Dorzolamide Hydrochloride / Timolol Maleate

Pronunciation: dor-ZOE-la-mide HYE-droe-KLOR-ide/TIM-oh-lol MAL-ee-ate
Class: Agent for glaucoma

Trade Names

Cosopt
- Solution, ophthalmic dorzolamide 2%/timolol 0.5%

Cosopt PF
- Solution, ophthalmic dorzolamide 2%/timolol 0.5%

Cosopt, Preservative Free (Canada)

Pharmacology

Dorzolamide

Inhibits carbonic anhydrase enzyme, reducing rate of aqueous humor formation, lowering IOP.

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Timolol

Reduces elevated and normal IOP via decreasing production of aqueous humor or increasing flow.

Indications and Usage

Reduction of IOP in patients with ocular hypertension or open-angle glaucoma who are insufficiently responsive to beta-blockers.

Contraindications

Bronchial asthma; history of bronchial asthma; severe COPD; sinus bradycardia; second- or third-degree AV block; overt cardiac failure; cardiogenic shock; hypersensitivity to any component of product.

Dosage and Administration

Adults and Children 2 y and older

Ophthalmic 1 drop in affected eye(s) twice daily.

General Advice

  • For ophthalmic use only.
  • If using other topical ophthalmic drugs, separate each medication by at least 5 min ( Cosopt PF ) or 10 min ( Cosopt ).

Storage/Stability

Cosopt

Store at 59° to 86°F. Protect from light.

Cosopt PF

Store at 68° to 77°F. Do not freeze. Store in the original pouch. After the pouch is opened, store the remaining containers in the foil pouch to protect from light. Discard any unused containers 15 days after first opening the pouch. Because sterility cannot be maintained after the individual unit is opened, the remaining contents should be discarded immediately after administration.

Drug Interactions

Beta-adrenergic blocking agents (eg, propranolol)

Potential additive effect on beta blockade. Monitor the clinical response.

Calcium antagonists (eg, diltiazem, verapamil)

Possible increased risk of AV conduction disturbances, left ventricular failure, and hypotension. Use with caution. Avoid coadministration in patients with impaired cardiac function.

Carbonic anhydrase inhibitors (eg, acetazolamide)

Potential additive effect on patients receiving an oral carbonic anhydrase inhibitor. Use with caution. Close clinical observation is warranted.

Catecholamine-depleting drugs (eg, reserpine)

Possible additive effect with timolol, producing hypotension and bradycardia, which may result in vertigo, syncope, and postural hypotension. Close clinical observation is warranted.

Cimetidine

The pharmacologic effects of timolol may be increased. Bradycardia and hypotension may occur. Close clinical monitoring is warranted. Ranitidine, nizatidine, and famotidine are potential alternatives for cimetidine.

Clonidine

Increased risk of rebound hypertension following clonidine withdrawal may be exacerbated. This has not been reported with concurrent ophthalmic timolol use. However, use with caution.

Digitalis glycosides (eg, digoxin)

With these agents, timolol has an additive effect in prolonging AV conduction. Use with caution. Close clinical and laboratory monitoring is warranted.

Epinephrine

The beta-adrenergic activity of epinephrine is blocked by timolol, while the alpha-adrenergic effects are unopposed. Patients may experience increased BP and bradycardia because of the unopposed alpha-adrenergic effects of epinephrine. In addition, epinephrine resistance may occur.

Flecainide

Pharmacological effects of flecainide and timolol may be increased. The risk of severe bradycardia and cardiac arrest may be increased. Clinical importance is not known. Use with caution and close clinical monitoring.

Insulin

The hypoglycemic effect of insulin may be prolonged. Unexpected effects (hypertension, bradycardia) may occur. Use with caution. Certain symptoms of hypoglycemia (palpitations) may be masked.

Quinazolines (eg, alfuzosin, prazosin)

The severity and duration of hypotension following the first dose of a quinazoline may be enhanced by timolol. Coadminister with caution. Consider starting with a small dose of quinazolines.

Quinidine

Systemic effect of timolol (eg, decreased heart rate) may be potentiated because of increased plasma levels. Use with caution. Close clinical and laboratory monitoring is warranted.

Salicylates (eg, aspirin)

Although not reported with ophthalmic use of dorzolamide, the risk of acid-base and electrolyte disturbances may be increased by coadministration of dorzolamide with high-dose salicylates. In addition, alkalinization of the urine because of dorzolamide may increase salicylate excretion. Use with caution.

SSRIs (eg, fluoxetine)

The systemic effects of timolol (eg, decreased heart rate, depression) may be potentiated. Close clinical monitoring is warranted.

Sympathomimetics (eg, albuterol)

Pharmacologic effects of sympathomimetics may be decreased by timolol. Untoward physiologic effects, characterized by bronchospasm, may occur. Avoid coadministration.

Theophyllines

The bronchodilating effect of theophyllines may be impaired by timolol. Avoid coadministration.

Adverse Reactions

Cardiovascular

Hypertension (1% to 5%); bradycardia, cardiac failure, cerebral vascular accident, chest pain, heart block, hypotension, MI (postmarketing).

CNS

Dizziness, headache (1% to 5%); depression, paresthesia (postmarketing).

Dermatologic

Photophobia, skin rashes, Stevens-Johnson syndrome, TEN (postmarketing).

EENT

Ocular burning and/or stinging (up to 30%); blurred vision, conjunctival hyperemia, eye itching, superficial punctate keratitis (5% to 15%); blepharitis, cloudy vision, conjunctival discharge, conjunctival edema, conjunctival follicles, conjunctival injection, conjunctivitis, corneal erosion, corneal staining, cortical lens opacity, dry eyes, eye debris, eye discharge, eye pain, eye tearing, eyelid edema, eyelid erythema, eyelid exudates, eyelid pain or discomfort, eyelid scales, foreign body sensation, glaucomatous cupping, lens nucleus coloration, lens opacity, nuclear lens opacity, post-subcapsular cataract, visual field defect, vitreous detachment (1% to 5%); choroidal detachment following filtration surgery, iridocyclitis, nasal congestion (postmarketing).

GI

Bitter, sour, or unusual taste (up to 30%); abdominal pain, dyspepsia, nausea (1% to 5%); diarrhea, dry mouth, vomiting (postmarketing).

Genitourinary

UTI (1% to 5%); urolithiasis (postmarketing).

Respiratory

Bronchitis, cough, pharyngitis, sinusitis, upper respiratory tract infection (1% to 5%); dyspnea, respiratory failure (postmarketing).

Miscellaneous

Back pain, influenza (1% to 5%).

Precautions

Monitor

Ensure that IOPs have been measured and documented in the patient's record.


Pregnancy

Category C .

Lactation

Dorzolamide

Undetermined.

Timolol

Excreted in breast milk.

Children

Safety and efficacy not established in pediatric patients younger than 2 y.

Hypersensitivity

Dorzolamide is a sulfonamide, and serious reactions may occur (eg, Stevens-Johnson syndrome, TEN, fulminant hepatic necrosis, agranulocytosis, aplastic anemia).

Renal Function

Not recommended in patients with severe renal impairment.

Hepatic Function

Use with caution.

Bacterial keratitis

Has been reported.

Beta-adrenergic effects

Severe respiratory reactions, including death caused by bronchospasm in patients with asthma, and rarely, death in association with cardiac failure, have been reported following timolol administration.

Cardiac failure

Inhibition of beta-adrenergic receptor blockade may precipitate more severe cardiac failure in patients with diminished myocardial contractility.

Corneal edema

May occur in patients with low endothelial cell counts; use with caution in these patients.

Diabetes mellitus

Use with caution; beta-adrenergic blocking agents may mask the signs and symptoms of acute hypoglycemia.

Major surgery

Some patients receiving beta-adrenergic receptor blocking agents have experienced protracted severe hypotension during surgery.

Obstructive pulmonary/Bronchospastic disease

In general, avoid use in patients with mild to moderate COPD or bronchospastic disease.

Ophthalmic effects

Conjunctivitis and lid reactions may occur with long-term use. Choroidal detachment has been reported after filtration procedures.

Muscle weakness

Has been reported or potentiated in patients with myasthenia gravis or myasthenic symptoms.

Thyroid effects

Beta-adrenergic blocking agents may mask certain signs of hyperthyroidism (eg, tachycardia); abrupt withdrawal of agent may precipitate thyroid storm.

Overdosage

Symptoms

Acidotic state, bradycardia, bronchospasm, cardiac arrest, dizziness, electrolyte imbalance, headache, possible CNS effects, shortness of breath.

Patient Information

  • Advise patients that the usual dose is 1 drop in the affected eye(s) twice daily.
  • Teach patients the proper technique for instilling eye drops: wash hands; do not allow dropper to touch eye. Tilt head back, look up; pull lower eyelid down; instill prescribed number of drops. Close eye for 1 to 2 min and apply gentle pressure to bridge of nose for 3 to 5 min. Do not rub eye.
  • Advise patients that if more than 1 topical ophthalmic drug is being used, administer the drugs at least 5 min ( Cosopt PF ) or 10 min ( Cosopt ) apart.
  • Inform patients that taste abnormalities (eg, bitter, sour, unusual taste) and burning or stinging of the eye are the most common adverse reactions. Inform patients to contact their health care provider if adverse reactions occur and are bothersome.
  • Advise patients who wear contact lenses to remove their lenses before instilling Cosopt and to wait at least 15 min after instilling the eye drop(s) before inserting their lenses.
  • Advise patients to contact their eye care physician if eye or eyelid inflammation is noted or if they injure their eye or are going to have surgery on their eye.
  • Remind patients that eye examinations and measurement of IOP will be necessary while using this medication and to be sure to keep appointments.

Copyright © 2009 Wolters Kluwer Health.

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