STERILE PHENYLEPHRINE HYDROCHLORIDE
`OPHTHALMIC SOLUTION. USP
`Fix only
`
`oi
`solutions
`Ophthalmic
`CONTRAINDICATIONS:
`phenylephrine hydrochloride are contraindicated In persons
`with narrow angle glaucorna (and in those individuals rrrrito
`are hypersensitive to phenyiephrine or to any or
`the
`components of the product}. Fhenylephrine I-lydrochloride
`Ophthalmic Solution in the 10% strength is contraindicated in
`infants and in patients with aneurysms.
`WARNINGS: There have been rare reports associating the
`use or Phenylephrine l-lydrocitlorlda Ophthalmic Solution.
`10%, with the development of serious cardiovascular
`reactions. including ventricular arrhythmias and rrryocardlal
`lniarctions. These episodes. some ending fatally. have
`usually occurred in elderly patients with preexisting
`cardiovascular diseases.
`recommended
`PHEOAUTIONS: General: Exceeding
`dosages
`or
`applying
`Phenylephrlne Hydrochloride
`Ophthalmic solution to the instrumented.
`traumatized.
`diseased or post surgical eye or adnetta. or to patients with
`suppressed lacrimetion, as during anesthesia. may result In
`the absorption of sufficient quantities of phenylephrlne to
`produce a systemic vasopreesor response.
`A significant elevation in blood pressure is rare but has been
`reported following conjunctiva] instillation of recommended
`doses of Pherryiephrlne Hydrochloride Ophthalmic Solution.
`10%. Caution.
`therefore.
`should
`be
`exercised
`in
`administering the 10% solution to children of
`low body
`weight.
`the elderly. and patients with Insulin-dependent
`diabetes.
`hypertension.
`hyperthyroidism.
`generalized
`arteriosclerosis. or cardiovascular disease. The posttreatment
`blood pressure of these patients. and any patients who
`develop symptoms. should be ceretuliy monitored.
`Ordinarily.
`any mydrietlo.
`including
`phenyiephrine
`hydrochloride.
`is contraindicated in patients with glaucoma.
`since it may occasionally raise lntraocular pressure.
`However, when temporary dilatation oi‘ the pupil may free
`sdheslons or when vasoconstrlction of intrinsic vessels may
`lower intraocuiar tension. these advantages may temporarily
`outweigh the danger from coincident dilatation of the pupil.
`Rebound miosls has been reported In older persons one day
`after receiving Fhenyiepl-rrlne Hydrochloride Ophthalmic
`Solutions. and reinstillation oi the dmg produced a reduction
`in mydrissia. This may be of clinical importance in dilating the
`pupils oi older subjects prior to retinal detachment or cataract
`surgery
`Due to a strong action of the drr.rg on the dilator musds. older
`individuals may also develop transient pigment floaters in the
`aqueous humor so to 45 minutes following the adrninietraiion
`of Phenylephrine Hydrochloride Ophthalmic Solutions. The
`appearance may be similar
`to anterior Lrveitis or to a
`microscopic hypherna.
`To prevent pain, a drop of suitable topical anesthetic may be
`applied before using the 10% ophtitalrnlc solution.
`Drug Intereotiort: As with all other adrenergio drugs. when
`Pnenyiephrlne Hydrochloride Ophthalmic Solutions 109$ or
`2.5% are administered simultaneously with, or up to 21 chys
`after, administration of monoemine oiridaae [MAO] irrttibltors.
`careful supervision and adjustment oi‘ dosages are required
`since exaggerated sdrenerglc effects may occur. The preasor
`response of sdrenerglc agents may also be poteniiatsd by
`tricyciic
`antidepressants.
`prcpranoiol,
`reserpine.
`guartettricline. methyloopa. and atropine-iiirra drugs.
`carcinogenesis,
`taluteget-reels, impairment or Fertility:
`No long-term animal studies have been done to evaluate the
`potential of Phenylephrine Hydrochloride Ophthalmic
`Solution in these areas.
`
`Exhibit 1018- Page 1 of 2
`
`
`
`
`
`SHOULD COMPLETELY
`F'HYSlO|-ANS
`WARNING:
`FAMILIAFIIZE THEMSELVES WITH THE COMPLETE
`CONTENTS OF Tl-liS LEAFLET E-EFOFIE PRES-ORIEING
`PHENYLEPHFIINE HYDROCHLORIDE OPHTHALMIC
`SOl.UTiON.
`
`DESCRIPTION: Phenylaphrlne Hydrochloride Ophthalmic
`Solution is a sterile solution used as a vasoconstrlctor and
`rnydriatlc for use in ophthalmology.
`Phenytephrlne hydrochloride is a synthetic syrnpathomimetic
`compound structurally similar to epinephrine and ephedrine.
`Pttenylepl-rrine hydrochloride has the following structural
`formula:
`OH
`
`
`
`c—cH,NHcH3- Hci
`
`9''
`
`benzyi
`
`coder
`alcohol
`
`is
`
`ctr
`CgH13NO2.HCi
`(-}-rrr-Hydrorty-ct-Iimetl-ryiamlnolrnathyi]
`hydrochloride
`Phenyiephrine Hydrochloride Ophthalmic Solution
`available in two strengths, 2.5% and 10%.
`Each mL of
`the 2.5% solution contains: Phenylephrine
`Hydrochloride 2.5%. Dlbasic and Monobssio Sodium
`Phosphates. Boric Acid. with Senzallronium chloride as
`preservative in Water for injection q.s.
`Each mL of the 10% solution contains: Phenylepi-rrine
`Hydrochloride 10%. Dlbeslc and ltionobasic Sodium
`Phosphates, with Benzalkonlum Chloride as preservative in
`Water for lnlection q.e.
`Hydrochicrk: Acid andior Sodium Hydroxide may have been
`used to adjust pH of both solutions.
`Phenylephrine
`CLINIGAL
`PHARMACOLOGY:
`possesses
`Hydrochloride
`Ophthalmic
`Solution
`the
`eye.
`in
`predominantly
`ct-adre ltergic
`effects.
`phenyiephrin-e eels locally as a potent vasoconetrictor and
`rrrydrietlc. by constricting ophthalmic blood vessels and the
`radial muscle of the iris.
`phenyiephrine
`of
`usefulness
`The
`ophtitaimologic
`hydrochloride is due to its rapid efisct and moderately
`prolonged action, as well as to the fact that it produces no
`compensatory vasodiiatatlon.
`The action of different concentrations of ophthalmic solutions
`of phenylepl-rrlrre hydrochloride is shown in the following
`table:
`
`
`
`Although rare. systemic absorption of sufficient quantities of
`phanylephrine may lead to systemic ct-sdrenerglc effects.
`such as rise in blood pressure which may be accompanied
`by a teller: atropine-sensitive bradycerdia.
`|NDicA'i1ON8 AND USAGE: Phsnyiepttrine hydrochloride is
`recommended
`for
`use
`as
`a
`dacongeatant
`and
`vasoconstrictor and for pupil dilatation in uvettis {posterior
`syneci-rise). wide angle glaucoma. prior to surgery. refraction.
`ophthalmosoopic examination. and diagnostic procedures.
`
`Exhibit 1018- Page 1 of 2
`
`

`
`Pregnancy category G: Animal reproduction studies have
`not been conducted with Phenyiephrlne Hydrochloride
`Ophthalmic Solution.
`it
`is also not known whether
`Phenylephrins Hydrochloride Ophthalmic Solution can cause
`ietal harm when administered to a pregnant woman or can
`aflect reproduction capacity, Phenytephrlne Hydrochloride
`Ophthalmic Solution should be given to a pregnant women
`only it clearly needed.
`is not known whether this drug is
`Nursing Mothers:
`it
`ettctoted in milk; many are. Caution should be stnerclsed
`when Phenylephrine Hydrochloride Ophthalmic Solution is
`administered to a nursing woman.
`Pediatric Use: Phenylephrine Hydrochloride Ophthalmic
`Solution.
`1D%,
`is
`contraindicated in
`infants.
`{Sea
`GDN‘l'HAiNDlCATl-OHS.) For use In older children {See
`DOSAGE AND ADti|lNiSTFlilt'l1ON.l
`applying
`or
`Exceeding
`recommended
`dosages
`Phanylephrlns Hydrochloride Ophthalmic Solutions to the
`instrumented. traumatized. diseased or post aurgicai eye or
`adnaxa. or to patients with suppressed ieorlmstlon. as during
`anesthesia. may result
`in the absorption or sufficient
`quantities of phenylephrine to produce
`a
`systemic
`vasopressor response.
`The hypertensive effects oi phenylephrlne may be treated
`wtth
`an alpha-sdrenergic
`biooi-ring agent
`such as
`phentolsmlne mesyiste. 5 mg to to my intravenously.
`repeated as necessary
`The oral LD 59 of phenylephrihs In the rat: 350 mgikg, in the
`l'rIDl.ise: 120 mgikg.
`To
`report
`aU8PEt.'.'TED ADVERSE REAGTIONS.
`contact Aitalre Pharnteceuticate. lrrc. at {$31) T22-E058
`Dent-open HT Monday-Friday.
`DOSAGE AND ADllllNi8‘i'fl.t\‘i1ON: Prolonged exposure to
`air or strong light may cause oxidation and discoloration. Do
`not use it solution is brown or contains a precipitate.
`To avoid contamination. do not touch dropper tip to any
`surlaoe.
`trasocorietriolien end Pupil Dilatation: Fhenylephrlns
`Hydrochloride Ophthalmic Solution. 10%. is especially useful
`when rapid and powerful dilatation of the pupil and reduction
`of congestion in the capillary bed are desired. A drop of a
`suitable topical anesthetic may be applied. ioliowed in a law
`n'linLites by 1 drop of
`the Phenylephrine i-iydrochloride
`Ophthatrnic Eiolution. 10%. on the upper limbua. The
`anesthetic prevents stinging and consequent dilution of the
`solution by lscrlmation. it may occasionally be necessary to
`repeat the instillation alter one hour, again preceded by the
`use of the topical anesthetic.
`Phenylephrlne
`Utrattlat
`Poiberior
`Syrteohlaer
`Hydrochloride Ophthalmic Solution. 10%. may be used in
`patients with uveitls when synsohiae are present or may
`devsIop.‘l'he formation of synechlae may be prevented by the
`use of the 16% ophthalmic solution and atropine to produce
`wide dilatation oi
`the pupil.
`it should be emphasized.
`however,
`that
`the vasooonstrlctor street of pnsnyiephrlne
`hydrochloride may be antagonistic to the increase of local
`blood flow in uveai infection.
`1 drop of the
`To free recently iorrned posterior aynechiae.
`10% ophthalmic solution may be applied to the upper surface
`of
`the cornea. On the following day.
`treatment may be
`continued lineceesary. in the interim. hot compresses should
`he applied for live or ten minutes three times a day. with 1
`drop of a 1 or 2% solution of atropine sulfate betore and after
`each series or compresses.
`temporary
`Glaucoma: in certain patients with glaucoma.
`reduction or lntraocuiar tension may be attained by producing
`vasoconalrictlon of the lntraocuiar vessels; this may be
`aocornplistled by placing 1 drop of
`the 10% ophthalmic
`solution on the upper suriace oi the cornea. This treatment
`may be repeated as often as necessary.
`Phenylaphrine hydrochloride may be used with mlotice in
`patients with wide angle glaucoma. It reduces the dltflcultlee
`experienced by the patient because of the small
`field
`produced by miosia. and still it permits and often supports the
`
`""'\
`
`the robotic in lowering the lntraocuiar pressure.
`effect of
`Hence. there may be marked improvement in visual acuity
`after using phsnylaphrine hydrochloride in conjunction with
`rniotlc drugs.
`surgery: when a short-acting mydriaiio is needed for wide
`dilatation oi the pupil heiore lntraocuiar surgery the 1lJ‘lia or
`2.5% ophthalmic solutions may be applied topically from 30
`to 50 minutes before the operation.
`refrectlve errors.
`Hetreotlon: Prior to determination of
`Phenylephrlrte Hydrochloride Ophthalmic Solution. 2.5%.
`may be used stlectivsly with homatropine hydrohrornlde.
`atropine sulfate. or a oornblnsdon oi hornatroplns and
`cocaine hydrochloride.
`For ADULTS. a drop of the preferred cyolopl-epic is plllced in
`each eye, followed in live minutes by 1 drop oi Phenylephrine
`l-iydroohloride Ophthalmic Solution. 2.5%. and in ten minutes
`by another drop of the cycioplegic. In 50 to 60 minutes. the
`eyes are ready tor retraction.
`For CHILDREN, a drop of atropine eultate 1% is placed in
`each eye.
`ioliowed in 10 to 15 minutes by 1 drop of
`Phenyiephrlrle Hydrochloride Ophthalmic Solution, 2.5%.
`and in live to ten minutes by a second drop of atropine sulfate
`1%. in one to two hours. the eyes are needy for retraction.
`For a ‘one application method’. Phenyiephrine Hydroctlloride
`ophthatrnlc Solution. 2.5%. may be combined with a
`cyclopleglc to elicit synergistic action. The additive stisct
`varies depending on the patient. Therefore. when using a
`"one application method.“ it may be desirable to increase the
`concentration oi‘ the cyclopiegic.
`or
`drop
`one
`ophthairnoeoopic
`Examination:
`Phenylephrine Hydrochloride Ophthalmic Solution, 2.5%. is
`placed in each eye. Suiilolsnt mydriasls
`to permit
`atiamination is produced In 15 to 30 minutes. Dilatation lasts
`from one to three hours.
`Diegnoattc Procedures: PFIDVOCATWE TEST FOFI
`ANGLE BLOCK IN PKTIENTS WITH C-ILAUCOMA: The 2.5%
`ophthalmic solution may be used as a provocative test when
`latent increased lntraocuiar preesure is suspected. Tension is
`measured betore application of phanylephrlne hydrochloride
`and again attar dilatation. A 3 to 5 mm of mercury-rise in
`pressure suggests the presence of angle block in patients
`with glaucoma; however. lallura to obtain such a rise does not
`preclude the presence of glaucoma from other causes.
`SHADOW TEST (FIETINOSCOPY): When dilatation oi the
`pupil without cyclopleglc action is desired for the shadow
`test. the 2.5% ophthalmic solution may be used alone.
`BL.-|.NCHlhiG TEST: one or 2 drops at the 2.5% ophlhalrnlc
`solution should he applied to the Injected eye. Alter live
`minutes. examine tor perillmbal blanching.
`ll blanching
`occurs. the congestion is superficial and probably does not
`indicate little.
`Phenylephrihe Hydrochloride
`HOW SUPPLIED:
`Ophthairnio Solution. 2.5%.
`is available in sterile plastic
`dropper bottles or 5 mL and 15 mL. Phenylephrine
`Hydrochloride Dpitthlirnlc Solution. 10%. is available in
`sterile plastic dropper bottles or 5 mL and 15 mL.
`Keep container tightly closed.
`Store at 2‘ - s°c (3B‘ - 6o‘F}.
`PROTECT FROM LIGHT.
`Solution should be cololtess to light yellow. Do not use if it is
`brown or contains a precipitate.
`Keep this and all medications out oi the reach of children.
`Literature revised: August 2010
`
`Mid. by: amtme Pl-ierrnaceuticsls.inc.
`Aqueboguc. NY 11931
`
`MG #1 65136
`
`Exhibit 1018- Page 2 of 2
`
`Exhibit 1018- Page 2 of 2