Optipranolol

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.

DO NOT USE IF IMPRINTED NECKBAND IS NOT INTACT.

FOR OPHTHALMIC USE ONLY.

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

OptiPranolol (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) Ophthalmic Solution is not known to be of benefit. Concomitant therapy to lower intraocular pressure can be instituted.

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

Hypersensitivity to any component of this product.

OptiPranolol (metipranolol ophthalmic solution) 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.

WARNINGS

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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) Ophthalmic Solution should be discontinued at the first evidence of cardiac failure.

OptiPranolol (metipranolol ophthalmic solution) 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.

PRECAUTIONS

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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) Ophthalmic Solution is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when OptiPranolol (metipranolol ophthalmic solution) 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.

SIDE EFFECTS

In clinical trials, the use of OptiPranolol (metipranolol ophthalmic solution) 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.

DRUG INTERACTIONS

OptiPranolol® (metipranolol ophthalmic solution) 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 (metipranolol ophthalmic solution) 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.

In clinical trials, the use of OptiPranolol (metipranolol ophthalmic solution) 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.

No information is available on overdosage of OptiPranolol (metipranolol ophthalmic solution) 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.