Latanoprost: Ocular pigment changes: Latanoprost has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris and periorbital tissue (eyelid) and increased pigmentation and growth of eyelashes. These changes may be permanent. Pigmentation is expected to increase as long as latanoprost is administered. After discontinuation of latanoprost, pigmentation of the iris is likely to be permanent while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The effects of increased pigmentation beyond 5 years are not known.
Latanoprost sterile ophthalmic solution may gradually change eye color, increasing the amount of brown pigment in the iris by increasing the number of melanosomes (pigment granules) in melanocytes. The long-term effects on the melanocytes and the consequences of potential injury to the melanocytes or deposition of pigment granules to other areas of the eye are currently unknown. The change in iris color occurs slowly and may not be noticeable for several months to years. Patients should be informed of the possibility of iris color change.
Eyelid skin darkening has also been reported in association with the use of latanoprost.
Latanoprost may gradually change eyelashes and vellus hair; these changes include increased length, thickness, pigmentation, and number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation treatment.
Patients who are expected to receive treatment in only 1 eye should be informed about the potential for increased brown pigmentation of the iris, periorbital tissue, and eyelashes in the treated eye and thus, heterochromia between the eyes. They should also be advised of the potential for a disparity between the eyes in length, thickness, or number of eyelashes. These changes in pigmentation and lash growth may be permanent.
Other forms of glaucoma: There is limited experience with latanoprost in the treatment of angle closure, inflammatory or neovascular glaucoma.
Infections: There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These container has been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.
Contact lenses: Contact lenses should be removed prior to the administration of latanoprost, and may be reinserted 15 minutes after administration.
Active intraocular inflammation (iris/uveitis): Latanoprost should be used with caution in patients with a history of intraocular inflammation (iris/uveitis) and should generally not be used in patients with active intraocular inflammation.
Macular edema, including cystoid macular edema: Macular edema, including cystoid macular edema, has been reported during treatment with latanoprost. These reports have mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Latanoprost should be used with caution in patients who do not have an intact posterior capsule or who have known risk factors for macular edema.
Timolol: Systemic absorption: It may be absorbed systemically. The same adverse reactions found with systemic β-blockers may occur with topical use. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in asthmatics, and rarely, death associated with cardiac failure, have been reported with topical β-blockers.
Cardiovascular: Timolol may decrease resting and maximal exercise heart rate even in healthy subjects.
Non-allergic bronchospasm: Patients with a history of chronic bronchitis, emphysema, etc, should receive β-blockers with caution; they may block bronchodilation produced by catecholamine stimulation of β2-receptors.
Major surgery: Withdrawing β-blockers before major surgery is controversial. Beta-receptor blockade impairs the heart's ability to respond to β-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia. Some patients on β-blockers have had protracted severe hypotension during anesthesia. Difficulty restarting and maintaining heartbeat has been reported. In elective surgery, gradual withdrawal of β-blockers may be appropriate.
Diabetes mellitus: Administer with caution to patients subject to spontaneous hypoglycemia or to diabetic patients (especially labile diabetics). Beta-blocking agents may mask signs and symptoms of acute hypoglycemia.
Thyroid: Beta-adrenergic blocking agents may mask clinical signs of hyperthyroidism (eg. tachycardia). Manage patients suspected of developing thyrotoxicosis carefully to avoid abrupt withdrawal of β-blockers, which might precipitate thyroid storm.
Cerebrovascular insufficiency: Because of potential effects of β-blockers on blood pressure and pulse, use with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow develop, consider alternative therapy.
Angle-closure glaucoma: The immediate objective is to reopen the angle, requiring constriction of the pupil with a miotic. These agents have little or no effect on the pupil. When they are used to reduce elevated IOP in angle-closure glaucoma, use with miotic.
Muscle weakness: Beta-blockade may potentiate muscle weakness consistent with certain myasthenic symptoms (eg. diplopia, ptosis, generalized weakness). Timolol has increased muscle weakness in some patients with myasthenic symptoms or myasthenia gravis.
Long-term therapy: In long-term studies (2 and 3 years), no significant difference in mean IOP were observed after initial stabilization.
Effects on ability to drive and use machine: Instillation of eye drops may cause transient blurring of vision. Until this has resolved, patients should not drive or use machine.
Use in Children: Safety and efficacy in children have not been established.
Use in Elderly: Latanoprost: No overall differences in safety or efficacy have been observed between geriatric and younger patients. Results from phase III clinical studies indicate that age does not appear to affect IOP response to latanoprost.
Timolol: Safety and efficacy were similar in patients 65 years of age or older compared with younger patients, however, the possibility that some older patients may exhibit increased sensitivity to the preparation cannot be ruled out.