Alphagan/Alphagan P 0.1% Adverse Reactions

Alphagan: Adverse events occurring in approximately 10-30% of the subjects, in descending order of incidence, included oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions and ocular pruritus.
Events occurring in approximately 3-9% of the subjects, in descending order included corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision and muscular pain.
The following adverse reactions were reported in less than 3% of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, conjunctival papillae, depression, hypertension, anxiety, palpitations, nasal dryness and syncope.
Postmarketing Experience: Brimonidine Ophthalmic Solution 0.2%: The following adverse reactions have been identified during postmarketing use of ALPHAGAN 0.2% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
Eye disorders: Iritis, iridocyclitis (anterior uveitis), miosis, conjunctivitis, eyelids pruritus.
Immune system disorders: Hypersensitivity, skin reaction (including erythema, face edema, pruritus, rash, and vasodilatation).
Cardiac disorders: Palpitations/arrhythmias (including bradycardia or tachycardia).
Vascular disorders: Hypotension, syncope.
Carcinogenesis, mutagenesis, 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).
ALPHAGAN was not mutagenic or cytogenic in a series of in vitro and in vivo stdies including the Ames test, host-mediated assay, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, cytogenic studies in mice and dominant lethal assay.
Alphagan P 0.1%: Adverse events occurring in approximately 10-20% of the subjects included: allergic conjunctivitis and conjunctival hyperemia.
Adverse events occurring in approximately 5-9% of the subjects included: conjunctival folliculosis.
Events occurring in approximately 1-4% of subjects included: somnolence, oral dryness, asthenia, burning sensation in the eye, foreign body sensation, ocular pruritus/eye pruritus, erythema eyelid, eye pain (ocular ache/pain), ocular dryness/eye dryness, follicular conjunctivitis, superficial punctate keratitis and conjunctivitis.
Postmarketing Experience: Brimonidine Ophthalmic Solution 0.1%: The following adverse reactions have been identified during postmarketing use of ALPHAGAN P 0.1% in clinical practice.
Eye disorders: Lacrimation increased, blurred vision.
Nervous system disorders: Dizziness, headache.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: Carcinogenesis and Mutagenesis Studies: No compound-related carcinogenic effects were observed in either mice or rats following a 21-month and 24-month study, respectively. 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 118 times, respectively, the plasma drug concentration estimated in humans treated with one drop of ALPHAGAN P into both eyes 3 times per day.
Brimonidine tartrate was not mutagenic or clastogenic 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 assay, and dominant lethal assay.
Fertility Studies: No impairment of fertility and reproduction occurred in male rats when treated for 70 days prior to mating and female rats when treated for 14 days prior to mating and continuing through gestation and lactation with oral doses of brimonidine tartrate. The highest dose (0.66 mg base/kg/day) produced 244 times the plasma drug concentration seen in humans treated multiple times with 1 drop of brimonidine tartrate ophthalmic solution 0.2% into each eye twice a day. Although no blood drug levels were determined in this study, it is estimated that the highest dose of brimonidine tartrate (0.66 mg base/kg/day), achieved AUC values 60 times those seen in humans treated with 1 drop of brimonidine tartrate ophthalmic solution 0.15% in both eyes 3 times per day. These reproduction and fertility studies in rats with brimonidine tartrate demonstrated no adverse effect on male or female fertility at doses which achieve up to approximately 477 and 302 times the systemic exposure following the maximum recommended human ophthalmic dose of ALPHAGAN P 0.1% or 0.15%, respectively.