WARNINGS

No information provided.

PRECAUTIONS

General

Although brimonidine tartrate had minimal effect on blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease.

Brimonidine tartrate has not been studied in patients with hepatic or renal impairment; caution should be used in treating such patients.

Brimonidine tartrate should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

During the studies there was a loss of effect in some patients. The IOP-lowering efficacy with brimonidine tartrate ophthalmic solution during the first month of therapy may not always reflect the long-term level of IOP reduction. Patients prescribed IOP-lowering medication should be routinely monitored for IOP.

Information for the Patient

The preservative in brimonidine tartrate, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after instilling brimonidine tartrate to insert soft contact lenses.

As with other drugs in this class, brimonidine tartrate may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No compound-related carcinogenic effects were observed in 21 month and 2 year studies in mice and rats given oral doses of 2.5 mg/kg/day (as the free base) and 1.0 mg/kg/day, respectively (~77 and 118 times, respectively, the human plasma drug concentration following the recommended ophthalmic dose).

Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, host-mediated assay, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, cytogenic studies in mice and dominant lethal assay.

Pregnancy

Teratogenic Effects, Pregnancy Category B: Reproduction studies performed in rats with oral doses of 0.66 mg base/kg revealed no evidence of impaired fertility or harm to the fetus due to brimonidine tartrate. Dosing at this level produced 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses. There are no studies of brimonidine tartrate in pregnant women, however in animal studies, brimonidine tartrate crossed the placenta and entered into the fetal circulation to a limited extent. Brimonidine tartrate 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. 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

Safety and effectiveness in pediatric patients has not been established.