BMKY ~
`
`
`
`(Exceeds 300 pages)
`
`Proceeding] Sexial No: 9 1 182488
`
`9'-9-09
`
`‘rifle: Endo Phaxmaceuticals Inc. V. Intervenltional
`alpine Inc.
`
`Part 1 of 2
`
`
`
`
`
`
`
`Processed by Curtis Puryear
`
`

`
`S
`
`C
`
`d
`h
`E l’
`n a
`"T"'°“NEY5 AT LAW
`
`750 9TH STREET, NW SUITE 550
`WASHINGTON. DC 20001-4534
`202.419.4200 mx 202.419.3454 schnadencom
`
`BRUCE A MCDONALD
`PARTNER
`(202)-1l‘)—~1235
`
`September 8, 2009
`
`TTAB
`
`Trademark Trial and Appeal Board
`U .S. Patent and Trademark Office
`
`P.O. Box 1451
`
`Alexandria, VA 22312-1451
`
`.4;‘t77c;f7c.1‘l‘/at
`
`‘
`
`Re:
`
`Ertdo Pharmaceuticals Inc. v. Interventional Spine, Inc., Opposition No.
`91182488 (Our Ref. 0222552.0052)
`
`Dear Sir or Madam:
`
`Enclosed for filing in this matter please find the Attachments to the Declaration of Guy
`
`Donatiello. The Declaration of Mr. Donatiello has been electronically filed as Exhibit A to
`
`Opposer’s Motion for Summary Judgment.
`
`Sincerely,
`
`KPK . /VH1/Kant/Vx avQ——»{
`
`Bruce A. McDonald
`
`BAM:me
`
`Attachments
`
`cc:
`
`Endo Pharmaceuticals Inc. (w/o att.)
`Sm“ Nataupsky’ Esq‘ ‘W/at”
`
`lllllllllll\\l\\\\\\\\\\\\\\\\l\\\\l\\\\\\\\\\\\\
`09-09-2009
`
`,
`
`.._‘,A-_ :._;s_
`
`NEW YORK
`
`& Lewis LLP
`Schnader Harrison Segal
`PENNSYLVANlA
`CAL|FOHNlA WASH|NGTON,DC
`NEW JERSEY
`
`

`
`-tsJam?
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE TRADEMARK TRIAL AND APPEAL BOARD
`
`In the matter of Application Serial No. 77/070,442: PERCUDYN
`Published in the Oflicial Gazette of January 15, 2008, in International Class 10
`
`Endo Pharmaceuticals lnc.,
`
`Opposer,
`
`V.
`
`Interventional Spine, Inc.,
`
`Applicant.
`
`\/\/\y\./§/\/\/&/\/\;
`
`Opposition No. 91 182488
`
`Application Serial No. 77/070,442
`
`ATTACHMENTS TO DECLARATION OF GUY DONATIELLO
`
`The following attachments accompany the Declaration of Guy Donatiello, submitted as
`
`Exhibit A to Opposer’s Motion for Summary Judgment, filed September 8, 2009.
`
`F
`
`Attachment
`
`1
`
`Percodan®, U.S. Trademark Registration No. 507,983, registered March 22,
`
`Description
`
`1949
`
`2
`
`3
`4
`
`5
`
`6
`
`7
`
`8
`
`9
`
`10
`
`11
`
`Percocet®, U.S. Trademark Registration No. 1,051,682, registered November 2,
`1976
`
`‘LPercodan® Product Information from PDF at website
`Recent Press Releases
`
`
`
`Index of 340+ Newspaper Articles From 1959 — 2005 Appearing Principally in the
`Los Angeles Times, Washington Post, Chicago Tribune, and Wall Street Journal
`
`Internet References to Percodan® Downloaded April 12, 2009
`
`New York Times article referring to Percodan® as a “famous narcotic”
`
`New York Times article describing Percocet® as “one of the most popular
`prescription painkillers in the world”
`
`Sample of Recently Issued Trademark Registrations Covering Both
`Pharmaceuticals and Medical Devices
`
`Sample of U.S. Trademark Registrations Owned by PhRMA Member Johnson &
`Johnson in international Classes 5 and 10
`
`Sample of U.S. Trademark Registrations Owned by PhRMA Member Bayer
`Healthcare LLC and Affiliates
`
`i—‘
`
`F
`
`

`
`Attachment
`12
`
`13
`
`14
`
`Description
`Sample of U.S. Trademark Registrations Owned by PhRMA Member Abbott
`Laboratories and Affiliates
`
`Class 5 and Medical Equipment and Devices, in International Class 10
`
`Sample of U.S. Trademark Registrations Owned by PhRMA Member Genzyme
`Corporation and Affiliates
`
`U.S. Trademark Registrations Covering Analgesic Products in Both lnternatlonal
`
`Respectfully submitted,
`
`ENDO PHARMACEUTICALS INC.
`
`/M‘, /2/Lt/Vawuvx M, ,4
`
`Bruce A. McDonald
`
`SCHNADER HARRISON SEGAL & LEWIS LLP
`750 9”‘ St., N.W., Suite 550
`Washington, D.C. 20001
`Tel.:
`(202) 419-4235
`Fax:
`(202) 419-3454
`e-mail bmcd<mald’c17sclmadcizcom
`
`September 8, 2009
`
`

`
`CERTIFICATE OF SERVICE
`
`The undersigned hereby certifies that on September 8, 2009, a copy of the foregoing
`Attachments to the Declaration of Guy Donatiello were sent by United States mail first class
`prepaid, on the following counsel of record for the Applicant:
`
`Steven J. Nataupsky, Esq.
`KNOBBE MARTENS OLSON & BEAR LLP
`2040 Main Street, 14”‘ F1.
`Irvine, CA 92614
`E-mail: snataupsky@kmob.com
`
`_ /1/\.\ /7 (}\(A/\ ax
`
`,{
`
`Bruce A. McDonald
`
`Attorney
`SCHNADER HARRISON SEGAL & LEWIS LLP
`
`

`
`

`
`Attachment 1
`
`

`
`
`
`In testimony whereof I have hereunto set my hand
`and caused the seal of The Patent and Trademark
`Office to be affixed on July 4, 1989.
`
`COMMISSIONER OF PATENTS AND TRADEMARKS
`
`
`
`
`
`Int. CL: 5
`
`Prior U.S. CL: 18
`
`O Renewal
`
`Reg. No. 507,983
`United States Patent and Trademark Office
`Registered Men 22’ 1949
`
`
`OG Date July 4, 1989
`
`TRADEMARK
`PRINCIPAL REGISTER
`
`PERCODAN
`
`PHARMACEUTICALS
`(DELAWARE CORPO-
`
`FONT
`DU
`CARIBE,
`INC.
`“A710”?
`P.O. BOX 12
`HIGHWAY 63, KM.2.3.
`MANATI, PUERTO RICO 00701, ASSIGN-
`EE BY MESNE ASSIGNMENT AND
`CHANGE OF NAME FROM ENDO
`PRODUCTS INC. (NEW YORK CORPO-
`RATION) RICHMOND HILL, NY
`
`FOR: GENERAL ANALGESIC,
`CLASS 18 (INT. CL. 5).
`FIRST USE 1-15-1943; IN commence
`1_15_1948_
`
`IN
`
`sER_ No_ 553,092’ FILED 3_25_1943_
`
`

`
`Latest Status Info
`
`Page 1 of 3
`
`Thank you for your request. Here are the latest results from the TARR web server.
`
`This page was generated by the TARR system on 2009-08-04 21:50:14 ET
`
`Serial Number: 71553092 Assignment Information
`
`Trademark Document Retrieval
`
`Registration Number: 507983
`
`Mark (words only): PERCODAN
`
`Standard Character claim: No
`
`Current Status: This registration has been renewed.
`
`Date of Status: 2008-04-17
`
`Filing Date: 1948-03-26
`
`Transformed into a National Application: No
`
`Registration Date: 1949-03-22
`
`Register: Principal
`
`Law Office Assigned: (NOT AVAILABLE)
`
`If you are the applicant or applicant's attorney and have questions about this file, please contact
`the Trademark Assistance Center at TrademarkAssistanceCentera1}uspto.gov
`
`Current Location: 408 -Scanning On Demand
`
`Date In Location: 2009-01 -26
`
`LAST APPLICANT(S)/OWNER(S) OF RECORD
`
`1. l3ND() Pl lARMACF.UTl(‘ALS INC.
`
`Address:
`ENDO PHARMACEUTICALS INC‘.
`100 Endo Blvd.
`
`Chadds Ford, PA l93 l 7
`United States
`
`Legal Entity Type: Coiporation
`State or Country of Incorporation: Delaware
`
`GOODS AND/OR SERVICES
`
`U.S. Class: 0] 8 (lntemational Class 005)
`Class Status: Active
`
`http://tarr.uspto.gov/tarr?regser=registration&entry=507983
`
`8/4/2009
`
`

`
`Latest Status Info
`
`Page 2 of 3
`
`GEXIERAID. ANALGESIC
`
`. Basis: 1(a)
`
`First Use Date: 1948-01 - I 5
`First Use in Commerce Date: [9454-01-15
`
`(NOT AVAILABLE)
`
`(NOT AVAILABLE)
`
`ADDITIONAL INFORMATION
`
`MADRID PROTOCOL INFORMATION
`
`PROSECUTION HISTORY
`
`NOTE: To view any document referenced below, click on the link to "Trademark Document
`Retrieval" shown near the top of this page.
`
`2009-01-26 - (‘Lise File ln Tl(‘RS
`
`2008-0-1- I 7 — Third renewal 10 year
`
`2008-04-17 -- Section 8 ( 10-year) acceptedw’ Section 9 granted
`
`0
`
`2008-04-08 - Assigned To Pztrulcgal
`
`200X—()3-3|
`
`- TEAS Section rs’ & 9 Rcceixcd
`
`2008-03-31 -- Applicant (‘orrcspondcnce (‘lianges (T\lon-Responshc) lintcred
`
`2008-03-3|
`
`-- TEAS Change ()l'()wncr Address Reccixcd
`
`2()t)2-08- I 5 — Section I5 ackmiwlcdged
`
`2()()2—()5-30 - Section 15 z1t’l'1du\ it received
`
`1989-03-22 -- Second renewal
`
`1989-02-27 — Section 9 lilcdtcheck record for Section 8‘
`
`l9()9—(e)3—23 - First I‘CIlC\\'Lll
`
`ATTORNEY/CORRESPONDENT INFORMATION
`
`Attorney of Record
`JAMES R. =.\1F,YFR
`
`Correspondent
`
`http://tarr.uspto.gov/tarr?regser=regisHation&cnnF507983
`
`8/4/2009
`
`

`
`Latest Status Info
`
`Page 3 of 3
`
`JAMES R. MEYER
`SCHNADER HARRISON SEGAL & LEWIS LLP
`SUITE 3600
`1600 MARKET STREET
`PHILADIYLPIIIA PA 19103-7286
`Phone Numbcr: 215-751-2622
`Fax Number: 215-072-7677
`
`http://tarr.uspto.gov/tarr?regser=registration&enHF507983
`
`8/4/2009
`
`

`
`

`
`Attachment 2
`
`

`
`Latest Status Info
`
`Page 1 of 3
`
`Thank you for your request. Here are the latest results from the TARR web server.
`
`. This page was generated by the TARR system on 20()9-()8-()4 2 1 :53: 16 1ST
`
`Serial Number: 73072165 Assignment Information
`
`Trademark Document RC11‘lC\'£ll
`
`Registration Number: 105 1 (182
`
`Mark (words only): PliRC()('IiZT
`
`Standard Character claim: No
`
`Current Status: This registration has been renewed.
`
`Date of Status: 2()t)6—()2-27
`
`Filing Date: W75-12-18
`
`Transformed into a National Application: No
`
`Registration Date: l97(>~1 I-()2
`
`Register: Prineipal
`
`Law Office Assigned: (NOT AVAILABLE)
`
`If you are the applicant or applicant's attorney and have questions about this file, please contact
`the Trademark Assistance Center at TrademarkAssistancc(Icnter(a,uspto.go\'
`
`Current Location: 408 —Seunning On Demand
`
`Date In Location: 2007-] 1-05
`
`LAST APPLICANT(S)/OWNER(S) OF RECORD
`
`1. END() PllARMA(‘EUTl('Al.S INC.
`
`Address:
`ENDO PHAR.\/lACEUTl(‘ALS INC.
`l0() I3NI)() BLVD.
`CHADDS FORD. PA 19317
`United States
`
`Legal Entity Type: (‘omorution
`State or Country of Incorporation: Delaware
`
`International Class: 005
`. Class Status: .»\cti\*e
`
`GOODS AND/OR SERVICES
`
`http://tarr.uspto.gov/tarr?regser=registration&entr3:105 1682
`
`8/4/2009
`
`

`
`Latest Status Info
`
`Page 2 of 3
`
`PIIARMACEUTICAL ANALGESIC PREPARATIONS
`
`Basis: 1(u)
`First Use Date: 1975-12-15
`First Use in Commerce Date: 1975-12-15
`
`ADDITIONAL INFORMATION
`
`Prior Registration Number(s):
`5()79é<3
`953474
`
`MADRID PROTOCOL INFORMATION
`
`(NOT AVAILABLE)
`
`PROSECUTION HISTORY
`
`NOTE: To view any document referenced below, click on the link to "Trademark Document
`Retrieval" shown near the top of this page.
`
`2007-1 1-05 - (‘use File In T1(.‘RS
`
`2006-02-27 - Second rene\\'a1 10 year
`
`2006-02-27 - Section 8 (11)-year) accepted/‘ Section 9 giuiited
`
`2006-02-21 - Assigned TO Paralegal
`
`2005- 1 2-09 - Combined Section 8 (10-year)»Seciion 0 tiled
`
`2005-12-()9) - PAPER RF.(,‘1{1VF.D
`
`2005-03-17 - TEAS Change ()t‘Con‘espOndence RL‘CCi\ ed
`
`1996-1 1-25 - First renewal 10 year
`
`1996-10-25 - Section 9 tiled check record fo1'Scction ts’
`
`1982-06-02 — Section 8 (6-year) accepted & Section 15 ;1L.‘i\110\\viC(igCLi
`
`ATTORNEY/CORRESPONDENT INFORMATION
`
`Attorney of Record
`DON M KERR
`
`Correspondent
`.1AM1iSR .\/IlӤYl{1{
`SCHNADISZR HARRISON S1‘i(f}AL & LF.VV1S[.1_P
`
`http://tarr.uspto.gov/tarr?regser=registration&entr}m1051682
`
`8/4/2009
`
`

`
`Latest Status Info
`
`Page 3 of 3
`
`INTELLECTLAL PROPERTY DEPT. — TRADEMARKS
`
`1600 MARKET STREET. SUITE 3600
`PHILADELPHIA PA WI03
`
`Phone Number: 2 1 5-75 1 -2622
`Fax Numbcr: 215-972-7677
`
`http://tarr.uspto.gov/tarr?regser=registration&entry= 105 1682
`
`8/4/2009
`
`

`
`

`
`Attachment 3
`
`

`
`Endo Pharmaceuticals
`
`Page 1 of 2
`
`Endo Pharmaceuticals
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`
`PH/\HM;\CFU‘5lC/U. 3}
`
`PERCODAN®
`
`(Oxycodone and Aspirin Tablets, USP)
`
`CII
`
`Rx only
`
`DESCRIPTION
`
`Each PERCODAN Tablet contains:
`
`4.8355 mg*
`Oxycodone Hydrochloride, USP
`325 mg
`Aspirin, USP
`*4.8355 mg oxycodone HCl is equivalent to 4.3346 mg of oxycodone as the free base.
`
`PERCODAN Tablets also contain the following inactive ingredients: D&C Yellow 10, FD&C
`Yellow 6, microcrystalline cellulose and corn starch.
`
`The oxycodone hydrochloride component is Morphinan-6-one, 4,5-epoxy-l4-hydroxy-3-
`methoxy- l 7-methyl-, hydrochloride, (5a)-., a white to off-white, hygroscopic crystals or powder,
`odorless, soluble in water; slightly soluble in alcohol and is represented by the following
`structural formula:
`
`
`
`C]gH21NO4?HCl
`
`MW 351.82
`
`The aspirin component is 2-(acetyloxy)-, Benzoic acid, a white crystal, commonly tabular or
`needle- like, or white, crystalline powder. Is odorless or has a faint odor. Is stable in dry air; in
`moist air it gradually hydrolyzes to salicylic and acetic acids. Slightly soluble in water; freely
`soluble in alcohol; soluble in chloroform and in ether; sparingly soluble in absolute ether and is
`represented by the following structural formula:
`
`

`
`HO
`
`O
`
`H3C\/O
`
`O
`
`C9HgO 4 MW 180.16
`
`CLINICAL PHARMACOLOGY
`
`Central Nervous System
`
`Oxycodone is a semisynthetic pure opioid agonist whose principal therapeutic action is
`analgesia. Other pharmacological effects of Oxycodone include anxiolysis, euphoria and feelings
`of relaxation. These effects are mediated by receptors (notably u and K) in the central nervous
`system for endogenous opioid-like compounds such as endorphins and enkephalins. Oxycodone
`produces respiratory depression through direct activity at respiratory centers in the brain stem
`and depresses the cough reflex by direct effect on the center of the medulla.
`
`Aspirin (acetylsalicylic acid) works by inhibiting the body’s production of prostaglandins,
`including prostaglandins involved in inflammation. Prostaglandins cause pain sensations by
`stimulating muscle contractions and dilating blood vessels throughout the body. In the CNS,
`aspirin works on the hypothalamus heat-regulating center to reduce fever, however, other
`mechanisms may be involved.
`
`Gastrointestinal Tract and Other Smooth Muscle
`
`Oxycodone reduces motility by increasing smooth muscle tone in the stomach and duodenum.
`In the small intestine, digestion of food is delayed by decreases in propulsive contractions. Other
`opioid effects include contraction of biliary tract smooth muscle, spasm of the Sphincter of Oddi,
`increased ureteral and bladder sphincter tone, and a reduction in uterine tone.
`
`Aspirin can produce gastrointestinal injury (lesions, ulcers) through a mechanism that is not yet
`completely understood, but may involve a reduction in eicosanoid synthesis by the gastric
`mucosa. Decreased production of prostaglandins may compromise the defenses of the gastric
`mucosa and the activity of substances involved in tissue repair and ulcer healing.
`
`Cardiovascular System
`
`Oxycodone may produce a release of histamine and may be associated with orthostatic
`hypotension, and other symptoms, such as pruritus, flushing, red eyes, and sweating.
`
`Platelet Aggregation
`
`Aspirin affects platelet aggregation by irreversibly inhibiting prostaglandin cyclo-oxygenase.
`This effect lasts for the life of the platelet and prevents the formation of the platelet aggregating
`
`

`
`factor thromboxane A2. Nonacetylated salicylates do not inhibit this enzyme and have no effect
`on platelet aggregation. At somewhat higher doses, aspirin reversibly inhibits the formation of
`prostaglandin 12 (prostacyclin), which is an arterial vasodilator and inhibits platelet aggregation.
`
`Pharmacokinetics
`
`Absorption and Distribution
`
`The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about
`87%. Oxycodone has been shown to be 45% bound to human plasma proteins in vitro. The
`volume of distribution after intravenous administration is 21 1.9 i186.6 L.
`
`Aspirin is hydrolyzed primarily to salicylic acid in the gut wall and during first-pass metabolism
`through the liver. Salicylic acid is absorbed rapidly from the stomach, but most of the absorption
`occurs in the proximal small intestine. Following absorption, salicylate is distributed to most
`body tissues and fluids, including fetal tissues, breast milk, and the CNS. High concentrations
`are found in the liver and kidneys. Salicylate is variably bound to serum proteins, particularly
`albwnin.
`
`Metabolism and Elimination
`
`A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism.
`Oxymorphone, is formed by the O-demethylation of oxycodone. The metabolism of oxycodone
`to oxymorphone is catalyzed by CYP2D6. Free and conjugated noroxycodone, free and
`conjugated oxycodone, and oxymorphone are excreted in human urine following a single oral
`dose of oxycodone. Approximately 8% to 14% of the dose is excreted as free oxycodone over 24
`hours after administration. Following a single, oral dose of oxycodone, the mean i SD
`elimination half-life is 3.51 i 1.43 hours.
`
`The biotransformation of aspirin occurs primarily in the liver by the microsomal enzyme system.
`With a plasma half-life of approximately 15 minutes, aspirin is rapidly hydrolyzed to salicylate.
`At low doses, salicylate elimination follows first-order kinetics. The plasma half-life of salicylate
`is approximately 2 to 3 hours.
`
`Approximately 10% of aspirin is excreted as unchanged salicylate in the urine. The major
`metabolites excreted in the urine are salicyluric acid (75%), salicyl phenolic glucuronide (10%),
`salicyl acyl glucuronide (5%), and gentisic and gentisuric acid (less than 1%) each. Eighty to
`100% of a single dose is excreted in the urine within 24 to 72 hours.
`
`INDICATIONS AND USAGE
`
`PERCODAN tablets are indicated for the management of moderate to moderately severe pain.
`
`CONTRAINDICATIONS
`
`PERCODAN tablets are contraindicated in patients with known hypersensitivity to oxycodone or
`aspirin, and in any situation where opioids or aspirin are contraindicated. Aspirin is
`contraindicated for patients with hemophilia.
`
`

`
`. Reye Syndrome: Aspirin should not be used in children or teenagers for viral infections,
`with or without fever, because of the risk of Reye syndrome with concomitant use of aspirin
`in certain viral illnesses.
`
`Allergy: Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-
`inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal
`polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma).
`
`Oxycodone is contraindicated in patients with known hypersensitivity to oxycodone. Oxycodone
`is contraindicated in any situation where opioids are contraindicated including patients with
`significant respiratory depression (in unmonitored settings or the absence of resuscitative
`equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone is
`contraindicated in the setting of suspected or known paralytic ileus.
`
`WARNINGS
`
`Misuse, Abuse and Diversion of Opioids
`
`Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and
`people with addiction disorders and are subject to criminal diversion.
`
`Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This
`should be considered when prescribing or dispensing PERCODAN tablets in situations where the
`physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
`Concerns about misuse, addiction, and diversion should not prevent the proper management of
`pain.
`
`.
`
`Healthcare professionals should contact their State Professional Licensing Board, or State
`Controlled Substances Authority for information on how to prevent and detect abuse or diversion
`of this product.
`
`Administration of PERCODAN (Oxycodone and Aspirin Tablets, USP) tablets should be closely
`monitored for the following potentially serious adverse reactions and complications:
`
`Respiratory Depression
`
`Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in
`PERCODAN tablets, as with all opioid agonists. Elderly and debilitated patients are at particular
`risk for respiratory depression as are non-tolerant patients given large initial doses of oxycodone
`or when oxycodone is given in conjunction with other agents that depress respiration.
`Oxycodone should be used with extreme caution in patients with acute asthma, chronic
`obstructive pulmonary disorder (COPD), cor pulmonale, or preexisting respiratory impairment.
`In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the
`point of apnea. In these patients alternative non-opioid analgesics should be considered, and
`opioids should be employed only under careful medical supervision at the lowest effective dose.
`
`In case of respiratory depression, a reversal agent such as naloxone hydrochloride may be
`utilized (see OVERDOSAGE).
`
`

`
`Head Injury and Increased lntracranial Pressure
`
`The respiratory depressant effects of opioids include carbon dioxide retention and secondary
`elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of
`head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.
`Oxycodone produces effects on pupillary response and consciousness which may obscure
`neurologic signs of worsening in patients with_head injuries.
`
`Hypotensive Effect
`
`Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain
`blood pressure has been compromised by a depleted blood volume, or after concurrent
`administration with drugs which compromise vasomotor tone such as phenothiazines.
`Oxycodone, like all opioid analgesics of the morphine—type, should be administered with caution
`to patients in circulatory shock, since vasodilation produced by the drug may furtler reduce
`cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in
`ambulatory patients.
`
`Alcohol Warning
`
`Patients who consume three or more alcoholic drinks every day should be counseled about the
`bleeding risks involved with chronic, heavy alcohol use while taking aspirin.
`
`Coagulation Abnormalities
`
`Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time.
`This can adversely affect patients with inherited (hemophilia) or acquired (liver disease or
`vitamin K deficiency) bleeding disorders.
`
`GI Side Effects
`
`GI side effects include stomach pain, heartburn, nausea, vomiting, and gross GI bleeding.
`Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime
`during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the
`absence of previous GI symptoms. Physicians should inform patients about the signs and
`symptoms of GI side effects and what steps to take if they occur.
`
`Peptic Ulcer Disease
`
`Patients with a history of active peptic ulcer disease should avoid using aspirin, which can cause
`gastric mucosal irritation and bleeding.
`
`PRECAUTIONS
`
`General
`
`Opioid analgesics should be used with caution when combined with CNS depressant drugs, and
`should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of
`respiratory depression, altered mental state, and postural hypotension.
`
`PERCODAN tablets should be given with caution to patients with CNS depression, elderly or
`debilitated patients, patients with severe impairment of hepatic, pulmonary, or renal function,
`
`

`
`hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture, acute alcoholism,
`delirium tremens, kyphoscoliosis with respiratory depression, myxedema, and toxic psychosis.
`
`PERCODAN tablets may obscure the diagnosis or clinical course in patients with acute
`abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive
`disorders, and all opioids may induce or aggravate seizures in some clinical settings.
`
`Following administration of PERCODAN tablets, anaphylactic reactions have been reported in
`patients with a known hypersensitivity to codeine, a compound with a structure similar to
`morphine and oxycodone. The frequency of this possible cross-sensitivity is unknown.
`
`Aspirin has been associated with elevated hepatic enzymes, blood urea nitrogen and serum
`creatinine, hyperkalemia, proteinuria, and prolonged bleeding time.
`
`Hemorrhage
`
`Aspirin may increase the likelihood of hemorrhage due to its effect on the gastric mucosa and
`platelet function (prolongation of bleeding time). Salicylates should be used with caution in the
`presence of peptic ulcer or coagulation abnormalities.
`
`Pregnancy
`
`Aspirin can cause fetal harm when administered to a pregnant woman. Salicylates readily cross
`the placenta and by inhibiting prostaglandin synthesis, may cause constriction of ductus
`arteriosus, resulting in pulmonary hypertension and increased fetal mortality and, possibly other
`untoward fetal effects. Aspirin use in pregnancy can also result in alteration in maternal and
`neonatal hemostasis mechanisms. Maternal aspirin use during later stages of pregnancy may
`cause low birth weight, increased incidence of intracranial hemorrhage in premature infants,
`stillbirths and neonatal death. The use of aspirin during pregnancy especially in the third
`trimester should be avoided. If PERCODAN tablets are used during pregnancy, or if the patient
`becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to
`the fetus.
`
`Renal Failure
`
`Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than
`10 mL/minute).
`
`Hepatic Insufficiency
`
`Avoid aspirin in patients with severe hepatic insufficiency.
`
`Interactions with Other CNS Depressants
`
`Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other
`tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants
`(including alcohol) concomitantly with PERCODAN tablets may exhibit an additive CNS
`depression. When such combined therapy is contemplated, the dose of one or both agents should
`be reduced.
`
`

`
`Interactions with Mixed AgonistIAntagonist Opioid Analgesics
`
`Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should be
`administered with caution to a patient who has received or is receiving a course of therapy with a
`pure opioid agonist analgesic such as oxycodone, In this situation, mixed agonist/antagonist
`analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal
`symptoms in these patients.
`
`Ambulatory Surgery and Postoperative Use
`
`Oxycodone and other morphine-like opioids have been shown to decrease bowel motility. Ileus
`is a common postoperative complication, especially after intra-abdominal surgery with use of
`opioid analgesia. Caution should be taken to monitor for decreased bowel motility in
`postoperative patients receiving opioids. Standard supportive therapy should be implemented.
`
`Use in PancreaticlBiliary Tract Disease
`
`Oxycodone may cause spasm of the sphincter of Oddi and should be used with caution in
`patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone may
`cause increases in the serum amylase level.
`
`Tolerance and Physical Dependence
`
`Tolerance is the need for increasing doses of opioids to maintain a defined effect such as
`analgesia (in the absence of disease progression or other external factors). Physical dependence
`is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon
`administration of an antagonist. Physical dependence and tolerance are not unusual during
`chronic opioid therapy.
`
`The opioid abstinence or withdrawal syndrome is characterized by some or all of the following:
`restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other
`symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness,
`abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure,
`respiratory rate, or heart rate.
`
`In general, opioids should not be abruptly discontinued (see DOSAGE AND
`ADMINISTRATION: Cessation of Therapy).
`
`Information for Patientslcaregivers
`
`The following information should be provided to patients receiving PERCODAN tablets by their
`physician, nurse, pharmacist, or caregiver:
`
`1. Patients should be aware that PERCODAN tablets contain oxycodone, which is a
`morphine- like substance.
`2. Patients should be instructed to keep PERCODAN tablets in a secure place out of the
`reach of children. In the case of accidental ingestions, emergency medical care should be
`sought immediately.
`3. When PERCODAN tablets are no longer needed, the unused tablets should be destroyed
`by flushing down the toilet.
`
`

`
`4. Patients should be advised not to adjust the medication dose themselves. Instead, they
`must consult with their prescribing physician.
`5. Patients should be advised that PERCODAN tablets may impair mental and/or physical
`ability required for the performance of potentially hazardous tasks (e.g., driving,
`operating heavy machinery).
`6. Patients should not combine PERCODAN tablets with alcohol, opioid analgesics,
`tranquilizers, sedatives, or other CNS depressants unless under the recommendation and
`guidance of a physician. When co-administered with another CNS depressant,
`PERCODAN tablets can cause dangerous additive central nervous system or respiratory
`depression, which can result in serious injury or death.
`7. The safe use of PERCODAN tablets during pregnancy has not been established; thus,
`women who are planning to become pregnant or are pregnant should consult with their
`physician before taking PERCODAN tablets.
`8. Nursing mothers should consult with their physicians about whether to discontinue
`nursing or discontinue PERCODAN tablets became of the potential for serious adverse
`reactions to nursing infants.
`9. Patients who are treated with PERCODAN tablets for more than a few weeks should be
`
`advised not to abruptly discontinue the medication. Patients should consult with their
`physician for a gradual discontinuation dose schedule to taper off the medication.
`10. Patients should be advised that PERCODAN tablets are a potential drug of abuse. They
`should protect it from theft, and it should never be given to anyone other than the
`individual for whom it was prescribed.
`
`Laboratory Tests
`
`Although oxycodone may cross-react with some drug urine tests, no available studies were found
`which determined the duration of detectability of oxycodone in urine drug screens. However,
`based on phannacokinetic data, the approximate duration of detectability for a single dose of
`oxycodone is roughly estimated to be one to two days following drug exposure.
`
`Urine testing for opiates may be performed to determine illicit drug use and for medical reasons
`such as evaluation of patients with altered states of consciousness or monitoring efficacy of drug
`rehabilitation efforts. The preliminary identification of opiates in urine involves the use of an
`immunoassay screening and thin- layer chromatography (TLC). Gas chromatography/mass
`spectrometry (GC/MS) may be utilized as a third-stage identification step in the medical
`investigational sequence for opiate testing after immunoassay and TLC. The identities of 6-keto
`opiates (e.g.. oxycodone) can further be differentiated by the analysis of their methoxime-
`trimethylsilyl (MO-TMS) derivative.
`
`DruglDrug Interactions with Oxycodone
`
`Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants
`and produce an increase in the degree of respiratory depression.
`
`Patients receiving CNS depressants such as other opioid analgesics, general anesthetics,
`phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other
`CNS depressants (including alcohol) concomitantly with PERCODAN tablets may exhibit an
`
`

`
`additive CNS depression. When such combined therapy is contemplated, the dose of one or both
`agents should be reduced.
`
`Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and butorphanol) should
`be administered with caution to a patient who has received or is receiving a pure opioid agonist
`such as oxycodone. These agonist/antagonist analgesics may reduce the analgesic effect of
`oxycodone or may precipitate withdrawal symptoms.
`
`DruglDrug Interactions with Aspirin
`
`Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of
`ACE inhibitors may be diminished by the concomitant administration of aspirin due to its
`indirect effect on the renin-angiotensin conversion pathway.
`
`Acetazo lamide: Concurrent use of aspirin and acetazolamide can lead to high serum
`concentrations of acetazolamide (and toxicity) due to comp