Professional Drug Information > Indometacin

Anti-inflammatory Drugs, Nonsteroidal (Ophthalmic)

This monograph includes information on the following:

1) Diclofenac
2) Flurbiprofen
3) Indomethacin  ^*
4) Suprofen  ^†


INN:
Indomethacin—Indometacin

VA CLASSIFICATION
Diclofenac
Primary: OP302
Secondary: OP900

Flurbiprofen
Primary: OP302
Secondary: OP900

Indomethacin
Primary: OP302
Secondary: OP900

Suprofen
Primary: OP900


Commonly used brand name(s): Indocid³; Ocufen²; Profenal⁴; Voltaren Ophtha¹; Voltaren Ophthalmic¹.

Another commonly used name for — indomethacin ^*
is indometacin .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

^*Not commercially available in the U.S.

^†Not commercially available in Canada.

Category:


Prostaglandin synthesis inhibitor, ophthalmic—Diclofenac; Flurbiprofen; Indomethacin; Suprofen;  ^†

Anti-inflammatory, nonsteroidal, ophthalmic—Diclofenac; Flurbiprofen; Indomethacin;

Miosis inhibitor, in ophthalmic surgery—Diclofenac; Flurbiprofen; Indomethacin; Suprofen;  ^†

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Inflammation, ocular (treatment)—Diclofenac is indicated to reduce postoperative inflammation following cataract surgery. ^{{01} {44} {56}} [Diclofenac is also indicated in the treatment of conjunctivitis, keratoconjunctivitis, corneal ulcers, and posttraumatic inflammation of the cornea and conjunctiva, provided that these conditions are not associated with an ocular infection.] ^{{44} {57}} [Flurbiprofen] and indomethacin¹ are indicated to reduce inflammation of the anterior segment of the eye following ocular surgery or laser trabeculoplasty. ^{{03} {07} {08} {09} {10} {22} {43}} However, flurbiprofen and indomethacin have produced inconsistent results in clinical studies ^{46} and may not produce clinically significant reductions in postprocedure inflammation. ^{45} In one study, these nonsteroidal anti-inflammatory drugs (NSAIDs) reduced conjunctival injection, but not the anterior chamber reaction, following argon laser trabeculoplasty. ^{08}
—Ophthalmic NSAIDs may be administered concurrently with an ophthalmic corticosteroid, if necessary. ^{{44} {46}} There is some evidence of a synergistic or additive effect when the two types of medication are used together. ^{{22} {46}}

Miosis, during ophthalmic surgery (prophylaxis)—[Diclofenac], flurbiprofen, ^{55} indomethacin, and suprofen ^{60} are indicated to inhibit intraoperative miosis, which may occur in response to surgical trauma ^{{02} {03} {06} {20} {23} {34} {44}} despite preoperative establishment of mydriasis. These NSAIDs may facilitate cataract extraction and lens implantation. ^{{11} {12} {13} {14} {15}} However, published clinical studies have shown small and variable effects on pupil size, ^{46} and some investigators have reported flurbiprofen to be ineffective. ^{{14} {16} {46}} Also, studies demonstrating that ophthalmic NSAIDs produce clinically significant inhibition of miosis in surgical procedures other than cataract surgery have not been published. ^{45}
—Use of ophthalmic NSAIDs to inhibit miosis during surgery does not eliminate the need for mydriatic agents prior to and during surgery. ^{46}

Edema, cystoid macular, following cataract surgery (prophylaxis and treatment)—[Diclofenac] and indomethacin are indicated to reduce the occurrence and severity of cystoid macular edema following cataract surgery. ^{{04} {05} {17} {34} {44} {59}} These agents are usually used concurrently with an ophthalmic corticosteroid; clinical studies indicate that concurrent use of both types of medication provides a synergistic effect. ^{46}
—There is insufficient evidence to determine whether flurbiprofen or suprofen is effective in reducing cystoid macular edema following cataract surgery. ^{45}

Photophobia, following incisional refractive surgery (treatment)^{56}—Diclofenac is indicated for the treatment of photophobia in patients who have undergone incisional refractive surgery. ^{56}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—


Anti-inflammatory drug, nonsteroidal (NSAID):
    Indoleacetic acid derivative—Indomethacin.
    Phenylacetic acid derivative—Diclofenac.
    Propionic acid derivatives—Flurbiprofen, suprofen.

Molecular weight—
    Diclofenac sodium: 318.13 ^{19}
    Flurbiprofen sodium: 302.28
    Indomethacin: 357.79
    Suprofen: 260.31

Mechanism of action/Effect:

Ophthalmic NSAIDs inhibit the activity of the enzyme cyclo-oxygenase in ocular tissues, resulting in decreased formation of precursors of prostaglandins from arachidonic acid ^{{01} {02} {03} {06}} and subsequent inhibition of prostaglandin synthesis. ^{{01} {02} {03} {04} {05} {06}} These medications do not inhibit the actions of prostaglandins. ^{20} Studies in animals have shown that trauma ^{{04} {05} {20}} to the anterior segment of the eye, especially the iris, ^{20} increases endogenous prostaglandin synthesis; ^{{04} {05} {20}} that endogenous prostaglandins produce constriction of the iris sphincter ^{{04} {05} {11} {15} {20} {25}} independently of cholinergic mechanisms; ^{{02} {06}} and that endogenous prostaglandins may contribute to the development of intraocular inflammation ^{{01} {02} {03} {06} {07} {08}} by causing disruption of the blood–aqueous humor barrier, vasodilatation, increased vascular permeability, and leukocytosis. ^{{01} {02} {03} {04} {05} {06} {07} {08}} It is proposed that inhibition of prostaglandin synthesis in ocular tissues by ophthalmic NSAIDs decreases these effects, thereby reducing the severity of intraoperative miosis, ^{{02} {03} {06}} signs and symptoms of postoperative inflammation, ^{01} and postoperative cystoid macular edema (which may occur, independently of inflammation, because of prostaglandin-induced alterations in vascular permeability). ^{21} Diclofenac and indomethacin have been shown to stabilize, or speed postoperative re-establishment of, the blood–aqueous humor barrier. ^{{01} {04} {24}} However, the clinical consequences (benefit or harm) of this action in the treatment of postoperative inflammation have not been determined. ^{01} Also, studies of flurbiprofen's or indomethacin's efficacy in reducing ocular inflammation following ophthalmic procedures have produced conflicting results. ^{{07} {08} {22} {23}} It is proposed that the anti-inflammatory activity of these medications may be limited, possibly because they do not inhibit the formation or activity of mediators of inflammation in the eye other than prostaglandins. ^{{07} {08}}


Other actions/effects:

Clinical studies indicate that perioperative use of ophthalmic NSAIDs does not significantly affect intraocular pressure. ^{{01} {02} {03} {06} {07} {08}}

Ophthalmic NSAIDs may increase the risk of bleeding in ocular tissues following ophthalmic procedures; ^{{01} {02} {06}} postoperative bleeding, including hyphema, has been documented with flurbiprofen. ^{02}

Studies in animals have shown that ophthalmic flurbiprofen may delay wound healing following certain types of surgery. ^{{02} {03} {26}} Diclofenac also may slow or delay healing postoperatively. ^{01} However, ophthalmic suprofen did not delay wound healing in a study in animals. ^{27}

The anti-inflammatory activity of ophthalmic NSAIDs may mask the onset and/or progression of ocular infections. ^{03}

Absorption:

Diclofenac—Studies suggest that limited, if any, systemic absorption occurs ^{01} after a single application of up to 16 drops of a 0.1% solution ^{44}.

Flurbiprofen—Flurbiprofen penetrates the cornea; significant systemic absorption may occur. ^{{02} {11}} In one study, 74% of the quantity of flurbiprofen applied to the conjunctiva appeared in the systemic circulation. ^{48}

Indomethacin—The medication has not been detected in serum after ophthalmic administration. ^{04} However, the possibility of significant systemic absorption must be considered, because a bronchospastic reaction has been reported in one asthmatic patient following ophthalmic administration of the medication. ^{28}

Suprofen—No data regarding the extent of systemic absorption following ophthalmic application are available. ^{06}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to aspirin or other systemically administered nonsteroidal anti-inflammatory drugs (NSAIDs) may be sensitive to ophthalmic NSAIDs also. ^{{01} {02} {03} {04} {05} {06}}

Carcinogenicity

Diclofenac—No evidence of carcinogenicity was found in long-term studies in rats or mice receiving up to 2 mg per kg of body weight (mg/kg) per day orally. ^{01}

Flurbiprofen—No evidence of carcinogenicity was found in a 24-month study in rats receiving up to 4 mg/kg per day, a second 24-month study in rats receiving 12 mg/kg per day for 32 weeks followed by 5 mg/kg per day thereafter, or an 80-week study in mice receiving up to 12 mg/kg per day orally. ^{29}

Indomethacin—No evidence of carcinogenicity was found in long-term studies in rats or mice receiving up to 1.5 mg/kg per day orally. ^{30}

Suprofen—No evidence of carcinogenicity was found in long-term studies in rats or mice receiving up to 40 mg/kg per day orally. ^{06}

Tumorigenicity

Diclofenac—A slight increase in the occurrence of benign mammary fibroadenomas was found in female rats, but the increase was not significant for this common rat tumor. No other evidence of tumorigenicity was found in rats receiving up to 2 mg/kg per day orally. ^{01}

Flurbiprofen—No evidence of tumorigenicity was found in a 2-year study in rats receiving up to 12 mg/kg per day for 32 weeks, followed by up to 5 mg/kg per day orally for the remainder of the study period. ^{29}

Indomethacin—No evidence of tumorigenicity was found in an 81-week study in rats receiving up to 1 mg/kg per day orally. ^{30}

Suprofen—An increased incidence of benign hepatomas occurred in female mice receiving 40 mg/kg per day and in male mice receiving 2 mg/kg per day or more orally. ^{06}

Mutagenicity

Diclofenac—No mutagenic activity was found in in vitro tests using mammalian cells or bacteria (with or without microsomal activation) or in various in vivo tests. ^{31}

Flurbiprofen—Long-term mutagenicity studies have not been performed. ^{02}

Indomethacin—No mutagenic activity was found in in vitro tests (Ames test or E. coli , with or without metabolic activation) or in in vivo tests (host-mediated assay, sex-linked recessive lethals in Drosophila , and micronucleus test in mice). ^{30}

Suprofen—No mutagenic activity was found in the Ames, micronucleus, and dominant lethal tests. ^{06}

Pregnancy/Reproduction
Fertility—
Diclofenac: No impairment of fertility was found in reproduction studies in rats receiving up to 4 mg/kg per day orally. ^{{01} {31} {32}}

Flurbiprofen: No impairment of fertility was found in reproduction studies in rats receiving up to 4 mg/kg per day orally. ^{33}

Indomethacin: No impairment of fertility was found in a two-generation reproduction study in rats or in a two-litter reproduction study in rats receiving up to 0.5 mg/kg per day orally. ^{30}

Suprofen: No impairment of fertility was found in reproduction studies in rats receiving up to 40 mg/kg per day. However, a slight reduction in fertility was found in rats receiving 80 mg/kg per day orally. Testicular atrophy and hypoplasia occurred in a 6-month study in dogs receiving 80 mg/kg per day and a 12-month study in rats receiving 40 mg/kg per day orally. ^{06}

Pregnancy—
Adequate and well-controlled studies with ophthalmic NSAIDs have not been performed in pregnant women. ^{{01} {02} {04} {06}} However, use of ophthalmic NSAIDs late in pregnancy is not recommended because oral NSAIDs caused premature closure of the ductus arteriosus in animal studies. ^{{01} {06} {29} {30} {32}}


First trimester


Diclofenac—

Diclofenac readily crosses the placenta. ^{31}

No teratogenicity occurred in reproduction studies in mice receiving up to 20 mg/kg per day orally and in rats and rabbits receiving up to 10 mg/kg per day orally. ^{{01} {31} {32}} However, maternal toxicity and embryotoxicity (reduced fetal weights and growth, reduced fetal survival) occurred in studies in rats receiving 2 or 4 mg/kg per day. ^{{01} {31} {32}} Also, increases in resorption rates, decreased fetal weight, abnormal skeletal findings, and definite embryotoxicity occurred in studies in rabbits receiving 5 or 10 mg/kg per day orally. ^{31}

FDA Pregnancy Category B.



Flurbiprofen—

Flurbiprofen crosses the placenta. ^{33}

No teratogenicity occurred in reproduction studies in mice receiving up to 12 mg/kg per day, rats receiving up to 25 mg/kg per day, or rabbits receiving up to 7.5 mg/kg per day, orally. ^{29} However, studies in rats have shown doses of 0.4 mg/kg per day or higher to be embryotoxic or embryocidal (causing reduced weight or slower fetal growth, increased stillbirths, and decreased pup survival). Also, stillbirths, retained fetuses, and/or fetal distress occurred in studies in rats receiving as little as 0.2 mg/kg per day. In addition, fetotoxicity related to maternal toxicity (gastrointestinal ulceration, retardation of weight gain, intrauterine hemorrhage, and maternal deaths) occurred in rats receiving 25 mg/kg per day from Days 1 through 20 of pregnancy. With lower doses (0.2, 0.675, or 2.25 mg/kg per day), such effects did not occur when the medication was discontinued on Day 17 of pregnancy. Maternal deaths due to gastrointestinal ulceration also occurred in rabbits receiving the medication. ^{33}

FDA Pregnancy Category C.



Indomethacin—

Indomethacin crosses the placenta. ^{30}

Studies in rats and mice have shown that indomethacin in doses of 4 mg/kg per day orally causes retarded ossification secondary to decreased average fetal weight. In other studies in mice, higher doses (5 to 15 mg/kg per day orally) caused maternal toxicity and death, increased fetal resorptions, and fetal malformations. Doses lower than 4 mg/kg per day produced no adverse effects in these studies. ^{30}



Suprofen—

Studies in rats receiving 40 mg/kg or more per day, and rabbits receiving 80 mg/kg or more per day, orally have shown that suprofen causes an increased incidence of fetal resorption associated with maternal toxicity. In rats receiving 2.5 mg/kg or more per day orally, there was an increase in stillbirths and a decrease in pup survival. ^{06}

FDA Pregnancy Category C. ^{06}




Third trimester


Diclofenac—

Studies in animals have shown that maternally toxic doses, administered orally, are associated with prolonged gestation ^{{01} {32}} and dystocia. ^{32}



Flurbiprofen—

Studies in rats have shown that administration of 0.4 mg/kg or more per day orally causes prolonged gestation and delayed parturition. ^{02}



Indomethacin—

Studies in rats and mice have shown that administration of 4 mg/kg per day orally during the last 3 days of gestation is associated with an increased incidence of neuronal necrosis in the diencephalon and some maternal and fetal deaths. ^{30} Indomethacin also caused a slight delay in the onset of parturition in rats, ^{{04} {30}} but not in rabbits. ^{04}



Suprofen—

Studies in rats have shown that suprofen causes a delay in parturition. ^{06}



Breast-feeding

Although it is not known whether NSAIDs are distributed into breast milk after ophthalmic administration, ^{{02} {04}} it is known that orally administered diclofenac, indomethacin, and suprofen are distributed into human breast milk. ^{{06} {30} {32}} It is not known whether orally administered flurbiprofen is distributed into breast milk. ^{02} However, problems in humans have not been documented with any of these medications.

Pediatrics

Appropriate studies on the relationship of age to the effects of ophthalmic NSAIDs have not been performed in the pediatric population. Safety and efficacy have not been established. ^{{01} {02} {03} {04} {05} {06}}


Geriatrics


Studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of ophthalmic NSAIDs in the elderly. ^{34}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Acetylcholine chloride^{02}{35} or
Carbachol^{02}    (these medications may be less effective ^{49} when administered after an ophthalmic NSAID ^{45} has been used to inhibit miosis during ocular surgery; although the pharmacologic basis for the interaction has not been established, it has been suggested that NSAID-induced maintenance of a larger pupillary diameter during surgery, and the possibility that the duration of action of the NSAID may exceed that of acetylcholine chloride, may account for the apparent reduction in the ability of acetylcholine chloride to reverse mydriasis postoperatively ^{35})


Any medication that may interfere with blood clotting or prolong bleeding time, such as:
Anticoagulants, coumarin- or indandione-derivative or
Heparin or
Platelet aggregation inhibitors    (concurrent use with ophthalmic NSAIDs, which may also increase the bleeding tendency, may increase the risk of postoperative ocular bleeding ^{{01} {02} {03} {06}})


Epinephrine (ophthalmic) and possibly other antiglaucoma agents    (the possibility should be considered that ophthalmic flurbiprofen may decrease the intraocular pressure–lowering effects of these medications ^{36}; however, in one study, administration of ophthalmic flurbiprofen [1 drop every 10 minutes for 4 doses] had no effect on the intraocular pressure–lowering effect of 1% apraclonidine or 0.5% timolol ^{37})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Allergic reaction, such as anaphylaxis, bronchospasm, angioedema, allergic rhinitis, or urticaria, to aspirin or other systemic NSAIDs, history of    (possibility of cross-sensitivity)


Epithelial herpes simplex keratitis, active^{02}    (in one study in rabbits, ophthalmic flurbiprofen exacerbated herpes simplex keratitis [i.e., increased ulceration and conjunctivitis] and delayed healing; ^{38} however, in another study in rabbits, neither flurbiprofen nor diclofenac exacerbated or prolonged acute herpes keratitis or prolonged viral shedding; ^{39} although the risk of exacerbation or delayed healing of active epithelial herpes simplex keratitis in humans has not been determined, it is recommended that ophthalmic NSAIDs be administered with caution and in conjunction with an antiviral agent ^{40})

    (suprofen is contraindicated in patients with active herpes simplex keratitis ^{60})


Epithelial herpes simplex keratitis, history of    (close monitoring of the patient following flurbiprofen administration is recommended because the risk of reactivation has not been determined ^{40})

    (close monitoring of the patient following suprofen administration is recommended ^{60})


Hemophilia or other bleeding problems or coagulation defects^{{01}{02}{03}{06}} or
Prolonged bleeding time    (increased risk of bleeding)


» Sensitivity to the ophthalmic NSAID considered for use
Soft contact lenses, use of^{56}    (wearing hydrogel soft contact lenses while using diclofenac is contraindicated because ocular irritation, such as redness and burning of the eye, may occur ^{56})




Side/Adverse Effects

Note: Oral administration of suprofen has caused acute flank pain and renal insufficiency, possibly manifestations of acute uric acid nephropathy. This reaction has occurred after ingestion of as few as 1 or 2 doses of 200 mg, > 25 times more than the total quantity of suprofen that would be administered over 2 days with recommended ophthalmic doses. ^{06} The risk of such a reaction occurring after ophthalmic administration is unknown.
Keratitis, elevated intraocular pressure, corneal edema, chemosis, and anterior chamber reaction have also been reported with various ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs). ^{{01} {03} {06}} Since these effects frequently occur following some types of ophthalmic procedures, a causal relationship has not been established.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
For diclofenac
    
Allergic reaction^{01}{50} (itching; tearing)—in a patient hypersensitive to systemic NSAIDs
    
corneal opacity^{56} (blurred vision or other change in vision)
    
discharge, ocular^{56} (sticky or matted eyelashes)
    
facial edema^{56} (swelling of face)
    
fever or chills^{56}
    
iritis^{56} (throbbing pain; tearing; sensitivity to light)
    
nausea or vomiting^{56}
    
pain^{56}

For flurbiprofen
    
Bleeding in eye
    
redness in eye^{02} —not resulting from surgery and not present before use
    
fibrosis^{55}

For indomethacin
    
Bronchospastic allergic reaction^{28} (shortness of breath; troubled breathing; tightness in chest; wheezing)—reported in an asthmatic patient
    
corneal epithelial defects, including corneal abrasion and punctate keratitis^{03}
    
redness in eye^{03} —not resulting from surgery and not present before use
    
striate keratopathy^{03}

For suprofen
    
Iritis (throbbing pain; tearing; sensitivity to light)
    
punctate epithelial staining^{06}

Note: Eye pain and photophobia have also been reported independently of iritis. ^{06}





Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Dry eye^{56}
    
irritation, ocular^{{01}{02}{03}{04}{06}} (burning; stinging; itching; mild discomfort)

Incidence less frequent or rare
    
Asthenia^{56} (unusual weakness)
    
headache^{56}
    
insomnia^{56}
    
miosis^{55} (smaller pupils [black part of eye])
    
mydriasis^{55} (bigger pupils [black part of eye])
    
rhinitis^{56} (runny or stuffy nose)





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Recommended treatment in case of accidental ingestion consists of drinking large quantities of fluids to dilute the medication. ^{{01} {02} {03} {06}}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Anti-inflammatory Drugs, Nonsteroidal (Ophthalmic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to aspirin or other systemic nonsteroidal anti-inflammatory drugs (NSAIDs), or to the ophthalmic NSAID considered for use

Pregnancy—Diclofenac, flurbiprofen, and indomethacin known to cross the placenta when administered systemically





Breast-feeding—Indomethacin and suprofen known to be distributed into breast milk after oral administration

Proper use of this medication
Proper administration technique

Preventing contamination: Not touching dropper or applicator tip to any surface and keeping container tightly closed

» Importance of not using more medication than the amount prescribed

» Checking with physician before using medication for future eye problems

Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose

» Proper storage

Precautions while using this medication
» For diclofenac: Not wearing soft contact lenses during treatment


Side/adverse effects
Signs of potential side effects, especially allergic reaction; corneal opacity; ocular discharge; facial edema; fever or chills; iritis; nausea or vomiting; pain, bleeding or redness in the eye; fibrosis; bronchospastic allergic reaction; corneal epithelial defects, including corneal abrasion, and punctate keratitis; striate keratopathy; and punctate epithelial staining.


General Dosing Information
When an ophthalmic nonsteroidal anti-inflammatory drug (NSAID) is used to prevent or reduce postoperative inflammation and/or cystoid macular edema, therapy should be started prior to the procedure. ^{{05} {41}} Ophthalmic NSAIDs are more effective in inhibiting the development of these complications than in treating them after they have fully developed. ^{46}

DICLOFENAC

Additional Dosing Information
It is recommended that patients not wear hydrogel soft contact lenses during diclofenac therapy. Ocular irritation manifested by redness and burning has occurred in patients wearing this type of contact lens while using the medication. ^{01}


Ophthalmic Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

DICLOFENAC SODIUM OPHTHALMIC SOLUTION

Usual adult dose
Anti-inflammatory, nonsteroidal, ophthalmic
Treatment of inflammation following cataract surgery: Topical, to the conjunctiva, 1 drop in the affected eye four times a day, starting twenty-four hours postoperatively and continuing for the first two postoperative weeks. ^{56} In some patients, treatment has been continued for six weeks ^{01} or longer. ^{52}
[Treatment of conjunctivitis, keratoconjunctivitis, corneal ulcers, or post-traumatic inflammation]: Topical, to the conjunctiva, 1 drop in the affected eye four to five times a day, depending on the severity of the disease. ^{{44} {57}}

[Miosis inhibitor, in ophthalmic surgery] or
[Prostaglandin synthesis inhibitor, ophthalmic]
Prevention or reduction of intraoperative miosis and postoperative cystoid macular edema: Topical, to the conjunctiva, 1 drop in the affected eye, applied up to five times during the three hours prior to surgery; fifteen minutes, thirty minutes, and forty-five minutes postoperatively; then three to five times a day for as long as needed. ^{44}

Photophobia, in incisional refractive surgery ^{56}
Topical, to the conjunctiva, 1 drop in the affected eye within one hour prior to surgery, then 1 drop within fifteen minutes after surgery, then 1 drop four times a day beginning four to six hours after surgery and continuing for up to three days as needed. ^{56}


Usual pediatric dose
Safety and efficacy have not been established. ^{{01} {56}}

Strength(s) usually available
U.S.—


0.1% (1 mg per mL) (Rx) [Voltaren Ophthalmic^{56} (boric acid) (edetate disodium 1 mg per mL) (polyoxyl 35 castor oil) (sorbic acid 2 mg per mL) (tromethamine)]

Canada—


0.1% (1 mg per mL) (Rx) [Voltaren Ophtha^{57} (boric acid) (cremophor EL) (edetate disodium^{57}) (sorbic acid^{57}) (tromethamine [TRIS])]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), protected from light and from freezing, unless otherwise directed by manufacturer.

Auxiliary labeling:
   • For the eye.

Note: Dispense in original unopened container.



FLURBIPROFEN

Ophthalmic Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

FLURBIPROFEN SODIUM OPHTHALMIC SOLUTION USP

Usual adult dose
Miosis inhibitor, in ophthalmic surgery
Topical, to the conjunctiva, 1 drop every thirty minutes, beginning two hours prior to surgery, for a total of 4 drops. ^{{02} {03} {55}}

[Anti-inflammatory, nonsteroidal, ophthalmic]
Treatment of inflammation following ophthalmic surgery or laser trabeculoplasty: Topical, to the conjunctiva, 1 drop every four hours for one to three weeks. ^{03}


Usual pediatric dose
Safety and efficacy have not been established. ^{55}

Strength(s) usually available
U.S.—


0.03% (Rx) [Ocufen^{55} (polyvinyl alcohol 1.4%) (edetate disodium) (thimerosal 0.005%) (potassium chloride) (sodium chloride) (sodium citrate) (citric acid) (hydrochloric acid and/or sodium hydroxide)][Generic]

Canada—


0.03% (Rx) [Ocufen^{58} (citric acid) (edetate disodium) (hydrochloric acid and/or sodium hydroxide) (polyvinyl alcohol) (potassium chloride) (sodium chloride) (sodium citrate) (thimerosal)^{58}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from freezing.

Auxiliary labeling:
   • For the eye.

Note: Dispense in original unopened container.



INDOMETHACIN

Additional Dosing Information
Because an ophthalmic dosage form of indomethacin is not commercially available in the U.S., ophthalmic preparations are being compounded extemporaneously in some pharmacies. Eye injuries resulting from Pseudomonas contamination have occurred following use of such preparations. Pharmacists are advised not to use the contents of commercially available indomethacin capsules in the preparation of ophthalmic indomethacin solutions or suspensions, because of a lack of data on stability, concentration, and possible effects of excipients. Also, the sterility of compounded preparations must be assured. ^{42}


Ophthalmic Dosage Forms

INDOMETHACIN OPHTHALMIC SUSPENSION

Usual adult dose
Prostaglandin synthesis inhibitor, ophthalmic ^{59} or
Miosis inhibitor, in cataract surgery ^{59}
Prevention or reduction of intraoperative miosis and postoperative cystoid macular edema: Topical, to the conjunctiva, 1 drop four times a day on the day prior to surgery, 1 drop forty-five minutes before surgery, then 1 drop four times a day ^{03} for ten to twelve weeks postoperatively ^{59} or as long as needed. ^{51}


Usual pediatric dose
Safety and efficacy have not been established. ^{{03} {59}}

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


1% (10 mg per mL) (Rx) [Indocid^{53}{59} (lecithin) (sodium bisulfite) (sodium chloride) (polysorbate 80) (hydroxyethylcellulose) (sorbitol) (disodium edetate) (benzalkonium chloride solution 0.02%) (benzyl alcohol 0.25%) (phenylethyl alcohol 0.25%)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), protected from light and from freezing, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • For the eye.
   • Shake well before using.

Note: Dispense in original unopened container.



SUPROFEN

Ophthalmic Dosage Forms

SUPROFEN OPHTHALMIC SOLUTION^{54} USP

Usual adult dose
Miosis inhibitor, in ophthalmic surgery
Topical, to the conjunctiva, 2 drops three, two, and one hour prior to surgery. If desired, 2 drops may be applied every four hours while the patient is awake on the day prior to surgery. ^{{06} {60}}


Usual pediatric dose
Safety and efficacy have not been established. ^{60}

Strength(s) usually available
U.S.—


1% (10 mg per mL) (Rx) [Profenal^{60} (thimerosal 0.005%) (caffeine 2%) (edetate disodium) (dibasic sodium phosphate) (monobasic sodium phosphate) (sodium chloride) (sodium hydroxide and/or hydrochloric acid)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), protected from freezing, unless otherwise directed by manufacturer.

Auxiliary labeling:
   • For the eye.

Note: Dispense in original unopened container.

Revised: 09/10/1998

References

1. Prescribing information, Voltaren Ophthalmic, CIBA Vision, U.S., new 4/91; rec'd 5/24/91.
   

2. Package insert, Ocufen, Allergan (US), 12/86 (received 1/87).
   

3. Prescribing information, Ocufen, Allergan (Canada), in: Krogh CME, ed. Compendium of pharmaceuticals and specialties, 26th ed. Ottawa: Canadian Pharmaceutical Association; 1991: 850.
   

4. Product monograph, Indocid Ophthalmic Suspension, MSD Canada, rev 12/13/85; rec'd 2/23/88.
   

5. Prescribing information, Indocid Ophthalmic Suspension, MSD Canada, in: Krogh CME, ed. Compendium of pharmaceuticals and specialties, 26th ed. Ottawa: Canadian Pharmaceutical Association; 1991: 579.
   

6. Package insert, Profenal, Alcon (US) rev 2/90; rec'd 5/91.
   

7. Weinreb RN, Robin AL, Baerveldt G, Drake MV, Blumenthal M, Wilensky J. Flurbiprofen pretreatment in argon laser trabeculoplasty for primary open-angle glaucoma. Arch Ophthalmol 1984; 102: 1629-32.
   

8. Hotchkiss ML, Robin AL, Pollack IP, Quigley HA. Nonsteroidal anti-inflammatory agents after argon laser trabeculoplasty. Ophthalmology 1984; 91: 969-76.
   

9. Sabiston D, Tessler H, Sumers K, Osterle C, Cheetham JK, Duzman E, DeGryse R. Reduction of inflammation following cataract surgery by the nonsteroidal anti-inflammatory drug, flurbiprofen. Ophthalmic Surg 1987; 18: 873-7.
   

10. Panel consensus, Flurbiprofen, ballot 5/90.
    

11. Keates RH, McGowan KA. Clinical trial of flurbiprofen to maintain pupillary dilation during cataract surgery. Ann Ophthalmol 1984; 16: 919-21.
    

12. Heinrichs DA, Leith AB. Effect of flurbiprofen on the maintenance of pupillary dilation during cataract surgery. Can J Ophthalmol 1990; 25: 239-42.
    

13. Drews RC, Katsev DA. Ocufen and pupillary dilation during cataract surgery. J Cataract Refract Surg 1989; 15: 445-8.
    

14. Tsuchisaka H, Takase M. Topical flurbiprofen in intraocular surgery on diabetic and nondiabetic patients. Ann Ophthalmol 1990; 22: 15-9, 23.
    

15. Stark WJ, Fagadau WR, Stewart RH, et al. Reduction of pupillary constriction during cataract surgery using suprofen. Arch Ophthalmol 1986; 104: 364-6.
    

16. Vander JF, Greven CM, Maguire JI, Moreno RJ, Shakin EP, Lucier AC. Flurbiprofen sodium to prevent intraoperative miosis during vitreoretinal surgery. Am J Ophthalmol 1989; 108: 288-91.
    

17. Yannuzzi LA, Landau AN, Turtz AI. Incidence of aphakic cystoid macular edema with the use of topical indomethacin. Ophthalmology 1981; 88: 947-54.
    

18. Open.
    

19. Fleeger CA, ed. USAN and the USP dictionary of drug names. Rockville: The U.S. Pharmacopeial Convention, Inc. 1992.
    

20. Keulen-DeVos HCJ, Van Rij G, Renardel De Lavalette JCG, et al. Effect of indomethacin in preventing surgically induced miosis. Br J Ophthalmol 1983; 67: 94-6.
    

21. Meredith TA, Kenyon KR, Singerman LJ, Fine SL. Perifoveal vascular leakage and macular oedema after intracapsular cataract extraction. Br J Ophthalmol 1976; 60: 765-9.
    

22. Sanders DR, Kraff M. Steroidal and nonsteroidal anti-inflammatory agents. Effect on postsurgical inflammation and blood-aqueous humor barrier breakdown. Arch Ophthalmol 1984; 102: 1453-6.
    

23. Sand BB, Krogh E. Topical indometacin, a prostaglandin inhibitor, in acute anterior uveitis. A controlled clinical trial of non-steroid versus steroid anti-inflammatory treatment. Acta Ophthal 1991; 69: 145-8.
    

24. Kraff MC, Sanders DR, McGuigan L, Raanan MG. Inhibition of blood-aqueous humor barrier breakdown with diclofenac. A fluorophotometric study. Arch Ophthalmol 1990; 108: 380-3.
    

25. Duffin RM, Camras CB, Gardner SK, et al. Inhibitors of surgically induced miosis. Ophthalmology 1982; 89: 966-79.
    

26. Miller D, Gruenberg P, Miller R, Bergamini MVW. Topical flurbiprofen or prednisolone. Effect on corneal wound healing in rabbits. Arch Ophthalmol 1981; 99: 681-2.
    

27. Lee BP, Kupferman A, Leibowitz HM. Effect of suprofen on corneal wound healing. Arch Ophthalmol 1985; 103: 95-7.
    

28. Sheehan GJ, Kutzner MR, Chin WD. Acute asthma attack due to ophthalmic indomethacin. Ann Int Med 1989; 111: 337-8.
    

29. Prescribing information Ansaid (flurbiprofen oral) (Upjohn U.S.), in: Physician's desk reference, 45th ed. Montvale: Medical Economics Data; 1991: 2215-7.
    

30. Package insert Indocin (oral), MSD (U.S.), in: Physician's desk reference, 45th ed. Montvale: Medical Economics Data; 1991: 1442-5.
    

31. Product monograph Voltaren (oral), Geigy (Canada), rev. 7/85 rec. 7/87.
    

32. Prescribing information Voltaren (oral), Geigy (U.S.), in Physicians desk reference, 45th ed. Montvale: Medical Economics Data; 1991: 1024-6.
    

33. Product monographs Froben (Organon, Canada, rev.11/85, rec'd 3/88) and Ansaid (Winthrop, Canada, rev. 2/85, rec'd 5/87).
    

34. Panel consensus, Flurbiprofen draft 4/87.
    

35. Holmes JM, Jay WM. The effect of preoperative flurbiprofen on miosis produced by acetylcholine during cataract surgery. Am J Ophthalmol 1991; 111: 735-8.
    

36. Manufacturer comment Flurbiprofen (Ophthalmic) monograph, draft 4/87.
    

37. Sulewski ME, Robin AL, Cummings HL, Arkin LM. Effects of topical flurbiprofen on the intraocular pressure lowering effects of apraclonidine and timolol. Arch Ophthalmol 1991; 109: 807-9.
    

38. Trousdale MD, Dunkel ED, Nesburn AB. Effect of flurbiprofen on herpes simplex keratitis in rabbits. Invest Ophthalmol Vis Sci 1980; 19: 267-70.
    

39. Trousdale MD, Barlow WE, McGuigan LJ. Assessment of diclofenac on herpes keratitis in rabbit eyes. Arch Ophthalmol 1989; 107: 1664-6.
    

40. Panelist comments, Flurbiprofen monograph draft 4/87.
    

41. Panelist comment, Flurbiprofen monograph draft 4/87.
    

42. Dickinson's FDA 1990 Dec 1; 6 (22): 1-2.
    

43. Panel consensus, monograph draft 1/3/92.
    

44. Product monograph Voltaren Ophtha, CIBA Vision (Canada), new 10/91; rec'd 3/92.
    

45. Panel consensus, ballot 2/18/92.
    

46. Flach AJ. Cyclo-oxygenase inhibitors in ophthalmology. Surv Ophthalmol 1992; 36: 259-84.
    

47. Open.
    

48. Tang-Lui DD, Liu SS, Weinkam RJ, et al. Ocular and systemic bioavailability of ophthalmic flurbiprofen. J Pharmacokin Biopharm 1984; 12: 611-26.
    

49. Panelist comment, draft 1/92.
    

50. Personal communication, CibaVision (U.S.), via telephone 7/7/92.
    

51. Panelist comments, ballot 2/92 and draft 5/92.
    

52. Panelist comment, draft 5/92.
    

53. Indomethacin (Indocid, MSD). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 607.
    

54. The United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1995: 1473.
    

55. Flurbiprofen (Ocufen, Allergan). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Company, 1998. p. 235-6.
    

56. Diclofenac (Voltaren Ophthalmic, Ciba Vision). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Company, 1998. p. 257-8.
    

57. Diclofenac (Voltaren Ophtha, Ciba Vision). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1830-1.
    

58. Flurbiprofen (Ocufen, Allergan). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1202.
    

59. Indomethacin (Indocid, MSD). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 772.
    

60. Suprofen package insert (Profenal, Alcon Surgical—US), Rec 6/98.
    

Link to this page

Printable Version

Email Page