Bimatoprost/Brimonidine/Timolol

LUMIGAN 0.01% contains: Active: Bimatoprost 0.1 mg/mL. Preservative: Benzalkonium chloride 0.2 mg/mL.

LUMIGAN 0.01% (bimatoprost ophthalmic solution) is a synthetic prostaglandin analog with ocular hypotensive activity. Its chemical name is (Z)-7[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3-hydroxy- 5-phenyl-1-pentenyl]cyclopentyl]-5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C₂₅H₃₇NO₄.

Bimatoprost is a powder, which is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water. LUMIGAN 0.01% is a clear, isotonic, colorless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

Excipients/Inactive Ingredients: Sodium chloride, dibasic sodium phosphate, citric acid, and purified water. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8-7.8.

Brimonidine is a drug used to treat glaucoma. It acts via decreasing aqueous humor synthesis. [Wikipedia] A topical gel formulation, marketed under the name Mirvaso, was FDA approved on August 2013 for the treatment of rosacea.

Each mL of Timolol 0.5% contains 5 mg of timolol (6.8 mg of timolol maleate). It also contains the following inactive ingredients: Gellan gum, tromethamine, mannitol and water for injection. Benzododecinium bromide 0.012% is added as preservative.

Preservative-free Timolol contains the previously mentioned active and inactive ingredients except for the preservative benzododecinium bromide.

Timolol maleate is a β-adrenergic receptor blocking agent. It is (S)-1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol (Z)-2-butenedioate (1:1) (salt). Timolol maleate possesses an asymmetric carbon atom and is provided as the levo isomer. The empirical formula is C₁₃H₂₄N₄0₃S·C₄H₄0₄.

Timolol maleate has a molecular weight of 432.50. It is a white, odourless, crystalline powder which is soluble in water, methanol and alcohol.

Gellan solution contains a highly purified anionic heteropolysaccharide derived from gellan gum. Aqueous solutions of gellan gum form a clear transparent gel in the presence of cations. The concentration of sodium cations in tears is ideally suited to cause gelation of the material when topically instilled in the conjunctival sac.

LUMIGAN 0.01% (bimatoprost ophthalmic solution) is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

Brimonidine Tartrate Ophthalmic Solution is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of Brimonidine Tartrate Ophthalmic Solution diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored.

Hypertension

Timolol (timolol) is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Myocardial Infarction

Timolol (timolol) is indicated in patients who have survived the acute phase of myocardial infarction, and are clinically stable, to reduce cardiovascular mortality and the risk of reinfarction.

Migraine

Timolol (timolol) is indicated for the prophylaxis of migraine headache.

Bimatoprost ophthalmic (eye) drop is used to treat certain diseases of the eye like open-angle glaucoma and ocular (eye) hypertension which occurs in many people as they grow older. Glaucoma is caused by high pressure in your eye and can lead to pain from pressure in your eye and then can eventually harm your vision. bimatoprost can help you keep your sight by reducing the pressure in your eye and stopping eye pain.

Bimatoprost ophthalmic (eye) solution is also used to treat eyelash hypotrichosis (not enough eyelashes) by increasing their growth and making the eyelashes longer, thicker, and darker.

bimatoprost is available only with your doctor's prescription.

Brimonidine ophthalmic (eye) drops is used alone or together with other medicines to treat increased pressure in the eye that is caused by open-angle glaucoma or a condition called hypertension of the eye (ocular hypertension). brimonidine is an alpha-adrenergic agonist.

brimonidine is available only with your doctor's prescription.

Timolol is used alone or together with other medicines (such as hydrochlorothiazide) to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

Timolol is also used after an acute heart attack to decrease its severity and prevent another heart attack. It may also be used to help prevent migraine headaches.

timolol is a beta-blocker. It works by affecting the response to nerve impulses in certain parts of the body, like the heart. As a result, the heart beats slower and decreases the blood pressure. When the blood pressure is lowered, the amount of blood and oxygen is increased to the heart.

timolol is available only with your doctor's prescription.

The recommended dosage is one drop in the affected eye(s) once daily in the evening.

Bimatoprost Ophthalmic Solution, 0.03% should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect.

Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

Bimatoprost Ophthalmic Solution, 0.03% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

The recommended dose is one drop of Brimonidine® (brimonidine tartrate ophthalmic solution), 0.15% in the affected eye(s) three-times daily, approximately 8 hours apart.

Brimonidine® (brimonidine tartrate ophthalmic solution), 0.15% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic product is being used, the products should be administered at least 5 minutes apart.

How supplied

Dosage Forms And Strengths

Brimonidine tartrate ophthalmic solution, 1.5 mg/mL.

Storage And Handling

Brimonidine® (brimonidine tartrate ophthalmic solution), 0.15% is supplied sterile in opaque white LDPE plastic bottles and natural tips with purple polypropylene caps as follows:

5 mL in 8 mL bottle NDC 61314-144-05

10 mL in 10 mL bottle NDC 61314-144-10

15 mL in 15 mL bottle NDC 61314-144-15

Storage

Store at 15° - 25° C (59° - 77°F).

Manufactured by: Alcon Laboratories, Inc. Fort Worth, Texas 76134. Revised: n/a

Hypertension

The usual initial dosage of Timolol (timolol) is 10 mg twice a day, whether used alone or added to diuretic therapy. Dosage may be increased or decreased depending on heart rate and blood pressure response. The usual total maintenance dosage is 20-40 mg per day. Increases in dosage to a maximum of 60 mg per day divided into two doses may be necessary. There should be an interval of at least seven days between increases in dosages.

Timolol (timolol) may be used with a thiazide diuretic or with other antihypertensive agents. Patients should be observed carefully during initiation of such concomitant therapy.

Myocardial Infarction

The recommended dosage for long-term prophylactic use in patients who have survived the acute phase of a myocardial infarction is 10 mg given twice daily.

Migraine

The usual initial dosage of Timolol (timolol) is 10 mg twice a day. During maintenance therapy the 20 mg daily dosage may be administered as a single dose. Total daily dosage may be increased to a maximum of 30 mg, given in divided doses, or decreased to 10 mg once per day, depending on clinical response and tolerability. If a satisfactory response is not obtained after 6-8 weeks use of the maximum daily dosage, therapy with Timolol (timolol) should be discontinued.

How supplied

No. 3343 — Tablets Timolol (timolol), 5 mg, are light blue, round, compressed tablets, with code MSD 59 on one side and Timolol (timolol) on the other. They are supplied as follows:

NDC 0006-0059-68 bottles of 100.

No. 3344 — Tablets Timolol (timolol), 10 mg, are light blue, round, scored, compressed tablets, with code MSD 136 on one side and Timolol (timolol) on the other. They are supplied as follows:

NDC 0006-0136-68 bottles of 100

No. 3371 — Tablets Timolol (timolol), 20 mg, are light blue, capsule shaped, scored, compressed tablets, with code MSD 437 on one side and Timolol (timolol) on the other. They are supplied as follows:

NDC 0006-0437-68 bottles of 100

Storage

Store at controlled room temperature, 15-30°C (59-86°F). Keep container tightly closed. Protect from light.

MERCK AND CO., INC., Whitehouse Station, NJ 08889, USA. Issued April 2001. FDA Rev date: 2/25/2003

See also:
What is the most important information I should know about Bimatoprost?

LUMIGAN 0.01% is contraindicated in patients with clinically significant hypersensitivity to bimatoprost or to any of the excipients.

See also:
What is the most important information I should know about Brimonidine?

Do not use brimonidine ophthalmic if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days.

Before using brimonidine ophthalmic, tell your doctor if you have kidney or liver disease, heart disease, high blood pressure, circulation problems such as Raynaud's or Buerger's disease, or a history of fainting or low blood pressure.

Do not use this medication 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 brimonidine before putting your contact lenses in.

Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

See also:
What is the most important information I should know about Timolol?

Do not stop taking timolol without first talking to your doctor. Stopping suddenly may make your condition worse.

If you need to have any type of surgery, you may need to temporarily stop using timolol. Be sure the surgeon knows ahead of time that you are using timolol.

Timolol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid drinking alcohol, which could increase drowsiness and dizziness while you are taking timolol.

Timolol is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.

Hypertension often has no symptoms, so you may not even feel that you have high blood pressure. Continue using this medicine as directed, even if you feel well. You may need to use blood pressure medication for the rest of your life.

Use Bimatoprost as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Bimatoprost. Talk to your pharmacist if you have questions about this information.
• Use Bimatoprost once nightly unless your doctor tells you otherwise.
• Remove contact lenses before you use Bimatoprost; lenses may be placed back in the eyes 15 minutes after use of Bimatoprost.
• Wash your hands and face and remove any makeup before you use Bimatoprost.
• Place one drop of the medicine on the area of the applicator closest to the tip but not on the tip. Immediately draw the applicator carefully across the skin of the upper eyelid margin at the base of the eyelashes (where the eyelashes meet the skin) going from the inner part of your lash line to the outer part. Blot any excess solution beyond the eyelid margin. Throw the applicator away after one use. Repeat this process for the opposite upper eyelid margin using a new sterile applicator. Do not apply Bimatoprost to the lower eyelash line.
• To prevent germs from contaminating your medicine, do not touch the applicator tip or the tip of the bottle to any surface, including the fingers. Do not reuse applicators and do not use any other brush/applicator to apply Bimatoprost.
• Hair may also grow in other areas where Bimatoprost comes in repeated contact with skin surfaces. It is important to apply it as directed.
• Use Bimatoprost at least 5 minutes apart from any other medicine that you put in your eye.
• If you miss a dose of Bimatoprost, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Bimatoprost.

Use brimonidine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• To use brimonidine in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.
• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.
• More than 1 eye medicine may be used to lower eye pressure. If you use other medicines in your eye, wait at least 5 minutes between using brimonidine and your other eye medicines.
• If your medicine comes with a special cap, follow the directions on how to use this properly.
• If brimonidine changes color or becomes cloudy, do not use it. Do not use brimonidine after the expiration date on the bottle.
• Contact your health care provider at once if you feel you have used too much of brimonidine.
• If you miss a dose of brimonidine, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use brimonidine.

Use Timolol as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Timolol. Talk to your pharmacist if you have questions about this information.
• Timolol is only for the eye. Do not get it in your nose or mouth.
• Soft contact lenses may absorb a chemical contained in some brands of Timolol. Remove contact lenses before you use Timolol; lenses may be placed back in the eyes 15 minutes after use of Timolol.
• To use Timolol in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.
• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.
• Use Timolol at least 10 minutes before or after any other medicine that you put in your eye.
• Using Timolol at the same time each day will help you remember to use it.
• Continue to use Timolol even if you feel well. Do not miss any doses.
• If you miss a dose of Timolol, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Timolol.

This medication is used to treat patients with not enough or inadequate eyelashes. Bimatoprost makes the eyelashes more noticeable by causing more eyelashes to grow and making them longer, thicker, and darker. Bimatoprost is similar to a natural chemical in the body (prostaglandin).

Bimatoprost is also used to treat glaucoma. If you are already using or are directed to use bimatoprost to treat glaucoma, be careful not to get this eyelash medication into your eyes. Getting extra bimatoprost in your eyes may make it less effective for treating glaucoma. Talk to your doctor or pharmacist for more details.

How to use Bimatoprost

Read the Patient Information Leaflet provided by your pharmacist before you start using bimatoprost and each time you get a refill. Learn how to properly apply this medication. If you have any questions, consult your doctor or pharmacist.

Use this medication once daily in the evening or as directed by your doctor.

To apply this medication, first wash your hands and face. Remove any makeup and contact lenses. Contact lenses may be reinserted 15 minutes after applying this medication. Place one drop of this medication onto the provided applicator. Then right away draw the applicator carefully across the skin of the upper eyelid margin at the bottom of the eyelashes going from the inner part of your lash line to the outer part. Blot any excess solution that is applied beyond the eyelid margin. Throw away the applicator after applying the medication. Repeat with a new applicator for the other upper eyelid. This medication is not for use on the lower eyelids.

If any medication gets into the eye, do not rinse your eye. It is not likely to cause any harm if this medication gets into the eye, because it is the same medication that is used in the eyes to treat glaucoma.

To avoid contamination, do not touch the dropper tip or let it touch your eyelashes or any other surface. Do not rinse the dropper. Replace the dropper cap after each use, and keep the cap tightly closed.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each evening. Do not use more of this medication than recommended. Using more will not make this medication work faster. It may take up to 2 months before the full benefits of using this medication are seen.

When this medication is stopped, expect the appearance of the eyelashes to return to the way they looked before starting treatment with bimatoprost.

It is possible that the effects between your two sets of eyelashes may not be the same. There may be differences in eyelash length, thickness, fullness, color, number or direction of growth. If any of these occur, talk to your doctor.

Brimonidine is used for the treatment of open angle glaucoma or ocular hypertension (increased pressure inside the eye).

Use: Labeled Indications

Hypertension: Management of hypertension. Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2017]).

Migraine prophylaxis: Prophylaxis of migraine

Myocardial infarction (secondary prevention): To reduce mortality following MI

Off Label Uses

Atrial fibrillation (rate-control)

Data from a randomized, placebo-controlled trial in patients with atrial fibrillation (AF) associated with a rapid ventricular response while receiving digoxin supports the use of oral timolol in patients with chronic AF.

Based on the 2014 AHA/ACC/HRS guideline for the management of patients with AF, the use of beta-blockers for ventricular rate control in patients with paroxysmal, persistent, or permanent AF is effective and recommended for this condition.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain glaucoma eye drops (such as bimatoprost, latanoprost, travoprost).

This is not a complete list of possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

See also:
What other drugs will affect Brimonidine?

Anti-hypertensives / Cardiac Glycosides

Alpha-2 agonists, as a class, may reduce blood pressure. Caution in using drugs such as beta-blockers (ophthalmic and systemic), anti-hypertensives and/or cardiac glycosides is advised.

CNS Depressants

Although specific drug interaction studies have not been conducted with Brimonidine® (brimonidine tartrate ophthalmic solution), 0.15%, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.

Tricyclic Antidepressants

Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with Brimonidine® (brimonidine tartrate ophthalmic solution), 0.15% in humans can lead to resulting interference with its IOP-lowering effect. Caution, however, is advised in patients taking tricyclic antidepressants, which can affect the metabolism and uptake of circulating amines.

Monoamine Oxidase Inhibitors

Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

See also:
What other drugs will affect Timolol?

Beta-adrenergic blocking agents: Patients who are receiving a beta-adrenergic blocking agent orally and Timolol GFS should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. Patients should not usually receive two topical ophthalmic beta-adrenergic blocking agents concurrently.

Calcium antagonists: Caution should be used in the co-administration of beta-adrenergic blocking agents, such as Timolol GFS, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, or hypotension. In patients with impaired cardiac function, co-administration should be avoided.

ENDOCRINE

Masked symptoms of hypoglycemia in diabetic patients. SPECIAL SENSES

Signs and symptoms of ocular irritation including blepharitis, keratitis, and dry eyes; ptosis; decreased corneal sensitivity; cystoid macular edema; visual disturbances including refractive changes and diplopia; pseudopemphigoid; tinnitus and choroidal detachment following filtration surgery.

UROGENITAL

Retroperitoneal fibrosis, decreased libido, impotence and Peyronieís disease.

The following additional adverse effects 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, vomiting, 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 neuropsychometric tests; Respiratory: Rales, bronchial obstruction; Urogenital: Urination difficulties.

See also:
What are the possible side effects of Bimatoprost?

Applies to bimatoprost ophthalmic: ophthalmic solution

In addition to its needed effects, some unwanted effects may be caused by bimatoprost ophthalmic. In the event that any of these side effects do occur, they may require medical attention.

Major Side Effects

You should check with your doctor immediately if any of these side effects occur when taking bimatoprost ophthalmic:

Less common:

• Blindness
• bloody eye
• blurred or decreased vision
• change in color vision
• color changes in the skin around the eyes
• difficulty seeing at night
• disturbed color perception
• double vision
• dry eyes
• eye color changes
• fever or chills
• halos around lights
• lack or loss of strength
• loss of vision
• night blindness
• overbright appearance of lights
• redness, burning, dry, or itching eyes
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• tunnel vision

Minor Side Effects

Some of the side effects that can occur with bimatoprost ophthalmic may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Body aches or pain
• cough
• difficulty with breathing
• ear congestion
• headache
• loss of voice
• nasal congestion
• redness of the white part of eyes or inside of the eyelids
• runny nose
• sneezing
• sore throat
• unusual tiredness or weakness

• Darkening of the eyelashes
• eye discharge or excessive tearing
• eye strain
• feeling of having something in the eye
• increase in hair growth
• increased sensitivity of the eyes to sunlight

See also:
What are the possible side effects of Brimonidine?

Clinical Studies Experience

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

Adverse reactions occurring in approximately 10-20%of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Adverse reactions occurring in approximately 5-9% included: burning sensation, conjunctival folliculosis, hypertension, ocular allergic reaction, oral dryness, and visual disturbance.

Adverse reactions occurring in approximately 1-4% of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: abnormal taste, allergic reaction, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, fatigue, flu syndrome, follicular conjunctivitis, foreign body sensation, gastrointestinal disorder, headache, hypercholesterolemia, hypotension, infection (primarily colds and respiratory infections), insomnia, keratitis, lid disorder, pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis, somnolence, stinging, superficial punctate keratopathy, tearing, visual field defect, vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity.

The following reactions were reported in less than 1% of subjects: corneal erosion, hordeolum, nasal dryness, and taste perversion.

Postmarketing Experience

The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination of these factors, include: bradycardia, depression, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin reactions (including erythema, eyelid pruritus, rash, and vasodilation), syncope, and tachycardia. Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions.

See also:
What are the possible side effects of Timolol?

Timolol (timolol) is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.

In a multicenter (12-week) clinical trial comparing timolol maleate and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to timolol maleate:

These data are representative of the incidence of adverse effects that may be observed in properly selected patients treated with Timolol (timolol), i.e., excluding patients with bronchospastic disease, congestive heart failure or other contraindications to beta blocker therapy.

In patients with migraine the incidence of bradycardia was 5 percent.

In a coronary artery disease population studied in the Norwegian multi-center trial, the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the timolol and placebo groups were

The following additional adverse effects have been reported in clinical experience with the drug: Body as a Whole: anaphylaxis, extremity pain, decreased exercise tolerance, weight loss, fever; Cardiovascular: cardiac arrest, cardiac failure, cerebral vascular accident, worsening of angina pectoris, worsening of arterial insufficiency, Raynaud's phenomenon, palpitations, vasodilatation; Digestive: gastrointestinal pain, hepatomegaly, vomiting, diarrhea, dyspepsia; Hematologic: nonthrombocytopenic purpura; Endocrine: hyperglycemia, hypoglycemia; Skin: rash, skin irritation, increased pigmentation, sweating, alopecia; Musculoskeletal: arthralgia; Nervous System: local weakness, increase in signs and symptoms of myasthenia gravis; Psychiatric: depression, nightmares, somnolence, insomnia, nervousness, diminished concentration, hallucinations; Respiratory: cough; Special Senses: visual disturbances, diplopia, ptosis, dry eyes; Urogenital: impotence, urination difficulties.

There have been reports of retroperitoneal fibrosis in patients receiving timolol maleate and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.

Potential Adverse Effects: In addition, a variety of adverse effects not observed in clinical trials with Timolol (timolol), but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of Timolol (timolol) : Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics; Cardiovascular: Intensification of AV block; Digestive: Mesenteric arterial thrombosis, ischemic colitis; Hematologic: Agranulocytosis, thrombocytopenic purpura; Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Miscellaneous: Peyronie's disease.

There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with Timolol (timolol).

Clinical Laboratory Test Findings: Clinically important changes in standard laboratory parameters were rarely associated with the administration of Timolol (timolol). Slight increases in blood urea nitrogen, serum potassium, uric acid, and triglycerides, and slight decreases in hemoglobin, hematocrit and HDL cholesterol occurred, but were not progressive or associated with clinical manifestations. Increases in liver function tests have been reported.