timolol/dorzolamide (Rx)

>10%

Dorzolamide

• Ocular burning, stinging, discomfort (33%)
• Bitter taste (25%)
• Superficial punctate keratitis (10-15%)
• Ocular allergic reactions (10%)

Frequency Not Defined

Dorzolamide

• Blurred vision
• Ocular dryness
• Photophobia
• Ocular redness
• Tearing
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Timolol

• Arrythmia
• Bradycardia
• Syncope
• Fatigue
• Headache
• Dyspnea
• Bronchospasm
• Chest pain
• Edema
• Paresthesia
• Nausea
• Rales
• Depression
• Decreased exercise tolerance
• Raynaud's phenomenon

Contraindications

Age <2 years

Hypersensitivity, asthma, severe COPD, sinus bradycardia, 2nd/3rd degree AV block (except in patients with artificial pacemaker), overt CHF, cardiogenic shock

Cautions

Dorzolamide (a sulfonamide) and, although administered topically, is absorbed systemically; same types of adverse reactions attributable to sulfonamides may occur with topical administration, including severe skin reactions

Bacterial keratitis associated with use of multiple-dose containers of topical ophthalmic products, inadvertently contaminated by patients who, in most cases, had concurrent corneal disease or disruption of ocular epithelial surface

Conjunctivitis reported with chronic administration (may resolve upon discontinuation of therapy)

Sympathetic stimulation may be essential for support of circulation in diminished myocardial contractility; its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure; in patients without history of cardiac failure continued depression of myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure; discontinue therapy at first sign or symptom of cardiac failure

Not for use as monotherapy in angle-closure glaucoma

Use caution in diabetes, heart failure, psychiatric disease (may cause or exacerbate CNS depression), peripheral vascular disease

Not for administration to 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 timiool is contraindicated)

Patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions; 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 Increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms reported

Beta-adrenergic receptor blocking agents may mask signs and symptoms of acute hypoglycemia; administer 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 blocking agents may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism; manage carefully patients suspected of developing thyrotoxicosis to avoid abrupt withdrawal of beta-adrenergic blocking agents that might precipitate thyroid storm

Not studied in patients with severe renal impairment (CrCl <30 mL/min); not recommended; dorzolamide and its metabolite are excreted predominantly by kidney

Use with caution in hepatic impairment; not studed

Patients receiving beta-adrenergic receptor blocking agents have experienced protracted severe hypotension during anesthesia; difficulty in restarting and maintaining heartbeat has also reported; gradual withdrawal of beta-adrenergic receptor blocking agents recommended; the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists if necessary

There is increased potential for developing corneal edema in patients with low endothelial cell counts; use caution

Avoid concomitant administration with systemic beta-blockers or carbonic anhydrase inhibitors

Use caution in patients taking calcium channel blockers, cardiac glycosides, or inhaled anesthetic agents

Pregnancy Category: C

Lactation: Excreted in breast milk; not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Dorzolamide: Sulfonamide and carbonic anhydrase inhibitor; inhibition of carbonic anhydrase in ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport

Timolol: Nonselective beta-adrenergic receptor blocker; reduces IOP by reducing production of aqueous humor