Dose\ParametersAuc.(ngxhr/mL)Cmax(ng /mL)Tmax(hr)Cmin(ng /mL)Cavg(ng /mL)Half-Life(hr)Single Dose PharmacokineticsROXICODONE 5mg tabsx3133.2±3322.3±8.21.8±1.8n/an/a3.73±0.9ROXICODONE 15 mg tab128.2±35.122.2±7.61.4±0.7n/an/a3.55±1.0ROXICODONE Intensol15mg oral solution130.6±34.721.1±6.11.9±1.5n/an/a3.71±0.8ROXICODONE 30 mg tab268.2±60.739.3±14.02.6±3.0n/an/a3.85±1.3Food-Effect,Single DoseROXICODONE 10mg/lOmloralSol’n(fasted)105±6.219.0±3.71.25±0.5n/an/a2.9±0.4ROXICODONE10mg/lOmloralSol’n(fed)133±25.217.7±3.02.54±1.2n/an/a3.3±0.5Multiple-Dose StudiesAUC(72-84)ROXICODONE 5mg tabsq6h x 14 doses113.3±24.015.7±3.21.3±0.37.4±1.89.4±2.0n/aROXICODONE3.33mg(3.33ml)oral sol’n. q4hx21 doses99.0±24.812.9±3.11.0±0.37.2±2.39.7±2.6n/aAbsorption: About 60% to 87% of an oral dose of oxycodone reaches the systemic circulation incomparison to a parenteral dose. This high oral bioavailability (compared to other oral opioids) isdue to lower pre-systemic and/or first-pass metabolism of oxycodone. The relative oralbioavailability of ROXICODONE™ 15 mg and 30 mg tablets, compared to the 5mgROXICODONE™ tablets, is 96% and 101% respectively. ROXICODONE™ 15 mg tablets and 30mg tablets are bioequivalent to the 5 mg ROXICODONE™ tablet (see Table 1 forpharmacokinetic parameters). Dose proportionality of oxycodone has been established using theROXICODONE™ 5mg tablets at doses of 5 mg, 15 mg (three 5mg tablets) and 30 mg (six 5mgtablets) based on extent of absorption (AUC) (see Figure 1). It takes approximately 18 to 24hours to reach steady-state plasma concentrations of oxycodone with ROXICODONE™.Figure 1 - Roxicodone Dose-Proportionality Study 5mg, 15mg and 30mg(single-dose)010203040500510152025time (hours)Oxycodone 5mg x 1Oxycodone 5mg x 3Oxycodone 5mg x 6
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4Food Effect: A single-dose food effect study was conducted in normal volunteers using the 5 mg/5 ml solution. The concurrent intake of a high fat meal was shown to enhance the extent, (27%increase in AUC), but not the rate of oxycodone absorption from the oral solution. (See Table 1).In addition, food caused a delay in Tmax (1.25 to 2.54 hour). Similar effects of food are expectedwith the 15mg and 30 mg tablets.Distribution: Following intravenous administration, the volume of distribution (Vss) for oxycodonewas 2.6 L/kg. Plasma protein binding of oxycodone at 37°C and a pH of 7.4 was about 45%.Oxycodone has been found in breast milk. (See PRECAUTIONS-Nursing Mothers.)Metabolism:Oxycodone hydrochloride is extensively metabolized tonoroxycodone,oxymorphone, and their glucuronides. The major circulating metabolite is noroxycodone with anAUC ratio of 0.6 relative to that of oxycodone. Oxymorphone is present in the plasma only in lowconcentrations. The analgesic activity profile of other metabolites is not known at present.The formation of oxymorphone, but not noroxycodone, is mediated by CYP2D6 and as such itsformation can, in theory, be affected by other drugs. (See PRECAUTIONS -Drug Interactions.)Elimination: Oxycodone and its metabolites are excreted primarily via the kidney. The amountsmeasured in the urine have been reported as follows: free oxycodone up to 19%; conjugatedoxycodone up to 50%; free oxymorphone 0%; conjugated oxymorphone < 14%; both free andconjugated noroxycodone have been found in the urine but not quantified. The total plasmaclearance was 0.8 L/min for adults. Apparent elimination half-life of oxycodone following theadministration of ROXICODONE™ was 3.5 to 4 hours.Special Populations:Geriatric: Population pharmacokinetic studies conducted with ROXICODONE™, indicated thatthe plasma concentrations of oxycodone did not appear to be increased in patients over the ageof 65.Gender: Population pharmacokinetic analyses performed in the clinical study support the lack ofgender effect on the pharmacokinetics of oxycodone from ROXICODONE™.Race: Population pharmacokinetic analyses support the lack of race effect on oxycodonepharmacokinetics after administration of ROXICODONE™, but these data should be interpretedconservatively, since the majority of patients enrolled into the studies were Caucasians (94%).Renal Insufficiency: In a clinical trial supporting the development of ROXICODONE™, too fewpatients with decreased renal function were evaluated to study these potential differences. Inprevious studies, patients with renal impairment (defined as a creatinine clearance <60mL/min)had concentrations of oxycodone in the plasma that were higher than in subjects with normalrenal function. Based on information available on the metabolism and excretion of oxycodone,dose initiation in patients with renal impairment should follow a conservative approach. Dosagesshould be adjusted according to the clinical situation.Hepatic Failure: In a clinical trial supporting the development of ROXICODONE™, too fewpatients with decreased hepatic function were evaluated to study these potential differences.However, since oxycodone is extensively metabolized, its clearance may decrease in hepaticfailure patients. Dose initiation in patients with hepatic impairment should follow a conservativeapproach. Dosages should be adjusted according to the clinical situation.
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5INDICATIONS AND USAGEROXICODONE™ tablets are an immediate-release oral formulation of oxycodone hydrochlorideindicated for the management of moderate to severe pain where the use of an opioid analgesic isappropriate.CONTRAINDICATIONSROXICODONE™ is contraindicated in patients with known hypersensitivity to oxycodone, or inany situation where opioids are contraindicated. This includes patients with significant respiratorydepression (in unmonitored settings or the absence of resuscitative equipment) and patients withacute or severe bronchial asthma or hypercarbia. ROXICODONE™ is contraindicated in anypatient who has or is suspected of having paralytic ileus.WARNINGSRespiratory Depression:Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratorydepression occurs most frequently in elderly or debilitated patients, usually following large initialdoses in non-tolerant patients, or when opioids are given in conjunction with other agents thatdepress respiration.ROXICODONE™ should be used with extreme caution in patients with significant chronicobstructive pulmonary disease or cor pulmonale, and in patients having substantially decreasedrespiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In suchpatients, even usual therapeutic doses of ROXICODONE™ may decrease respiratory drive to thepoint of apnea. In these patients alternative non-opioid analgesics should be considered, andopioids should be employed only under careful medical supervision at the lowest effective dose.Hypotensive Effect:ROXICODONE™, like all opioid analgesics, may cause severe hypotension in an individualwhose ability to maintain blood pressure has been compromised by a depleted blood volume, orafter concurrent administration with drugs such as phenothiazines or other agents whichcompromise vasomotor tone. ROXICODONE™ may produce orthostatic hypotension inambulatory patients. ROXICODONE™, like all opioid analgesics, should be administered withcaution to patients in circulatory shock, since vasodilatation produced by the drug may furtherreduce cardiac output and blood pressure.Head Injury and Increased Intracranial Pressure:The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluidpressure may be markedly exaggerated in the presence of head injury, other intracranial lesionsor a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adversereactions which may obscure the clinical course of patients with head injuries.PRECAUTIONSGeneral:ROXICODONE™ tablets are intended for use in patients who require oral pain therapy with anopioid agonist. As with any opioid analgesic, it is critical to adjust the dosing regimen individuallyfor each patient (see DOSAGE AND ADMINISTRATION).
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6Selection of patients for treatment with ROXICODONE™ should be governed by the sameprinciples that apply to the use of other potent opioid analgesics. Opioid analgesics given on afixed-dosage schedule have a narrow therapeutic index in certain patient populations, especiallywhen combined with other drugs, and should be reserved for cases where the benefits of opioidanalgesia outweigh the known risks of respiratory depression, altered mental state, and posturalhypotension. Physicians should individualize treatment in every case, using nonopioid analgesics,prn opioids and /or combination products, and chronic opioid therapy with drugs such asROXICODONE™ (oxycodone hydrochloride) in a progressive plan of pain management such asoutlined by the World Health Organization, the Agency for Health Care Policy and Research, andthe American Pain Society.Use of ROXICODONE™ is associated with increased potential risks and should be used only withcaution in the following conditions: acute alcoholism; adrenocortical insufficiency (e.g., Addison'sdisease); convulsive disorders; CNS depression or coma; delirium tremens; debilitated patients;kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatichypertrophy or urethral stricture; severe impairment of hepatic, pulmonary or renal function; andtoxic psychosis.The administration of ROXICODONE™, like all opioid analgesics, may obscure the diagnosis orclinical course in patients with acute abdominal conditions. Oxycodone may aggravateconvulsions in patients with convulsive disorders, and all opioids may induce or aggravateseizures in some clinical settings.Tolerance and Physical Dependence:Physical dependence and tolerance are not unusual during chronic opioid therapy. Significanttolerance should not occur in most patients treated with the lowest doses of oxycodone. It shouldbe expected, however, that a fraction of patients will develop some degree of tolerance andrequire progressively higher dosages of ROXICODONE™ to maintain pain control during chronictreatment. The dosage should be selected according to the patient's individual analgesicresponse and ability to tolerate side effects. Tolerance to the analgesic effects of opioids isusually paralleled by tolerance to side effects except for constipation.Physical dependence results in withdrawal symptoms in patients who abruptly discontinue thedrug or may be precipitated through the administration of drugs with opioid antagonist activity. IfROXICODONE™ is abruptly discontinued in a physically dependent patient, an abstinencesyndrome may occur (See DRUG ABUSE AND DEPENDENCE). If signs and symptoms ofwithdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradualtapered dose reduction of ROXICODONE™ combined with symptomatic support (see DOSAGEAND ADMINISTRATION: Cessation of Therapy).Use In Pancreatic/Biliary Tract Disease:ROXICODONE™ may cause spasm of the sphincter of Oddi and should be used with caution inpatients with biliary tract disease, including acute pancreatitis. Opioids like ROXICODONE™ maycause increases in the serum amylase level.Information for Patients/Caregivers:If clinically advisable, patients (or their caregivers) receiving ROXICODONE™ (oxycodonehydrochloride Immediate-release) tablets should be given the following information by thephysician, nurse, pharmacist or caregiver:
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71.Patients should be advised to report episodes of breakthrough pain and adverseexperiences occurring during therapy. Individualization of dosage is essential to makeoptimal use of this medication.2.Patients should be advised not to adjust the dose of ROXICODONE™ without consultingthe prescribing professional.3.Patients should be advised that ROXICODONE™ may impair mental and/or physicalability required for the performance of potentially hazardous tasks (e.g. driving, operatingheavy machinery).4.Patients should not combine ROXICODONE™ with alcohol or other central nervoussystem depressants (sleep aids, tranquilizers) except by the orders of the prescribingphysician, because additive effects may occur.5.Women of childbearing potential who become, or are planning to become, pregnantshould be advised to consult their physician regarding the effects of analgesics and otherdrug use during pregnancy on themselves and their unborn child.6.Patients should be advised that ROXICODONE™ is a potential drug of abuse. Theyshould protect it from theft, and it should never be given to anyone other than theindividual for whom it was prescribed.7.Patients should be advised that if they have been receiving treatment withROXICODONE™ for more than a few weeks and cessation of therapy is indicated, it maybe appropriate to taper the ROXICODONE™ dose, rather than abruptly discontinue it,due to the risk of precipitating withdrawal symptoms. Their physician can provide a doseschedule to accomplish a gradual discontinuation of the medication.Drug Interactions:Oxycodone is metabolized in part to oxymorphone via the cytochrome p450 isoenzyme CYP2D6.While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs andantidepressants), such blockade has not yet been shown to be of clinical significance with thisagent. However, clinicians should be aware of this possible interaction.Neuromuscular Blocking AgentsOxycodone, as well as other opioid analgesics, may enhance the neuromuscular blocking actionof skeletal muscle relaxants and produce an increased degree of respiratory depression.CNS Depressants: Patients receiving narcotic analgesics, general anesthetics, phenothiazines,other tranquilizers, sedative-hypnotics or other CNS depressants (including alcohol)concomitantly with ROXICODONE™ may exhibit an additive CNS depression. Interactive effectsresulting in respiratory depression, hypotension, profound sedation, or coma may result if thesedrugs are taken in combination with the usual dosage of ROXICODONE™. When suchcombined therapy is contemplated, the dose of one or both agents should be reduced.Mixed Agonist/Antagonist Opioid Analgesics: Agonist/antagonist analgesics (i.e., pentazocine,nalbuphine, butorphanol and buprenorphine) should be administered with caution to patients whohave received or are receiving a course of therapy with a pure opioid agonist analgesic such asROXICODONE™. In this situation, mixed agonist/antagonist analgesics may reduce theanalgesic effect of ROXICODONE™ and/or may precipitate withdrawal symptoms in thesepatients.Monoamine Oxidase Inhibitors (MAOIs): MAOIs have been reported to intensify the effects of atleast one opioid drug causing anxiety, confusion and significant depression of respiration orcoma. The use of ROXICODONE™ is not recommended for patients taking MAOIs or within 14days of stopping such treatment.Carcinogenesis, Mutagenesis, Impairment of Fertility:
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8Long-term studies have not been performed in animals to evaluate the carcinogenic potential ofROXICODONE™ or oxycodone. The possible effects on male or female fertility have not beenstudied in animals.Pregnancy:Teratogenic Effects: Category B: Reproduction studies in Sprague-Dawley rats and New Zealandrabbits revealed that when oxycodone was administered orally at doses up to 16 mg/kg(approximately 2 times the daily oral dose of 90 mg for adults on a mg/m2basis) and 25 mg/kg(approximately 5 times the daily oral dose of 90 mg on a mg/m2basis), respectively was notteratogenic or embryo-fetal toxic. There are no adequate and well controlled studies ofoxycodone in pregnant women. Because animal reproductive studies are not always predicitiveof human responses, ROXICODONE should be used during pregnancy only if potential benefitjustifies the potential risk to the fetus.Nonteratogenic Effects: Neonates whose mothers have taken oxycodone chronically may exhibitrespiratory depression and/or withdrawal symptoms, either at birth and/or in the nursery.Labor and Delivery:ROXICODONE™ is not recommended for use in women during or immediately prior to labor.Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce thestrength, duration and frequency of uterine contractions. Neonates, whose mothers receivedopioid analgesics during labor, should be observed closely for signs of respiratory depression. Aspecific narcotic antagonist, naloxone, should be available for reversal of narcotic-inducedrespiratory depression in the neonate.Nursing Mothers:Oxycodone has been detected in breast milk. Withdrawal symptoms can occur in breast-feedinginfants when maternal administration of an opioid analgesic is stopped. Ordinarily, nursingshould not be undertaken while a patient is receiving ROXICODONE™ since oxycodone may beexcreted in milk.Pediatric Use:The safety and efficacy of oxycodone IR in pediatric patients have not been evaluated.Geriatric Use:Of the total number of subjects in clinical studies of ROXICODONE™, 20.8% (112/538) were 65and over, while 7.2% (39/538) were 75 and over. No overall differences in safety or effectivenesswere observed between these subjects and younger subjects, and other reported clinicalexperience has not identified differences in responses between the elderly and younger patients,but greater sensitivity of some older individuals cannot be ruled out.Hepatic Impairment:Since oxycodone is extensively metabolized, its clearance may decrease in hepatic failurepatients. Dose initiation in patients with hepatic impairment should follow a conservativeapproach. Dosages should be adjusted according to the clinical situation.
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9Renal Impairment:Published data reported that elimination of oxycodone was impaired in end-stage renal failure.Mean elimination half-life was prolonged in uremic patients due to increased volume ofdistribution and reduced clearance. Dose initiation should follow a conservative approach.Dosages should be adjusted according to the clinical situation.Ambulatory Patients:ROXICODONE™ may impair the mental and/or physical abilities required for the performance ofpotentially hazardous tasks such as driving a car or operating machinery. The patient using thisdrug should be cautioned accordingly.ADVERSE REACTIONSROXICODONE™ tablets have been evaluated in open label clinical trials in patients with cancerand nonmalignant pain. ROXICODONE™ tablets are associated with adverse experiencessimilar to those seen with other opioids.Serious adverse reactions that may be associated with ROXICODONE™ therapy in clinical useare those observed with other opioid analgesics and include: respiratory depression, respiratoryarrest, circulatory depression, cardiac arrest, hypotension, and/or shock (see OVERDOSE,WARNINGS).The less severe adverse events seen on initiation of therapy with ROXICODONE™ are alsotypical opioid side effects. These events are dose dependent, and their frequency depends onthe clinical setting, the patient’s level of opioid tolerance, and host factors specific to theindividual. They should be expected and managed as a part of opioid analgesia. The mostfrequent of these include nausea, constipation, vomiting, headache, and pruritus.In many cases the frequency of adverse events during initiation of opioid therapy may beminimized by careful individualization of starting dosage, slow titration and the avoidance of largerapid swings in plasma concentration of the opioid. Many of these adverse events will abate astherapy is continued and some degree of tolerance is developed, but others may be expected toremain throughout therapy.In all patients for whom dosing information was available (n=191) from the open-label anddouble-blind studies involving ROXICODONE™, the following adverse events were recorded inROXICODONE™ treated patients with an incidence ≥ 3%. In descending order of frequency theywere: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, andsomnolence.The following adverse experiences occurred in less than 3% of patients involved in clinical trialswith oxycodone:Body as a Whole: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever,fever, flu syndrome, infection, neck pain, pain, photosenstivity reaction, and sepsis.Cardiovascular: deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine,palpitation, and tachycardia.Digestive: anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea andvomiting.Hemic and Lymphatic: anemia and leukopenia.Metabolic and Nutritional: edema, gout, hyperglycemia, iron deficiency anemia and peripheraledema.Musculoskeletal: arthralgia, arthritis, bone pain, myalgia and pathological fracture.
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10Nervous: agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness,neuralgia, personality disorder, tremor, and vasodilation.Respiratory: bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder,pharyngitis, rhinitis, and sinusitis.Skin and Appendages: herpes simplex, rash, sweating, and urticaria.Special Senses: amblyopia.Urogenital: urinary tract infectionDRUG ABUSE AND DEPENDENCEControlled Substance:ROXICODONE™ is a Schedule II narcotic under the U.S. Controlled Substances Act (CSA) (21U.S.C. 801-886). ROXICODONE™ can produce drug dependence of the morphine type, andtherefore, has the potential for being abused. Psychic dependence, physical dependence andtolerance may develop upon repeated administration. ROXICODONE™ should be prescribed andadministered with the same degree of caution appropriate to the use of other narcotic-containingmedications.Abuse:Since ROXICODONE™ is a mu-opioid agonist, it may be subject to misuse, abuse, andaddiction. Addiction to opioids prescribed for pain management has not been estimated.However, requests for opioids from opioid-addicted patients occur. As such, physicians shouldtake appropriate care in prescribing ROXICODONE™.Dependence:Opioid analgesics may cause psychological and physical dependence. Physical dependenceresults in withdrawal symptoms in patients who abruptly discontinue the drug after long termadministration, Also, symptoms of withdrawal may be precipitated through the administration ofdrugs with mu-opioid antagonist activity, e.g., naloxone or mixed agonist/antagonist analgesics(pentazocine, butorphanol, nalbuphine, dezocine). (See also OVERDOSAGE Section). Physicaldependence usually does not occur to a clinically significant degree, until after several weeks ofcontinued opioid usage. Tolerance, in which increasingly larger doses are required to producethe same degree of analgesia, is initially manifested by a shortened duration of an analgesiceffect and subsequently, by decreases in the intensity of analgesia.In chronic pain patients, and in opioid-tolerant cancer patients, the administration ofROXICODONE™ should be guided by the degree of tolerance manifested and the doses neededto adequately relieve pain.The severity of the ROXICODONE™ abstinence syndrome may depend on the degree ofphysical dependence. Withdrawal is characterized by rhinitis, myalgia, abdominal cramping, andoccasional diarrhea. Most observable symptoms disappear in 5 to 14 days without treatment;however, there may be a phase of secondary or chronic abstinence which may last for 2 to 6months characterized by insomnia, irritability, and muscular aches. The patient may be detoxifiedby gradual reduction of the dose. Gastrointestinal disturbances or dehydration should be treatedwith supportive care.
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11OVERDOSAGESigns and Symptoms:Acute overdose with ROXICODONE™ can be manifested by respiratory depression, somnolenceprogressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constrictedpupils, bradycardia, hypotension, and death.Treatment:To treat ROXICODONE™ overdose, primary attention should be given to the re-establishment ofa patent airway and institution of assisted or controlled ventilation. Supportive measures(including oxygen and vasopressors) should be employed in the management of circulatory shockand pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias mayrequire cardiac massage or defibrillation.The narcotic antagonists, naloxone or nalmefene, are specific antidotes for opioid overdose.Opioid antagonists should not be administered in the absence of clinically significantrespiratory or circulatory depression secondary to ROXICODONE™ overdose. If neededthe appropriate dose of naloxone hydrochloride or nalmefene should be administeredsimultaneously with efforts at respiratory resuscitation (see package insert for each drug for thedetails). Since the duration of action of oxycodone may exceed that of the antagonist, the patientshould be kept under continued surveillance and repeated doses of the antagonist should beadministered as needed to maintain adequate respiration. Gastric emptying may be useful inremoving unabsorbed drug.Opioid antagonists should be administered cautiously to persons who are suspected to bephysically dependent on any opioid agonist, including oxycodone. (see Opioid-TolerantIndividuals)Opioid-Tolerant Individuals: In an individual physically dependent on opioids, administration ofa usual dose of antagonist will precipitate an acute withdrawal. The severity of the withdrawalsyndrome produced will depend on the degree of physical dependence and the dose of theantagonist administered. Use of an opioid antagonist should be reserved for cases where suchtreatment is clearly needed. If it is necessary to treat serious respiratory depression in thephysically dependent patient, administration of the antagonist should be begun with care and bytitration with smaller than usual doses.DOSAGE AND ADMINISTRATIONROXICODONE™ is intended for the management of moderate to severe pain in patients whorequire treatment with an oral opioid analgesic. The dose should be individually adjustedaccording to severity of pain, patient response and patient size. If the pain increases in severity, ifanalgesia is not adequate, or if tolerance occurs, a gradual increase in dosage may be required.Patients who have not been receiving opioid analgesics should be started on ROXICODONE™ in adosing range of 5 to 15 mg every 4 to 6 hours as needed for pain. The dose should be titrated basedupon the individual patient’s response to their initial dose of ROXICODONE™. Patients with chronicpain should have their dosage given on an around-the-clock basis to prevent the reoccurrence ofpain rather than treating the pain after it has occurred. This dose can then be adjusted to anacceptable level of analgesia taking into account side effects experienced by the patient.For control of severe chronic pain, ROXICODONE™ should be administered on a regularlyscheduled basis, every 4-6 hours, at the lowest dosage level that will achieve adequateanalgesia.
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12As with any potent opioid, it is critical to adjust the dosing regimen for each patient individually,taking into account the patient’s prior analgesic treatment experience. Although it is not possibleto list every condition that is important to the selection of the initial dose of ROXICODONE™,attention should be given to: 1) the daily dose, potency, and characteristics of a pure agonist ormixed agonist/antagonist the patient has been taking previously, 2) the reliability of the relativepotency estimate to calculate the dose of oxycodone needed, 3) the degree of opioid tolerance,4) the general condition and medical status of the patient, and 5) the balance between paincontrol and adverse experiences.Conversion From Fixed-Ratio Opioid/Acetaminophen, Opioid/Aspirin, orOpioid/Nonsteroidal Combination Drugs:When converting patients from fixed ratio opioid/non-opioid drug regimens a decision should bemade whether or not to continue the non-opioid analgesic. If a decision is made to discontinuethe use of non-opioid analgesic, it may be necessary to titrate the dose of ROXICODONE™ inresponse to the level of analgesia and adverse effects afforded by the dosing regimen. If thenon-opioid regimen is continued as a separate single entity agent, the starting doseROXICODONE™ should be based upon the most recent dose of opioid as a baseline for furthertitration of oxycodone. Incremental increases should be gauged according to side effects to anacceptable level of analgesia.Patients Currently on Opioid Therapy:If a patient has been receiving opioid-containing medications prior to taking ROXICODONE™, thepotency of the prior opioid relative to oxycodone should be factored into the selection of the totaldaily dose (TDD) of oxycodone.In converting patients from other opioids to ROXICODONE™ close observation and adjustmentof dosage based upon the patient’s response to ROXICODONE™ is imperative. Administrationof supplemental analgesia for breakthrough or incident pain and titration of the total daily dose ofROXICODONE™ may be necessary, especially in patients who have disease states that arechanging rapidly.Maintenance of Therapy:Continual re-evaluation of the patient receiving ROXICODONE™ is important, with specialattention to the maintenance of pain control and the relative incidence of side effects associatedwith therapy. If the level of pain increases, effort should be made to identify the source ofincreased pain, while adjusting the dose as described above to decrease the level of pain.During chronic therapy, especially for non-cancer-related pain (or pain associated with otherterminal illnesses), the continued need for the use of opioid analgesics should be re-assessed asappropriate.Cessation of Therapy:When a patient no longer requires therapy with ROXICODONE™or other opioid analgesics forthe treatment of their pain, it is important that therapy be gradually discontinued over time toprevent the development of an opioid abstinence syndrome (narcotic withdrawal). In general,therapy can be decreased by 25% to 50% per day with careful monitoring for signs andsymptoms of withdrawal (see Drug Abuse and Dependence section for description of the signsand symptoms of withdrawal). If the patient develops these signs or symptoms, the dose shouldbe raised to the previous level and titrated down more slowly, either by increasing the intervalbetween decreases, decreasing the amount of change in dose, or both. It is not known at whatdose of ROXICODONE™that treatment may be discontinued without risk of the opioidabstinence syndrome.
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13HOW SUPPLIEDROXICODONE™ (oxycodone hydrochloride tablets, USP)15 mg green tablets scored(Identified 54 710)[Embossed 54 710 on one side]NDC 0054-4658-25 :Bottles of 100 tabletsNDC 0054-8658-24:Unit dose. 25 tablets per card (reverse numbered), 4 cards per shipper30 mg blue tablets scored (Identified 54 199)[Embossed 54 199 on one side]NDC 0054-4665-25:Bottles of 100 tabletsNDC 0054-8665-24:Unit dose. 25 tablets per card (reverse numbered), 4 cards per shipperDEA Order Form RequiredDispense in a tight, light-resistant container.Protect from moisture.Store at 25°C (77°F) Controlled Room Temperature with brief excursions permitted between 15°-30°C (59°-86°F). (see U.S.P.)Roxane Laboratories, Inc.Columbus, Ohio 43216