedema, hypersensitivity reaction

Neuromuscular & skeletal: Systemic lupus erythematosus

Ophthalmic: Blepharitis, blepharoptosis, blurred vision, cataract, choroidal detachment (following filtration surgery), conjunctival injection, conjunctivitis, cystoid macular edema, decreased corneal sensitivity, decreased visual acuity, diplopia, eye discharge, eye pain, eye pruritus, foreign body sensation of eye, hyperemia, keratitis, lacrimation, visual disturbance (including refractive changes), xerophthalmia

Otic: Tinnitus

Respiratory: Bronchospasm, cough, dyspnea, nasal congestion, pulmonary edema, respiratory failure

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not use this medicine while wearing contact lenses. Timolol ophthalmic may contain a preservative that can discolor soft contact lenses. Wait at least 15 minutes after using this medicine before putting in your contact lenses.

Wash your hands before using the eye drops.

To apply the eye drops:

• Tilt your head back slightly and pull down your lower eyelid to create a small pocket. Hold the dropper above the eye with the tip down. Look up and away from the dropper and squeeze out a drop.

• Close your eyes for 2 or 3 minutes with your head tipped down, without blinking or squinting. Gently press your finger to the inside corner of the eye for about 1 minute, to keep the liquid from draining into your tear duct.

• Use only the number of drops your doctor has prescribed. If you use more than one drop, wait about 5 minutes between drops.

• Wait at least 10 minutes before using any other eye drops your doctor has prescribed.

Do not touch the tip of the eye dropper or place it directly on your eye. A contaminated dropper can infect your eye, which could lead to serious vision problems.

Do not use the eye drops if the liquid has changed colors or has particles in it. Call your pharmacist for new medicine.

It may take a few weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment.

If you need surgery, including eye surgery, tell the surgeon ahead of time that you are using timolol ophthalmic. You may need to stop using the medicine for a short time.

You should not stop using this medicine suddenly. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture, heat, and light. Do not freeze. Keep the bottle tightly closed when not in use. Keep each single-use ampule inside its foil pouch until you are ready to use your dose.

A single-use ampule is for one use only. Throw it away after one use, even if there is still medicine left inside.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

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.

General

Because of potential effects of beta-adrenergic blocking agents on blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop following initiation of therapy with timolol, alternative therapy should be considered.

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 PRECAUTIONS, Information for Patients).

Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy (e.g., timolol).

Angle-closure glaucoma: In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil. Timolol Maleate has little or no effect on the pupil. Timolol Maleate should not be used alone in the treatment of angle-closure glaucoma.

Anaphylaxis: 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.

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.

Information for Patients

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

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 PRECAUTIONS, General).

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.

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 be advised that Timolol Maleate ophthalmic solution 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 Timolol Maleate ophthalmic solution administration.

Drug Interactions

Although timolol used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with timolol and epinephrine has been reported occasionally.

Beta-adrenergic blocking agents: Patients who are receiving a beta-adrenergic blocking agent orally and timolol 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.

Calcium antagonists: Caution should be used in the coadministration of beta-adrenergic blocking agents, such as timolol, 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.

Catecholamine-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.

Digitalis 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.

CYP2D6 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.

Clonidine: 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.

Injectable Epinephrine: (see PRECAUTIONS, General, Anaphylaxis)

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 TA 100 (in seven replicate assays), but not in the remaining three strains. In the assays with tester strain TA 100, 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.

Pregnancy

Teratogenic Effects

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. Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Timolol Maleate has been detected in human milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions from timolol 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.

Pediatric Use

Safety and effectiveness of timolol maleate ophthalmic solution have been established when administered in pediatric patients aged 2 years and older. Use of timolol maleate ophthalmic solution 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

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

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: oral beta-blockers (e.g., propranolol), clonidine, certain antidepressants (e.g., SSRIs such as fluoxetine), digoxin, epinephrine, fingolimod, methyldopa, quinidine, reserpine.