C the followingstructuralformula: opiate, non-salicylateanalgesicandantipyretic.Ithas bitter, powder, white,odorless,crystalline isanon- moderate tomoderatelyseverepain. corresponding 6- N-demethylation and6-ketoreductiontothe of metabolismincludingO-demethylation, 0.3 hours.Hydrocodoneexhibitsacomplexpattern 0.3 hoursandthehalf-lifewasdeterminedtobe3.8± Maximum serumlevelswereachievedat1.3± 5.2ng/mL. the meanpeakconcentrationwas23.6± hydrocodone administeredtofiveadultmalesubjects, povidone, andstearicacid. cellulose, magnesium stearate,microcrystalline croscarmellose sodium,dibasiccalciumphosphate, inactive ingredients:colloidalsilicondioxide,starch, OVERDOSAGE fortoxicityinformation. or diversion(seeDRUGABUSEANDDEPENDENCE). is concernedaboutanincreasedriskofmisuse,abuse tablets insituationswherethephysicianorpharmacist considered whenprescribingordispensingVICODIN to otheropioidagonists,legalorillicit.Thisshouldbe subject todiversion. abusers andpeoplewithaddictiondisorders,are have thepotentialforbeingabusedandaresoughtby a ScheduleIIIcontrolledsubstance.Opioidagonists tablets containshydrocodone,anopioidagonist,andis Misuse, Abuse,andDiversionofOpioids: of patientswithacuteabdominalconditions. narcotics mayobscurethediagnosis orclinicalcourse Acute AbdominalConditions: course ofpatientswithheadinjuries. adverse reactions,whichmayobscuretheclinical intracranial pressure.Furthermore,narcotics produce other intracraniallesionsorapreexistingincreasein markedly exaggeratedinthepresenceofheadinjury, capacity toelevatecerebrospinalfluidpressuremaybe depressanteffectsofnarcoticsrespiratory andtheir andIncreasedIntracranialPressure: Head Injury produce irregularandperiodicbreathing. rhythm,andmay center thatcontrolsrespiratory center.stem respiratory Hydrocodonealsoaffectsthe depressionbyactingdirectlyonthebrain respiratory patients, hydrocodonemayproducedose-related OVERDOSAGE fortoxicityinformation. of otherconjugatesandunchangeddrug.See most astheglucuronideconjugate,withsmallamounts appears intheurinewithin24hoursofadministration, metabolites. Approximately85%ofanoraldose (conjugation) andsubsequentrenalexcretionof acetaminophen isprincipallybylivermetabolism damage andfollowingoverdosage.Eliminationof is 1.25to3hours,butmaybeincreasedbyliver throughout mostbodytissues.Theplasmahalf-life from thegastrointestinaltractandisdistributed Pharmacokinetics rapid, shallowbreathing. however, toxicdosesmaycausecirculatory failureand systems; effects onthecardiovascularorrespiratory Therapeutic dosesofacetaminophenhavenegligible Acetaminophen inhibitsprostaglandinsynthetase. through hypothalamicheatregulatingcenters. yet undetermined.Antipyreticactivityismediated peripheral influences,butthespecificmechanismisas clouding. produce drowsiness,changesinmoodandmental system. Inadditiontoanalgesia,narcotics may the existenceofopiatereceptorsincentralnervous opiates isnotknown,althoughitbelievedtorelate precise mechanismofactionhydrocodoneandother systemandsmoothmuscle.The central nervous similar tothoseofcodeine.Mosttheseinvolvethe and antitussivewithmultipleactionsqualitatively may exhibitcross-sensitivitytohydrocodone. Patients knowntobehypersensitiveotheropioids hydrocodone oracetaminophen. who havepreviouslyexhibitedhypersensitivityto CLINICAL PHARMACOLOGY DESCRIPTION November, 2006 1949)03-5543-R3-Rev. (No. hepatic, renal,orcardiacfunction,andofconcomitant range, reflectingthegreaterfrequencyofdecreased cautious, usuallystartingatthelowendofdosing general, doseselectionforanelderlypatientshouldbe responses betweentheelderlyandyoungerpatients.In clinical experiencehasnotidentifieddifferencesin differently fromyoungersubjects.Otherreported aged 65andovertodeterminewhethertheyrespond 500 mg)didnotincludesufficientnumbersofsubjects (hydrocodone bitartrate5mgandacetaminophen Special RiskPatients General PRECAUTIONS Depression Respiratory WARNINGS CONTRAINDICATIONS INDICATIONS ANDUSAGE name is:4,5 powder.crystalline Itisaffectedbylight.Thechemical orasa antitussive andoccursasfine,whitecrystals supplied intabletformfororaladministration. Cough Reflex depression shouldbekeptinmind. andthepossibilityofrespiratory should beobserved hypertrophy orurethralstricture.Theusualprecautions hypothyroidism, Addison'sdisease,prostatic severe impairmentofhepaticorrenalfunction, in elderlyordebilitatedpatientsandthosewith agent, VICODINTablets shouldbeusedwithcaution components isdescribedbelow. Geriatric Use: population havenotbeenestablished. Pediatric Use: into accounttheimportanceofdrugtomother. discontinue nursingortothedrug,taking acetaminophen, adecisionshouldbemadewhetherto in nursinginfantsfromhydrocodoneand because ofthepotentialforseriousadversereactions Because manydrugsareexcretedinhumanmilkand whether hydrocodoneisexcretedinhumanmilk. on nursinginfantsisnotknown.Itknown milk insmallamounts,butthesignificanceofitseffects Nursing Mothers: higher dosesareused. depressioninthenewborn,especiallyif respiratory mayresultinsomedegreeof shortly beforedelivery administration ofVICODINTablets tothemother Labor andDelivery: withdrawal. no consensusonthebestmethodofmanaging duration ofmaternalopioiduseordose.Thereis the syndromedoesnotalwayscorrelatewith sneezing, yawning,vomiting,andfever. Theintensityof rate,increasedstools, reflexes, increasedrespiratory tremors,hyperactive irritability andexcessivecrying, be physicallydependent.Thewithdrawalsignsinclude will have beentakingopioidsregularlypriortodelivery Nonteratogenic Effects: potential risktothefetus. pregnancy onlyifthepotentialbenefitjustifies women. VICODINTablets shouldbeusedduring no adequateandwell-controlledstudiesinpregnant Teratogenic Effects: Pregnancy: mutagenesis, orimpairmentoffertility. acetaminophen haveapotentialforcarcinogenesis, animals todeterminewhetherhydrocodoneor Fertility: Carcinogenesis, Mutagenesis,Impairmentof 5-hydroxyindoleacetic acid. may producefalse-positivetestresultsforurinary TestDrug/Laboratory Interactions: hydrocodone. increase theeffectofeitherantidepressantor antidepressants withhydrocodonepreparationsmay be reduced. contemplated, thedoseofoneorbothagentsshould additive CNSdepression.Whencombinedtherapyis concomitantly withVICODINTablets mayexhibitan agents, orotherCNSdepressants(includingalcohol) analgesics, antihistamines,antipsychotics,antianxiety Drug Interactions: with serialliverand/orrenalfunctiontests. renal disease,effectsoftherapyshouldbemonitored Tests:Laboratory prescribed. amounts prescribed,andnomorefrequentlythan take thedrugonlyforaslongitisprescribed,in combination product,andshouldbeavoided. additive CNSdepression,whentakenwiththis patientsshouldbecautionedaccordingly.machinery; hazardous taskssuchasdrivingacaroroperating ofpotentially abilities requiredfortheperformance narcotics, mayimpairthementaland/orphysical Information forPatients: disease. patients withpulmonary when VICODINTablets areusedpostoperativelyandin reflex; aswithallnarcotics, cautionshouldbeexercised C structural formula: 6-one tartrate(1:1)hydrate(2:5).Ithasthefollowing 5 mg/500mg acetaminophen tablets,USP) bitartrate and (hydrocodone 8 18 H ctmnpe 500mg Meets USPDissolutionTest 2. 5mg Acetaminophen Hydrocodone Bitartrate Each VICODINtabletcontains: Acetaminophen VICODIN tabletscanbeabusedinamannersimilar Hydrocodone isasemisyntheticnarcotic analgesic This productshouldnotbeadministeredtopatients Hydrocodone bitartrateisanopioidanalgesicand Hydrocodone maybehabitforming.Patientsshould Alcohol andotherCNSdepressantsmayproducean The analgesicactionofacetaminopheninvolves VICODIN tabletsareindicatedforthereliefof Acetaminophen, 4’-hydroxyacetanilide,aslightly Hydrocodone In additioneachtabletcontainsthefollowing Hydrocodone bitartrateandacetaminophenis The useofMAOinhibitorsortricyclic H 9 NO 21 NO 2 : No adequatestudieshavebeenconductedin 3 •C α OCH 4 -epoxy-3-methoxy-17-methylmorphinan- : Hydrocodonesuppressesthecough H Safety andeffectivenessinthepediatric 6 : Followinga10mgoraldoseof 3 0 α : Acetaminophenisrapidlyabsorbed 6 Acetaminophen isexcretedinbreast : - and6- •2 Clinical studiesofVICODIN In patientswithseverehepaticor O Patients receivingothernarcotic Pregnancy Category C.Thereare Pregnancy Category The behavioroftheindividual 1 : Aswithanynarcotic analgesic ⁄ 3 2 ® H 2 : HN-CH Babies borntomotherswho NHCOCH OH M.W. 494.50 0 CH At highdosesorinsensitive CH β + As withallnarcotics, O 2 -hydroxy- metabolites.See 2 3 Hydrocodone, likeall (CHOH) 3 COOH COO The administrationof

0102FnL1 E0FiYm90dCBMYWJvcmF0b3JpZXMLSnVsaWUgU21pdGgARVBK6w== 02 0052 035543 2 2 Acetaminophen 1 / 2 M.W. 151.16 H 2 O VICODIN only The ® VICODIN Drowsiness, mental Prolonged administration of Hydrocodone bitartrate may Ureteral spasm, spasm of Cases of hearing impairment or NORTH CHICAGO,NORTH IL 60064, U.S.A. LABORATORIES Skin rash, pruritus. controlled drug substance. : In acetaminophen overdosage: dose- is supplied as white, capsule-shaped A single or multiple overdose with : Serious overdose with hydrocodone is 3 ® a Store at 25°C (77°F); excursions permitted to Hydrocodone and the major metabolites of Hydrocodone may cause confusion and over- Immediate treatment includes support of can reverse antagonist, Naloxone, a narcotic Addiction is a primary, chronic, neurobiologic Addiction is a primary, The most frequently reported adverse reactions Other adverse reactions include: The following adverse drug events may be borne in Potential effects of high dosage are listed in the Following an acute overdosage, toxicity may result Dosage should be adjusted according to the severity The usual adult dosage is one or two tablets every VICODIN “Drug seeking” behavior is very common in addicts Abuse and addiction are separate and distinct from Proper assessment of the patient, proper prescribing Early symptoms following a potentially hepatotoxic In adults, hepatic toxicity has rarely been reported Meticulous attention should be given to maintaining If the dose of acetaminophen may have exceeded Methemoglobinemia over 30% should be treated The toxic dose for adults for acetaminophen is 10 g. ABBOTT include: lightheadedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients and some of these adverse reactions may be alleviated if the patient lies down. Central Nervous System: impairment of mental and physical clouding, lethargy, dysphoria, psychic fear, performance, anxiety, dependence, mood changes. Gastrointestinal System: mind as potential effects of acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis. OVERDOSAGE section. VICODIN Tablets may produce constipation. VICODIN Tablets Genitourinary System: vesical sphincters and urinary retention have been reported with opiates. Respiratory Depression: produce dose-related respiratory depression by acting (see directly on the brain stem respiratory center. OVERDOSAGE). Special Senses: permanent loss have been reported predominantly in patients with chronic overdose. Dermatological: characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle cold and clammy skin, and sometimes flaccidity, bradycardia and hypotension. In severe overdosage, collapse, cardiac arrest and death apnea, circulatory may occur. Acetaminophen from hydrocodone or acetaminophen. Signs and Symptoms: Hydrocodone it of the pain and the response of the patient. However, should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related. four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets. OVERDOSAGE DOSAGE AND ADMINISTRATION HOW SUPPLIED Hospital Unit Dose Package-100 tablets (4x25 tablets)— NDC 0074-1949-12. Storage: 15°-30°C (59°-86°F). [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP. A Schedule contains hydrocodone, an opioid agonist, and is a Schedule III controlled substance. VICODIN, and other opioids, used in analgesia can be abused and are subject to criminal diversion. disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease utilizing a multidisciplinary approach, but relapse is common. and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. physical dependence and tolerance. Physical dependence usually assumes clinically significant dimensions only after several weeks of continued opioid use, although a mild degree of physical dependence may develop after a few days of opioid in which increasingly large doses Tolerance, therapy. are required in order to produce the same degree of analgesia, is manifested initially by a shortened duration of analgesic effect, and subsequently by decreases in the intensity of analgesia. The rate of development of tolerance varies among patients. Physicians should be aware that abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. VICODIN, like other opioids, may be diverted for non-medical use. Record-keeping of frequency, prescribing information, including quantity, and renewal requests is strongly advised. and proper practices, periodic re-evaluation of therapy, dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. disease or other drug therapy. acetaminophen are known to be substantially excreted Thus the risk of toxic reactions may be by the kidney. greater in patients with impaired renal function due to accumulation of the parent compound and/or metabolites in the plasma. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. sedation in the elderly; elderly patients generally should be started on low doses of hydrocodone bitartrate and acetaminophen tablets and observed closely. ADVERSE REACTIONS DRUG ABUSE AND DEPENDENCE Misuse, Abuse, and Diversion of Opioids: tablets containing 5 mg hydrocodone bitartrate and 500 mg acetaminophen, bisected on one side and debossed with “VICODIN” on the other. Bottles of 100—NDC 0074-1949-14. Bottles of 500—NDC 0074-1949-54. dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. with acute overdoses of less than 10 grams and fatalities with less than 15 grams. Treatment: hydrocodone and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. cardiorespiratory function and measures to reduce should be induced drug absorption. Vomiting or with syrup of ipecac, if the patient is mechanically, alert (adequate pharyngeal and laryngeal reflexes). should follow gastric (1 g/kg) Oral activated charcoal emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and and other should respond to fluids. Vasopressors supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted before gastric lavage of the unconscious patient and, when to provide assisted respiration. necessary, adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously. respiratory depression and coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to Since the duration of action 2 mg is given parenterally. of hydrocodone may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate should not be antagonist respiration. A narcotic administered in the absence of clinically significant respiratory or cardiovascular depression. 140 mg/kg, acetylcysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels four or more hours following Do not ingestion help predict acetaminophen toxicity. await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained and repeated at 24-hour intervals. initially, with methylene blue by slow intravenous administration. ©Abbott All rights reserved 2006 November, 03-5543-R3-Rev.