Cosopt Pf

COSOPT® PF is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers (failed to achieve target IOP determined after multiple measurements over time). The IOP-lowering of COSOPT® administered twice a day was slightly less than that seen with the concomitant administration of 0.5% timolol administered twice a day and 2% dorzolamide administered three times a day

The dose is one drop of COSOPT PF in the affected eye(s) two times daily.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart

The solution from one individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be maintained after the individual unit is opened, the remaining contents should be discarded immediately after administration.

Solution containing 20 mg/mL dorzolamide (22.26 mg of dorzolamide hydrochloride) and 5 mg/mL timolol (6.83 mg timolol maleate).

Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity.

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

• Potentiation of Respiratory Reactions Including Asthma (
  
  
  
  5.1 Potentiation of Respiratory Reactions Including Asthma

  COSOPT PF contains timolol maleate, a beta-adrenergic blocking agent; and although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory 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)and Patient Counseling Information (17.1)].
  )
  
  
• 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, COSOPT PF should be discontinued

  [see Contraindications (4.2)and Patient Counseling Information (17.2)].
  )
  
  
• Sulfonamide Hypersensitivity (
  
  
  
  5.3 Sulfonamide Hypersensitivity

  COSOPT PF contains dorzolamide, a sulfonamide; and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of COSOPT PF. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation

  [see Contraindications (4.3)and Patient Counseling Information (17.3)].
  )
  
  
• Obstructive Pulmonary Disease (
  
  
  
  5.4 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 COSOPT PF is contraindicated) should, in general, not receive beta-blocking agents, including COSOPT PF

  [see Contraindications (4.1)and Patient Counseling Information (17.1)].
  )
  
  
• 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.
  )
  
  
• Renal and Hepatic Impairment (
  
  
  
  5.9 Renal and Hepatic Impairment

  Dorzolamide has not been studied in patients with severe renal impairment (CrCl <30 mL/min). Because dorzolamide and its metabolite are excreted predominantly by the kidney, COSOPT PF is not recommended in such patients.

  Dorzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.
  )
  
  
• Impairment of Beta-Adrenergically Mediated Reflexes During Surgery (
  
  
  
  5.10 Impairment of Beta-Adrenergically Mediated Reflexes During Surgery

  The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have experienced protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents.

  If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists.
  )