Cosopt

COSOPT (dorzolamide hydrochloride-timolol maleate ophthalmic solution) is the combination of a topical carbonic anhydrase inhibitor and a topical beta-adrenergic receptor blocking agent.

Dorzolamide hydrochloride is described chemically as: (4S-trans)-4-(ethylamino)-5,6-dihydro-6­methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide monohydrochloride. Dorzolamide hydrochloride is optically active. The specific rotation is:

[α] 25°Cm 405nm (C=1, water) = ~ -17°.

Its empirical formula is C10H16N2O4S3•HCl and its structural formula is:

Dorzolamide hydrochloride has a molecular weight of 360.91. It is a white to off-white, crystalline powder, which is soluble in water and slightly soluble in methanol and ethanol.

Timolol maleate is described chemically as: (-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5­thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt). Timolol maleate possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer. The optical rotation of timolol maleate is:

[α] 25°C 405 nm in 1N HCl (C = 5) = -12.2° (-11.7° to -12.5°).

Its molecular formula is C13H24N4O3S•C4H4O4 and its structural formula is:

Timolol maleate has a molecular weight of 432.50. It is a white, odorless, crystalline powder which is soluble in water, methanol, and alcohol. Timolol maleate is stable at room temperature.

COSOPT is supplied as a sterile, clear, colorless to nearly colorless, isotonic, buffered, slightly viscous, aqueous solution. The pH of the solution is approximately 5.65, and the osmolarity is 242­323 mOsM. Each mL of COSOPT contains 20 mg dorzolamide (22.26 mg of dorzolamide hydrochloride) and 5 mg timolol (6.83 mg timolol maleate). Inactive ingredients are sodium citrate, hydroxyethyl cellulose, sodium hydroxide, mannitol, and water for injection. Benzalkonium chloride 0.0075% is added as a preservative.

Dorzolamide ophthalmic reduces the amount of fluid in the eye, which decreases pressure inside the eye.

Timolol ophthalmic is a beta-blocker that also reduces pressure inside the eye.

Dorzolamide and timolol ophthalmic (for the eyes) is a combination medicine used to treat certain types of glaucoma and other causes of high pressure inside the eye.

Dorzolamide and timolol ophthalmic may also be used for purposes not listed in this medication guide.

You should not use this medication if you have a history of asthma, chronic obstructive pulmonary disease (COPD), or a serious heart condition such as "AV block," slow heartbeats, heart failure, or if you have recently had a heart attack.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling short of breath, confusion, muscle pain or weakness, fast or slow heart rate, wheezing, trouble breathing, chest pain, fainting, or seizure (convulsions).

In the U.S.

• Cosopt
• Cosopt Ocumeter
• Cosopt Ocumeter Plus
• Cosopt PF

Available Dosage Forms:

• Solution

Therapeutic Class: Antiglaucoma, Beta-Adrenergic Blocker/Carbonic Anhydrase Inhibitor Combination

Pharmacologic Class: Dorzolamide

Dorzolamide and timolol ophthalmic (eye) drops is used to treat increased pressure in the eye caused by open-angle glaucoma or a condition called hypertension of the eye. Both eye conditions are caused by high pressure in your eye and can lead to pain from pressure in your eye and then can eventually harm your vision. This medicine can help you keep your sight by reducing the pressure in your eye and stopping eye pain.

This medicine is available only with your doctor's prescription.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have your eye pressure and eyesight checked as you have been told by the doctor.
• Tell your doctor if you have an eye infection, eye injury, or will be having eye surgery.
• This medicine may hide the signs of low blood sugar. Talk with the doctor.
• If you have had a very bad allergic reaction, talk with your doctor. You may have a chance of an even worse reaction if you come into contact with what caused your allergy. If you use epinephrine to treat very bad allergic reactions, talk with your doctor. Epinephrine may not work as well while you are taking Cosopt.
• This medicine may make it harder to tell if you have signs of an overactive thyroid like fast heartbeat. If you have an overactive thyroid and stop taking this medicine all of a sudden, it may get worse and could be life-threatening. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Cosopt while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Asthma, COPD

Cosopt is contraindicated in patients with bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease [see Warnings and Precautions (5.1)].

Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock

Cosopt is contraindicated in patients with sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, and cardiogenic shock [see Warnings and Precautions (5.2)].

Hypersensitivity

Cosopt is contraindicated in patients who are hypersensitive to any component of this product [see Warnings and Precautions (5.3)].

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Cosopt was evaluated in 1035 patients with elevated intraocular pressure treated for open-angle glaucoma or ocular hypertension for up to 15 months. Approximately 5% of all patients discontinued therapy because of adverse reactions.

The most frequently reported adverse reactions occurring in up to 30% of patients were taste perversion (bitter, sour, or unusual taste) or ocular burning and/or stinging. The following adverse reactions were reported in 5 to 15% of patients: conjunctival hyperemia, blurred vision, superficial punctate keratitis or eye itching.

The following adverse reactions were reported in 1 to 5% of patients: abdominal pain, back pain, blepharitis, bronchitis, cloudy vision, conjunctival discharge, conjunctival edema, conjunctival follicles, conjunctival injection, conjunctivitis, corneal erosion, corneal staining, cortical lens opacity, cough, dizziness, dryness of eyes, dyspepsia, eye debris, eye discharge, eye pain, eye tearing, eyelid edema, eyelid erythema, eyelid exudate/scales, eyelid pain or discomfort, foreign body sensation, glaucomatous cupping, headache, hypertension, influenza, lens nucleus coloration, lens opacity, nausea, nuclear lens opacity, pharyngitis, post-subcapsular cataract, sinusitis, upper respiratory infection, urinary tract infection, visual field defect, vitreous detachment.

Other adverse reactions that have been reported with the individual components are listed below:

Dorzolamide 2%

Angioedema, asthenia/fatigue, bronchospasm, contact dermatitis, epistaxis, eyelid crusting, ocular discomfort, photophobia, signs and symptoms of ocular allergic reaction, transient myopia.

Timolol (ocular administration)

Body as a Whole: Asthenia/fatigue; Cardiovascular: Arrhythmia, syncope, cerebral ischemia, worsening of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud's phenomenon, and cold hands and feet; Digestive: Anorexia, abdominal pain; Immunologic: Systemic lupus erythematosus; Nervous System/ Psychiatric: Increase in signs and symptoms of myasthenia gravis, somnolence, insomnia, nightmares, behavioral changes and psychic disturbances including confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss; Skin: Alopecia, psoriasiform rash or exacerbation of psoriasis; Hypersensitivity: Signs and symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and localized and generalized rash; Respiratory: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease); Endocrine: Masked symptoms of hypoglycemia in diabetic patients; Special Senses: Ptosis, decreased corneal sensitivity, cystoid macular edema, visual disturbances including refractive changes and diplopia, pseudopemphigoid, and tinnitus; Urogenital: Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie's disease; Musculoskeletal: Myalgia.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Cosopt. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: bradycardia, cardiac failure, cerebral vascular accident, chest pain, choroidal detachment following filtration surgery, depression, diarrhea, dry mouth, dyspnea, heart block, hypotension, iridocyclitis, myocardial infarction, nasal congestion, Stevens-Johnson syndrome, toxic epidermal necrolysis, paresthesia, photophobia, respiratory failure, skin rashes, urolithiasis, and vomiting.

Timolol (oral administration)

The following additional adverse reactions have been reported in clinical experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ophthalmic timolol maleate: Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Body as a Whole: Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular: Worsening of arterial insufficiency, vasodilatation; Digestive: Gastrointestinal pain, hepatomegaly, mesenteric arterial thrombosis, ischemic colitis; Hematologic: Nonthrombocytopenic purpura; thrombocytopenic purpura, agranulocytosis; Endocrine: Hyperglycemia, hypoglycemia; Skin: Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal: Arthralgia; Nervous System/Psychiatric: Vertigo, local weakness, diminished concentration, reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics; Respiratory: Riles, bronchial obstruction; Urogenital: Urination difficulties.

Cosopt eye drops contain a combination of dorzolamide and timolol. Dorzolamide ophthalmic (for the eyes) reduces the amount of fluid in the eye, which decreases pressure inside the eye. Timolol ophthalmic is a beta-blocker that also reduces pressure inside the eye.

Cosopt is used to treat certain types of glaucoma and other causes of high pressure inside the eye.

Cosopt may also be used for purposes not listed in this medication guide.

Use Cosopt exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Do not use Cosopt while you are wearing contact lenses. This medication may contain a preservative that can be absorbed by soft contact lenses. Wait at least 15 minutes after using the eye drops before putting your contact lenses in.

Cosopt comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Wash your hands before using the eye drops.

To apply the eye drops:

• Tilt your head back slightly and pull down your lower eyelid to create a small pocket. Hold the dropper above the eye with the tip down. Look up and away from the dropper and squeeze out a drop.

• Close your eyes for 2 or 3 minutes with your head tipped down, without blinking or squinting. Gently press your finger to the inside corner of the eye for about 1 minute, to keep the liquid from draining into your tear duct.

• Use only the number of drops your doctor has prescribed. If you use more than one drop, wait about 5 minutes between drops.

• Wait at least 10 minutes before using any other eye drops your doctor has prescribed.

Do not touch the tip of the eye dropper or place it directly on your eye. A contaminated dropper can infect your eye, which could lead to serious vision problems.

Do not use the eye drops if the liquid has changed colors or has particles in it. Call your pharmacist for new medicine.

Tell your doctor right away if you have any eye injury or infection, or if you need to have any type of surgery, especially eye surgery. You may need to stop using Cosopt for a short time.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.