Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Ophthalmic:
Generic: 0.3% (5 mL [DSC], 10 mL [DSC])
Pharmacology
Mechanism of Action
Beta-adrenoceptor-blocking agent; lacks intrinsic sympathomimetic activity and membrane-stabilizing effects and possesses only slight local anesthetic activity; mechanism of action of metipranolol in reducing intraocular pressure appears to be via reduced production of aqueous humor. This effect may be related to a reduction in blood flow to the iris root-ciliary body. It remains unclear if the reduction in intraocular pressure observed with beta-blockers is actually secondary to beta-adrenoceptor blockade.
Pharmacokinetics/Pharmacodynamics
Metabolism
Rapid and complete to deacetyl metipranolol, an active metabolite
Onset of Action
≤30 minutes; Peak effect: Maximum: ~2 hours
Duration of Action
Intraocular pressure reduction: Up to 24 hours
Half-Life Elimination
~3 hours
Use: Labeled Indications
Elevated intraocular pressure: Treatment elevated intraocular pressure in patient with chronic open-angle glaucoma or ocular hypertension
Contraindications
Hypersensitivity to metipranolol or any component of the formulation; bronchial asthma or history of bronchial asthma; severe COPD; sinus bradycardia; second- and third-degree AV block; cardiac failure; cardiogenic shock
Dosage and Administration
Dosing: Adult
Elevated intraocular pressure: Ophthalmic: Instill 1 drop in the affected eye(s) twice daily
Dosing: Geriatric
Refer to adult dosing.
Administration
For ophthalmic use only. Wash hands before use. To avoid contamination, do not touch dropper tip to eyelids or other surfaces when placing drops in eyes. Remove contact lenses prior to administration and wait 15 minutes before reinserting.
Drug Interactions
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Consider therapy modification
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Consider therapy modification
EPINEPHrine (Nasal): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Monitor therapy
Epinephrine (Racemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Monitor therapy
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Consider therapy modification
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Adverse Reactions
Frequency not defined.
Cardiovascular: Angina, atrial fibrillation, bradycardia, hypertension, MI, palpitation
Central nervous system: Anxiety, depression, dizziness, headache, nervousness, somnolence
Dermatologic: Rash
Gastrointestinal: Nausea
Neuromuscular & skeletal: Arthritis, myalgia, weakness
Ocular: Abnormal vision, blepharitis, blurred vision, browache, conjunctivitis, discomfort, edema, eyelid dermatitis, photophobia, tearing, uveitis
Respiratory: Bronchitis, cough, dyspnea, epistaxis, rhinitis
Miscellaneous: Allergic reaction
Warnings/Precautions
Concerns related to adverse events:
- Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
Disease-related concerns:
- Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
- Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
- Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
- Heart failure: Use with caution in patients with compensated heart failure (HF) and monitor for a worsening of the condition. In a scientific statement from the American Heart Association, metipranolol has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
- Myasthenia gravis: Use with caution in patients with myasthenia gravis.
- Peripheral vascular disease (PVD): Use with caution in patients with PVD (including Raynaud's).
- Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
Special populations:
- Contact lens wearers: Some products may contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting.
Other warnings/precautions:
- Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
- Absorption: Systemic absorption and adverse effects may occur with ophthalmic use, including bradycardia and/or hypotension.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies. The same adverse effects observed with systemic administration of beta-blockers may occur following ophthalmic use of metipranolol. If ophthalmic agents are needed for the treatment of glaucoma during pregnancy, the minimum effective dose should be used in combination with punctal occlusion to decrease potential exposure to the fetus (Johnson 2001; Salim 2014; Samples 1988).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience blurred vision or watery eyes. Have patient report immediately to prescriber vision changes, eye pain, severe eye irritation, slow heartbeat, muscle weakness, shortness of breath, excessive weight gain, severe dizziness, passing out, or swelling of arms or legs (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
