Usual Adult Dose for Pain

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time

Immediate-release:
As First Opioid Analgesic: 5 to 15 mg orally every 4 to 6 hours

• Oral solution: To avoid dosing errors include total dose in mg and mL

CONVERSION from Other Oral Opioids: There is great inter-patient variability in the potency of opioid drugs and their formulations; when converting patients to this drug from other opioids or when switching from controlled-release products, it is best to underestimate the oxycodone requirement and provide rescue medication than to overestimate and manage an overdose.

Comments:

• Doses should be individually titrated to provide adequate analgesia while minimizing adverse reactions.
• Because of the risks of addiction, abuse and misuse, the lowest effective dose for the shortest duration consistent with individual patient treatment goals should be used.
• Monitor patients closely for respiratory depression within the first 24 to 72 hours of initiating therapy and following any increase in dose.

Use: For the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

Usual Adult Dose for Chronic Pain

The following dosing recommendations can only be considered suggested approaches to what is actually a series of clinical decisions over time

60 and 80 mg extended-release (ER) tablets, a single dose greater than 40 mg (36 mg oxycodone base), a total daily dose greater than 80 mg (72 mg oxycodone base), or use of the 100 mg/5 mL (20 mg/mL) oral solution should be restricted to use in opioid-tolerant patients only

Extended-release (ER):
Initial dose for OPIOID-NAIVE and OPIOID NON-TOLERANT patients:

• Oxycodone hydrochloride ER tablets: 10 mg orally every 12 hours
• Oxycodone (base) ER capsules: 9 mg orally every 12 hours with food

Immediate-release (IR):

• Initial dose for OPIOID-NAIVE patients: 5 to 15 mg orally every 4 to 6 hours on an around-the-clock basis
• Oral solution: To avoid dosing errors total dose should be included in both mg and mL

MAINTENANCE: Adjust dose every 1 to 2 days as needed to obtain an appropriate balance between pain management and opioid-related adverse reactions; goal should be to find the lowest effective dosage for the shortest duration consistent with individual patient treatment goals
Maximum daily dose: Oxycodone (base) ER capsules: 288 mg as the safety of the excipients has not been established; maximum dose of oxycodone hydrochloride tablets has not been established

EQUIVALENCE OF OXYCODONE HYDROCHLORIDE TO OXYCODONE BASE:

• Oxycodone hydrochloride 10 mg = Oxycodone base 9 mg
• Oxycodone hydrochloride 15 mg = Oxycodone base 13.5 mg
• Oxycodone hydrochloride 20 mg = Oxycodone base 18 mg
• Oxycodone hydrochloride 30 mg = Oxycodone base 27 mg
• Oxycodone hydrochloride 40 mg = Oxycodone base 36 mg

Comments:

• Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression with first dose; selection of initial dose should take into account degree of opioid tolerance, patient's general condition, medical status, concurrent medications, type and severity of pain, and risk factors for abuse, addiction, or diversion.
• Opioid tolerant patients are those who have received for 1 week or longer: oral morphine 60 mg/day; transdermal fentanyl 25 mcg/hr; oral oxycodone 30 mg/day; oral hydromorphone 8 mg/day; oral oxymorphone 25 mg/day or an equianalgesic dose of another opioid.
• Extended-release products are reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; these products are not intended to be used as as-needed (prn) analgesics.

• DOSE CONVERSIONS from other opioids should be done carefully and with close monitoring due to large patient variability in opioid analgesic response; consult dose adjustment section for recommendations.

Use: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Usual Pediatric Dose for Chronic Pain

Prior to initiating therapy, patients must be receiving and tolerating opioids for at least 5 consecutive days; for the 2 days immediately preceding initiation, patients must be taking a minimum of 20 mg/day of oxycodone or its equivalent.

• Discontinue all around-the-clock opioid drugs when oxycodone ER tablets are initiated

11 years or older: Extended-release (ER) tablets only:

• Initial dose: One-half of calculated total oxycodone daily dose orally every 12 hours

DOSE CALCULATION:

• Multiply total daily dose of prior opioid by the conversion factor (CF) provided below to obtain oxycodone dose in mg/day; divide oxycodone mg/day dose by 2 to get 12-hour oxycodone ER dose; if rounding is necessary, always round down to the nearest tablet strength available
• For prior opioid use of OXYCODONE: Oral CF is 1
• For prior opioid use of HYDROCODONE: Oral CF is 0.9
• For prior opioid use of HYDROMORPHONE: Oral CF is 4; Parenteral CF is 20*
• For prior opioid use of MORPHINE: Oral CF is 0.5; Parenteral CF is 3*
• For prior opioid use of TRAMADOL: Oral CF is 0.17; Parenteral CF is 0.2*

*For patients receiving high-dose parenteral opioids, a more conservative CF is warranted (e.g., for high-dose parenteral morphine, use a CF of 1.5 instead of a CF of 3)
The CFs provided above convert prior opioid use to oxycodone ER tablet dose; do not use the CF to convert from oxycodone ER tablets to another opioid as doing so will result in an over-estimation of the new opioid dose and possibly a fatal overdose.
CONVERSION FROM TRANSDERMAL FENTANYL: Remove patch 18 hours prior to starting oxycodone ER tablets; substitute one 10 mg oxycodone ER tablet every 12 hours for each 25 mcg/hr fentanyl transdermal patch; monitor closely during conversion as there is limited assessment of this conversion

Titration and Maintenance:

• Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments can be made every 1 to 2 days; when a dose increase is clinically indicated, it is suggested that the total daily oxycodone dose not be increased by more than 25% at a time.

Comments:

• Oxycodone HCl ER tablets is not appropriate for pediatric patients taking less than a 20 mg total daily dose.
• Dose conversions should be done carefully and with close monitoring due to large patient variability in opioid analgesic response; it is preferable to underestimate a patient's 24-hour oral oxycodone requirement and provide rescue medication than to overestimate and manage an adverse reaction.
• See manufacturer's prescribing information for further details about dose conversion.
• Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression with first dose; selection of initial dose should take into account degree of opioid tolerance, patient's general condition, medical status, concurrent medications, type and severity of pain, and risk factors for abuse, addiction, or diversion.
• Extended-release oxycodone products are reserved for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain; these products are not intended to be used as as-needed (prn) analgesics.

Use: For the opioid-tolerant pediatric patient 11 years of age or older who is already receiving and tolerating a minimum oral opioid dose of at least oxycodone 20 mg/day or its equivalent and who has pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

Usual Pediatric Dose for Pain

OPIOID NAIVE PATIENTS OVER 6 MONTHS OF AGE

• Weight less than 50 kg:

Usual initiation dose: 0.1 to 0.2 mg/kg every 3 to 4 hours orally as needed

• Weight 50 kg or higher:

Usual initiation dose: 5 to 10 mg every 3 to 4 hours orally as needed

OPIOID NAIVE PATIENTS UNDER 6 MONTHS OF AGE

• Initiation doses: Roughly 25% of the per-kilogram dose recommended for patients over 6 months of age.

Comments:

• Higher doses are usually required for patients receiving mechanical ventilation.
• All dosages should be adjusted according to the individual characteristics of each patient and the clinical circumstances.

Use: Pain management in opioid naive pediatric patients

Renal Dose Adjustments

CrCl less than 60 mL/minute: Start conservatively with a lower than usual dose; titrate carefully to desired effect

Extended-release tablets/capsules:

• Alternative analgesics may be necessary if patient is not a candidate for lowest available dose strength

Liver Dose Adjustments

Hepatic impairment: Start conservatively with a lower than usual dose; titrate carefully to desired effect

Extended-release tablets/capsules

• Initial dose: One-third to one-half of the usual dose; titrate carefully to desired effect
• Alternative analgesics may be necessary if patient is not a candidate for lowest available dose strength

Dose Adjustments

Elderly, Cachectic, or Debilitated Patients:

• Use with caution generally starting at the low end of the dosing range, titrate slowly while monitoring closely for signs of CNS or respiratory depression.
• For Extended-release products: Consider initial doses of one-third to one-half the recommended starting doses; titrate carefully

Concomitant Use of CNS depressants:

• If an opioid analgesic is initiated in a patient already taking a benzodiazepine or CNS depressant: a lower initial dose of the opioid analgesic is recommended; titrate based on clinical response
• If a CNS depressant or benzodiazepine are needed in a patient already on an opioid analgesic: initiate with a lower initial dose of the benzodiazepine or other CNS depressant; titrate based on clinical response

Concomitant use of CYP450 3A4 inducers or inhibitors may require dose adjustment: Consult drug interactions

DOSE CONVERSIONS TO EXTENDED-RELEASE (ER) TABLETS or CAPSULES

• Dose conversions should be done carefully and with close monitoring due to large patient variability in opioid analgesic response; discontinue all other around the clock opioid drugs when initiating ER therapy

CONVERSION FROM OTHER ORAL OXYCODONE FORMULATIONS:

• Administer one-half of the total daily oxycodone hydrochloride dose as ER tablet or ER capsule orally every 12 hours

CONVERSION FROM OTHER ORAL OPIOIDS:

• Oxycodone hydrochloride ER tablets: 10 mg orally every 12 hours
• Oxycodone (base) ER capsules: 9 mg orally every 12 hours with food

CONVERSION FROM TRANSDERMAL FENTANYL: Remove transdermal fentanyl patch and 18 hours later initiate oxycodone hydrochloride ER tablets 10 mg (or oxycodone ER capsules 9 mg) orally every 12 hours for each fentanyl transdermal 25 mcg/hr patch; monitor closely as there is limited documented experience with this conversion

CONVERSION FROM METHADONE: Close monitoring is of particular importance due to methadone's long half-life

DISCONTINUATION of Therapy in the Physically Dependent Patient:

• Taper dose gradually, by 25% to 50% every 2 to 4 days
• Monitor for signs and symptoms of withdrawal; if they occur, raise the dose to the previous level and taper more slowly
• Do not abruptly discontinue in the physically dependent patient

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for all opioids intended for outpatient use. The new FDA Opioid Analgesic REMS is a designed to assist in communicating the serious risks of opioid pain medications to patients and health care professionals. It includes a medication guide and elements to assure safe use. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYP450 3A4 INTERACTION and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS:

• Risk of Medication Errors: Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution; dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.
• Addiction, Abuse, and Misuse: Oxycodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
• Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required 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. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
• Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation or following a dose increase. Instruct patients to swallow tablets whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose.
• Accidental Ingestion: Accidental ingestion of even 1 dose of extended-release oxycodone, especially by children, can result in a fatal overdose.
• Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, the patient should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
• CYP450 3A4 Interaction: The concomitant use with CYP450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used CYP450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone and any CYP450 3A4 inhibitor or inducer.
• Concomitant Use with Benzodiazepines or Other CNS Depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Concomitant use should be reserved for those patients for whom alternative treatment options are inadequate. If needed, limit dose and duration to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

CONTRAINDICATIONS:

• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity to the active components or any of the product ingredients

Safety and efficacy of the immediate-release products have not been established in patients younger than 18 years.

Safety and efficacy of oxycodone extended-release capsules (Xtampza ER[R]) has not been established in patients younger than 18 years.

Safety and efficacy of oxycodone extended-release tablets (OxyContin ER[R]) has have not been established in patients younger than 11 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:

• Oxycodone oral solution is available in 2 concentrations (5 mg/mL and 20 mg/mL); to avoid dosing errors, be sure to verify dose in both mg and mL when prescribing and dispensing
• The calibrated oral measuring cup (5 mg/mL) or oral syringe (20 mg/mL) should be provided to the patient and used for measuring

Immediate-release tablets:

• Swallow whole with enough water to ensure complete swallowing

Extended-release tablets:

• Swallow whole; do not break, chew, crush, or dissolve as this may lead to rapid release and absorption of a potentially fatal dose
• Take with enough water to ensure complete swallowing; do not pre-soak, lick or otherwise wet prior to swallowing.

Extended-release capsules:

• Take each dose with approximately the same amount of food
• Swallow whole or open the capsule and sprinkle contents onto soft food or into a cup, administer directly into mouth and swallow immediately; rinse mouth to ensure all capsule contents have been swallowed.
• Alternatively, administer through a nasogastric tube: flush tube with water, open capsule and pour microspheres directly into tube (do not premix the capsule contents with liquid), flush microspheres through the tube with 15 mL of water; repeat flush 2 more times with 10 mL of water each time to ensure no microspheres remain in the tube. Milk or liquid nutrition may be used as the vehicle for administration or flush through feeding tubes.

General:

• This drug should be prescribed by a healthcare professional that is knowledgeable in the use of potent opioids for the management of pain.
• Due to the risk of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, extended-release oxycodone is for use in patients for whom alternative treatment options (non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
• For patients receiving other opioid analgesics and switching to this drug or to the extended-release formulations of this drug, it is safer to underestimate a patient's 24-hour oral requirement and provide rescue medication than overestimate and manage an adverse reaction; there is substantial inter-patient variation in the relative potency of different opioid drugs that conversion tables are not able to capture.
• During chronic therapy, periodically reassess the continued need for opioid analgesics.

Monitoring:

• Monitor for respiratory depression, especially during initiation and following any increase in dose; close monitoring will be necessary in patients at increased risk and/or those receiving concomitant medications that increase the risk of respiratory depression
• Monitor for signs of hypotension
• Monitor for signs of constipation
• Monitor for the development of behaviors indicative of addiction, abuse, or misuse

Patient advice:

• Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
• Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
• Patients should understand that even when taken as recommended, use may result in addiction, abuse, and misuse; instruct patients not to share their drug with others and protect their drug from theft or misuse.
• Patients should be instructed to check with their healthcare provider before taking any new medications, herbal supplements, and over the counter products; patients should not drink alcohol while taking this drug.
• Patients should understand the risks of life-threatening respiratory depression, and be informed as to when this risk is greatest; patients and caregivers should be instructed to get emergency help right away if too much drug is taken or if breathing problems occur.
• Patients should be made aware that crushing, chewing, or dissolving extended-release products will result in uncontrolled delivery of oxycodone and can lead to overdose or death.
• This drug may cause drowsiness, dizziness, or impair thinking or motor skills; patients should avoid driving or operating machinery until adverse effects are determined.
• Women of child bearing potential should understand that prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome and that prompt recognition and treatment will be necessary.

Frequently asked questions

• Which painkiller should you use?
• Oxycodone vs Hydrocodone - How do they compare?
• How long does Percocet stay in your system?
• Which drugs cause opioid-induced constipation?
• What is hydrochloride?
• How long does oxycodone stay in your system?
• How long does opioid withdrawal last?
• Oxycodone vs OxyContin - What's the difference?
• How long does oxycodone take to work?
• What are the withdrawal symptoms of oxycodone?