PDW
`54
`2000
`
`EDITION
`
`YSICIANS’
`
`RRNOfi
`
`Senior Vice President, Directory Services: Paul Walsh
`
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`Copyright ' 2000 and published by Medical Economics Company, Inc. at Montvale, NJ 07645-1742. All rights reserved. None of the content of this publication may
`be reproduced, stored in a retrieval system, resold, redistributed, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or
`otherwise) without the prior written permission of the publisher. PHYSICIANS’ DESK REFERENCE, PDR, PDR For Ophthalmology, Pocket PDR’, and The PDRI Family
`Guide to Prescription Druge are registered trademarks used herein under license. PDR For Nonprescription Drugs and Dietary Supplement'M, PDIR Companion Guide",
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`OQ
`Printed on recycled paper (cid:9)
`
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`LUPIN EX 1029
`
`Page 1 of 3
`
`

`
`PHYSICIANS’ DESK REFERENC~ % "PP’ (cid:9)
`r (cid:9)
`-,r. C) C) U(-"
`
`- (cid:9)
`
`Preservative: POLYQUADfi (Polyquaternium-1) 0.001%
`active: Sodium Borate, Potassium Chloride, Sodium (cid:9)
`ride, Purified Water. May contain Hydrochloric Acid
`Sodium Hydroxide to adjust pH.
`TEARS NATURALE FREE: Each mL contains:
`Active: DUASORBfi, a water soluble polymeric sys50
`containing Dextran 70 0.1% and Hydroxypropyl Methyl551
`lulose 2910 0.3%.
`Inactives: Sodium Borate, Potassium Chloride, SodiuH
`Chloride, Purified Water. May contain Hydrochloric Acid
`and/or Sodium Hydroxide to adjust pH.
`INDICATIONS
`For the temporary relief of burning and irritation due
`to
`dryness of the eye and for use as a protectant against hir
`ther irritation. For the temporary relief of discomfort duets
`minor irritations of the eye or to exposure to wind or 5u
`
`490/ALCON
`
`NAPHCONfi A (cid:9)
`Eye Drops
`Relieves Itching & Redness
`EVE ALLERGY RELIEF
`
`OTC
`
`WARNINGS
`PATANOLfi is for topical use only and not for injection or
`oral use.
`
`Temporary relief of the minor eye symptoms of itching and
`redness caused by ragweed, pollen, grass, animal hair, and
`dander.
`
`DESCRIPTION
`Active: Pheniramine Maleate 0.3%, Naphazoline Hydro-
`chloride 0.025%. Preservative: Benzalkenium Chloride
`0.01%. Inactive: Sodium Chloride, Boric Acid, Sodium Bo-
`rate, Edetate Disodium 0.01%, Sodium Hydroxide and/or
`Hydrochloric Acid (to adjust pH), Purified Water. The sterile
`ophthalmic solution has a pH of about 6 and a tonicity of
`about 270 mOsm.’Kg.
`
`DIRECTIONS
`Instill 1 or 2 drops in the affected eye(s) up to 4 times daily.
`
`WARNINGS
`To avoid contamination, do not touch tip of container to any
`surface. Replace cap after using.
`If solution changes color or becomes cloudy, do not use.
`If you experience eye pain, changes in vision, continued red-
`ness or irritation of the eye, or if the condition worsens, or
`persists for more than 72 hours, discontinue use and consult
`a physician. Overuse of this product may produce increased
`redness of the eye.
`If you are sensitive to any ingredient in this product, do not
`use. Do not use use this product if you have heart disease,
`high blood pressure, difficulty in urination due to enlarge-
`ment of the prostate gland or narrow angle glaucoma unless
`directed by a physician.
`Accidental oral ingestion in infants and children may lead
`to coma and marked reduction in body temperature. Before
`using in children under 6 years of ago, consult your physi-
`cian.
`Keep this and all drugs out of reach of children. In case of
`accidental ingestion, seek professional assistance or contact
`a Poison Control Center immediately.
`Remove contact lenses before using.
`Store at 36-80F (2-27C).
`Protect from light.
`Use before the expiration date marked on the carton or bat-
`tie.
`Keep this and all drugs out of reach of children.
`
`PATANOLfi
`(olopatadine hydrochloride ophthalmic solution) 0.1%
`
`DESCRIPTION
`PATANOLfi (olopatadine hydrochloride ophthalmic solu-
`tion) 0.1% is a sterile ophthalmic solution containing olo-
`patadine, a relatively selective H l-receptor antagonist and
`inhibitor of histamine release from the mast cell for topical
`administration to the eyes. Olopatadino hydrochloride is a
`white, crystalline, water-soluble powder with a molecular
`weight of 373.88.
`Chemical Name: 11l(Z).3(Dimethylamino)propylidenel -6-
`11-dthydrodibenzlb,el oxepin-2-acetic acid hydrochloride
`Each all, ofPATANOL contains: Active: 1.11 mg olopatadine
`hydrochloride equivalent to 1 mg olopatadine. Preservative:
`Inactives: dibasic sodium
`benzalkonium chloride 0.01%.
`phosphate; sodium chloride; hydrochloric acid/sodium hy-
`droxide (adjust pH); and purified water.
`It has a pH of approximately 7 and an osmolality of approx-
`imately 300 mOsnilkg.
`CLINICAL PHARMACOLOGY
`Olopatadine is an inhibitor of the release of histamine from
`the mast cell and a relatively selective histamine H l-antag-
`onist that inhibits the in vise and in vitro type 1 immediate
`hypersensitivity reaction. Olopatadino is devoid of effects on
`in
`alpha-adrenergic, dopamine, muscaric type 1 and 2, and
`serotonin receptors. Following topical ocular administration
`in man, olopatadine was shown to have low systemic expo-
`sure. Two studies in normal volunteers (totaling 24 sub-
`jects) dosed bilaterally with olopatadine 0.15% ophthalmic
`solution once every 12 hours for 2 weeks demonstrated
`plasma concentrations to be generally below the quantita-
`tion limit of the assay (<0.5 ng/mL). Samples in which nb-
`patadine was quantifiable were typically found within 2
`hours of dosing and ranged from 0.5 to 1.3 ng/mL. The half-
`life in plasma was approximately 3 hours, and elimination
`was predominantly through renal excretion. Approximately
`60-70% of the dose was recovered in the urine as parent
`drug. Two metabolites, the mono-desmethyl and the N-
`oxide, were detected at low Concentrations in the urine.
`Results from conjunctival antigen challenge studies demon-
`strated that PATANOL, when subjects were challenged with
`antigen both initially and up to 8 hours after dosing, was
`significantly more effective than its vehicle in preventing oc-
`ular itching associated with allergic conjunctivitis.
`INDICATIONS AND USAGE
`PATANOL (olopatadine hydrochloride ophthalmic solution)
`0.1% is indicated for the temporary prevention of itching ol
`the eye due to allergic conjunctivitis.
`CONTRAINDICATIONS
`PATANOL is contraindicated in persons with a known hy-
`persensitivity to olopatadine hydrochloride or any compo-
`nents of PATANOL.
`
`-
`
`PRECAUTIONS
`Information for Patients: To prevent contaminating the
`dropper tip and solution, care should be taken not to touch
`the eyelids or surrounding areas with the dropper tip of the
`bottle. Keep bottle tightly closed when not in use.
`Patients should be advised not to wear a contact lens if their
`eye is red. PATANOLfi should not be used to treat contact
`lens related irritation. The preservative in PATANOL, benz-
`alkonium chloride, may be absorbed by soft contact lenses.
`Patients who wear soft contact lenses and whose eyes are
`not red, should be instructed to wait at least ton minutes
`after instilling PATANOL before they insert their contact
`lenses.
`Carcinogenesis Mutagenesis Impairment of Fertility: Olo-
`patadine administered orally was not carcinogenic in mice
`and rats in doses up to 500 mg/kg/day and 200 mg/kg/day,
`respectively. Based on a 40 p1 drop size, these doses were
`78,125 and 31,250 times higher than the maximum recom-
`mended ocular human doss (MROHD). No mutagenic poten-
`tial was observed when olopatadine was tested in an in vitro
`bacterial reverse mutation (Ames) test, an in vitro mamma-
`lian chromosome aberration assay or an in vise mouse mi-
`cronucleus test. Olopatadine administered to male and fe-
`male rats at oral doses of 62,500 times MROHD level re-
`sulted in a slight decrease in the fertility index and reduced
`implantation rate; no effects on reproductive function were
`observed at doses of 7,800 times the maximum recom-
`mended ocular human use level.
`Pregnancy: Pregnancy Category C. Olopatadine was found
`not to be teratogenic in rats and rabbits. However, rats
`treated at 600 mg/kg/day, or 93,750 times the MROHD and
`rabbits treated at 400 mg/kg/day, or 62,500 times the
`MROHD, during organogenesis showed a decrease in live
`fetuses. There are, however, no adequate and well con-
`trolled studies in pregnant women. Because animal studies
`are not always predictive of human responses, this drug
`should be used in pregnant women only if the potential ben-
`efit to the mother justifies the potential risk to the embryo
`or fetus.
`Nursing Mothers: Olopatadine has been identified in the
`milk of nursing rats following oral administration. It is not
`known whether topical ocular administration could result in
`sufficient systemic absorption to produce detectable quanti-
`ties in the human breast milk. Nevertheless, caution should
`be exercised when PATANOLfi is administered to a nursing
`mother.
`Pediatric Use: Safety and effectiveness in pediatric pa-
`tients below the age of 3 years have not been established.
`
`ADVERSE REACTIONS
`Headaches were reported at an incidence of 7%. The follow -
`ing adverse experiences were reported in less than 5% of
`patients: Asthenia, burning or stinging, cold syndrome, dry
`eye, foreign body sensation, hyperemia, keratitis, lid edema,
`pharyngitis, pruritus, rhinitis, sinusitis, and taste perver-
`sion. Some of those events were similar to the underlying
`disease being studied.
`DOSAGE AND ADMINISTRATION
`The recommended dose is one to two drops in each affected
`eye two times per day at an interval of 6 to 8 hours.
`
`HOW SUPPLIED
`PATANOLfi (olopatadine hydrochloride ophthalmic solu-
`tion) 0.1% is supplied as follows: 5 mL in plastic DROP-
`TAINERfi dispenser.
`NDC 0065-0271-05
`5 mL: (cid:9)
`Storage: Store at 39F to 86SF (4CC to 30CC).
`U.S. Patents Nos. 4,871,865; 4,923,892; 5,116,863;
`5,641,805.
`Rx Only.
`
`TEARS NATURALEfi II (cid:9)
`Lubricant Eye Drops
`TEARS NATURALE FREEfi
`Lubricant Eye Drops
`
`OTC
`
`DESCRIPTION
`TEARS NATURALEfi II is the only lubricant eye drop pre-
`served with safe, nonsensitizing POLYQUAD 0.001%. In vi-
`tro studies have shown that POLYQUAD substantially
`avoids the damaging effects of epithelial cell toxicity possi-
`ble with other tear substitute preservatives and allows eps-
`thelial cell growth. POLYQUAD has been shown to be 99%
`reaction-free in normal subjects and 97% reaction-free in
`subjects known to be preservative sensitive.
`TEARS NATURALE FREE is a preservative-free version of
`TEARS NATU1IALE II.
`With their unique mucin like polymeric formulation, and
`with their natural pH, low viscosity , and isotorncity, TEARS
`NATURALE II and TEARS NATURALE FREE provide dry
`eye patients with comfort and prompt relief of dry eye symp-
`toms.
`Sterile-For Topical Eye Use Only
`
`INGREDIENTS
`TEARS NATURALE II: Each mL contains: Active:
`DUASORBfi, a water soluble polymeric system containing
`Dextran 70 0.1% and Hydroxypropyl Methylcellulose 2910
`0.3%.
`
`4.
`
`WARNINGS
`If you experience eye pain, changes in vision, continued red-
`ness or irritation of the eye, or if the condition worsens or
`persists for more than 72 hours, discontinue use and consult
`a doctor.
`If solution changes color or becomes cloudy, do not use.
`To avoid contamination, do not touch tip of container to any
`surface. Replace cap after using. Keep this and all drugs out
`of the reach of children. In case of accidental ingestion, seek
`professional assistance or contact a Poison Control Cente r
`immediately.
`DIRECTIONS
`TEARS NATURALEfi II: Instill 1 or 2 drops in the af-
`fected eye(s) as needed. TEARS NATURALE FREE: Make
`sure container is intact before use. To open, completel y
`TWIST off tab. DO NOT pull off. Instill 1 or 2 drops in the
`affected eye(s) as needed. To close, align cap at right angle
`(90) to vial and firmly press down. Improved vial design
`reduces chance of leakage. DISCARD CONTAINER 12
`HOURS AFTER OPENING.
`HOW SUPPLIED
`TEARS NATIJRALE II Lubricant Eye Drops are supplied in
`15 mL and 30 mL plastic DROP-TAINERfi bottles.
`15 mL NDC 0065-0418-15
`30 mL NDC 0065-0418-30
`TEARS NATURALE FREE Lubricant Eye Drops are sup-
`plied in boxes of 35 0.03 fl. oz. re-closable vials.
`NDC 0065-0416-32
`
`STORAGE:
`
`Store at room temperature.
`
`TOBRADEXfi
`(tobramycin and dexamethasone
`ophthalmic suspension and ointment)
`Sterile
`
`DESCRIPTION
`TOBRADEXfi (tobramycin and dexamethasone ophthalmic
`suspension and ointment) are sterile, multiple dose antibi-
`otic and steroid combinations for topical ophthalmic use.
`Tobramycin
`Chemical name:
`[2,6.di-
`o (cid:9)
`amino-2,3,6-trideoxy-o-D-ribO -hexopyranosyl- (1-.6)
`deoxy.L-etreptamine
`Dexamethasone
`Chemical Name:
`
`ene-3,20-dione
`Each mL of TOBRADEXfi Suspension contains: Active. T0
`bramycin 0.3% (3 mg) and Dexamethasone 0.1% (1 mg)
`Preservative: Benzalkonium Chloride 0.01%. Inactives Ty
`loxapol, Edetate Disodium, Sodium Chloride, HydreXyetlfil
`Cellulose, Sodium Sulfate, Sulfuric Acid and/or Sodium Ily-
`droxide (to adjust ph) and Purified Water.
`:
`Each gram of TOBRADEXfi Ointment contains: Actives
`bramycin 0.3% (3 mg) and Dexamethasone 0.1% (1 g)
`Preservative: Chiorobutanol 0.5%. Inactives: Mineral Oh
`and White Petrolatum.
`
` if-
`
`CLINICAL PHARMACOLOGY
`Corticoids suppress the inflammatory response to a varie ty
`.
`of agents and they probably delay or slow healing. Since cci
`st
`ticoids may inhibit the body’s defense mechanism again
`infection, a concomitant antimicrobial drug may be
`when this inhibition is considered to be clinically 5i8(cid:176)
`cant. Dexamethasone is a potent corticoid.
`The antibiotic component in the combination (tobran’Y e’ll
`s
`.
`is included to provide action against susceptible org5(cid:176)(cid:176) (cid:176)1 5
`c
`In vitro studies have demonstrated that tobramycin is a
`tive against susceptible strains of the following micrsorg 5
`isms:
`Staphylococci, including S. aureus and S. epidernsi is
`ulase-positive and coagulase-negative), including perlic’
`resistant strains.
`Streptococci, including some of the Group Abeta-h 0ri(cid:176)
`species, some nonhemolytic species, and some StrcPteC0C
`pneumoniae.
`Pseudomonas aeruginosa, Escherichia coli, Klebsiello
`moniae, Enterebacter aerogenes, Proteus ,nirabilb5,
`ganella morganii, most Proteus vulgaris strains, IIaeifl(cid:176)
`Ins influenzae and H. aegyptius, Moraxelia iacuncht0,
`tobacter vaicoaceticus and some Neisseria species.
`
`111 11,
`
`
`5i
`
`0r-
`
`P..,.
`
`studies demonstr ate that in some
`,eptibilitY
`cefl1 resistant to gent5flicin remain -sue-
`SLIS
`
`’ (cid:9)
`
`.
`
`e5 micr0(cid:176)smyci:. the extent of systemic absorption
`,:- 1ible
`
`to ophthalmic Suspension or Ointment;
`data (cid:9)
`at some systemic absorption can oc-
`th
`1ied drugs. If the maximum dose of
`i
`r. (cid:9).:,weve
`
`nc Suspension is given for the first
`. with 0 (cid:9)
`,sell eye every 2 hours) and complete
`,5tpE (cid:9)
`hOUm (tuhottonoccurs, which is highly unlikely, the
`sone would be 2.4 mg. The usual
`- , steiiiic a -
`ha
`Of dexalre (cid:9)
`055 is 0.75 mg daily. If TOBRA-
`ptecementd (cid:9)
`dose
`:Jh1Y (cid:9)
`is given after the first 48
`ysi
`
`Ophthalmic’
`each eye every 4 hours, the adminis-
`lXfi
`hssone would be 1.2 mg daily. The ad-
`lw
`,irs
`nd dose Ofd5xme, OBffi&D EX Ophthalmic Ointment in
`., ,aistwdfur times daily would be 0.4 mg of dexametha-
`,hh eyes
`. . se day.
`AND USAGE
`I .plCATI0’iS . 1JIIIADEXfi Ophthalmic Suspension and Ointment are
`
`,ficated for stero id - responsiveinflammatory ocular condi-
`a corticostei’oid is indicated and where su-
`55for (cid:9)
` aculai’ infection or a risk of bacterial ocu-
`:.iicial bacterial
`
`. I infection ex ists ’
`ilar steroids are indicated in inflammatory conditions of
`,
`palpebral and bulbar conjunctiva, cornea and anterior
`: ,oiieflt5f the globe where the inherent risk of steroid use
`certain infective conjunctivitis is accepted to obtain a
`i Utisii in edema and inflammation. They are also mdi-
`,id in chro nic anterior uveitis and corneal injury from
`,.siical, radiation or thermal burns, or penetration of for-
`’11 bodies.
`he USII if a combination drug with an anti -infective corn-
`_
`hieflt is indicated where the risk of superficial ocular in-
`.: iiOi is high or where there is an expectation that poten-
`_I lly dangerous numbers of bacteria will be present in the
`i’ particular anti-infective drug in this product is active
`<inst the following common bacterial eye pathogens:
`-.iphybsrocci, including S. aureus and S. epiderinidis (coag-
`se-positive and coagulase-negative), including penicillin-
`, -istaflt strains.
`.. reptsCocci, including some of the Group A-beta-hensolytic
`cries. some nsnhemolytic species, and some Streptococcus
`.’apbo,iiae.
`udomonao seruginesa, Escherichia coli, Kiebsiella pneu-
`, ’iliac, Eiiterobocter aerogenes, Proteus mirobijis, Mor-
`,,hciia iibsigonii, most Proteus vulgaris strains, Haernophi-
`, iiflsenzac and H. oegyptius, Moraxella lacunata, Acme-
`’ocher ceicoareticus and some Neisseria species.
`CONTRAINDICATIONS
`:ithelial herpes simplex keratitis (dendritic keratitis),
`. cciiiIa, varicella, and many other viral diseases of the car-
`,, a and conjunctiva Mycobacterial infection of the eye.
`sgal diseases of ocular structures. Hypersensitivity to a
`ihpOnent of the medication.
`’\ARMNGS
`
`.
`
`.
`
`:
`
`.-
`
`.
`
`.
`
`.
`
`,
`
`,
`
`.
`
`t (cid:9)
`
`:
`
`’iT FOR INJECTION INTO THE EYE. Sensitivity to top-
`.dly applied aminoglycosides may occur in some patients.
`:
` sensitivity reaction does occur, discontinue use.
`i longed use of steroids may result in glaucoma, with
`!,chirps
`to the optic nerve, defects in visual acuity and fields
`rhaian, and posterior subcapsular cataract formation. In-
`.hscular pressure should be routinely monitored even
`nigh it may be difficult in children and uncooperative pa-
`’bits Prolonged use may suppress the host response and
`
`Os
`increase the hazard of secondary ocular infections. In
`’se
`1 atiomis have been
`diseases Causing thinning of the cornea or sclera, per-
`known to occur with the use of topical
`.raids I (cid:9)
`acute purulent conditions of the eye, steroids
`,r
`, mask infection or enhance existing infection.
`I ’RECAUTIONS
`General T1
`Possibility of fungal infections of the cornea
`considered after long -termsteroid dosing. As with
`e
`Antibi
`otic Preparations prolonged use may result in
`"’ growth
`Peri nfecti
`n5n5u5ceptible organisms, including fungi. If
`Whon n sccuro, appropriate therapy should be initi-
`. ir c11 rnultipl5 prescriptions are required, or when-
`judgem ent
`iced
` dictates, the patient should be ex-
`hicroacnp the aid Ofmagnificj0 such as slit lamp hi-
`ss.s5051.and, where appropriate, fluorescein staining.
`’ar, f8
`"ity to Other aminoglycoside antibiotics may
`Use 51555nsitivity develops with this product, discon-
`ifOrati
`d institute appropriate therapy .
`for Pat-
`ents:
`a
`D5 not touch dropper or tube tip
`genesis,
`ce, a this may contaminate the contents.
`Mutagenesis Impairment of Fertility. No
`UhOge1
`tec onducted to evaluate the carcinogenic or
`tudie (cid:176)entia),
`i bOo
`impairment of fertility was noted
`g% us tobramyci n in rats at doses of 50
`9fleri5 r’
`terate1tegory C.C
`orticosteroids have been found to
`1 fetal (cid:9)
`animal studies Ocular administration of
`resulted in 15.6% and 32.3% incidence
`- wre5t5rdatiO0 11 two groups of pregnant rabbits. Fetal
` ratincreased mortality rates have been
`slid
`Ctisnfotud with c
`hronic dexamethasone therapy. Re-
`Ob (cid:9)ray55
`
`id (cid:9)
` iso have been performed in rats and rabbits
`th 5’ reVealed O5e
`up to 100 mg/kg/day parenterally
`Ther(cid:176) evidenc e of impaired fertility or harm
`ii
`PregReOt are no adequate and well-controlled
`Woinen. TOBBADEXfi Ophthalmic Sus-
`
`Ca
`
`-
`
`-
`
`pension and Ointment should be used during pregnancy
`only ifthe potential benefit justifies the potential risk to the
`fetus.
`Nursing Mothers. Systemically administered corticoster-
`sids appear in human milk and could suppress growth, in-
`terfere with endogenous corticosteroid production, or cause
`other untoward effects. It is not known whether topical ad-
`ministration of corticostei-oida could result in sufficient sys-
`temic absorption to produce detectable quantities in human
`milk. Because many drugs are excreted in human milk, cau-
`tion should be exercised when TOBRADEXfi Ophthalmic
`Suspension or ointment is administered to a nursing
`woman.
`Pediatric Use. Safety and effectiveness in pediatric patients
`have not been established.
`ADVERSE REACTIONS
`Adverse reactions have occurred with steroid/anti-infective
`combination drugs which can be attributed to the steroid
`component, the anti-infective component, or the combina-
`tion. Exact incidence figures are net available. The most fre-
`quent adverse reactions to topical ocular tobramycin (TO-
`BREXfi) are hypersensitivity and localized ocular toxicity,
`including lid itching and swelling, and conjunctival ery-
`thema. These reactions occur in less than 4% of patients.
`Similar reactions may occur with the topical use of other
`ansinoglycoside antibiotics. Other adverse reactions have
`not been reported; however, if topical ocular tobramycin is
`administered concomitantly with systemic aminoglycoside
`antibiotics, care should be taken to monitor the total serum
`concentration. The reactions due to the steroid component
`are: elevation of intraocular pressure (TOP) with possible
`development of glaucoma, and infrequent optic nerve dam-
`ago; posterior subcapsular cataract formation; and delayed
`wound healing.
`Secondary Infection. The development of secondary infec-
`tion has occurred after use of combinations containing ste-
`roids and antimicrobials. Fungal infections ofthe cornea are
`particularly prone to develop coincidentally with long-term
`applications of steroids. The possibility of fungal invasion
`must be considered in any persistent cornea) ulceration
`where steroid treatment has been used. Secondary bacterial
`ocular infection following suppression of host responses also
`occurs.
`OVERDOSAGE
`Clinically apparent signs and symptoms of an overdose of
`TOBEADEX Ophthalmic Suspension or Ointment (punctate
`keratitis, erythema, increased lacrimation, edema and lid
`itching) may be similar to adverse reaction effects seen in
`some patients.
`DOSAGE AND ADMINISTRATION
`Suspension: One or two drops instilled into the conjuncti-
`val sac(s) every four to six hours. During the initial 24 to 48
`hours, the dosage may be increased to one or two drops ev-
`ery two (2) hours. Frequency should be decreased gradually
`as warranted by improvement in clinical signs. Care should
`be taken not to discontinue therapy prematurely. Ointment:
`Apply a small amount (approximately (cid:9)
`inch ribbon) into
`the conjunctival sac(s) up to three or four times daily.
`Not more than 20 ml, or 8 g should be prescribed initially
`and the prescription should not be refilled without further
`evaluation as outlined in PRECAUTIONS above.
`HOW SUPPLIED
`Sterile ophthalmic suspension in 2.5 mL (NDC 0065-0647-
`25), 5 mL (NDC 0065-0647-05) and 10 mL (NDC 0065-0647-
`10) DROP-TAINERfi dispensers. Sterile ophthalmic oint-
`ment in 3.5 g ophthalmic tube (NDC 0065-0648-35).
`STORAGE
`Store at 8’ to 27C (46’ to 80’F).
`Store suspension upright and shake well before using.
`Fix Only.
`U.S. Patent No. 5,149,694
`
`Allergan, Inc.
`2525 DUPONT DRIVE
`P.O. BOX 19534
`IRVINE, CA 92623-9534
`
`Direct Inquiries to:
`(714) 246-4500
`
`OPHTHALMIC PRODUCTS
`
`For information on Allergan, Inc., prescription, OTC, and
`ophthalmic products, consult the Physicians’ esk Refer-
`D
`ence for Ophthalmology. For literature, service items, or
`sample material, contact Aliergan directly. See a complete
`listing of products in the Manufacturers’ Index section of
`this book.
`
`ACULARfi (cid:9)
`(ketorolac tromethamine ophthalmic solution) 0.5%
`Sterile
`
`1
`
`PRODUCT OVERVIEW
`ACULARfi (ketorolac tromethamine ophthalmic solution)
`0.5% is the only topical NSAID indicated for the temporary
`
`ALLERGAN/491
`
`relief of ocular itching due to seasonal allergic conjunctivi-
`tis. ACULARfi is also indicated for the treatment of
`postoperative inflammation in patients who have under-
`gone cataract extraction.
`ACULARfi relieves the ocular itch associated with seasonal
`allergic conjunctivitis and inflammation following cataract
`surgery due in part to its ability to inhibit prostaglandin
`biosynthesis.
`In two double -masked, paired studies (N-=241), ACULARfi
`Solution was found to be superior to placebo in relieving the
`ocular itch of seasonal allergic conjunctivitis. 1
`Two controlled clinical studies showed that patients treated
`for two weeks with ACULARfi ophthalmic solution were
`lees likely to have measurable signs of inflammation (cell
`and flare) than patients treated with its vehicle.
`ACULARfi Solution is also proven safe in clinical trials, and
`avoids steroid-like side effects (e.g., no significant effect
`upon lOP). 1 There is no significant ocular toxicity reported
`in clinical studies to date with ACULARfi.
`The most frequently reported adverse events have been
`transient stinging and burning on instillation (approxi -
`mately 40%). Caution should be used in patients with sen-
`sitivities to other NSAlDs.
`ACULARfi Solution is available in 3 mL, 5 mL and 10 mL
`plastic bottles with a controlled-dropper tip.
`Please see full prescribing information included.
`1. Data on file, Syntex (U.S.A.) Inc.
`ACULARfi, a registered trademark of Syntex (U.S.A.) Inc.,
`is manufactured and distributed by Allergan, Inc. under
`license from its developer, Syntex (U.S.A.) Inc., Palo Alto,
`CA.
`ACULARfi is marketed by Allsrgan, Inc.
`PRESCRIBING INFORMATION
`ACULARfi
`)ketorolac tromethamine ophthalmic solution) 0.5%
`Sterile
`DESCRIPTION
`ACULARfi (ketorolac tronsethamine ophthalmic solution) is
`a member of the pyrrslo-pyrrole group of nonsteroidal anti-
`inflammatory drugs (NS.AJDs) for ophthalmic use. Its chem-
`ical name is ( – ) - 5 -bonzoyl-2,3-dihydro-lHpyrrolizine1
`carboxylic acid compound with 2-amino-2-(hydroxymethyfl
`1,3-propanecliol (1:1).
`ACULARfi is supplied as a sterile isotonic aqueous 0.5%
`solution, with a pH of 7.4. ACULARfi is a racemic mixture
`of R-(+)- and S-(-)- ketorolac tromethamine. Ketorolac
`tromethanilne may exist in three crystal forms. All forms
`are equally soluble in water. The pKa of ketorolac is 3.5.
`This white to off-white crystalline substance discolors on
`prolonged exposure to light. The molecular weight of
`ketorolac tromsthaniine is 376.41. Each mL of ACULA.Rfi
`ophthalmic solution contains: Active: ketorolac
`tiomethamine 0.5%. Preservative: benzalkonium chloride
`0.01%. Inactives: edetate disodium 0.1%; octoxynol 40:
`sodium chloride; hydrochloric acid and/or sodium hydroxide
`to adjust the PH; and purified water. The osmolality of
`ACULABfi is 290 mOsmol/kg.
`
`ANIMAL PHARMACOLOGY
`Ketorolac troinethamine prevented the development of
`increased intraocular pressure induced in rabbits with top-
`ically applied arachidonic acid. Ketorolac did not inhibit
`rabbit lens aldose reductase in vitro.
`Ketorolac tromethamine ophthalmic solution did not
`enhance the spread of ocular infections induced in rabbits
`with Candor/a albicans, Herpes simplex virus type one, or
`Pseudomossas aerugiisosa.
`CLINICAL PHARMACOLOGY
`Ketorolac tromethainine is nonsteroidal anti-inflammatory
`drug which, when administered systemically, has demon-
`strated analgesic, anti-inflammatory, and anti-pyretic activ-
`ity. The mechanism of its action is thought to be due, in
`part, to its ability to inhibit prostaglandin biosynthesis.
`Ketorolac tromethamme given systemically does not cause
`Pupil constriction.
`Prostaglandins have been shown in many animal models to
`be mediators of certain kinds of intraocular inflammation.
`In studies performed in animal eyes, Prostaglandins have
`been shown to produce disruption of the blood-aqueous
`humor barrier, vasodilation, increased vascular permeabil-
`ity, leukocytosis, and increased intraocular pressure. Pros-
`taglandins also appear to play a role in the miotic response
`produced during ocular surgery by constricting the iris
`sphincter independently of cholinergic mechanisms.
`Two drops (0.1 mL) of 0.5% ACULARfi ophthalmic solution
`instilled into the eyes of patients 12 hours and 1 hour prior
`to cataract extraction achieved measurable levels in 8 of 9
`patients’ eyes (mean ketorolac concentration 95 ng/mL
`aqueous humor, range 40 to 170 ng/mL). Ocular administra-
`tion of ketorolac tromethamine reduces prostaglandin E 2
`(PGE 2) levels in aqueous humor. The mean concentration of
`PGE2 was 80 pg/mL in the aqueous humor of eyes receiving
`vehicle and 28 pg/mL in the eyes recoivingACULARfi 0.5%
`ophthalmic solution.
`One chop (0.05 mL) ofO.5%ACUL(cid:176),Jffi ophthalmic solution
`was instilled into one eye and one drop of vehicle into the
`other eye TID in 26 normal subjects. Only 5 of 26 subjects
`had a detectable amount of ketorolac in their plasma (range
`10.7 to 22.5 ng/mL) at Day 10 during topical ocular treat-
`
`Consult 2000 PDRfi supplements and future editions
`
`for revisions
`
`Continued on next page
`
`Page 2 of 3
`
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`(cid:9)
`

`
`490/ALCON
`
`NAPHCONfi A (cid:9)
`Eye Drops
`Relieves Itching & Redness
`EYE ALLERGY RELIEF
`
`OTC
`
`Temporary relief of the minor eye symptoms of itching and
`redness caused by ragweed, pollen, grass, animal hair, and
`dander.
`DESCRIPTION
`Active: Pheniramine Maleate 0.3%, Naphazoline Hydro-
`chloride 0.025%. Preservative: Benzalkonium Chloride
`0.01%. Inactive: Sodium Chloride, Boric Acid, Sodium Bo-
`rate, Edetate Disodium 0.01%, Sodium Hydroxide and/or
`Hydrochloric Acid (to adjust pH), Purified Water. The sterile
`ophthalmic solution has a pH of about 6 and a tonicity of
`about 270 mOsmlKg.
`DIRECTIONS
`Instill 1 or 2 drops in the affected eye(s) up to 4 times daily.
`WARNINGS
`To avoid contamination, do not touch tip of container to any
`surface. Replace cap after using.
`If solution changes color or becomes cloudy, do not use.
`If you experience eye pain, changes in vision, continued red-
`ness or irritation of the eye, or i