Ophthalmic:

>10%: Ocular: Burning, stinging

1% to 10%:

Cardiovascular: Hypertension

Central nervous system: Headache

Ocular: Blurred vision, cataract, conjunctival injection, itching, visual acuity decreased

Miscellaneous: Infection

Systemic:

1% to 10%:

Cardiovascular: Bradycardia

Central nervous system: Fatigue, dizziness

Respiratory: Dyspnea

Frequency not defined (reported with any dosage form):

Cardiovascular: Angina pectoris, arrhythmia, bradycardia, cardiac failure, cardiac arrest, cerebral vascular accident, cerebral ischemia, edema, hypotension, heart block, palpitation, Raynaud's phenomenon

Central nervous system: Anxiety, confusion, depression, disorientation, dizziness, hallucinations, insomnia, memory loss, nervousness, nightmares, somnolence

Dermatologic: Alopecia, angioedema, pseudopemphigoid, psoriasiform rash, psoriasis exacerbation, rash, urticaria

Endocrine & metabolic: Hypoglycemia masked, libido decreased

Gastrointestinal: Anorexia, diarrhea, dyspepsia, nausea, xerostomia

Genitourinary: Impotence, retoperitoneal fibrosis

Hematologic: Claudication

Neuromuscular & skeletal: Myasthenia gravis exacerbation, paresthesia

Ocular: Blepharitis, conjunctivitis, corneal sensitivity decreased, cystoid macular edema, diplopia, dry eyes, foreign body sensation, keratitis, ocular discharge, ocular pain, ptosis, refractive changes, tearing, visual disturbances

Otic: Tinnitus

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

Miscellaneous: Allergic reactions, cold hands/feet, Peyronie's disease, systemic lupus erythematosus

Albuterol (and other beta2 agonists): Effects may be blunted by nonspecific beta-blockers.

Alpha-blockers (prazosin, terazosin): Concurrent use of beta-blockers may increase risk of orthostasis.

AV conduction-slowing agents (digoxin): Effects may be additive with beta-blockers.

Clonidine: Hypertensive crisis after or during withdrawal of either agent (not reported with timolol ophthalmic solution)

CYP2D6 inhibitors: May increase the levels/effects of timolol. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole.

Epinephrine (including local anesthetics with epinephrine): Timolol may cause hypertension.

Glucagon: Timolol may blunt hyperglycemic action.

Insulin and oral hypoglycemics: May mask symptoms of hypoglycemia.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers.

Timoptic Occudose®: Store in the protective foil wrap and use within 1 month after opening foil package

Onset of action:

Hypotensive: Oral: 15-45 minutes

Peak effect: 0.5-2.5 hours

Intraocular pressure reduction: Ophthalmic: 30 minutes

Peak effect: 1-2 hours

Duration: ~4 hours; Ophthalmic: Intraocular: 24 hours

Protein binding: 60%

Metabolism: Extensively hepatic; extensive first-pass effect

Half-life elimination: 2-2.7 hours; prolonged with renal impairment

Excretion: Urine (15% to 20% as unchanged drug)

Ophthalmic:

Children and Adults:

Solution: Initial: Instill 1 drop (0.25% solution) twice daily; increase to 0.5% solution if response not adequate; decrease to 1 drop/day if controlled; do not exceed 1 drop twice daily of 0.5% solution

Gel-forming solution (Timoptic-XE®): Instill 1 drop (either 0.25% or 0.5% solution) once daily

Adults: Solution (Istalol®): Instill 1 drop (0.5% solution) once daily in the morning

Oral: Adults:

Hypertension: Initial: 10 mg twice daily, increase gradually every 7 days, usual dosage: 20-40 mg/day in 2 divided doses; maximum: 60 mg/day

Prevention of myocardial infarction: 10 mg twice daily initiated within 1-4 weeks after infarction

Migraine headache: Initial: 10 mg twice daily, increase to maximum of 30 mg/day

Ophthalmic: For ophthalmic use only. Apply prescribed amount as often as directed. Wash hands before using. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). Tilt head back and look upward. Gently pull down lower lid and put drop(s) inside lower eyelid at inner corner. Close eye and roll eyeball in all directions. Do not blink for ¹/2 minute. Apply gentle pressure to inner corner of eye for 30 seconds. Wipe away excess from skin around eye. Do not use any other eye preparation for at least 10 minutes. Do not share medication with anyone else. Temporary stinging or blurred vision may occur. If using Istalol™, remove contact lenses prior to administration. Lenses may be reinserted 15 minutes following administration. Immediately report any adverse cardiac or CNS effects (usually signifies overdose). Report persistent eye pain, redness, burning, watering, dryness, double vision, puffiness around eye, vision changes, other adverse eye response, worsening of condition or lack of improvement.

Myocardial Infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Unstable angina/non-ST-segment elevation MI: In the treatment of unstable angina/non-ST-segment elevation MI, a beta-blocker, with the first dose administered intravenously if there is ongoing chest pain, followed by oral administration, is recommended (in the absence of contraindications).

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA Class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

Note: Strength expressed as base.

Gel-forming solution, ophthalmic, as maleate: 0.25% (5 mL); 0.5% (2.5 mL, 5 mL)

Timoptic-XE®: 0.25% (2.5 mL [DSC], 5 mL); 0.5% (2.5 mL [DSC], 5 mL)

Solution, ophthalmic, as hemihydrate (Betimol®): 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]

Solution, ophthalmic, as maleate: 0.25% (5 mL, 10 mL, 15 mL); 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]

Istalol™: 0.5% (10 mL) [contains benzalkonium chloride and potassium sorbate]

Timoptic®: 0.25% (5 mL, 10 mL); 0.5% (5 mL, 10 mL) [contains benzalkonium chloride]

Solution, ophthalmic, as maleate [preservative free] (Timoptic® OcuDose®): 0.25% (0.2 mL); 0.5% (0.2 mL) [single use]

Tablet, as maleate (Blocadren®): 5 mg, 10 mg, 20 mg

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