Brimonidine Tartrate/timolol Maleate Ophthalmic Solution

Brimonidine Tartrate/Timolol Maleate Ophthalmic Solution 0.2%/0.5% is an alpha-adrenergic receptor agonist with a beta-adrenergic receptor inhibitor indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy due to inadequately controlled IOP; the IOP-lowering of brimonidine tartrate/timolol maleate ophthalmic solution dosed twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol maleate ophthalmic solution dosed twice a day and 0.2% brimonidine tartrate ophthalmic solution dosed three times per day.

The recommended dose is one drop of brimonidine tartrate/timolol maleate ophthalmic solution in the affected eye(s) twice daily approximately 12 hours apart. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

Solution containing 2 mg/mL brimonidine tartrate and 5 mg/mL timolol (6.8 mg/mL timolol maleate).

Not for use in children below the age of 2 years. Use with caution in children ≥ 2 years of age. (

• Potential for Severe Respiratory or Cardiac Reactions (
  5.1 Potential for Severe Respiratory or Cardiac Reactions

  Brimonidine tartrate/timolol maleate ophthalmic solution contains timolol maleate; and although administered topically can be absorbed systemically. Therefore, the same types of 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 systemic or ophthalmic administration of timolol maleate

  [ see Contraindications (4.1)]

  . Additionally, ophthalmic beta-blockers may impair compensatory tachycardia and increase risk of hypotension.
  )
• Cardiac Failure (
  5.2 Cardiac Failure

  Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure.

  In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, brimonidine tartrate/timolol maleate ophthalmic solution should be discontinued

  [ see Contraindications (4.2)]

  .
  )
• Obstructive Pulmonary Disease (
  5.3 Obstructive Pulmonary Disease

  Patients with chronic obstructive pulmonary disease (e.g., chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma, in which brimonidine tartrate/timolol maleate ophthalmic solution is contraindicated

  [see Contraindications (4.1)]

  ) should, in general, not receive beta-blocking agents, including brimonidine tartrate/timolol maleate ophthalmic solution.
  )
• Potentiation of Vascular Insufficiency (
  5.4 Potentiation of Vascular Insufficiency

  Brimonidine tartrate/timolol maleate ophthalmic solution may potentiate syndromes associated with vascular insufficiency. Brimonidine tartrate/timolol maleate ophthalmic solution should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.
  )
• Increased Reactivity to Allergens (
  5.5 Increased Reactivity to Allergens

  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.
  )
• Potentiation of Muscle Weakness (
  5.6 Potentiation of 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.
  )
• Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus (
  5.7 Masking of Hypoglycemic Symptoms in Patients with Diabetes Mellitus

  Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.
  )
• Masking of Thyrotoxicosis (
  5.8 Masking of Thyrotoxicosis

  Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate a thyroid storm.
  )
• Ocular Hypersensitivity (
  5.9 Ocular Hypersensitivity

  Ocular hypersensitivity reactions have been reported with brimonidine tartrate ophthalmic solutions 0.2%, with some reported to be associated with an increase in intraocular pressure

  [ see Contraindications (4.4)].
  )