2.1 Important Dosage and Administration Instructions

Ensure accuracy when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution to avoid dosing errors due to confusion between mg and mL, and with other oxycodone hydrochloride solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume.

Always use the enclosed calibrated measuring cup when administering Oxycodone Hydrochloride Oral Solution 5 mg per 5 mL (1 mg/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 a tablespoon instead of a teaspoon could lead to overdosage.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5) ] .

Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.2) ].

Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with oxycodone hydrochloride solution and adjust the dosage accordingly [see Warnings and Precautions ( 5.4) ].

2.2 Initial Dosage

Although it is not possible to list every condition that is important to the selection of the initial dose of Oxycodone Hydrochloride Oral Solution, attention must be given to:

1. the daily dose, potency and characteristics of a full agonist or mixed agonist/antagonist the patient has been taking previously

2. the reliability of the relative potency estimate to calculate the dose of oxycodone HCl needed

3. the degree of opioid tolerance

4. the general condition and medical status of the patient, including the patient’s weight and age

5. the balance between pain management and adverse reactions

6. the type and severity of the patient’s pain

7. risk factors for abuse or addiction, including a prior history of abuse or addiction

Use of Oxycodone Hydrochloride Oral Solution as the First Opioid Analgesic

Initiate treatment with Oxycodone Hydrochloride Oral Solution: 5 to 15 mg every 4 to 6 hours as needed for pain. Titrate the dose based upon the individual patient’s response to their initial dose of Oxycodone Hydrochloride Oral Solution. Patients with chronic pain should have their dosage given on an around-the-clock basis to prevent the reoccurrence of pain rather than treating the pain after it has occurred. This dose can then be adjusted to an acceptable level of analgesia taking into account side effects experienced by the patient.

For control of severe chronic pain, Oxycodone Hydrochloride Oral Solution should be administered on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia.

Conversion from Other Opioids to Oxycodone Hydrochloride Oral Solution

There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Oxycodone Hydrochloride Oral Solution. It is safer to underestimate a patient’s 24-hour Oxycodone Hydrochloride Oral Solution dosage than to overestimate the 24-hour Oxycodone Hydrochloride Oral Solution dosage and manage an adverse reaction due to overdose. If a patient has been receiving opioid-containing medications prior to taking Oxycodone Hydrochloride Oral Solution, the potency of the prior opioid relative to oxycodone should be factored into the selection of the total daily dose (TDD) of oxycodone.

In converting patients from other opioids to Oxycodone Hydrochloride Oral Solution close observation and adjustment of dosage based upon the patient’s response to Oxycodone Hydrochloride Oral Solution is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of Oxycodone Hydrochloride Oral Solution may be necessary, especially in patients who have disease states that are changing rapidly.

Conversion from Oxycodone Hydrochloride Oral Solution to Extended-Release Oxycodone

The relative bioavailability of Oxycodone Hydrochloride Oral Solution compounds to extended -release oxycodone is unknown, so conversion to extended-release tablets/capsules must be accompanied by close observation for signs of excessive sedation and respiratory depression.

2.3 Titration and Maintenance of Therapy

Individually titrate Oxycodone Hydrochloride Oral Solution to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Oxycodone Hydrochloride Oral Solution to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions ( 5.2) ].  Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during 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 before increasing the Oxycodone Hydrochloride Oral Solution dosage.  If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.4 Safe Reduction or Discontinuation of Oxycodone Hydrochloride Oral Solution

Do not abruptly discontinue Oxycodone Hydrochloride Oral Solution in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid- dependent patient taking Oxycodone Hydrochloride Oral Solution, there are a variety of factors that should be considered, including the dose of Oxycodone Hydrochloride Oral Solution the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on Oxycodone Hydrochloride Oral Solution who are physically opioid- dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose- lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions ( 5.14), Drug Abuse and Dependence ( 9.3) ] . 

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 confusion between mg and mL and confusion with oxycodone solutions of different concentrations, when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution. Ensure that the dose is communicated clearly and dispensed accurately. Always use the enclosed calibrated measuring cup when administering Oxycodone Hydrochloride Oral Solution to ensure the dose is measured and administered accurately.

Do not use a teaspoon or a tablespoon to measure a dose. A household teaspoon or tablespoon is not an adequate measuring device. Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that, if the enclosed calibrated measuring cup becomes lost, caregivers obtain and use a calibrated measuring device. Health care providers should recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instruct caregivers 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 Abuse and Dependence ( 9) ].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Oxycodone Hydrochloride Oral Solution. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Oxycodone Hydrochloride Oral Solution, and monitor all patients receiving Oxycodone Hydrochloride Oral Solution for the development of these behaviors 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 these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Oxycodone Hydrochloride Oral Solution, but use in such patients necessitates intensive counseling about the risks and proper use of Oxycodone Hydrochloride Oral Solution along with intensive monitoring for signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Oxycodone Hydrochloride Oral Solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information ( 17) ]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.3 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Prescribers are strongly encouraged to do all of the following:

•

Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.

•

Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.

•

Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.

•

Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.

To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

5.4 Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid 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 Oxycodone Hydrochloride 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 with and following dosage increases of Oxycodone Hydrochloride Oral Solution.

To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone Hydrochloride Oral Solution are essential [see Dosage and Administration ( 2) ]. Overestimating the Oxycodone Hydrochloride Oral Solution dosage 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 (in) children, can result in respiratory depression and death due to an overdose of oxycodone. 

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.4)].

5.5 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 not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations ( 8.1), Patient Counseling Information ( 17) ] . 

5.6 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), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions ( 5.4) ], particularly when an inhibitor is added after a stable dose of Oxycodone Hydrochloride Oral Solution is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in Oxycodone Hydrochloride Oral Solution-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using Oxycodone Hydrochloride Oral Solution with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in Oxycodone Hydrochloride Oral Solution-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of Oxycodone Hydrochloride Oral 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 CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using Oxycodone Hydrochloride Oral Solution with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Dosage and Administration ( 2.1), Drug Interactions ( 7) ].

5.7 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Oxycodone Hydrochloride Oral Solution with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/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 whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7) ] .

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxycodone Hydrochloride Oral Solution is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine 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 of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions ( 7) and Patient Counseling Information ( 17) ] .

5.8 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 an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: Oxycodone Hydrochloride Oral Solution-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Oxycodone Hydrochloride Oral Solution [see Warnings and Precautions ( 5.4) ].

Elderly, Cachetic, 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 to younger, healthier patients [see Warnings and Precautions ( 5.4) ].

Monitor such patients closely, particularly when initiating and titrating Oxycodone Hydrochloride Oral Solution and when Oxycodone Hydrochloride Oral Solution is given concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.4) ]. Alternatively, consider the use of non-opioid analgesics in these patients.

5.9 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. 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 the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.

Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

5.10 Severe Hypotension

Oxycodone Hydrochloride Oral Solution may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised 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 hypotension after 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 blood pressure. Avoid the use of Oxycodone Hydrochloride Oral Solution in patients with circulatory shock.  

5.11 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 increased intracranial pressure or brain tumors), Oxycodone Hydrochloride Oral Solution may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory 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 Oxycodone Hydrochloride Oral Solution in patients with impaired consciousness or coma. 

5.12 Risks of Use in Patients with Gastrointestinal Conditions

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

The oxycodone in Oxycodone Hydrochloride Oral Solution may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.  

5.13 Increased Risk of Seizures in Patients with Seizure Disorders

The oxycodone in Oxycodone Hydrochloride Oral Solution may increase the frequency of seizures in patients with seizure 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 Hydrochloride Oral Solution therapy.  

5.14 Withdrawal

Do not abruptly discontinue Oxycodone Hydrochloride Oral Solution in a patient physically dependent on opioids. When discontinuing Oxycodone Hydrochloride Oral Solution in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.4), Drug Abuse and Dependence (9.3)].

Additionally, 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 full opioid agonist analgesic, including Oxycodone Hydrochloride Oral Solution. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].

5.15 Risks of Driving and Operating Machinery

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

Table 1 includes clinically significant drug interactions with Oxycodone Hydrochloride Oral Solution.

8.1 Pregnancy

8.2 Lactation

Risk Summary

Oxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone in breast 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 been conducted with Oxycodone Hydrochloride Oral Solution, and no information is available on the effects of the drug on 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 need for Oxycodone Hydrochloride Oral Solution and any potential adverse effects on the breastfed infant from Oxycodone Hydrochloride Oral Solution or from the underlying maternal condition.

Clinical Considerations

Monitor infants exposed to Oxycodone Hydrochloride Oral Solution through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

8.3 Females and Males of Reproductive Potential

Infertility

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

8.4 Pediatric Use

The safety and efficacy of Oxycodone Hydrochloride Oral Solution in pediatric patients 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 when selecting a dose for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency 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 doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Oxycodone Hydrochloride Oral Solution slowly in geriatric patients and monitor closely 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 may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Hepatic Impairment

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

8.7 Renal Impairment

Information from oxycodone tablets indicate that patients with renal impairment had higher plasma concentrations of oxycodone than subjects with normal renal function. Initiate therapy with a lower than usual dosage of Oxycodone Hydrochloride Oral Solution and titrate carefully. Monitor closely for adverse events such as respiratory depression, 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 to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, and tapentadol. Oxycodone Hydrochloride Oral Solution can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.2)] .

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic 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 rewarding psychological or physiological effects. 

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain 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 should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all 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 channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Oxycodone Hydrochloride Oral Solution

Oxycodone 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 drug abuse 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 for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of 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), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Do not abruptly discontinue Oxycodone Hydrochloride Oral Solution in a patient physically dependent on opioids. Rapid tapering of Oxycodone Hydrochloride Oral Solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing Oxycodone Hydrochloride Oral Solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Oxycodone Hydrochloride Oral Solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.4), Warnings and Precautions (5.14)].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations ( 8.1) ].

Clinical Presentation

Acute 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, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2) ].

Treatment of Overdose

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid 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 clinically significant 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 Oxycodone Hydrochloride Oral Solution, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.

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 other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequate analgesia 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 endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

12.2 Pharmacodynamics

12.3 Pharmacokinetics

The activity of Oxycodone Hydrochloride Oral Solution is primarily due to the parent drug oxycodone.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Oxycodone Hydrochloride Oral Solution, USP, 5 mg per 5 mL (1 mg/mL) is available as follows:

NDC# 0904-6678-40: 500 mL bottle packaged with calibrated measuring cup

NDC# 0904-6828-94: Case contains 40 unit dose cups of 5 mL, packaged in 4 trays of 10 unit dose cups each

NDC# 0904-6828-92: Case contains 50 unit dose cups of 5 mL, packaged in 5 trays of 10 unit dose cups each

Dispense in a tight, light-resistant container as defined in the USP/NF.

Store at controlled room temperature 20°-25°C (68°- 77°F); excursions are permitted to 15° - 30°C (59° - 86°F). [See USP Controlled Room Temperature]

Store Oxycodone Hydrochloride Oral Solution securely and dispose of properly [see Patient Counseling Information (17)].