Alphagan P

An overdose of brimonidine ophthalmic is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• eye pain or increased watering; or

• severe swelling, redness, burning, or discomfort in or around your eye.

Common side effects may include:

• drowsiness, tired feeling;

• dry mouth, blurred vision;

• mild itching, redness, or irritation of your eyes; or

• mild stinging or burning when using the eye drops.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Using brimonidine ophthalmic with other drugs that make you sleepy or slow your breathing can increase these effects. Ask your doctor before using brimonidine ophthalmic with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with brimonidine ophthalmic, especially:

• digoxin, digitalis;

• an antidepressant--amitriptyline, bupropion, clomipramine, desipramine, doxepin, duloxetine, fluoxetine, imipramine, nortriptyline, paroxetine;

• an MAO inhibitor--isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, tranylcypromine; or

• heart or blood pressure medicine--amlodipine, diltiazem, methyldopa, nifedipine, quinidine, verapamil, and others.

This list is not complete. Other drugs may interact with brimonidine ophthalmic, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

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). This medicine is an alpha-adrenergic agonist.

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

The eye doctor will want to examine your or your child's eyes at regular visits to make sure the medicine is working properly and is not causing unwanted effects.

If itching, redness, swelling, or other signs of eye or eyelid irritation occur, stop using this medicine and check with your doctor. These symptoms may mean that you or your child are allergic to this medicine.

If you or your child have an eye injury or infection, or need to have eye surgery, talk with your doctor right away. You may need to change the medicine or stop using it.

This medicine may cause some people to become lightheaded, dizzy, drowsy, tired, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert.

This medicine may add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicines for allergies; sedatives or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Brimonidine may cause your eyes to become more sensitive to light than they are normally. Wearing sunglasses and avoiding too much exposure to bright light may help lessen the discomfort.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Blurred or loss of vision
• burning, dry, or itching eyes
• discharge or excessive tearing
• disturbed color perception
• double vision
• halos around lights
• headache
• itching of the eye
• night blindness
• overbright appearance of lights
• redness of the eye or inner lining of the eyelid
• swelling of the eyelid
• tearing of the eye
• tunnel vision

• Ache or pain in the eye
• blindness
• bloody eye
• blurred vision or other change in vision
• change in color vision
• confusion
• decreased vision
• difficult or labored breathing
• difficulty seeing at night
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drainage from the eye
• fainting
• fast heartbeat
• feeling of something in the eye
• gradual blurring or loss of vision
• increased blood pressure
• increased sensitivity of the eye to light
• mental depression
• muscle pain
• nausea or vomiting
• oozing in the eye
• redness, swelling, or itching of the eye or eyelid
• runny or stuffy nose
• seeing flashes or sparks of light
• seeing floating dark spots or material before eyes
• seeing floating spots before the eyes or a veil or curtain appearing across part of vision
• shortness of breath
• skin rash
• sneezing
• sweating
• swelling of the eye
• tightness in the chest
• unusual tiredness or weakness
• watery eyes
• wheezing

• Bluish lips or skin
• chest pain or discomfort
• confusion
• fast, pounding, or irregular heartbeat or pulse
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• irregular, fast, slow, or shallow breathing
• low body temperature
• muscle aches or weakness
• shivering
• slow or irregular heartbeat
• weak or feeble pulse
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Burning, stinging, or tearing of the eye
• drowsiness or tiredness
• dryness of the mouth

• Acid or sour stomach
• anxiety
• bad, unusual, or unpleasant (after) taste
• belching
• body aches or pain
• change in taste
• chills
• congestion
• cough
• cough producing mucus
• crusting on eyelid or corner of eye
• diarrhea
• difficulty breathing
• discoloration of white part of the eye
• dryness of the eye
• dryness or soreness of the throat
• fever
• general feeling of discomfort or illness
• hoarseness
• indigestion
• joint pain
• lack or loss of strength
• large amounts of cholesterol in the blood
• lid disorder
• loss of appetite
• muscle aches and pains
• pain or tenderness around the eyes and cheekbones
• paleness of the eye or inner lining of the eyelid
• passing of gas
• pounding heartbeat
• rash
• shivering
• sleepiness or unusual drowsiness
• sleeplessness
• sneezing
• sore throat
• stomach discomfort, fullness, upset, or pain
• tender, swollen glands in the neck
• trouble with sleeping
• trouble with swallowing
• troubled breathing
• unable to sleep
• voice changes

• Constricted, pinpoint, or small pupils (black part of the eye)
• redness of the skin
• sensitivity to light
• throbbing pain
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• unusual weak feeling
• unusually warm skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Neonates and Infants (under the age of 2 years)

ALPHAGAN® P is contraindicated in neonates and infants (under the age of 2 years).

Hypersensitivity Reactions

ALPHAGAN® P is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past.

Pregnancy

Pregnancy Category B: Teratogenicity studies have been performed in animals.

Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 through 18 in rabbits. The highest doses of brimonidine tartrate in rats (2.5 mg/kg/day) and rabbits (5.0 mg/kg/day) achieved AUC exposure values 360- and 20-fold higher, or 260- and 15-fold higher, respectively, than similar values estimated in humans treated with ALPHAGAN® P 0.1% or 0.15%, 1 drop in both eyes three times daily.

There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Because animal reproduction studies are not always predictive of human response, ALPHAGAN® P should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether brimonidine tartrate is excreted in human milk, although in animal studies, brimonidine tartrate has been shown to be excreted in breast milk. Because of the potential for serious adverse reactions from ALPHAGAN® P in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

ALPHAGAN® P is contraindicated in children under the age of 2 years (see CONTRAINDICATIONS, 4.1). During postmarketing surveillance, apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine. The safety and effectiveness of brimonidine tartrate have not been studied in children below the age of 2 years.

In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse reactions with brimonidine tartrate ophthalmic solution 0.2% dosed three times daily were somnolence (50-83% in patients ages 2 to 6 years) and decreased alertness. In pediatric patients 7 years of age (>20 kg), somnolence appears to occur less frequently (25%). Approximately 16% of patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Special Populations

ALPHAGAN® P has not been studied in patients with hepatic impairment.

ALPHAGAN® P has not been studied in patients with renal impairment. The effect of dialysis on brimonidine pharmacokinetics in patients with renal failure is not known.

Mechanism of Action

ALPHAGAN® P is a relatively selective alpha-2 adrenergic receptor agonist with a peak ocular hypotensive effect occurring at two hours post-dosing.

Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.

Pharmacokinetics

Absorption

After ocular administration of either a 0.1% or 0.2% solution, plasma concentrations peaked within 0.5 to 2.5 hours and declined with a systemic half-life of approximately 2 hours.

Distribution

The protein binding of brimonidine has not been studied.

Metabolism

In humans, brimonidine is extensively metabolized by the liver.

Excretion

Urinary excretion is the major route of elimination of brimonidine and its metabolites. Approximately 87% of an orally-administered radioactive dose of brimonidine was eliminated within 120 hours, with 74% found in the urine.

Summary of Use during Lactation

Limited information indicates that maternal use of brimonidine 0.2% ophthalmic drops do not adversely affect their nursing infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

Topical brimonidine gel used to treat rosacea has not been studied during breastfeeding. It is unlikely that the topical gel would affect the breastfed infant, but the manufacturer states that it should not be used during nursing. Until more data are available, an alternative topical agent might be preferred

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

A woman used brimonidine 0.2%, timolol gel-forming solution 0.5%, dipiverin 0.2%, and dorzolamide 0.5% drops for glaucoma while nursing a newborn. The frequency of medication use and extent of nursing were not stated. All medications were given immediately after nursing with punctal occlusion of the tear duct. The infant's vital signs were closely monitored with no signs of bradycardia or apnea.[1]

A woman was using ophthalmic drops containing 0.5% timolol and 0.2% brimonidine twice daily in the right eye for 6 months. During this time, she breastfed her infant (extent not stated) apparently without harm to her infant.[2]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Topical for Rosacea) Azeleic Acid, Metronidazole

References

1. Johnson SM, Martinez M, Freedman S. Management of glaucoma in pregnancy and lactation. Surv Ophthalmol. 2001;45:449-54. PMID: 11274697

2. Madadi P, Koren G, Freeman DJ et al. Timolol concentrations in breast milk of a woman treated for glaucoma: calculation of neonatal exposure. J Glaucoma. 2008;17:329-31. PMID: 18552619

Contraindications

Hypersensitivity to product or components

Children <2 years

Concurrent MAO inhibitors

Cautions

Wait 15 min before inserting soft contact lenses

Use caution in severe cardiovascular disease, cerebral insufficiency, depression, hepatic impairment, orthostatic hypotension, renal impairment, thromboangiitis obliterans

May cause CNS depression, which may impair mental abilities

Children are at higher risk of adverse effects

Bradycardia, hypotension (including orthostatic hypotension) and dizziness reported

Avoid applying topical gel to skin or open wounds

Some patients have experienced erythema involving areas of face that were previously not affected by erythema and in areas (e.g., neck and chest) outside of treatment sites

Some patients have experienced increased frequency of flushing and/or increased depth of erythema with flushing; some patients reported new onset of flushing

Some patients have experienced pallor or excessive whitening at or outside application site following therapy

Allergic contact dermatitis was reported for topical gel

Adverse events reported for topical gel include angioedema, throat tightening, tongue swelling, and urticarial; institute appropriate therapy and discontinue therapy, if clinically significant hypersensitivity reaction occurs