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`[Cut off: Third class mail, ISSN 0913-7505 CODEN: RYCHEI]
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` Special Feature 
`The Future of Osteoporosis Treatment
`in Primary Care
` Drug of the Month 
`Anti-epileptic drugs
`
` THE TOPICS 
`Japanese Psychogeriatric Society Specialist System
`From the Clinic / Evaluation of New Drugs by Clinicians
`
`
`Metrics EX1002, Page 1
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`

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`induction of inflammation. This activity is said to be
`11 times greater than that of indomethacin, which is
`synonymous with NSAIDs. 1)
`
` Comparison with existing analogues
`There are 3 types of NSAID ophthalmic drugs
`
`that are currently available on the market:
`pranoprofen, indomethacin and diclofenac sodium.
`
`Pranoprofen (Niflan) is an anti-inflammatory
`drug that is indicated for use in treating inflammation
`of the outer ocular and anterior ocular areas, and it is
`the most commonly used drug today. However, the
`efficacy of pranoprofen is weaker than that of this
`drug, and pranoprofen cannot completely inhibit the
`generation of fibrin in uveitis such as iritis, or in post-
`operative inflammation.
`
`Indomethacin (Indomelol) is used to prevent the
`generation of fibrin following surgery and to
`maintain mydriasis during surgery. However, it is an
`oil-based drug, and therefore, an oil film may remain
`on the operative field during the procedure as a result
`of pre-operative instillation, which can sometimes
`prevent the progress of the surgery. Though this
`product resulted in a marked decrease in the
`generation of fibrin following surgery, it is mostly no
`longer used.
`
`Diclofenac sodium (Diclod) is an NSAID drug
`that is indicated for use in treating anterior ocular
`segment inflammation following cataract surgery,
`and it shows particular efficacy in preventing the
`generation of fibrin, with superior anti-inflammatory
`efficacy. As is the case with bromfenac sodium
`hydrate, diclofenac sodium has a chemical structure
`in which two chlorine atoms (Cl) have been added to
`the basic structure. Problems with the generation of
`fibrin following surgery have mostly disappeared.
`Based on the pharmacological activity of the drug, it
`is believed to be effective in treating not only post-
`operative inflammation but also in treating outer
`ocular area inflammation and uveitis of the anterior
`ocular area, such as iritis. However, the range of
`
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`
`Commentary
`
`Sumitomo Hospital, Department
`of Ophthalmology, Chief Director
`Yoshiyuki Hara
`
`
`Adrenocortical hormone (steroid) drugs are the
`
`most commonly used anti-inflammatory drugs to
`treat local inflammation in the field of ophthalmology.
`Steroids show superior pharmacological efficacy, and
`are used very frequently in everyday
`ophthalmological applications. However, there have
`also been many reports of adverse drug reactions
`such as corneal ulcers or corticosteroid glaucoma, etc.
`In consideration of these types of adverse drug
`reactions to steroids, there is also significant demand
`for non-steroidal anti-inflammatory drugs (NSAIDs).
`Currently, there are fewer types of NSAID
`ophthalmic drugs in comparison to steroid
`ophthalmic drugs, resulting in limited choices.
`
`Bromfenac sodium hydrate is a type of NSAID
`that was developed in order to address the needs of
`clinical sites, and it is indicated for use in a broad
`range of conditions, from inflammation of the outer
`ocular area to post-operative inflammation of the
`anterior ocular segment.
`
`The active ingredient in this drug is bromfenac
`sodium hydrate. Enhancement of anti-inflammatory
`action and maintenance of analgesic action is
`achieved through the addition of a bromine atom (Br)
`to the 4th position of the basic amfenac structure. The
`drug was given the name Bronuck by taking part of
`the name of the active ingredient.
`
`The mechanism of activity of this drug involves
`activity to inhibit cyclooxygenase (COX) during the
`arachidonic acid cascade that is involved in the
`
`Evaluation of New Drugs by Clinicians
`
` Non-steroidal anti-inflammatory ophthalmic solution
`Bromfenac sodium hydrate
`Start of sales: July 2000
`
`
`Bronuck ophthalmic solution
`(Senju Pharmaceutical Co., Ltd. – Takeda
`Pharmaceutical Co., Ltd.)
`
`Metrics EX1002, Page 2
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`

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`applications is limited because the drug is indicated
`only for use in treating inflammation following
`cataract surgery.
`
` 
`
` Tips in using the drug
`Aqueous ophthalmic solutions of bromfenac
`
`sodium hydrate contain 0.1% of the drug, and are
`clear, yellow solutions with a pH of 8.0 ~ 8.6. The
`solutions also contain benzalkonium chloride in
`addition to buffers and stabilizers. These solutions
`are used twice a day, with the instillation of 1 ~ 2
`drops per dose. 2)
`
`It is necessary to keep in mind the fact that this
`drug is used not to treat the underlying disease, but as
`symptomatic therapy. Therefore, in the case of eye
`inflammation resulting from an infectious disease or
`the like, the fundamental treatment should involve
`localized or systemic dosing of antibiotics or
`antibacterial drugs.
` With eye inflammation, once the arachidonic
`acid cascade has started, the inflammation can
`worsen suddenly, and the arachidonic acid that has
`been released can cause an inflammatory response
`based on COX. With drugs such as steroids that
`inhibit the release of an arachidonic acid cascade by
`being taken up into cells, it is necessary to administer
`sufficient drug during the early stage of the
`inflammation, or before the inflammation starts. In
`contrast, this drug acts on COX, and therefore, it will
`inhibit the production of prostaglandin, which is a
`phlogogenic substance, by free arachidonic acid in
`the presence of COX. Therefore, one of the strengths
`of this drug is that sufficient efficacy can be expected
`even after the inflammation has been induced. 3)
`
` 
`
` Precautions
`Adverse drug reactions include blepharitis and
`
`corneal erosion, corneal edema, corneal abrasion and
`conjunctival hyperemia, etc. The frequency of the
`occurrence of adverse drug reactions was 16 out of a
`total of 423 cases (3.78%) in a Phase III clinical
`study. In terms of the occurrence of corneal disorders,
`COX inhibitory activity is said to be involved, even
`in healthy tissue such as the cornea. Therefore,
`sufficient care is required when using this drug. 2)
`
`
`
`Also, there have been foreign reports of serious
`
`liver disorders, including cases of death, when oral
`bromfenac sodium was used for at least one month.
`Therefore, this drug is meant to be used for less than
`one month.
`
`
`Comments
`This drug shows superior efficacy in treating
`
`anterior eye inflammation and post-operative
`inflammation. Unfortunately, this drug has not been
`approved for use in the treatment of anterior uveitis.
`This is due to the fact that, in the clinical studies,
`steroid drugs were used as the control in the
`comparisons, and therefore, there was insufficient
`significant difference in order to obtain approval.
`Based on the fact that the drug shows results that are
`not inferior to other NSAIDs when used to treat
`anterior uveitis, there are hopes that additional
`indications will be approved for the drug in the
`future. 3 ~ 5)
`
` 
`
` Literature
`1) Shimizu H, et al: Clinical efficacy of Bromfenac Sodium
`ophthalmic solution in treating inflammation following
`intraocular lens insertion – Study of the number of
`instillations. Journal of the Eye 14: 309-316, 1997
`2) Masuda K, et al: Clinical efficacy of Bromfenac Sodium
`ophthalmic solution in treating inflammation following
`intraocular lens insertion – Study of the optimal
`concentration. Folia Japonica de Ophthalmologica
`Clinica 91: 745-750, 1997
`3) Masuda K, et al: Efficacy of Bromfenac Sodium (AHR-
`10282B) ophthalmic solution in treating post-operative
`inflammation – A double-blind comparative study. Folia
`Ophthalmologica Japonica 48: 560-569, 1997
`4) Usui, M, Masuda K: Efficacy of Bromfenac Sodium
`(AHR-10282B) ophthalmic solution in treating anterior
`uveitis. Folia Japonica de Ophthalmologica Clinica 91:
`739-744, 1997
`5) Sawa M, et al: Clinical efficacy of 0.1% Bromfenac
`Sodium ophthalmic solution in treating outer ocular area
`inflammation. Folia Ophthalmologica Japonica 48: 717-
`724, 1997
`
`
`
`
`
` <
`
` Author contact > Yoshiyuki Hara, Sumitomo Hospital, Department of Ophthalmology, 5-3-20 Nakanoshima,
`Kita-ku, Osaka 530-0005
`
`
`Metrics EX1002, Page 3
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`

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`2j ~umcs & arug
`v. 19. no. 10 (no. 163} (Oct. 2000)
`General Collection
`1 RI217C
`
`iB.=~illtl~f!e4W~~iiJ ISSN 0913·7505 CODEN: RYCHEI
`
`e~~-;; I,~~-~-.---
`CLINICS &DRUG THERAPY 2000 Vol.19 No.1o
`" .
`
`PROPERlY OF THE
`NATIO.NAL
`LI·BRARY :OF
`MEDICINE
`
`Metrics EX1002, Page 4
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`
`Metrics EX1002, Page 6
`
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