Simbrinza

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.

You may have other signs of allergic reaction that develop more slowly while using this medicine. Call your doctor if you have:

• sudden liver failure--nausea, vomiting, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes), confusion, rapid weight gain, (especially in your midsection);
• bone marrow suppression--sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing, pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Stop using this medicine and call your doctor at once if you have:

• blurred vision, tunnel vision, eye pain, or seeing halos around lights; or
• eye swelling, redness, severe discomfort, crusting or drainage (may be signs of infection).

Common side effects may include:

• blurred vision;
• mild itching, redness, or irritation of your eyes; or
• dry mouth, unpleasant taste.

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.

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Other drugs may interact with brimonidine and brinzolamide ophthalmic, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

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.

You may have other signs of allergic reaction that develop more slowly while using this medicine. Call your doctor if you have:

• sudden liver failure--nausea, vomiting, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes), confusion, rapid weight gain, (especially in your midsection);

• bone marrow suppression--sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing, pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Stop using this medicine and call your doctor at once if you have:

• blurred vision, tunnel vision, eye pain, or seeing halos around lights; or

• eye swelling, redness, severe discomfort, crusting or drainage (may be signs of infection).

Common side effects may include:

• blurred vision;

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

• dry mouth, unpleasant taste.

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.

In the U.S.

• Simbrinza

Available Dosage Forms:

• Suspension

Therapeutic Class: Ophthalmologic Agent

Pharmacologic Class: Brimonidine

Your eye doctor will tell you how much of this medicine to use and how often. Do not use more medicine or use it more often than your doctor tells you to.

If you normally wear soft contact lenses, remove them before you use this medicine. Wait at least 15 minutes before putting the contact lenses back in.

To use the eye drops:

• Wash your hands with soap and water.
• Shake the eye drops well just before each use.
• Lie down or tilt your head back. With your index finger, pull down the lower lid of your eye to form a pocket.
• Hold the dropper close to your eye with the other hand. Drop the correct number of drops into the pocket made between your lower lid and eyeball.
• Gently close your eyes. Place your index finger over the inner corner of your eye for 1 minute.
• If you think you did not get the drop of medicine into your eye properly, repeat the process with another drop.
• Do not rinse or wipe the dropper or allow it to touch anything, including your eye.
• Put the cap on the bottle right away.
• Wash your hands after using the eye drops to remove any medicine.
• Do not use this medicine if the solution changes color or becomes cloudy.
• Never touch the applicator tip to any surface, including the eye, and keep the container tightly closed. This will keep the medicine as germ-free as possible.

If your doctor ordered two different eye drops to be used together, wait at least 5 minutes between the times you apply the medicines. This will help to keep the second medicine from “washing out” the first one.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For ophthalmic dosage form (eye drops):
  • For glaucoma or hypertension of the eye:
    • Adults—Use one drop in the affected eye three times a day.
    • Children 2 years of age and older—Use and dose must be determined by your doctor.
    • Children younger than 2 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

You may also keep the medicine in the refrigerator. Do not freeze.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how Simbrinza affects you.
• Have your blood pressure checked often if you have heart disease.
• Have your eye pressure checked. Talk with your doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Tell your doctor if you have an eye infection, eye injury, or will be having eye surgery.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use Simbrinza as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• For the eye only.
• Shake well before use.
• Take out contact lenses before using this medicine. Lenses may be put back in 15 minutes after Simbrinza is given. Do not put contacts back in if your eyes are irritated or infected.
• Do not touch the container tip to the eye, lid, or other skin.
• Tilt your head back and drop drug into the eye.
• After use, keep your eyes closed. Put pressure on the inside corner of the eye. Do this for 1 to 2 minutes. This keeps the drug in your eye.
• If more than 1 drug is being used in the same eye, use each drug at least 5 minutes apart.
• Do not use if the solution is cloudier than usual, leaking, or has particles.
• Do not use if the liquid changes color.

What do I do if I miss a dose?

• Use a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not use 2 doses or extra doses.

Pregnancy

Pregnancy Category C: Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 60, and 120 times the recommended human ophthalmic dose) produced maternal toxicity at 6 mg/kg/day and a significant increase in the number of fetal variations, such as accessory skull bones, which was only slightly higher than the historic value at 1 and 6 mg/kg. In rats, statistically decreased body weights of fetuses from dams receiving oral doses of 18 mg/kg/day (180 times the recommended human ophthalmic dose) during gestation were proportional to the reduced maternal weight gain, with no statistically significant effects on organ or tissue development. Increases in unossified sternebrae, reduced ossification of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were not statistically significant. No treatment-related malformations were seen. Following oral administration of 14C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Developmental toxicity studies performed in rats with oral doses of 0.66 mg brimonidine base/kg revealed no evidence of harm to the fetus. Dosing at this level resulted in a plasma drug concentration approximately 100 times higher than that seen in humans at the recommended human ophthalmic dose. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent.

There are no adequate and well-controlled studies in pregnant women.  Simbrinza should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15 mg/kg/day (150 times the recommended human ophthalmic dose) were observed during lactation. No other effects were observed. However, following oral administration of 14C-brinzolamide to lactating rats, radioactivity was found in milk at concentrations below those in the blood and plasma. In animal studies, brimonidine was excreted in breast milk.

It is not known whether brinzolamide and brimonidine tartrate are excreted in human milk following topical ocular administration. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Simbrinza (brinzolamide/brimonidine tartrate ophthalmic suspension) 1%/0.2%, 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

The individual component, brinzolamide, has been studied in pediatric glaucoma patients 4 weeks to 5 years of age. The individual component, brimonidine tartrate, has been studied in pediatric patients 2 to 7 years old. Somnolence (50-83%) and decreased alertness was seen in patients 2 to 6 years old. Simbrinza ophthalmic suspension is contraindicated in children under the age of 2 years [see Contraindications (4.2)].

Geriatric Use

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

Brinzolamide caused urinary bladder tumors in female mice at oral doses of 10 mg/kg/day and in male rats at oral doses of 8 mg/kg/day in 2 year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to 2 years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity. These levels of exposure cannot be achieved with topical ophthalmic dosing in humans.

The following tests for mutagenic potential of brinzolamide were negative: (1) in vivo mouse micronucleus assay; (2) in vivo sister chromatid exchange assay; and (3) Ames E. coli test. The in vitro mouse lymphoma forward mutation assay was negative in the absence of activation, but positive in the presence of microsomal activation. In this assay, there was no consistent dose-response relationship to the increased mutation frequency and cytotoxicity likely contributed to the high mutation frequency. Carbonic anhydrase inhibitors, as a class, are not mutagenic and the weight of evidence supports that brinzolamide is consistent with the class. In reproduction studies of brinzolamide in rats, there were no adverse effects on the fertility or reproductive capacity of males or females at doses up to 18 mg/kg/day (180 times the recommended human ophthalmic dose). 

Brimonidine tartrate was not carcinogenic in either a 21-month mouse or 24-month rat study. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats resulted in plasma drug concentrations 80 and 120 times higher than the human plasma drug level at the recommended clinical dose, respectively. Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and cytogenic studies in mice, and a dominant lethal assay. In reproductive studies performed in rats with oral doses of 0.66 mg brimonidine base/kg (approximately 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses), fertility was not impaired.

Other drugs may interact with Simbrinza, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.