Alphagan P

8.1        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.

8.3        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.

8.4        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. 

8.5        Geriatric Use

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

8.6        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.

5.1        Potentiation of Vascular Insufficiency

ALPHAGAN® P  may potentiate syndromes associated with vascular insufficiency. ALPHAGAN®  P  should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

5.2        Severe Cardiovascular Disease

Although brimonidine tartrate 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.

5.3        Contamination of Topical Ophthalmic Products After Use

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information (17)].