OptiPranolol® (metipranolol ophthalmic solution) 0.3% contains metipranolol, a non-selective beta-adrenergic receptor blocking agent. Metipranolol is a white, odorless, crystalline powder.

The chemical name of metipranolol is (± )-1-(4-Hydroxy-2, 3, 5-trimethylphenoxy)-3-(isopropylamino)-2-propanol-4-acetate.

The chemical structure of metipranolol is:

C₁₇H₂₇NO₄             Mol. Wt. 309.40

Each mL of OptiPranolol® contains 3 mg of metipranolol. INACTIVES: Povidone, Glycerin, Hydrochloric Acid, Sodium Chloride, Edetate Disodium, and Purified Water. Sodium Hydroxide and/or Hydrochloric Acid may be added to adjust pH. The product is produced at pH 5.0-5.8 and osmolality 265 to 330 mOsmol/kg. PRESERVATIVE ADDED: Benzalkonium Chloride 0.004%.

Last updated on RxList: 11/13/2008

OptiPranolol Ophthalmic Solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open angle glaucoma.

The recommended dose is one drop of OptiPranolol Ophthalmic Solution in the affected eye(s) twice a day.

If the patient's IOP is not at a satisfactory level on this regimen, use of more frequent administration or a larger dose of OptiPranolol Ophthalmic Solution is not known to be of benefit. Concomitant therapy to lower intraocular pressure can be instituted.

In clinical trials, OptiPranolol® Ophthalmic Solution was safely used during concomitant therapy with pilocarpine, epinephrine or acetazolamide.

OptiPranolol® (metipranolol ophthalmic solution) 0.3% is supplied in a plastic bottle with a controlled drop tip and a yellow plastic screw-top cap as follows:

5  mL: NDC 24208-275-07 - AB40207
10 mL: NDC 24208-275-09 - AB40209

Storage

Store between 15° - 30° C (59° - 86° F). Replace cap immediately after use.

FOR OPHTHALMIC USE ONLY.

Bausch & Lomb Incorporated, Tampa, FL 33637. REV. 11/03-91. FDA rev date: 11/21/2006

Last updated on RxList: 11/13/2008

In clinical trials, the use of OptiPranolol Ophthalmic Solution has been associated with transient local discomfort.

Other ocular adverse reactions, such as abnormal vision, blepharitis, blurred vision, browache, conjunctivitis, edema, eyelid dermatitis, photophobia, tearing, and uveitis have been reported in small numbers of patients.

Other systemic adverse reactions, such as allergic reaction, angina, anxiety, arthritis, asthenia, atrial fibrillation, bradycardia, bronchitis, coughing, depression, dizziness, dyspnea, epistaxis, headache, hypertension, myalgia, myocardial infarct, nausea, nervousness, palpitation, rash, rhinitis, and somnolence have also been reported in small numbers of patients.

OptiPranolol® Ophthalmic Solution should be used with caution in patients who are receiving a beta-adrenergic blocking agent orally, because of the potential for additive effects on systemic beta-blockade.

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 bradycardia.

Caution should be used in the coadministration of beta-adrenergic receptor blocking agents, such as metipranolol, and oral or intravenous calcium channel antagonists, because of possible precipitation of left ventricular failure, and hypotension. In patients with impaired cardiac function, who are receiving calcium channel antagonists, coadministration should be avoided.

The concomitant use of beta-adrenergic receptor blocking agents with digitalis and calcium channel antagonists may have additive effects, prolonging atrioventricular conduction time.

Caution should be used in patients using concomitant adrenergic psychotropic drugs.

Ocular

In patients with angle-closure glaucoma, the immediate treatment objective is to re-open the angle by constriction of the pupil with a miotic agent. OptiPranolol Ophthalmic Solution has little or no effect on the pupil, therefore, when it is used to reduce intraocular pressure in angle-closure glaucoma, it should be used only with concomitant administration of a miotic agent.

Last updated on RxList: 11/13/2008

As with other topically applied ophthalmic drugs, this drug may be absorbed systemically. Thus, 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 topical application of beta-adrenergic blocking agents (see CONTRAINDICATIONS).

Since OptiPranolol Ophthalmic Solution had a minor effect on heart rate and blood pressure in clinical studies, caution should be observed in treating patients with a history of cardiac failure. Treatment with OptiPranolol Ophthalmic Solution should be discontinued at the first evidence of cardiac failure.

OptiPranolol Ophthalmic Solution, or other beta-blockers, should not, in general, be administered to patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity (see CONTRAINDICATIONS). However, if the drug is necessary in such patients, then it should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta₂ receptors.

General

Because of potential effects of beta-adrenergic receptor blocking agents relative to 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 OptiPranolol Ophthalmic Solution, alternative therapy should be considered.

Some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents in patients undergoing elective surgery. If necessary during surgery, the effects of beta-adrenergic receptor blocking agents may be reversed by sufficient doses of such agonists as isoproterenol, dopamine, dobutamine or levarterenol.

While OptiPranolol Ophthalmic Solution has demonstrated a low potential for systemic effect, it should be used with caution in patients with diabetes (especially labile diabetes) because of possible masking of signs and symptoms of acute hypoglycemia.

Beta-adrenergic receptor blocking agents may mask certain signs and symptoms of hyperthyroidism, and their abrupt withdrawal might precipitate a thyroid storm.

Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness).

Risk of anaphylactic reaction: While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime studies with metipranolol have been conducted in mice at oral doses of 5, 50, and 100 mg/kg/day and in rats at oral doses of up to 70 mg/kg/day. Metipranolol demonstrated no carcinogenic effect. In the mouse study, female animals receiving the low, but not the intermediate or high dose, had an increased number of pulmonary adenomas. The significance of this observation is unknown. In a variety of in vitro and in vivo bacterial and mammalian cell assays, metipranolol was nonmutagenic.

Reproduction and fertility studies of metipranolol in rats and mice showed no adverse effect on male fertility at oral doses of up to 50 mg/kg/day, and female fertility at oral doses of up to 25 mg/kg/day.

Pregnancy-Teratogenic effects

Pregnancy Category C

No drug related effects were reported for the segment II teratology study in fetal rats after administration, during organogenesis, to dams of up to 50 mg/kg/day. OptiPranolol Ophthalmic Solution has been shown to increase fetal resorption, fetal death, and delayed development when administered orally to rabbits at 50 mg/kg/day during organogenesis.

There are no adequate and well-controlled studies in pregnant women. OptiPranolol Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether OptiPranolol Ophthalmic Solution is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when OptiPranolol Ophthalmic Solution is administered to nursing women.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

Last updated on RxList: 11/13/2008

No information is available on overdosage of OptiPranolol Ophthalmic Solution in humans. The symptoms which might be expected with an overdose of a systemically administered beta-adrenergic receptor blocking agent are bradycardia, hypotension and acute cardiac failure.

Hypersensitivity to any component of this product.

OptiPranolol Ophthalmic Solution is contraindicated in patients with bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease; symptomatic sinus bradycardia; greater than a first degree atrioventricular block; cardiogenic shock; or overt cardiac failure.

Last updated on RxList: 11/13/2008

Metipranolol blocks beta₁ and beta₂ (non-selective) adrenergic receptors. It does not have significant intrinsic sympathomimetic activity, and has only weak local anesthetic (membrane-stabilizing) and myocardial depressant activity.

Orally administered beta-adrenergic blocking agents reduce cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor antagonists may inhibit the sympathetic stimulatory effect necessary to maintain adequate cardiac output.

Beta-adrenergic receptor blockade in the bronchi and bronchioles may result in significantly increased airway resistance from unopposed parasympathetic activity. Such an effect is potentially dangerous in patients with asthma or other bronchospastic conditions (see CONTRAINDICATIONS and WARNINGS).

OptiPranolol Ophthalmic Solution, when applied topically in the eye, has the action of reducing elevated as well as normal intraocular pressure (IOP), 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 primary mechanism of the ocular hypotensive action of metipranolol is most likely due to a reduction in aqueous humor production. A slight increase in outflow may be an additional mechanism. OptiPranolol Ophthalmic Solution reduces IOP with little or no effect on pupil size or accommodation.

In controlled studies of patients with intraocular pressure greater than 24 mmHg at baseline, OptiPranolol Ophthalmic Solution reduced the average intraocular pressure approximately 20-26%.

The onset of action of OptiPranolol Ophthalmic Solution, as measured by a reduction in intraocular pressure, occurs within 30 minutes after a single administration. The maximum effect occurs at about 2 hours. A reduction in intraocular pressure can be demonstrated 24 hours after a single dose. Clinical studies in patients with glaucoma treated for up to two years indicate that an intraocular pressure lowering effect is maintained.

Animal pharmacology

In rabbits administered metipranolol in one eye at 2 to 4 fold increased concentrations, multi-focal interstitial nephritis was observed in male animals, and lympho-hystiocytic and heterophilic interstitial pneumonia was observed in female animals. The clinical relevance of these findings is unknown.

Last updated on RxList: 11/13/2008

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

Patients should be advised that OptiPranolol 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 OptiPranolol administration.

Last updated on RxList: 11/13/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

METIPRANOLOL - OPHTHALMIC

(met-eh-PRAN-oh-lol)

COMMON BRAND NAME(S): Optipranolol

USES: This medication is used alone or with other medications to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (e.g., ocular hypertension). Lowering high pressure inside the eye helps to prevent blindness. Levobunolol belongs to a class of drugs known as beta blockers and works by decreasing the amount of fluid production within the eye.

HOW TO USE: To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

If you are wearing contact lenses, remove them before using eye drops. Wait at least 15 minutes before replacing your contact lenses.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch, usually twice daily or as directed by your doctor. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 to 10 minutes before using the other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. It is important to continue using this medication even if you feel well. Most people with glaucoma or high pressure in the eyes do not feel sick.

SIDE EFFECTS: Temporary discomfort of the eye, blurred vision, watery eyes, headache, drowsiness, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain/swelling/discharge, increased eye sensitivity to light, vision changes, slow/irregular heartbeat, muscle weakness, mental/mood changes, tiredness, swelling of the ankles/feet, sudden/unexplained weight gain.

Seek immediate medical attention if any of these rare but very serious side effects occur: trouble breathing, chest/jaw/left arm pain, weakness on one side of the body, slurred speech, confusion.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using metipranolol, tell your doctor or pharmacist if you are allergic to it; or to other beta-blockers (e.g., timolol, levobunolol); or to the preservative in this product (benzalkonium chloride); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe breathing problems (e.g., asthma or a history of asthma, chronic obstructive pulmonary disease-COPD), certain types of heart rhythm problems (e.g., sinus bradycardia, second- or third-degree atrioventricular block), certain serious heart conditions (e.g., cardiogenic shock, severe heart failure).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: lung disease (e.g., bronchitis, emphysema), diabetes, heart failure (treated, stable type), blood circulation problems (e.g., cerebrovascular insufficiency), overactive thyroid (hyperthyroidism), muscle weakness disorders (e.g., myasthenia gravis).

Before having surgery, tell your doctor or dentist that you are taking this medication.

This drug may make you dizzy, drowsy, or cause blurred vision; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcoholic beverages.

If you have diabetes, this product may mask the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness/sweating, are unaffected by this drug.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain diabetes drugs (e.g., insulin, sulfonylureas such as glyburide), certain psychiatric drugs (e.g., venlafaxine, tricyclic antidepressants such as amitriptyline), digoxin, drugs for high blood pressure (e.g., clonidine, reserpine, oral beta blockers such as propranolol, calcium channel blockers such as diltiazem), epinephrine.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. If this product is accidentally swallowed, you may experience symptoms such as trouble breathing, slow/irregular heartbeat.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.