Echothiophate is an ophthalmic cholinesterase-inhibitor miotic agent. It is used in adults to decrease intraocular pressure. Echothiophate is also indicated for use in pediatric patients to diagnose and treat concomitant esotropias with a significant accommodative component. The drug is contraindicated for use in patients with active uveal inflammation, angle-closure glaucoma without iridectomy, or a hypersensitivity to the active or inactive ingredients.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-For topical application to the eye only.
-Instruct patient on proper instillation of eye suspension.
-Instruct patient to apply pressure to the inner corner of the eye for 1 to 2 minutes after instillation of the drops to help minimize drainage into the nose and throat, remove excess solution around the eyes with a tissue, and wash hands after use.
Extemporaneous Compounding-Ophthalmic
Compounding of Phospholine Iodide:
-Use aseptic technique.
-Tear off aluminum seals. Remove and discard rubber plugs from both drug and diluent containers.
-Pour diluent into the drug container.
-Unwrap and remove dropper. Holding the dropper by the screw cap, insert it into the drug container and screw down tightly without compressing the rubber bulb.
-Shake for several seconds to mix the solution.
Upon administration of echothiophate, ocular irritation and ocular pain (reported as stinging and burning), lacrimation, lid muscle twitching, conjunctival and ciliary redness, headache/browache, myopia with blurred vision, and paradoxical increase in intraocular pressure may occur. In the event of paradoxical ocular hypertension, the administration of a sympathomimetic mydriatic, such as phenylephrine, can be considered. There have been reports of lens opacities (cataracts) occurring in patients treated for glaucoma. Prolonged use may cause conjunctival thickening and obstruction of nasolacrimal canals.
Systemic effects may occur, especially following prolonged administration of echothiophate. Temporarily discontinue use if any of the following occur: cardiac irregularities, diarrhea, excessive sweating (hyperhidrosis), myasthenia, respiratory depression, or urinary incontinence.
There have been a few case reports of retinal detachment during the use of echothiophate ophthalmic solution in adult patients without a previous history of the disorder. The manufacturer states that the relationship, if any, of retinal detachment to the administration of echothiophate ophthalmic solution has not been established.
The activation of latent iritis or uveitis may occur with the use of echothiophate ophthalmic solution. Iris cysts may form and more frequently occur in children. The cysts usually shrink upon reducing the strength of the drops, reducing the frequency of administration, or discontinuing treatment. Rarely, they may rupture or break free into the aqueous, and, if treatment is continued, the cysts may enlarge and obscure vision.
There is a possibility of additive systemic effects in echothiophate recipients who are exposed to carbamate or organophosphate-type pesticides or insecticides (i.e., gardeners, farmers, or workers in plants manufacturing such products). During periods of prolonged exposure to such pesticides, instruct patients to wear respiratory masks and to frequently washing and change clothing.
Echothiophate is contraindicated for use in most patients with closed-angle glaucoma without iridectomy, because its action on the ciliary muscles can worsen blockage of aqueous humor outflow and increase intraocular pressure.
Due to the possibility of retinal detachment, echothiophate should be used with caution in patients with a history of retinal detachment, especially those with aphakia.
Use of echothiophate in patients with acute uveitis or other conditions that contraindicate pupillary constriction is contraindicated. The use of echothiophate may activate latent iritis or uveitis, aggravating the inflammatory process or predisposing the patient to posterior synechiae, respectively.
Administer echothiophate with caution in patients with hypotension, bradycardia, and acute myocardial infarction as treatment can increase vagal tone and worsen these conditions. The vagotonic effects of echothiophate may worsen cardiac disease and increase the risk of cardiac arrhythmias. Discontinue treatment if cardiac irregularities occur.
Treatment with echothiophate may precipitate an acute asthmatic attack in patients with asthma.
Contact lenses should be removed before treatment. If echothiophate drops are applied to the eyes when soft contact lenses are in place, the lenses can deteriorate or absorb the drug. It also is possible that hard contact lenses can cause corneal abrasion or roughening of the corneal surface. Corneal abrasion can increase systemic absorption, possibly causing toxicity.
The use of echothiophate prior to ocular surgery should be done with great caution due to the risk of hyphema.
Administer echothiophate with caution in patients whose conditions may be aggravated by the vagotonic effects, including GI obstruction, Parkinson's disease, peptic ulcer disease, seizure disorder, urinary tract obstruction, and vagotonia.
The use of echothiophate during pregnancy has not been evaluated. It is unknown if the drug can cause fetal harm or affect reproductive capacity. Administer echothiophate during pregnancy only if clearly needed.
It is not known whether echothiophate is excreted in human milk. Although the extent of absorption is unclear, chronic use of echothiophate ophthalmic solution may have systemic effects which indicates some degree of absorption occurs. According to the manufacturer, because many drugs are excreted in human milk, and because of the potential for serious adverse reactions from echothiophate, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. To minimize the amount of drug that reaches systemic circulation and breast milk, apply pressure over the tear duct by the corner of the eye for 1 minute after each topical application. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
For the treatment of increased intraocular pressure:
NOTE: Use is contraindicated in most cases of angle-closure glaucoma without iridectomy and in patients with active uveal inflammation.
Ophthalmic dosage:
Adults: 1 drop instilled in the eye(s) twice daily, in the morning and at bedtime, is the preferred regimen; however, a change in therapy is indicated if the tension fails to remain at an acceptable level while on this regimen. May consider reducing the dose to 1 drop per day or every other day if needed.
For the diagnosis and treatment of strabismus of the accommodative esotropia type:
-for diagnosis of accommodative strabismus:
Ophthalmic dosage:
Children and Adolescents: Instill 1 drop into both eyes once daily at bedtime for 2 for 3 weeks.
-for the treatment of accommodative strabismus:
Ophthalmic dosage:
Children and Adolescents: Initiate treatment using the lowest frequency that will give a satisfactory response. The maximum usual recommended dose is 1 drop daily, although more intensive therapy has been used for short periods. After the initial diagnostic period, the dose may be reduced to 1 drop every other day and gradually decreased as treatment progresses. Treatment may be continued for as long as the drug is tolerated. If tolerance develops, a rest period will restore the initial effect of the drug. If treatment is gradually withdrawn after 1 to 2 years and symptoms recur, surgery should be considered.
Maximum Dosage Limits:
-Adults
2 drops/day per affected eye.
-Geriatric
2 drops/day per affected eye.
-Adolescents
1 drop/day per affected eye.
-Children
1 drop/day per affected eye.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Echothiophate products.
Echothiophate is an indirect-acting parasympathomimetic agent. By interfering with the enzymatic destruction of acetylcholine, echothiophate potentiates the action of acetylcholine at cholinergic synapses. The pupil of the eye is constricted by contraction of the iris sphincter, producing miosis. Contraction of the ciliary muscle produces spasm of accommodation. In glaucoma, the intraocular pressure rises to an unacceptable level, producing pain and abnormal vision; if untreated, it can cause loss of sight. In open-angle glaucoma, echothiophate contracts the ciliary muscle and widens the trabecular meshwork, increasing the outflow of aqueous humor, which reduces intraocular pressure. In closed-angle glaucoma, echothiophate-induced miosis relieves the blockage of the trabecular meshwork by the peripheral iris, allowing the anterior chamber of aqueous humor to enter.
Echothiophate is administered topically to the eye. Echothiophate is protein-bound in blood and tissues and oxidized and hydrolyzed in tissues by phosphorylphosphatases. The drug is excreted almost entirely as metabolites in the urine.
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
A decrease in pressure occurs within 4 hours after application, with maximal effect achieved within 24 hours. Miosis occurs within an hour of application and peaks within 2 hours. Echothiophate penetrates into ocular tissue through the cornea, the amount varying according to a number of factors. Systemic absorption through the conjunctiva and lacrimal drainage system can produce parasympathomimetic effects. Following ophthalmic application of echothiophate, systemic anticholinesterase activity is detectable within a few minutes. Repeated administration will cause decreased cholinesterase concentrations in both plasma and erythrocytes in most patients. Application of finger pressure to the inner canthus for 1-2 minutes following instillation of the drops is important in reducing the amount of drug systemically absorbed.