General: Although ALPHAGAN® P ophthalmic solution had minimal effect on the blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease.
ALPHAGAN® P has not been studied in patients with hepatic or renal impairment; caution should be used in treating such patients. ALPHAGAN® P should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans. Patients prescribed IOP-lowering medication should be routinely monitored for IOP.
Information for Patients: As with other drugs in this class, ALPHAGAN® P ophthalmic solution 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.
Drug Interactions: Although specific drug interaction studies have not been conducted with ALPHAGAN® P, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered. Alpha-agonists, as a class, may reduce pulse and blood pressure. Caution in using concomitant drugs such as beta-blockers (ophthalmic and systemic), anti-hypertensives and/or cardiac glycosides is advised.
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 ALPHAGAN® P ophthalmic solution in humans can lead to resulting interference with the IOP lowering effect. No data on the level of circulating catecholamines after ALPHAGAN® P administration are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: No compound-related carcinogenic effects were observed in either mice or rats following a 21-month and 24-month study, respectively. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1.0 mg/kg/day in rats achieved 86 and 55 times, respectively, the plasma drug concentration estimated in humans treated with one drop of ALPHAGAN® P ophthalmic solution into both eyes 3 times per day.
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 dominant lethal assay.
Reproductive studies performed in rats with oral doses of 0.66 mg base/kg revealed no evidence of impaired fertility due to ALPHAGAN® P.
Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproductive studies performed in rats with oral doses of 0.66 mg base/kg revealed no evidence of harm to the fetus due to ALPHAGAN® P ophthalmic solution. Dosing at this level produced an exposure that is 189 times higher than the exposure seen in humans following multiple ophthalmic doses.
There are no adequate and well-controlled studies in pregnant women. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. 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 this drugis excreted in human milk; in animal studies brimonidine tartrate was 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: In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse events 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 or older (>20kg), somnolence appears to occur less frequently (25%). Approximately 16% of patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence.
The safety and effectiveness of brimonidine tartrate ophthalmic solution have not been studied in pediatric patients below the age of 2 years. Brimonidine tartrate ophthalmic solution is not recommended for use in pediatric patients under the age of 2 years. (Also refer to Adverse Reactions section.)
Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.