Chemical name: (2-mercaptoethyl) trimethylammonium iodide O,O-diethyl phosphorothioate

Structural formula

C₉H₂₃INO₃PS           M.W 383.23

Echothiophate iodide for ophthalmic solution occurs as a white, crystalline, water-soluble, hygroscopic solid having a slight mercaptan-like odor. When freeze-dried in the presence of potassium acetate, the mixture appears as a white amorphous deposit on the walls of the bottle.

Each package contains materials for dispensing 5 mL of eyedrops: (1) bottle containing sterile echothiophate iodide for ophthalmic solution in one of four potencies [1.5 mg (0.03%), 3 mg (0.06%), 6.25 mg (0.125%), or 12.5 mg (0.25%)] as indicated on the label, with 40 mg potassium acetate in each case. Sodium hydroxide or acetic acid may have been incorporated to adjust pH during manufacturing. (2) a 5 mL bottle of sterile diluent containing chlorobutanol (chloral derivative), 0.55%; mannitol, 1.2%; boric acid, 0.06%; and sodium phosphate, 0.026%. (3) sterilized dropper.

Last updated on RxList: 12/9/2008

Glaucoma

Chronic open-angle glaucoma. Subacute or chronic angle-closure glaucoma after iridectomy or where surgery is refused or contraindicated. Certain non-uveitic secondary types of glaucoma, especially glaucoma following cataract surgery.

Accommodative Esotropia

Concomitant esotropias with a significant accommodative component.

DIRECTIONS FOR PREPARING EYEDROPS

1. Use aseptic technique.
2. Tear off aluminum seals, and remove and discard rubber plugs from both drug and diluent containers.
3. Pour diluent into drug container.
4. Remove dropper assembly from its sterile wrapping. Holding dropper assembly by the screw cap and, WITHOUT COMPRESSING RUBBER BULB, insert into drug container and screw down tightly.
5. Shake for several seconds to ensure mixing.
6. Do not cover nor obliterate instructions to patient regarding storage of eyedrops.

Glaucoma

Selection of Therapy – The medication prescribed should be that which will control the intraocular pressure around-the-clock with the least risk of side effects or adverse reactions. "Tonometric glaucoma" (ocular hypertension without other evidence of the disease) is frequently not treated with any medication, and echothiophate iodide for ophthalmic solution is certainly not recommended for this condition. In early chronic simple glaucoma with field loss or disc changes, pilocarpine is generally used for initial therapy and can be recommended so long as control is thereby maintained over the 24 hours of the day.

When this is not the case, echothiophate iodide for ophthalmic solution 0.03% may be effective and probably has no greater potential for side effects. If this dosage is inadequate, epinephrine and a carbonic anhydrase inhibitor may be added to the regimen. When still more effective medication is required, the higher strengths of echothiophate iodide for ophthalmic solution may be prescribed with the recognition that the control of the intraocular pressure should have priority regardless of potential side effects. In secondary glaucoma following cataract surgery, the higher strengths of the drug are frequently needed and are ordinarily very well tolerated.

The dosage regimen prescribed should call for the lowest concentration that will control the intraocular pressure around-the-clock. Where tonometry around-the-clock is not feasible, it is suggested that appointments for tension-taking be made at different times of the day so that inadequate control may be more readily detected. Two doses a day are preferred to one in order to maintain as smooth a diurnal tension curve as possible, although a single dose per day or every other day has been used with satisfactory results. Because of the long duration of action of the drug, it is never necessary or desirable to exceed a schedule of twice a day. The daily dose or one of the two daily doses should always be instilled just before retiring to avoid inconvenience due to the miosis.

Early Chronic Simple Glaucoma – Echothiophate iodide for ophthalmic solution 0.03% instilled twice a day, just before retiring and in the morning, may be prescribed advantageously for cases of early chronic simple glaucoma that are not controlled around-the-clock with other less potent agents. Because of prolonged action, control during the night and early morning hours may then sometimes be obtained. A change in therapy is indicated if, at any time, the tension fails to remain at an acceptable level on this regimen.

Advanced Chronic Simple Glaucoma and Glaucoma Secondary to Cataract Surgery – These cases may respond satisfactorily to echothiophate iodide for ophthalmic solution 0.03% twice a day as above. When the patient is being transferred to echothiophate iodide for ophthalmic solution because of unsatisfactory control with pilocarpine, carbachol, epinephrine, etc., one of the higher strengths, 0.06%, 0.125%, or 0.25% will usually be needed. In this case, a brief trial with the 0.03% eyedrops will be advantageous in that the higher strengths will then be more easily tolerated.

Concomitant Therapy – Echothiophate iodide for ophthalmic solution may be used concomitantly with epinephrine, a carbonic anhydrase inhibitor, or both.

Technique – Good technique in the administration of echothiophate iodide for ophthalmic solution requires that finger pressure at the inner canthus should be exerted for a minute or two following instillation of the eyedrops, to minimize drainage into the nose and throat. Excess solution around the eye should be removed with tissue and any medication on the hands should be rinsed off.

Accommodative Esotropia (Pediatric Use)

In Diagnosis – One drop of 0.125% may be instilled once a day in both eyes on retiring, for a period of two or three weeks. If the esotropia is accommodative, a favorable response will usually be noted which may begin within a few hours.

In Treatment – Echothiophate iodide for ophthalmic solution is prescribed at the lowest concentration and frequency which gives satisfactory results. After the initial period of treatment for diagnostic purposes, the schedule may be reduced to 0.125% every other day or 0.06% every day. These dosages can often be gradually lowered as treatment progresses. The 0.03% strength has proven to be effective in some cases. The maximum usually recommended dosage is 0.125% once a day, although more intensive therapy has been used for short periods.

Technique – (See "DOSAGE AND ADMINISTRATION, Glaucoma.")

Duration of Treatment – In diagnosis, only a short period is required and little time will be lost in instituting other procedures if the esotropia proves to be unresponsive. In therapy, there is no definite limit so long as the drug is well tolerated. However, if the eyedrops, with or without eyeglasses, are gradually withdrawn after about a year or two and deviation recurs, surgery should be considered. As with other miotics, tolerance may occasionally develop after prolonged use. In such cases, a rest period will restore the original activity of the drug.

Each package contains sterile echothiophate iodide for ophthalmic solution, sterile diluent, and dropper for dispensing 5 mL eyedrops of the strength indicated on the label. Four potencies are available:

NDC 0046-1062-05....................................1.5 mg package for 0.03%

White amorphous deposit on bottle walls. Aluminum crimp seal is blue.

NDC 0046-1064-05...................................3 mg package for 0.06%

White amorphous deposit on bottle walls. Aluminum crimp seal is red.

NDC 0046-1065-05...................................6.25 mg package for 0.125%

White amorphous deposit on bottle walls. Aluminum crimp seal is green.

NDC 0046-1066-05...................................12.5 mg package for 0.25%

White amorphous deposit on bottle walls. Aluminum crimp seal is yellow.

Handling and Storage

Prior to reconstitution: Store under refrigeration (2° to 8° C).

After reconstitution: Store at room temperature (approximately 25° C). Do not refrigerate. Discard any unused solution after 4 weeks.

This product's label may have been updated. For current package insert and further product information, please visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. Manufactured for Wyeth Pharmaceuticals Inc. Philadelphia, PA 19101 by Chesapeake Biological Laboratories, Inc. Baltimore, MD 21230. FDA Rev date: 3/9/2006

Last updated on RxList: 12/9/2008

1. Although the relationship, if any, of retinal detachment to the administration of echothiophate iodide for ophthalmic solution has not been established, retinal detachment has been reported in a few cases during the use of echothiophate iodide for ophthalmic solution in adult patients without a previous history of this disorder.
2. Stinging, burning, lacrimation, lid muscle twitching, conjunctival and ciliary redness, browache, induced myopia with visual blurring may occur.
3. Activation of latent iritis or uveitis may occur.
4. Iris cysts may form, and if treatment is continued, may enlarge and obscure vision. This occurrence is more frequent in children. The cysts usually shrink upon discontinuance of the medication, reduction in strength of the drops or frequency of instillation. Rarely, they may rupture or break free into the aqueous. Regular examinations are advisable when the drug is being prescribed for the treatment of accommodative esotropia.
5. Prolonged use may cause conjunctival thickening, obstruction of nasolacrimal canals.
6. Lens opacities occurring in patients under treatment for glaucoma with echothiophate iodide for ophthalmic solution have been reported and similar changes have been produced experimentally in normal monkeys. Routine examinations should accompany clinical use of the drug.
7. Paradoxical increase in intraocular pressure may follow anticholinesterase instillation. This may be alleviated by prescribing a sympathomimetic mydriatic such as phenylephrine.
8. Cardiac irregularities.

Echothiophate iodide for ophthalmic solution potentiates other cholinesterase inhibitors such as succinylcholine or organophosphate and carbamate insecticides. Patients undergoing systemic anticholinesterase treatment should be warned of the possible additive effects of echothiophate iodide for ophthalmic solution.

Last updated on RxList: 12/9/2008

1. Succinylcholine should be administered only with great caution, if at all, prior to or during general anesthesia to patients receiving anticholinesterase medication because of possible respiratory or cardiovascular collapse.
2. Caution should be observed in treating glaucoma with echothiophate iodide for ophthalmic solution in patients who are at the same time undergoing treatment with systemic anticholinesterase medications for myasthenia gravis, because of possible adverse additive effects.

(See "PRECAUTIONS: DRUG INTERACTIONS" for further information.)

General

1. Gonioscopy is recommended prior to initiation of therapy. Routine examination to detect lens opacity should accompany clinical use of echothiophate iodide for ophthalmic solution.
2. Where there is a quiescent uveitis or a history of this condition, anticholinesterase therapy should be avoided or used cautiously because of the intense and persistent miosis and ciliary muscle contraction that may occur.
3. While systemic effects are infrequent, proper use of the drug requires digital compression of the nasolacrimal ducts for a minute or two following instillation to minimize drainage into the nasal chamber with its extensive absorption area. To prevent possible skin absorption, hands should be washed following instillation.
4. Temporary or permanent discontinuance of medication is necessary if cardiac irregularities occur.
5. Anticholinesterase drugs should be used with extreme caution, if at all, in patients with marked vagotonia, bronchial asthma, spastic gastrointestinal disturbances, peptic ulcer, pronounced bradycardia and hypotension, recent myocardial infarction, epilepsy, parkinsonism, and other disorders that may respond adversely to vagotonic effects.
6. Anticholinesterase drugs should be employed prior to ophthalmic surgery only as a considered risk because of the possible occurrence of hyphema.
7. Echothiophate iodide for ophthalmic solution should be used with great caution, if at all, where there is a prior history of retinal detachment.
8. Temporary discontinuance of medication is necessary if salivation, urinary incontinence, diarrhea, profuse sweating, muscle weakness, or respiratory difficulties occur.
9. Patients receiving echothiophate iodide for ophthalmic solution who are exposed to carbamate- or organophosphate-type insecticides and pesticides (professional gardeners, farmers, workers in plants manufacturing or formulating such products, etc.) should be warned of the additive systemic effects possible from absorption of the pesticide through the respiratory tract or skin. During periods of exposure to such pesticides, the wearing of respiratory masks, and frequent washing and clothing changes may be advisable.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No data is available regarding carcinogenesis, mutagenesis, and impairment of fertility.

Pregnancy

Teratogenic Effects – Pregnancy Category C

Animal reproduction studies have not been conducted with echothiophate iodide for ophthalmic solution. It is also not known whether echothiophate iodide for ophthalmic solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Echothiophate iodide for ophthalmic solution should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants from echothiophate iodide for ophthalmic solution, 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

Safety and effectiveness in pediatric patients have been established.

Geriatric Use

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

Last updated on RxList: 12/9/2008

No information provided.

1. Active uveal inflammation.
2. Most cases of angle-closure glaucoma, due to the possibility of increasing angle block.
3. Hypersensitivity to the active or inactive ingredients.

Last updated on RxList: 12/9/2008

Echothiophate iodide for ophthalmic solution is a long-acting cholinesterase inhibitor for topical use which enhances the effect of endogenously liberated acetylcholine in iris, ciliary muscle, and other parasympathetically innervated structures of the eye. It thereby causes miosis, increase in facility of outflow of aqueous humor, fall in intraocular pressure, and potentiation of accommodation.

Echothiophate iodide for ophthalmic solution will depress both plasma and erythrocyte cholinesterase levels in most patients after a few weeks of eyedrop therapy.

Last updated on RxList: 12/9/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 12/9/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ECHOTHIOPHATE SOLUTION - OPHTHALMIC

(eck-oh-THIGH-oh-fate)

COMMON BRAND NAME(S): Phospholine Iodide

USES: This medication is used alone or with other medications to treat certain types of glaucoma and other eye conditions (e.g., accommodative esotropia, synechial formation). It is also used to test for certain eye conditions (e.g., accommodative esotropia). It works by causing the pupil to shrink, decreasing the amount of fluid within the eye, and affecting certain eye muscles.

HOW TO USE: Follow all directions supplied by the manufacturer for mixing the eye drops.

To apply eye drops, wash your hands first. To avoid contamination, be careful not to touch the dropper to any surface or let it touch your eye.

If you are wearing contact lenses, remove them before using eye drops. Wait at least 15 minutes before replacing your contact lenses.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Let go of the eyelid and gently close your eyes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure for 1 to 2 minutes. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed or if your dose is for more than 1 drop.

Remove extra solution around the eye with a tissue, and wash your hands to remove any medicine that may be on them. Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 minutes before using the other medication. Use eye drops before ointments to allow the eye drops to enter the eye.

The dosage is based on your medical condition and response to therapy. Do not increase your dose or use more frequently than directed by your doctor. Doing so may increase the risk for serious side effects.

SIDE EFFECTS: Temporary irritation/burning/stinging of the eye, temporary blurred vision, eyelid muscle twitching, poor vision in dim light, headache, or brow ache may occur. If any of these effects persist or worsen, contact your doctor or pharmacist promptly. (See also Precautions section.)

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain, flushing, diarrhea, nausea, irregular heartbeat, stomach/abdominal pain or cramps, increased saliva, increased urination, unusual sweating, vision changes.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using echothiophate, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, epilepsy, other eye problems (e.g., iritis, uveitis, detached retina), heart disease (e.g., heart failure, recent heart attack), low or high blood pressure, myasthenia gravis, overactive thyroid (hyperthyroidism), Parkinsonism, stomach/intestinal problems (e.g., ulcers, spasms), certain urinary problems (e.g., blockage).

After you apply echothiophate, your vision may become temporarily blurred or unstable. Vision in dim light may be affected. Use caution while driving (especially at night), using machinery, or doing any activity that requires clear vision. Limit alcoholic beverages.

Avoid exposure to insecticides. Some types of insecticides may increase the risk of certain side effects. If you have contact with insecticides, wear a mask and/or gloves and wash or change clothing frequently. Consult your doctor or pharmacist for more information.

Before having surgery, tell your doctor or dentist that you are using this medication.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known if this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: other eye medications, certain drugs for myasthenia gravis (e.g., pyridostigmine, neostigmine), succinylcholine.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: increased saliva, irregular/slow heartbeat, nausea, diarrhea, increased sweating.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you are prescribed this medication on a once- or twice-daily schedule and miss a dose, apply it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Ask your doctor ahead of time what you should do if you miss a dose while using this medication on another schedule besides a daily one.

STORAGE: Store the unmixed product in the refrigerator at 36-46 degrees F (2-8 degrees C) away from light and moisture. The mixed solution may be stored at room temperature about 77 degrees F (25 degrees C) for up to 4 weeks. Do not freeze. Do not store in the bathroom. Discard the mixed solution if it changes color, becomes cloudy, or develops particles. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.