NDC 0904-6701 Oxycodone Hydrochloride

Oxycodone Hydrochloride

NDC Product Code 0904-6701

NDC 0904-6701-30

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 30 mL in 1 BOTTLE, PLASTIC

NDC Product Information

Oxycodone Hydrochloride with NDC 0904-6701 is a a human prescription drug product labeled by Major Pharmaceuticals. The generic name of Oxycodone Hydrochloride is oxycodone hydrochloride. The product's dosage form is solution and is administered via oral form.

Labeler Name: Major Pharmaceuticals

Dosage Form: Solution - A clear, homogeneous liquid1 dosage form that contains one or more chemical substances dissolved in a solvent or mixture of mutually miscible solvents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

DEA Schedule: Schedule II (CII) Substances What is the Drug Enforcement Administration (DEA) CII Schedule?
The controlled substances in the CII schedule have a high abuse potential with severe psychological or physical dependence liability, but have accepted medical use in the United States. Schedule CII controlled substances include certain narcotic, stimulant, and depressant drugs.

Oxycodone Hydrochloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • OXYCODONE HYDROCHLORIDE 20 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ANHYDROUS CITRIC ACID (UNII: XF417D3PSL)
  • D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
  • BERRY (UNII: FV3431923Z)
  • WATER (UNII: 059QF0KO0R)
  • TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K)
  • SODIUM BENZOATE (UNII: OJ245FE5EU)
  • SACCHARIN SODIUM (UNII: SB8ZUX40TY)
  • SORBITOL (UNII: 506T60A25R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Full Opioid Agonists - [MoA] (Mechanism of Action)
  • Opioid Agonist - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Major Pharmaceuticals
Labeler Code: 0904
FDA Application Number: ANDA209897 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 02-12-2018 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2019 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Oxycodone

Oxycodone is pronounced as (ox i koe' done)

Why is oxycodone medication prescribed?
Oxycodone is used to relieve moderate to severe pain. Oxycodone extended-release tablets and extended-release capsules are used to relieve severe pain in people who are e...
[Read More]

* Please review the disclaimer below.

Oxycodone Hydrochloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Warning: Risk Of Medication Errors; Addiction, Abuse, And Misuse; Life-Threatening Respiratory Depression; Accidental Ingestion; Neonatal Opioid Withdrawl Syndrome; Cytochrome P450 3A4 Interaction; And Risks From Concomitant Use With Benzodiazepines Or Other Cns Depressants

Risk of Medication ErrorsEnsure accuracy when prescribing, dispensing, and administering Oxycodone Hydrochloride OralSolution. Dosing errors due to confusion between mg and mL, and other oxycodone hydrochlorideoral solutions of different concentrations can results in accidental overdose. [see Dosage andAdministration (2.1), Warnings and Precautions (5.1)].Addiction, Abuse, and MisuseOxycodone Hydrochloride Oral Solution exposes users to risks of addiction, abuse, and misuse,which can lead to overdose and death. Assess patient’s risk prior to prescribing OxycodoneHydrochloride Oral Solution, and monitor all patients regularly for the development of thesebehaviors and conditions. [see Warnings and Precautions (5.2)].Life-Threatening Respiratory DepressionSerious, life-threatening, or fatal respiratory depression in may occur with use of OxycodoneHydrochloride Oral Solution. Monitor for respiratory depression, especially during initiation ofOxycodone Hydrochloride Oral Solution or following a dose increase. [see Warnings andPrecautions (5.3)].Accidental IngestionAccidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially bychildren, can result in a fatal overdose of oxycodone. [see Warnings and Precautions (5.3)].Neonatal Opioid Withdrawal SyndromeProlonged use of Oxycodone Hydrochloride Oral Solution during pregnancy can result in neonatalopioid withdrawal syndrome, which may be life-threatening if not recognized and treated, andrequires management according to protocols developed by neonatology experts. If opioid use isrequired for a prolonged period in a pregnant woman, advise the patient of the risk of neonatalopioid withdrawal syndrome and ensure that appropriate treatment will be available. [seeWarnings and Precautions (5.4)].Cytochrome P450 3A4 InteractionThe concomitant of Oxycodone Hydrochloride Oral Solution with all cytochrome P450 3A4inhibitors may result in an increase in oxycodone plasma concentrations, which could increase orprolong adverse reactions and may cause potentially fatal respiratory depression. In addition,discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase inoxycodone plasma concentration. Monitor patients receiving Oxycodone Hydrochloride OralSolution and any CYP3A4 inhibitor or inducer. [see Warnings and Precautions (5.5), DrugInteractions (7), Clinical Pharmacology (12.3)].Risks From Concomitant Use With Benzodiazepines Or Other CNS DepressantsConcomitant use of opioids with benzodiazepines or other central nervous system (CNS)depressants, including alcohol, may result in profound sedation, respiratory depression, coma, anddeath [see Warnings and Precautions (5.6), Drug Interactions (7)].• Reserve concomitant prescribing of Oxycodone Hydrochloride Oral Solution andbenzodiazepines or other CNS depressants for use in patients for whom alternative treatmentoptions are inadequate.• Limit dosages and durations to the minimum required.• Follow patients for signs and symptoms of respiratory depression and sedation.

1 Indications And Usage

Oxycodone Hydrochloride Oral Solution is indicated for the management of pain severe enough to require an opioidanalgesic and for which alternative treatments are inadequate.Limitations of UseBecause of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, [see Warnings andPrecautions (5.2)], reserve Oxycodone Hydrochloride Oral Solution for use in patients for whom alternativetreatment options [e.g., non-opioid analgesics or opioid combination products]:• Have not been tolerated, or are not expected to be tolerated,• Have not provided adequate analgesia, or are not expected to provide adequate analgesia

2.1. Important Dosage And Administration Instructions

Ensure accuracy when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution to avoiddosing errors due to confusion between mg and mL, and with other oxycodone hydrochloride solutions of differentconcentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated anddispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume.Always use the enclosed calibrated oral syringe when administering Oxycodone Hydrochloride Oral Solution 100 mgper 5 mL (20 mg per mL) to ensure that the dose is measured and administered accurately.Do not use household teaspoons or tablespoons to measure Oxycodone Hydrochloride Oral Solution, as using atablespoon instead of a teaspoon could lead to overdosage.Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [seeWarnings and Precautions (5)].Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patientresponse, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings andPrecautions (5.2)].Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy andfollowing dosage increases with Oxycodone Hydrochloride Oral Solution and adjust the dosage accordingly [seeWarnings and Precautions (5.3)].

2.2. Initial Dosage

Use of Oxycodone Hydrochloride Oral Solution as the First Opioid AnalgesicInitiate treatment with Oxycodone Hydrochloride Oral Solution in a dosing range of 5 to 15 mg every 4 to 6 hoursas needed for pain.Conversion from Other Opioids to Oxycodone Hydrochloride Oral SolutionThere is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservativeapproach is advised when determining the total daily dosage of Oxycodone Hydrochloride Oral Solution. It is saferto underestimate a patient’s 24-hour Oxycodone Hydrochloride Oral Solution dosage than to overestimate the24-hour Oxycodone Hydrochloride Oral Solution dosage and manage an adverse reaction due to overdose.Conversion from Oxycodone Hydrochloride Oral Solution to Extended-Release Oxycodone HydrochlorideThe relative bioavailability of Oxycodone Hydrochloride Oral Solution compared to extended-release oxycodone isunknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessivesedation and respiratory depression.

2.3. Titration And Maintenance Of Therapy

Individually titrate Oxycodone Hydrochloride Oral Solution to a dose that provides adequate analgesia andminimizes adverse reactions. Continually reevaluate patients receiving Oxycodone Hydrochloride Oral Solution toassess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for thedevelopment of addiction, abuse, or misuse [see Warnings and Precautions (5.2)]. Frequent communication isimportant among the prescriber, other members of the healthcare team, the patient, and the caregiver/familyduring periods of changing analgesic requirements, including initial titration.If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain beforeincreasing the Oxycodone Hydrochloride Oral Solution dosage. If unacceptable opioid-related adverse reactions areobserved, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between managementof pain and opioid-related adverse reactions.

2.4. Discontinuation Of Oxycodone Hydrochloride Oral Solution

When a patient who has been taking Oxycodone Hydrochloride Oral Solution regularly and may be physicallydependent no longer requires therapy with Oxycodone Hydrochloride Oral Solution, taper the dose gradually, by25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patientdevelops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasingthe interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinueOxycodone Hydrochloride Oral Solution in a physically-dependent patient [see Warnings and Precautions (5.13),Drug Abuse and Dependence (9.3)].

3 Dosage Forms And Strengths

Oxycodone Hydrochloride Oral Solution USP, 100 mg per 5 mL (20 mg per mL) Strength Oral Solution: Each 5 mL ofyellow Oxycodone Hydrochloride Oral Solution, USP contains oxycodone hydrochloride 100 mg.

4 Contraindications

Oxycodone Hydrochloride Oral Solution is contraindicated in patients with:• Significant respiratory depression [see Warnings and Precautions (5.3)]• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [seeWarnings and Precautions (5.7)]• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions(5.11)]• Hypersensitivity to oxycodone (e.g., angioedema) [see Adverse Reactions (6)]

5.1. Risk Of Accidental Overdose And Death Due To Medication Errors

Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusionbetween mg and mL and confusion with oxycodone hydrochloride solutions of different concentrations, whenprescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution. Ensure that the dose iscommunicated clearly and dispensed accurately. Always use the enclosed calibrated oral syringe when administeringOxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/ mL) to ensure the dose is measured andadministered accurately.Do not use a teaspoon or a tablespoon to measure a dose. A household teaspoon or tablespoon is not an adequatemeasuring device. Given the inexactitude of the household spoon measure and the possibility of using a tablespooninstead of a teaspoon, which could lead to overdosage, it is strongly recommended that, if the enclosed calibratedmeasuring syringe becomes lost, caregivers obtain and use a calibrated measuring device. Health care providersshould recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instructcaregivers to use extreme caution in measuring the dosage.

5.2. Addiction, Abuse, And Misuse

Oxycodone Hydrochloride Oral Solution contains oxycodone, a Schedule II controlled substance. As an opioid,Oxycodone Hydrochloride Oral Solution exposes users to the risks of addiction, abuse, and misuse [see Drug Abuseand Dependence (9)].Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribedOxycodone Hydrochloride Oral Solution. Addiction can occur at recommended dosages and if the drug is misused orabused.Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Oxycodone Hydrochloride OralSolution, and monitor all patients receiving Oxycodone Hydrochloride Oral Solution for the development of thesebehaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse(including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for theserisks should not, however, prevent the proper management of pain in any given patient. Patients at increased riskmay be prescribed opioids such as Oxycodone Hydrochloride Oral Solution, but use in such patients necessitatesintensive counseling about the risks and proper use of Oxycodone Hydrochloride Oral Solution along with intensivemonitoring for signs of addiction, abuse, and misuse.Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Considerthese risks when prescribing or dispensing Oxycodone Hydrochloride Oral Solution. Strategies to reduce these risksinclude prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal ofunused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or statecontrolled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.3. Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when usedas recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrestand death. Management of respiratory depression may include close observation, supportive measures, and use ofopioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2)retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OxycodoneHydrochloride Oral Solution, the risk is greatest during the initiation of therapy or following a dosage increase.Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy withand following dosage increases of Oxycodone Hydrochloride Oral Solution.To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone Hydrochloride Oral Solutionare essential [see Dosage and Administration (2)]. Overestimating the Oxycodone Hydrochloride Oral Solutiondosage when converting patients from another opioid product can result in a fatal overdose with the first dose.Accidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially by children, can result inrespiratory depression and death due to an overdose of oxycodone.

5.4. Neonatal Opioid Withdrawal Syndrome

Prolonged use of Oxycodone Hydrochloride Oral Solution during pregnancy can result in withdrawal in the neonate.Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if notrecognized and treated, and requires management according to protocols developed by neonatology experts. Observenewborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women usingopioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriatetreatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].

5.5. Risks Of Concomitant Use Or Discontinuation Of Cytochrome P450 3A4 Inhibitors And Inducers

Concomitant use of Oxycodone Hydrochloride Oral Solution with a CYP3A4 inhibitor, such as macrolide antibiotics(e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), mayincrease plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatalrespiratory depression [see Warnings and Precautions (5.3)], particularly when an inhibitor is added after a stabledose of Oxycodone Hydrochloride Oral Solution is achieved. Similarly, discontinuation of a CYP3A4 inducer, such asrifampin, carbamazepine, and phenytoin, in Oxycodone Hydrochloride Oral Solution-treated patients may increaseoxycodone plasma concentrations and prolong opioid adverse reactions. When using Oxycodone Hydrochloride OralSolution with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Oxycodone Hydrochloride Oral Solution -treatedpatients, monitor patients closely at frequent intervals and consider dosage reduction of Oxycodone HydrochlorideOral Solution until stable drug effects are achieved [see Dosage and Administration (2.1), Drug Interactions (7)].Concomitant use of Oxycodone Hydrochloride Oral Solution with CYP3A4 inducers or discontinuation of an CYP3A4inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to awithdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using OxycodoneHydrochloride Oral Solution with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely atfrequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or ifsymptoms of opioid withdrawal occur [see Dosage and Administration (2.1), Drug Interactions (7)].

5.6. Risks From Concomitant Use With Benzodiazepines Or Other Cns Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OxycodoneHydrochloride Oral Solution with benzodiazepines or other CNS depressants (e.g., non-benzodiazepinesedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids,alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whomalternative treatment options are inadequate.Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increasesthe risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacologicalproperties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioidanalgesics [see Drug Interactions (7)].If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioidanalgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients alreadyreceiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant thanindicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in apatient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioidanalgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratorydepression and sedation.Advise both patients and caregivers about the risks of respiratory depression and sedation when OxycodoneHydrochloride Oral Solution are used with benzodiazepines or other CNS depressants (including alcohol and illicitdrugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of thebenzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders,including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use ofadditional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) and Patient CounselingInformation (17)].

5.7. Life-Threatening Respiratory Depression In Patients With Chronic Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients

The use of Oxycodone Hydrochloride Oral Solution in patients with acute or severe bronchial asthma in anunmonitored setting or in the absence of resuscitative equipment is contraindicated.Patients with Chronic Pulmonary Disease: Oxycodone Hydrochloride Oral Solution-treated patients with significantchronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratoryreserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratorydrive including apnea, even at recommended dosages of Oxycodone Hydrochloride Oral Solution [see Warnings andPrecautions (5.3)].Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly,cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared toyounger, healthier patients [see Warnings and Precautions (5.7)].Monitor such patients closely, particularly when initiating and titrating Oxycodone Hydrochloride Oral Solution andwhen Oxycodone Hydrochloride Oral Solution is given concomitantly with other drugs that depress respiration [seeWarnings and Precautions (5.5)]. Alternatively, consider the use of non-opioid analgesics in these patients.

5.8. Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month ofuse. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting,anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm thediagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologicreplacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover andcontinue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reporteduse of a different opioid without recurrence of adrenal insufficiency. The information available does not identify anyparticular opioids as being more likely to be associated with adrenal insufficiency.

5.9. Severe Hypotension

Oxycodone Hydrochloride Oral Solution may cause severe hypotension including orthostatic hypotension and syncopein ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already beencompromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g.phenothiazines or general anesthetics) [see Drug Interactions (7)]. Monitor these patients for signs of hypotensionafter initiating or titrating the dosage of Oxycodone Hydrochloride Oral Solution. In patients with circulatory shock,Oxycodone Hydrochloride Oral Solution may cause vasodilation that can further reduce cardiac output and bloodpressure. Avoid the use of Oxycodone Hydrochloride Oral Solution in patients with circulatory shock.

5.10. Risks Of Use In Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, Or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increasedintracranial pressure or brain tumors), Oxycodone Hydrochloride Oral Solution may reduce respiratory drive, and theresultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation andrespiratory depression, particularly when initiating therapy with Oxycodone Hydrochloride Oral Solution.Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of OxycodoneHydrochloride Oral Solution in patients with impaired consciousness or coma.

5.11. Risks Of Use In Patients With Gastrointestinal Conditions

Oxycodone Hydrochloride Oral Solution is contraindicated in patients with known or suspected gastrointestinalobstruction, including paralytic ileus.

Oxycodone Hydrochloride Oral Solution is contraindicated in patients with known or suspected gastrointestinalobstruction, including paralytic ileus.The oxycodone in Oxycodone Hydrochloride Oral Solution may cause spasm of the sphincter of Oddi. Opioids maycause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis forworsening symptoms.

5.12. Increased Risk Of Seizures In Patients With Seizure Disorders

The oxycodone in Oxycodone Hydrochloride Oral Solution may increase the frequency of seizures in patients withseizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.Monitor patients with a history of seizure disorders for worsened seizure control during Oxycodone HydrochlorideOral Solution therapy.

5.13. Withdrawal

Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist(e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including OxycodoneHydrochloride Oral Solution. In these patients, mixed agonist/antagonist and partial agonist analgesics may reducethe analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].When discontinuing Oxycodone Hydrochloride Oral Solution in a physically-dependent patient, gradually taper thedosage [see Dosage and Administration (2.4)]. Do not abruptly discontinue Oxycodone Hydrochloride Oral Solutionin these patients [see Drug Abuse and Dependence (9.3)].

5.14. Risks Of Driving And Operating Machinery

Oxycodone Hydrochloride Oral Solution may impair the mental or physical abilities needed to perform potentiallyhazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerousmachinery unless they are tolerant to the effects of Oxycodone Hydrochloride Oral Solution and know how they willreact to the medication [see Patient Counseling Information (17)].

6 Adverse Reactions

The following serious adverse reactions are described, or described in greater detail, in other sections:• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.2)]• Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)]• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)]• Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.6)• Adrenal Insufficiency [see Warnings and Precautions (5.8)]• Severe Hypotension [see Warnings and Precautions (5.9)]• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.11)]• Seizures [see Warnings and Precautions (5.12)]• Withdrawal [see Warnings and Precautions (5.13)]The following adverse reactions associated with the use of oxycodone were identified in clinical studies orpostmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertainsize, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Serious adverse reactions associated with oxycodone use included: respiratory depression, respiratory arrest,circulatory depression, cardiac arrest, hypotension, and/or shock.The common adverse reactions seen on initiation of therapy with oxycodone are dose-related and are typicalopioid-related adverse reactions. The most frequent adverse events include nausea, constipation, vomiting,headache, and pruritus. The frequency of these reactions depended on several factors, including clinical setting, thepatient’s level of opioid tolerance, and host factors specific to the individual.In all patients for whom dosing information was available (n=191) from the open-label and double-blind studiesinvolving another formulation of immediate-release oxycodone, the following adverse events were recorded inoxycodone treated patients with an incidence ¦ 3%. In descending order of frequency, they were: nausea,constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The other less frequentlyobserved adverse reactions from opioid analgesics, including Oxycodone Hydrochloride Oral Solution included:Body as a Whole: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flusyndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis.Cardiovascular: deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, andtachycardia.Digestive: anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting.Hemic and Lymphatic: anemia and leukopenia.Metabolic and Nutritional: edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema.Musculoskeletal: arthralgia, arthritis, bone pain, myalgia and pathological fracture.Nervous: agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personalitydisorder, tremor, and vasodilation.Respiratory: bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, andsinusitis.Skin and Appendages: herpes simplex, rash, sweating, and urticaria.Special Senses: amblyopia.Urogenital: urinary tract infectionSerotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reportedduring concomitant use of opioids with serotonergic drugs.Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often followinggreater than one month of use.Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Oxycodone Hydrochloride Oral Solution.Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see ClinicalPharmacology (12.2)].

7 Drug Interactions

Table 1 includes clinically significant drug interactions with Oxycodone Hydrochloride Oral Solution.Table 1: Clinically Significant Drug Interactions with Oxycodone Hydrochloride Oral SolutionInhibitors of CYP3A4 and CYP2D6Clinical Impact: The concomitant use of Oxycodone Hydrochloride Oral Solution and CYP3A4 inhibitorscan increase the plasma concentration of oxycodone, resulting in increased orprolonged opioid effects. These effects could be more pronounced with concomitant useof Oxycodone Hydrochloride Oral Solution and CYP2D6 and CYP3A4 inhibitors,particularly when an inhibitor is added after a stable dose of Oxycodone HydrochlorideOral Solution is achieved [see Warnings and Precautions (5.5)].After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodoneplasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting indecreased opioid efficacy or a withdrawal syndrome in patients who had developedphysical dependence to oxycodone.Intervention: If concomitant use is necessary, consider dosage reduction of Oxycodone HydrochlorideOral Solution until stable drug effects are achieved Monitor patients for respiratorydepression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued,consider increasing the Oxycodone Hydrochloride Oral Solution dosage until stable drugeffects are achieved. Monitor for signs of opioid withdrawal.Examples Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole),protease inhibitors (e.g., ritonavir)CYP3A4 InducersClinical Impact: The concomitant use of Oxycodone Hydrochloride Oral Solution and CYP3A4 inducerscan decrease the plasma concentration of oxycodone [see Clinical Pharmacology(12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patientswho have developed physical dependence to oxycodone [see Warnings and Precautions(5.5)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, theoxycodone plasma concentration will increase [see Clinical Pharmacology (12.3)],which could increase or prolong both the therapeutic effects and adverse reactions, andmay cause serious respiratory depression.Intervention: If concomitant use is necessary, consider increasing the Oxycodone Hydrochloride OralSolution dosage until stable drug effects are achieved. Monitor for signs of opioidwithdrawal. If a CYP3A4 inducer is discontinued, consider Oxycodone HydrochlorideOral Solution dosage reduction and monitor for signs of respiratory depression.Examples Rifampin, carbamazepine, phenytoin(continuedTable 1 (continued): Clinically Significant Drug Interactions with Oxycodone Hydrochloride OralSolutionBenzodiazepines and other Central Nervous System (CNS) DepressantsClinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or otherCNS depressants including alcohol, increases the risk of respiratory depression,profound sedation, coma, and death.Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternativetreatment options are inadequate. Limit dosages and durations to the minimumrequired. Follow patients closely for signs of respiratory depression and sedation [seeWarnings and Precautions (5.6)].Examples Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, musclerelaxants, general anesthetics, antipsychotics, other opioids, alcohol.Serotonergic DrugsClinical Impact: The concomitant use of opioids with other drugs that affect the serotonergicneurotransmitter system has resulted in serotonin.Intervention: If concomitant use is warranted, carefully observe the patient, particularly duringtreatment initiation and dose adjustment. Discontinue Oxycodone Hydrochloride OralSolution if serotonin syndrome is suspected.Examples Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptakeinhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists,drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone,tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatricdisorders and also others, such as linezolid and intravenous methylene blue).Monoamine Oxidase Inhibitors (MAOIs)Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity(e.g., respiratory depression, coma) [see Warnings and Precautions (5.3)].Intervention: The use of Oxycodone Hydrochloride Oral Solution is not recommended for patientstaking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid isnecessary, use test doses and frequent titration of small doses to treat pain whileclosely monitoring blood pressure and signs and symptoms of CNS and respiratorydepression.Examples phenelzine, tranylcypromine, linezolidMixed Agonist/Antagonist and Partial Agonist Opioid AnalgesicsClinical Impact: May reduce the analgesic effect of Oxycodone Hydrochloride Oral Solution and/orprecipitate withdrawal symptoms.Intervention: Avoid concomitant use.Examples butorphanol, nalbuphine, pentazocine, buprenorphineMuscle RelaxantsClinical Impact: Oxycodone may enhance the neuromuscular blocking action of skeletal musclerelaxants and produce an increased degree of respiratory depression.Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwiseexpected and decrease the dosage of Oxycodone Hydrochloride Oral Solution and/orthe muscle relaxant as necessary.DiureticsClinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretichormone.Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure andincrease the dosage of the diuretic as needed.Anticholinergic DrugsClinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retentionand/or severe constipation, which may lead to paralytic ileus.Intervention: Monitor patients for signs of urinary retention or reduced gastric motility whenOxycodone Hydrochloride Oral Solution is used concomitantly with anticholinergicdrugs.

8.1 Pregnancy

Risk SummaryProlonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [seeWarnings and Precautions (5.4)]. Available data with Oxycodone Hydrochloride Oral Solution are insufficient toinform a drug-associated risk for major birth defects and miscarriage. Animal reproduction studies with oraladministrations of oxycodone hydrochloride in rats and rabbits during the period of organogenesis at doses 2.6 and8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetaltoxicity. In several published studies, treatment of pregnant rats with oxycodone at clinically relevant doses andbelow, resulted in neurobehavioral effects in offspring [see Data]. Based on animal data, advise pregnant womenof the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicatedpopulation is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Inthe U.S. general population, the estimated background risk of major birth defects and miscarriage in clinicallyrecognized pregnancies is 2-4% and 15-20%, respectively.Clinical ConsiderationsFetal/Neonatal Adverse ReactionsProlonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physicaldependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioidwithdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor,vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawalsyndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, andrate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawalsyndrome and manage accordingly [see Warnings and Precautions (5.4)].Labor or DeliveryOpioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depressionin the neonate. Oxycodone Hydrochloride Oral Solution is not recommended for use in pregnant women duringor immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics,including Oxycodone Hydrochloride Oral Solution, can prolong labor through actions which temporarily reducethe strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may beoffset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioidanalgesics during labor for signs of excess sedation and respiratory depression.DataAnimal DataIn embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodonehydrochloride administered during the period of organogenesis up to 16 mg/kg/day and up 25 mg/kg/day,respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. Thehighest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of60 mg/day, respectively, on a mg/m2 basis. In published studies, offspring of pregnant rats administered oxycodoneduring gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increasedanxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal Day 1, 3, and 5; 0.3-times an adulthuman dose of 60 mg/day, on a mg/m2 basis) and altered learning and memory (15 mg/kg/day orally frombreeding through parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m2 basis).

8.2 Lactation

Risk SummaryOxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone inbreast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period.The lactation studies did not assess breastfed infants for potential adverse reactions. Lactation studies have not beenconducted with Oxycodone Hydrochloride Oral Solution, and no information is available on the effects of the drugon the breastfed infant or the effects of the drug on milk production.The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical needfor Oxycodone Hydrochloride Oral Solution and any potential adverse effects on the breastfed infant fromOxycodone Hydrochloride Oral Solution or from the underlying maternal condition.Clinical ConsiderationsMonitor infants exposed to Oxycodone Hydrochloride Oral Solution through breast milk for excess sedation andrespiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of anopioid analgesic is stopped, or when breast-feeding is stopped.

8.3 Females And Males Of Reproductive Potential

InfertilityChronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not knownwhether these effects on fertility are reversible [see Adverse Reactions (6), Clinical Pharmacology (12.2)].

8.4 Pediatric Use

The safety and effectiveness and the pharmacokinetics of Oxycodone Hydrochloride Oral Solution in pediatricpatients below the age of 18 have not been established.

8.5 Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution whenselecting a dose for an elderly patient, usually starting at the low end of the dosing range, reflecting the greaterfrequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doseswere administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents thatdepress respiration. Titrate the dosage of Oxycodone Hydrochloride Oral Solution slowly in geriatric patients and monitorclosely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.7)].Oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug maybe greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renalfunction, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Hepatic Impairment

Since oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepaticimpairment. Initiate therapy in these patients with a lower than usual dosage of Oxycodone Hydrochloride OralSolution and titrate carefully. Monitor closely for adverse events such as respiratory depression, sedation, andhypotension [see Clinical Pharmacology (12.3)].

8.7 Renal Impairment

Information from oxycodone tablets indicate that patients with renal impairment had higher plasma concentrationsof oxycodone than subjects with normal renal function. Initiate therapy with a lower than usual dosage ofOxycodone Hydrochloride Oral Solution and titrate carefully. Monitor closely for adverse events such as respiratorydepression, sedation, and hypotension [see Clinical Pharmacology (12.3)].

9.1 Controlled Substance

Oxycodone Hydrochloride Oral Solution contains oxycodone, a Schedule II controlled substance.

9.2 Abuse

Oxycodone Hydrochloride Oral Solution contains oxycodone, a substance with a high potential for abuse similar toother opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, andtapentadol. Oxycodone Hydrochloride Oral Solution can be abused and is subject to misuse, addiction, and criminaldiversion [see Warnings and Precautions (5.2)].All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioidanalgesic products carries the risk of addiction even under appropriate medical use.Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewardingpsychological or physiological effects.Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeatedsubstance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its usedespite harmful consequences, a higher priority given to drug use than to other activities and obligations, increasedtolerance, and sometimes a physical withdrawal.“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics includeemergency 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 orcontact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers toobtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction.Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers shouldbe aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence inall addicts. In addition, abuse of opioids can occur in the absence of true addiction.Oxycodone Hydrochloride Oral Solution, like other opioids, can be diverted for non-medical use into illicit channelsof distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewalrequests, as required by state and federal law, is strongly advised.Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and properdispensing and storage are appropriate measures that help to limit abuse of opioid drugs.Risks Specific to Abuse of Oxycodone Hydrochloride Oral SolutionOxycodone Hydrochloride Oral Solution is for oral use only. Abuse of oxycodone poses a risk of overdose and death.The risk is increased with concurrent abuse of alcohol and other central nervous system depressants. Parenteral drugabuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

9.3 Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need forincreasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression orother external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop atdifferent rates for different effects.Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reductionof a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity(e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), orpartial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree untilafter several days to weeks of continued opioid usage.Oxycodone Hydrochloride Oral Solution should not be abruptly discontinued in a physically-dependent patient [seeDosage and Administration (2.4)]. If Oxycodone Hydrochloride Oral Solution is abruptly discontinued in aphysically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize thissyndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signsand 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.Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibitrespiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

10 Overdosage

Clinical PresentationAcute overdose with Oxycodone Hydrochloride Oral Solution can be manifested by respiratory depression,somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and,in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypicalsnoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [seeClinical Pharmacology (12.2)].Treatment of OverdoseIn case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted orcontrolled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in themanagement of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will requireadvanced life-support techniques.The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting fromopioid overdose. For clinically significant respiratory or circulatory depression secondary to oxycodone overdose,administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinicallysignificant respiratory or circulatory depression secondary to oxycodone overdose.Because the duration of opioid reversal is expected to be less than the duration of action of oxycodone in OxycodoneHydrochloride Oral Solution, carefully monitor the patient until spontaneous respiration is reliably re-established. Ifthe response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist asdirected by the product’s prescribing information.In an individual physically dependent on opioids, administration of the recommended usual dosage of theantagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced willdepend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made totreat serious respiratory depression in the physically dependent patient, administration of the antagonist should beinitiated with care and by titration with smaller than usual doses of the antagonist.

11 Description

Oxycodone Hydrochloride Oral Solution is an agonist, available as a yellow solution 100 mg/5 mL (20 mg/mL) fororal administration. The chemical name is (5R,9R,13S,14S)-4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride. The molecular weight is 351.82. Its molecular formula is C18H21NO4.HCl,and it has the following chemical structure.Oxycodone hydrochloride is a white, odorless crystalline powder derived from the opium alkaloid, thebaine.It issoluble in water and slightly soluble in alcohol.The inactive ingredients in Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/ mL): include: citricacid anhydrous, D&C Yellow #10, mixed berry flavor, purified water, sodium citrate dihydrate, sodium benzoate,saccharin sodium, sorbitol.

12.1 Mechanism Of Action

Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to otheropioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioidagonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequateanalgesia and may be limited by adverse reactions, including respiratory and CNS depression.The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenouscompounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought toplay a role in the analgesic effects of this drug.

12.2 Pharmacodynamics

Effects of the Central Nervous System (CNS)Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratorydepression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases incarbon dioxide tension and electrical stimulation.Oxycodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are notpathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Markedmydriasis rather than miosis may be seen due to hypoxia in overdose situations.Effects on the Gastrointestinal Tract and Other Smooth MuscleOxycodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of thestomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions aredecreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point ofspasm resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreaticsecretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.Effects on the Cardiovascular SystemOxycodone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestationsof histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/ororthostatic hypotension.Effects on the Endocrine SystemOpioids inhibit the secretion of adrenocorticotropic hormone (ACTH, cortisol), and luteinizing hormone (LH) inhumans [see Adverse Reactions (6)]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreaticsecretion of insulin and glucagon.Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency thatmay manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids inthe clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, andpsychological stressors that may influence gonadal hormone levels have not been adequately controlled for instudies conducted to date [see Adverse Reactions (6)].Effects on the Immune SystemOpioids have been shown to have a variety of effects on components of the immune system in in vitro and Animalmodels. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestlyimmunosuppressive.Concentration–Efficacy RelationshipsThe minimum effective analgesic concentration will vary widely among patients, especially among patients whohave been previously treated with potent agonist opioids The minimum effective analgesic concentration ofoxycodone for any individual patient may increase over time due to an increase in pain, the development of a newpain syndrome and/or the development of analgesic tolerance [see Dosage and Administration (2.1, 2.2)].Concentration–Adverse Reaction RelationshipsThere is a relationship between increasing oxycodone plasma concentration and increasing frequency ofdose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. Inopioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adversereactions [see Dosage and Administration (2.1, 2.2, 2.3)].

12.3 Pharmacokinetics

The activity of oxycodone hydrochloride is primarily due to the parent drug oxycodone.AbsorptionAbout 60 to 87% of an oral dose reaches the systemic circulation in comparison to a parenteral dose. This high oralbioavailability (compared to other opioids) is due to lower pre-systemic and/or first-pass metabolism of oxycodone.Food EffectWhen oxycodone capsules are administered with a high-fat meal, mean AUC values are increased by 23% and peakconcentrations are decreased by 14%. Food causes a delay in Tmax (1.00 to 3 hours). Similar effects of food areexpected with the oral solution.DistributionFollowing intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Plasma proteinbinding of oxycodone at 37 °C and a pH of 7.4 was about 45%. Oxycodone has been found in breast milk.EliminationMetabolismOxycodone hydrochloride is extensively metabolized by multiple metabolic pathways to noroxycodone,oxymorphone, and noroxymorphone, which are subsequently glucuronidated. CYP3A4 mediatedN-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with a less contribution fromCYP2D6 mediated O-demethylation to oxymorphone. Therefore, the formation of these and related metabolitescan, in theory, be affected by other drugs. The major circulating metabolite is noroxycodone with an AUC ratio of0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic thanoxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in lowconcentrations. The correlation between oxymorphone concentrations and opioid effects was much less than thatseen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.ExcretionOxycodone and its metabolites are excreted primarily via the kidney. The amounts measured in the urine havebeen reported as follows: free oxycodone up to 19%; conjugated oxycodone up to 50%; free oxymorphone 0%;conjugated oxymorphone < 14%; both free and conjugated noroxycodone have been found in the urine but notquantified. The total plasma clearance was 0.8 L/min for adults. Apparent elimination half-life of oxycodonefollowing the administration of oxycodone is approximately 4 hours.Specific PopulationsAge: Geriatric Population:Information obtained from oxycodone tablets indicate that the plasma concentrations of oxycodone did notappear to be increased in patients over of the age of 65.Hepatic Impairment:Because oxycodone is extensively metabolized in the liver, its clearance may decrease in hepatic-impairedpatients. A dose adjustment is recommended in these patients [see Use in Specific Populations (8.6)].Renal Impairment:Because this drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to thisdrug may be greater in patients with impaired renal function, a dose reduction is recommended for renalimpaired patients [see Use in Specific Populations (8.7)].Drug Interaction StudiesCYP3A4 InhibitorsCYP3A4 is the major enzyme involved in noroxycodone formation. A published study showed that theco-administration of voriconazole, a CYP3A4 inhibitor, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold,respectively.CYP3A4 InducersA published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer,decreased oxycodone AUC and Cmax values by 86% and 63%, respectively.CYP2D6 InhibitorsOxycodone is metabolized in part to oxymorphone via the cytochrome P450 isoenzyme CYP2D6. While thispathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), suchblockade has not yet been shown to be of clinical significance with this agent.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisLong-term studies in animals to evaluate the carcinogenic potential of oxycodone have not been conducted.MutagenesisOxycodone hydrochloride was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolicactivation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonellatyphimurium and Escherichia coli) and in an assay for chromosomal aberrations (in vivo mouse bone marrowmicronucleus assay).Impairment of FertilityStudies in animals to evaluate the potential impact of oxycodone on fertility have not been conducted.

16 How Supplied/Storage And Handling

Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL). is a yellow solution, supplied as:NDC # 0904-6701-30 : Bottle of 30 mL supplied with a calibrated oral syringeStore at Controlled Room Temperature, 25 °C (77 °F); excursions are permitted to 15° - 30 °C (59° - 86 °F).PROTECT from MOISTURE and LIGHT.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).Medication ErrorsAdvise patients that Oxycodone Hydrochloride Oral Solution is available in one concentration (100 mg/5 mL).Inform patients about which concentration they have been prescribed. Instruct patients how to measure and take thecorrect dose of Oxycodone Hydrochloride Oral Solution and to always use the enclosed calibrated oral syringe whenadministering Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/ mL) to ensure the dose ismeasured and administered accurately [see Warnings and Precautions (5.1)].If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose to avoiderrors which could result in accidental overdose and death.Addiction, Abuse, and MisuseInform patients that the use of Oxycodone Hydrochloride Oral Solution, even when taken as recommended, canresult in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.2)].Instruct patients not to share Oxycodone Hydrochloride Oral Solution with others and to take steps to protectOxycodone Hydrochloride Oral Solution from theft or misuse.Life-Threatening Respiratory DepressionInform patients of the risk of life-threatening respiratory depression, including information that the risk is greatestwhen starting Oxycodone Hydrochloride Oral Solution or when the dosage is increased, and that it can occur even atrecommended dosages [see Warnings and Precautions (5.3)]. Advise patients how to recognize respiratorydepression and to seek medical attention if breathing difficulties develop.Accidental IngestionInform patients that accidental ingestion, especially by children, may result in respiratory depression or death [seeWarnings and Precautions (5.3]. Instruct patients to take steps to store Oxycodone Hydrochloride Oral Solutionsecurely and to dispose of unused Oxycodone Hydrochloride Oral Solution by flushing done the toilet.Interactions with Benzodiazepines and Other CNS DepressantsInform patients and caregivers that potentially fatal additive effects may occur if Oxycodone Hydrochloride OralSolution is used with benzodiazepines or other CNS depressants, including alcohol, and not to use theseconcomitantly unless supervised by a health care provider [see Warnings and Precautions (5.6), Drug Interactions(7)].Serotonin SyndromeInform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitantadministration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medicalattention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, orplan to take serotonergic medications. [see Drug Interactions (7)].MAOI InteractionInform patients to avoid taking Oxycodone Hydrochloride Oral Solution while using any drugs that inhibitmonoamine oxidase. Patients should not start MAOIs while taking Oxycodone Hydrochloride Oral Solution [see DrugInteractions (7)].Adrenal InsufficiencyInform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenalinsufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue,weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience aconstellation of these symptoms [see Warnings and Precautions (5.8)].Important Administration InstructionsInstruct patients how to properly take Oxycodone Hydrochloride Oral Solution. [see Dosage and Administration(2.1), Warnings and Precautions (5.1)]• Advise patients to always use the enclosed calibrated oral syringe when administering OxycodoneHydrochloride Oral Solution to ensure the dose is measured and administered accurately [see Warnings andPrecautions (5.1)].• Advise patients never to use household teaspoons or tablespoons to measure Oxycodone Hydrochloride OralSolution.• Advise patients not to adjust the dose of Oxycodone Hydrochloride Oral Solution without consulting with aphysician or other healthcare provider.If patients have been receiving treatment with Oxycodone Hydrochloride Oral Solution for more than a few weeksand cessation of therapy is indicated, counsel them on the importance of safely tapering the dose as abruptdiscontinuation of the medication could precipitate withdrawal symptoms. Provide a dose schedule to accomplish agradual discontinuation of the medication [see Dosage and Administration (2.4)].HypotensionInform patients that Oxycodone Hydrochloride Oral Solution may cause orthostatic hypotension and syncope.Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of seriousconsequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [seeWarnings and Precautions (5.9)].AnaphylaxisInform patients that anaphylaxis has been reported with ingredients contained in Oxycodone Hydrochloride OralSolution. Advise patients how to recognize such a reaction and when to seek medical attention [see AdverseReactions (6)].PregnancyNeonatal Opioid Withdrawal SyndromeInform female patients of reproductive potential that prolonged use of Oxycodone Hydrochloride Oral Solutionduring pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if notrecognized and treated [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].Embryo-Fetal ToxicityInform female patients of reproductive potential that Oxycodone Hydrochloride Oral Solution can cause fetalharm and to inform the healthcare provider of a known or suspected pregnancy [see Use in Specific Populations(8.1)].LactationAdvise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, orlimpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in SpecificPopulations (8.2)].InfertilityInform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects onfertility are reversible [see Use in Specific Populations (8.3)].Driving or Operating Heavy MachineryInform patients that Oxycodone Hydrochloride Oral Solution may impair the ability to perform potentially hazardousactivities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until theyknow how they will react to the medication [see Warnings and Precautions (5.14)].ConstipationAdvise patients of the potential for severe constipation, including management instructions and when to seekmedical attention [see Adverse Reactions (6), Clinical Pharmacology (12.2)].Disposal of Unused Oxycodone Hydrochloride Oral SolutionAdvise patients to dispose of unused Oxycodone Hydrochloride Oral Solution by flushing the solution down the toiletor disposing of in accordance with local guidelines and/or regulations.Manufactured by and Distributed by:WES Pharma IncWestminster, MD 21157Distributed by:MAJOR® PHARMACEUTICALS17177 N Laurel Park Dr., Suite 233Livonia, MI 48152REFER TO PACKAGE LABEL FOR DISTRIBUTOR'S NDC NUMBER

Medication Guide

Medication GuideOxycodone Hydrochloride (ox-ee-CO-dohn) Oral Solution, CIIOxycodone Hydrochloride Oral Solution is:• A strong prescription pain medicine that contains an opioid (narcotic) that is used tomanage pain severe enough to require an opioid pain medicine, when other paintreatments such as non-opioid pain medicines do not treat your pain well enough oryou cannot tolerate them.• An opioid pain medicine that can put you at risk for overdose and death. Even if youtake your dose correctly as prescribed you are at risk for opioid addiction, abuse, andmisuse that can lead to death.Important information about Oxycodone Hydrochloride Oral Solution:• Get emergency help right away if you take too much Oxycodone Hydrochloride Oral Solution (overdose). When you first start taking OxycodoneHydrochloride Oral Solution, when your dose is changed, or if you take too much(overdose), serious or life-threatening breathing problems that can lead to death mayoccur.• Taking Oxycodone Hydrochloride Oral Solution with other opioid medicines,benzodiazepines, alcohol, or other central nervous system depressants (including streetdrugs) can cause severe drowsiness, decreased awareness, breathing problems, coma,and death.• Never give anyone else your Oxycodone Hydrochloride Oral Solution. They could diefrom taking it. Store Oxycodone Hydrochloride Oral Solution away from children and ina safe place to prevent stealing or abuse. Selling or giving away OxycodoneHydrochloride Oral Solution is against the law.The possible side effects of Oxycodone Hydrochloride Oral Solution:• constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.Get emergency medical help if you have:• trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.These are not all the possible side effects of Oxycodone Hydrochloride Oral Solution. Call your doctor for medical advice about side effects. You may report side effects to FDA at1-800-FDA-1088. For more information go to dailymed.nlm.nih.govManufactured by and Distributed by: WES Pharma Inc ,Westminster, MD 21157 or call 1-888-212-6921Distributed by: MAJOR® PHARMACEUTICALS, 17177 N Laurel Park Dr., Suite 233,Livonia, MI 48152REFER TO PACKAGE LABEL FOR DISTRIBUTOR'S NDC NUMBERThis Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: 12/17 Do not take Oxycodone Hydrochloride Oral Solution if you have:• severe asthma, trouble breathing, or other lung problems.• a bowel blockage or have narrowing of the stomach or intestines.• an allergy to oxycodone or any of the ingredients in Oxycodone Hydrochloride Oral Solution.Patient Instructions for UseOxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL) OralSyringe Important information about measuring Oxycodone Hydrochloride OralSolution• Always use the oral syringe provided with your Oxycodone HydrochlorideOral Solution to make sure you measure the right amount.• Measure the dose of medicine from the widest part of the plunger. Do notmeasure from the narrow tip. See Figure 1.Step 1. Insert the tip of the oral syringe into the medicine bottle.Step 2. Pull back the plunger to the line that matches the dose prescribed by your healthcare provider.Step 3. Remove the oral syringe from the medicine bottle.Step 4. Take your medicine by slowly pushing the plunger until the oral syringe is empty.Before taking Oxycodone Hydrochloride Oral Solution, tell your healthcare provider if you have a history of:• head injury, seizures• problems urinating• abuse of street or prescription drugs, alcohol addiction, or mental health problems.• liver, kidney, thyroid problems• pancreas or gallbladder problemsTell your healthcare provider if you are:• pregnant or planning to become pregnant. Prolonged use of Oxycodone Hydrochloride Oral Solution during pregnancy can cause withdrawal symptoms in yournewborn baby that could be life-threatening if not recognized and treated.• breastfeeding. Oxycodone Hydrochloride Oral Solution passes into breast milk and may harm your baby.• taking prescription or over-the-counter medicines, vitamins, or herbal supplements.Taking Oxycodone Hydrochloride Oral Solution with certain other medicines can causeserious side effects that could lead to death.Figure 1When taking Oxycodone Hydrochloride Oral Solution:• Do not change your dose. Take Oxycodone Hydrochloride Oral Solution exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.• See the detailed Instructions for Use for information about how to take Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL).• Always use the enclosed calibrated oral syringe that comes with Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL) to correctly measure your dose. Never use a household teaspoon or tablespoon to measure Oxycodone Hydrochloride Oral Solution.• Take your prescribed dose every 4 to 6 hours. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.• Call your healthcare provider if the dose you are taking does not control your pain.• If you have been taking Oxycodone Hydrochloride Oral Solution regularly, do not stop taking Oxycodone Hydrochloride Oral Solution without talking to yourhealthcare provider.• After you stop taking Oxycodone Hydrochloride Oral Solution, destroy the unused solution by flushing down the toilet.While taking Oxycodone Hydrochloride Oral Solution DO NOT:• Drive or operate heavy machinery, until you know how Oxycodone Hydrochloride OralSolution affects you. Oxycodone Hydrochloride Oral Solution can make you sleepy,dizzy, or lightheaded.• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.Using products containing alcohol during treatment with Oxycodone Hydrochloride OralSolution may cause you to overdose and die.

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