Brand names: Oxaydo, Oxecta, OxyCONTIN, Roxicodone, Xtampza ER
Drug class: Opiate Agonists
VA class: CN101
CAS number: 124-90-3

oxyCODONE Hydrochloride, oxyCODONE Myristate is also contained as an ingredient in the following combinations:
oxyCODONE and Acetaminophen
oxyCODONE and Aspirin

Medically reviewed by Drugs.com on Apr 19, 2023. Written by ASHP.

Introduction

Opiate agonist; phenanthrene-derivative.^a

Uses for Oxycodone

Acute Pain

Relief of moderate to severe pain when use of an opiate analgesic is appropriate and alternative treatments are inadequate.^{296 299 302 303 f g h}

Usually, temporary relief of moderate to moderately severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.^e

Opiates given orally in combination with acetaminophen or NSAIAs may produce greater analgesic effect than either drug alone; may also cause fewer adverse effects than equianalgesic doses of the individual drugs alone.^e

Extended-release oxycodone hydrochloride/acetaminophen in fixed combination: Relief of acute pain that is severe enough to require opiate therapy and for which alternative treatments (e.g., nonopiate analgesics) are inadequate or not tolerated.³⁰⁵

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.^{431 432 433 435} Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435} Optimize concomitant use of other appropriate therapies.^{432 434 435} (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

Reserve oxycodone hydrochloride extended-release tablets and oxycodone myristate extended-release capsules for relief of pain that is severe enough to require long-term, daily, around-the-clock use of an opiate analgesic and for which alternative treatment options (e.g., nonopiate analgesics or immediate-release opiates) are inadequate or not tolerated; not indicated for as-needed (“prn”) use.^{290 291}

Chronic Pain

For relief of moderate to severe malignant (cancer) pain and chronic nonmalignant pain when use of an opiate analgesic is appropriate and alternative treatments are inadequate.^{296 299 303 e f g h}

Oxycodone hydrochloride extended-release tablets and oxycodone myristate extended-release capsules: Use only for relief of pain that is severe enough to require long-term, daily, around-the-clock use of an opiate analgesic and for which alternative treatment options (e.g., nonopiate analgesics, immediate-release opiates) are inadequate or not tolerated.^{290 291} Not indicated for as-needed (“prn”) use.^{290 291}

In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.^e

Although consideration of the dependence potential of opiate agonists has often limited their effective use by many clinicians in terminally ill patients with severe, chronic pain, such consideration is irrelevant in the context of terminal illness.^e

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing^{410 411 412 413} ) that is not associated with active cancer treatment, palliative care, or end-of-life care only if other appropriate nonpharmacologic and nonopiate pharmacologic strategies have been ineffective and expected benefits for both pain relief and functional improvement are anticipated to outweigh risks.^{411 412 413 414 422 429}

If used for chronic pain, opiate analgesics should be part of an integrated approach that also includes appropriate nonpharmacologic modalities (e.g., cognitive-behavioral therapy, relaxation techniques, biofeedback, functional restoration, exercise therapy, certain interventional procedures) and other appropriate pharmacologic therapies (e.g., nonopiate analgesics, analgesic adjuncts such as selected anticonvulsants and antidepressants for certain neuropathic pain conditions).^{411 412 413 422 429}

Available evidence insufficient to determine whether long-term opiate therapy for chronic pain results in sustained pain relief or improvements in function and quality of life^{411 423 431 432 436} or is superior to other pharmacologic or nonpharmacologic treatments.⁴³² Use is associated with serious risks (e.g., opiate use disorder [OUD], overdose).^{411 431 436} (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Oxycodone Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

• Optimize concomitant use of other appropriate therapies.^{432 434 435}

• When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

• When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.⁴³²

• For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435} Do not prescribe larger quantities for use in case pain continues longer than expected;^{411 432} instead, reevaluate patient if severe acute pain does not remit.^{411 431 435}

• For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.^{430 431 432}

• Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.^{430 431}

• Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.^{430 432} When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.^{430 431}

Managing Opiate Therapy for Chronic Noncancer Pain

• Although specific recommendations may vary, common elements in clinical guideline recommendations include risk mitigation strategies, upper dosage thresholds, careful dosage titration, and consideration of risks associated with particular opiates and formulations, coexisting diseases, and concomitant drug therapy.^{410 411 414 415 423}

• Prior to initiating therapy, thoroughly evaluate patient; assess risk factors for misuse, abuse, and addiction;^{411 412 413 415 422 429} establish treatment goals (including realistic goals for pain and function); and consider how therapy will be discontinued if benefits do not outweigh risks.^{411 415}

• Regard initial opiate therapy for chronic noncancer pain as a therapeutic trial that will be continued only if there are clinically meaningful improvements in pain and function that outweigh treatment risks.^{411 412 413}

• Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.^{411 412 413 414 415}

• Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage.^{411 415} Individualize opiate selection, initial dosage, and dosage titration based on patient’s health status, prior opiate use, attainment of therapeutic goals, and predicted or observed harms.^{412 413}

• Evaluate benefits and harms within 1–4 weeks following initiation of therapy or dosage increase^{411 413} and reevaluate on ongoing basis (e.g., at least every 3 months⁴¹¹ ) throughout therapy.^{411 412 413} Document pain intensity and level of functioning and assess progress toward therapeutic goals, presence of adverse effects, and adherence to prescribed therapies.^{412 413 422 423} Anticipate and manage common adverse effects (e.g., constipation, nausea and vomiting, cognitive and psychomotor impairment).^{412 413 415} If benefits do not outweigh harms, optimize other therapies and taper opiate to lower dosage or taper and discontinue opiate.^{411 412 413 415}

• When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks.^{412 413} Although evidence is limited, some experts state that opiate rotation may be considered in patients with intolerable adverse effects or inadequate benefit despite dosage increases.^{412 413 415}

• Higher dosages require particular caution,^{410 412 415} including more frequent and intensive monitoring or referral to specialist.^{411 412 413} Greater benefits of high-dose opiates for chronic pain not established in controlled clinical studies; higher dosages associated with increased risks (motor vehicle accidents, overdosage, OUD).^{411 415 423 424 425 426}

• CDC states that primary care clinicians should carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥33 mg of oxycodone hydrochloride daily) for chronic pain and should avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥60 mg of oxycodone hydrochloride daily) or carefully justify decision to prescribe such dosages.⁴¹¹ Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.^{423 431} Some states have established opiate dosage thresholds (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with specialist is mandated or recommended)^{411 420 421 423} or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).^{411 419 423}

• Recommended strategies for managing risks include written treatment agreements or plans (e.g., “contracts”), urine drug testing, review of state PDMP data, and risk assessment and monitoring tools.^{410 411 412 413 414 415 422 423 429}

• Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion.^{412 413 415} Offer or arrange treatment for patients with OUD.^{411 412 413}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

Administration

Oral Administration

Conventional Tablets

Some manufacturers state that their oral tablet formulations should not be crushed and dissolved.³⁰² Do not administer these formulations via gastric, NG, or other feeding tube; they can obstruct the tube.³⁰² Administer these tablets intact with sufficient water to ensure that each tablet is completely swallowed immediately after it is placed in the mouth.³⁰² Consult respective manufacturer's labeling for specific recommendations.

Oral Solution and Oral Concentrate Solution

Take care to ensure that oxycodone hydrochloride solution (5 mg/5 mL) and oxycodone hydrochloride oral concentrate solution (100 mg/5 mL) are not confused.^{299 304} (See Medication Errors with Oral Solutions in Boxed Warning.)

Take care to ensure that the appropriate dose is communicated and dispensed.^{299 304} Prescriptions should specify the intended total dose of the drug (in mg) along with the corresponding total volume (in mL).^{299 304}

Always use the calibrated measuring device provided with the particular formulation to ensure that the dose is measured and administered accurately.^{299 304}

Oxycodone Hydrochloride Extended-release Tablets

Swallow tablets whole; do not break, cut, dissolve, crush, or chew.²⁹⁰ (See Respiratory Depression in Boxed Warning.)

Administer tablets one at a time with enough water to ensure that each tablet is completely swallowed immediately after it is placed in the mouth; do not wet the tablets (e.g., by soaking or licking) before placing in mouth for swallowing.²⁹⁰ (See GI Complications with Extended-release Tablets under Cautions.)

Food does not substantially affect the extent of oral absorption from extended-release tablets.²⁹⁰

Oxycodone Myristate Extended-release Capsules

Swallow capsules whole; alternatively, sprinkle capsule contents on food or administer capsule contents directly into the mouth or via NG or gastrostomy tube.²⁹¹

Must be administered orally with food.²⁹¹ Administer each dose (whether given as intact capsule or as capsule contents sprinkled on food or directly in mouth) with approximately the same amount of food to ensure consistent plasma concentrations.²⁹¹ (See Food under Pharmacokinetics.)

For patients who have difficulty swallowing, open capsule and sprinkle contents onto a small amount of soft food (e.g., applesauce, pudding, yogurt, ice cream, jam) or into a cup and administer directly into mouth.²⁹¹ Patient should swallow capsule contents immediately and rinse mouth to ensure entire dose is swallowed.²⁹¹

Administration via NG or gastrostomy tube: Flush tube with water, then open capsule and carefully pour contents directly into the tube; do not premix with liquid that will be used to flush the tube.²⁹¹ Then flush tube with 15 mL of liquid (water, milk, liquid nutritional supplement); flush 2 more times, each time with 10 mL of liquid, to ensure that the entire dose is delivered.²⁹¹

Oxycodone Hydrochloride/Acetaminophen Extended-release Tablets

Swallow tablets whole; do not break, cut, dissolve, crush, split, or chew.³⁰⁵ (See Respiratory Depression in Boxed Warning.)

Administer tablets one at a time with enough water to ensure that each tablet is completely swallowed immediately after it is placed in the mouth; do not wet the tablets (e.g., by soaking or licking) before placing in mouth for swallowing.³⁰⁵ (See GI Complications with Extended-release Tablets under Cautions.)

Administer without regard to meals.³⁰⁵

Do not administer through NG, gastric, or other feeding tube.³⁰⁵

Rectal Administration

When rectal administration was preferred, conventional oral tablets or solution has been administered rectally^{† [off-label]}.^g

If administered rectally^{† [off-label]}, insert the dosage form just inside the rectal sphincter for optimal systemic absorption of unmetabolized drug.^{h g} Administration high in the rectal vault can result in rapid first-pass hepatic metabolism, with greatly diminished efficacy.^{h g}

Not usually suitable for long-term administration due to rectal irritation from repeated dosing.^g

Although the manufacturer states that extended-release tablets should only be administered orally,²⁹⁰ rectal administration of extended-release formulations is used widely for opiate delivery in palliative care.^h

Dosage

Available as oxycodone hydrochloride; dosage expressed in terms of the salt.^{290 299 302 303} Also available as oxycodone myristate; dosage expressed in terms of oxycodone.²⁹¹

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.^{411 413 431 432 435}

When switching patients receiving chronic opiate therapy from one opiate analgesic to another, generally reduce the calculated equianalgesic dosage of the new opiate agonist by about 25–50% to avoid inadvertent overdosage.^{410 412} This calculation does not apply when switching to methadone; consult specific recommendations for methadone dosage.⁴¹²

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.^{700 703} (See Specific Drugs under Interactions.)

Pediatric Patients

Pain (Conventional Preparations)

Oral

Some experts have suggested a dosage of 0.05–0.15 mg/kg (up to 5 mg) every 4–6 hours as needed.^{296 297 298} Adjust according to response and tolerance.^{f g h}

Pain (Oxycodone Hydrochloride Extended-release Tablets)

Oral

Use only in opiate-tolerant children ≥11 years of age who have received and tolerated opiate analgesics for ≥5 consecutive days, and at a dosage of ≥20 mg of oxycodone hydrochloride daily (or equivalent) for ≥2 days immediately before initiating extended-release tablets.²⁹⁰

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.²⁹⁰ Individualize initial dosage based on patient's prior analgesic use and risk factors for addiction, abuse, and misuse.²⁹⁰

Supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for breakthrough pain may be necessary during therapy with oxycodone hydrochloride extended-release tablets.²⁹⁰

Discontinue all other around-the-clock opiates when therapy with oxycodone hydrochloride extended-release tablets is initiated.²⁹⁰

Because of substantial interpatient variability in relative potency of opiate analgesics and analgesic formulations, it is preferable to underestimate the patient's 24-hour opiate requirements and provide “rescue” therapy with an immediate-release opiate analgesic than to overestimate the requirements and manage an adverse reaction.²⁹⁰

When switching from other opiate therapy to oxycodone hydrochloride extended-release tablets, use conversion factors in Table 1 as a guide for selecting initial dosage.²⁹⁰ Doses in Table 1 are not equianalgesic doses; do not use these conversion factors to switch patients from oxycodone hydrochloride extended-release tablets to another opiate, as this will overestimate the dosage and may result in fatal overdosage.²⁹⁰

For patients receiving a single opiate analgesic, multiply the current total daily dosage of the opiate by the conversion factor to calculate the approximate daily dosage of oxycodone hydrochloride extended-release tablets; divide the calculated daily dosage in half for administration every 12 hours.²⁹⁰

For patients receiving >1 opiate analgesic, calculate the approximate daily dosage of extended-release oxycodone hydrochloride for each opiate and then add those totals to obtain the approximate total daily dosage of oxycodone hydrochloride extended-release tablets; divide the calculated total daily dosage in half for administration every 12 hours.²⁹⁰

For patients receiving analgesics containing opiates and nonopiates in fixed combination, consider only the opiate component in the conversion.²⁹⁰

If calculated doses do not correspond to an available tablet strength, always round dosage down to the nearest whole tablet.²⁹⁰

If calculated total daily dosage <20 mg, do not convert to the extended-release formulation.²⁹⁰

For asymmetric dosing, administer the higher dose in the morning and the lower dose in the evening.²⁹⁰

Monitor for opiate withdrawal and for oversedation or toxicity following switch to extended-release oxycodone hydrochloride.²⁹⁰

For patients receiving high-dose parenteral opiates, a more conservative conversion is warranted (e.g., for high-dose parenteral morphine, use 1.5 instead of 3 as a multiplication factor).

Patients receiving fentanyl transdermal systems may receive extended-release tablets beginning 18 hours after removal of the transdermal system.²⁹⁰ Use a conservative initial dosage of approximately 10 mg every 12 hours as extended-release tablets for each 25-mcg/hour increment in fentanyl transdermal system dosage.²⁹⁰ Monitor closely; experience with this dosage conversion is limited.²⁹⁰

Dosage Adjustment to Achieve Adequate Analgesia

Oral

May adjust dosage every 1–2 days, generally in increments of 25% of the current total daily dosage, to provide adequate analgesia and acceptable adverse effects; provide supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for relief of breakthrough pain.²⁹⁰

Safety and efficacy of dosing intervals <12 hours not established.²⁹⁰

If level of pain increases after dosage stabilization, attempt to identify cause of increased pain before increasing dosage of the extended-release tablets.²⁹⁰

Frequent communication among the prescriber, other members of the healthcare team, the patient, and the patient's caregiver or family is important during periods of changing analgesic requirements, including the initial dosage titration period.²⁹⁰

Maintenance Therapy

Oral

Continually assess adequacy of pain control and reevaluate for adverse effects, as well as for development of addiction, abuse, or misuse.²⁹⁰

During long-term therapy, periodically reevaluate need for continued opiate therapy.²⁹⁰

Discontinuance of Therapy

Oral

Discontinue therapy gradually to avoid precipitation of withdrawal symptoms.²⁹⁰

Adults

Pain (Conventional Preparations)

Oral

In opiate-naive patients, initiate with 5–15 mg every 4–6 hours as needed.^{299 302} Adjust according to response and tolerance.^{299 302 f g h}

Patients with chronic pain may require around-the-clock dosing.³⁰² Reserve fixed dosage schedules for patients for whom the benefits of opiate analgesia outweigh the risks of respiratory depression, altered mental state, and orthostatic hypotension; fixed dosage schedules have a narrow therapeutic index in certain patient populations, especially when used concomitantly with other drugs.³⁰²

In patients switching from other opiates or opiate formulations to conventional oxycodone preparations, consider the potency of the prior opiate relative to that of oxycodone, keeping in mind that published dosage conversion ratios are only approximations.^{299 302} Conservative initial dosages, patient monitoring, and dosage adjustment based on response are essential when the opiate or opiate formulation is switched.^{299 302}

During long-term therapy, continually reevaluate analgesic efficacy and adverse effects; periodically reassess the need for continued therapy, particularly in patients with chronic pain not associated with cancer or terminal illness.^{299 302}

Oxycodone-nonopiate-containing analgesic fixed combinations: Nonopiate component may limit dosage of oxycodone component.^{117 119 120 121} Nonopiate analgesics are available in various fixed ratios with oxycodone and also are available in many other prescription and OTC preparations; ensure that therapy is not duplicated and that nonopiate dosage does not exceed maximum recommended dosages.^{117 118 119 121}

When discontinuing oxycodone conventional preparations following long-term therapy, generally reduce dosage by 25–50% per day.^{299 302} If symptoms of withdrawal occur, increase the dose to the prior level and taper more slowly.^{299 302}

Pain (Oxycodone Hydrochloride/Acetaminophen Extended-release Tablets)

Oral

Oxycodone hydrochloride 15 mg (given in fixed combination with 650 mg of acetaminophen) every 12 hours.³⁰⁵ May give second dose as soon as 8 hours after the initial dose if required for adequate analgesia, but administer all subsequent doses at 12-hour intervals.³⁰⁵

When discontinuing therapy in patient who may be opiate dependent, reduce dosage by 50% every 2–4 days to avoid manifestations of abrupt withdrawal.³⁰⁵

Pain (Oxycodone Hydrochloride Extended-release Tablets)

Oral

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.²⁹⁰ Individualize initial dosage based on patient's prior analgesic use and risk factors for addiction, abuse, and misuse.²⁹⁰

Only use 60- and 80-mg formulations, single doses >40 mg, or total daily dosages >80 mg in patients with established tolerance to opiates of comparable potency.²⁹⁰

Patients are considered opiate tolerant if they have been receiving at least 60 mg of oral morphine sulfate daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone hydrochloride daily, 8 mg of oral hydromorphone hydrochloride daily, 25 mg of oral oxymorphone hydrochloride daily, or an equianalgesic dose of another opiate daily for at least 1 week.²⁹⁰

Supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for breakthrough pain may be necessary during therapy with oxycodone hydrochloride extended-release tablets; discontinue any other existing around-the-clock opiates when therapy with oxycodone hydrochloride extended-release tablets is initiated.²⁹⁰

Initial Therapy with Extended-release Tablets in Opiate-naive or Nontolerant Patients

Oral

Initially, 10 mg every 12 hours.²⁹⁰ Higher initial dosages in patients who are not opiate tolerant may result in fatal respiratory depression.²⁹⁰

Switching from Conventional Oxycodone Preparations to Extended-release Tablets

Oral

Calculate the total daily dosage of the conventional preparation and give as extended-release tablets in 2 divided doses at 12-hour intervals.²⁹⁰

Switching from Other Opiates to Extended-release Tablets

Oral

Manufacturer states that no equianalgesic conversion ratios have been established in clinical trials for transferring patients from other opiate analgesics to oxycodone hydrochloride extended-release tablets.²⁹⁰

Because of substantial interpatient variability in relative potency of opiate analgesics and analgesic formulations, it is preferable to underestimate the patient's 24-hour opiate requirements and provide “rescue” therapy with an immediate-release opiate analgesic than to overestimate the requirements and manage an adverse reaction.²⁹⁰

Manufacturer recommends initial dosage of 10 mg every 12 hours; administer supplemental analgesics (i.e., “rescue” therapy with an immediate-release analgesic) if necessary.²⁹⁰

Particularly close monitoring required following switch from methadone, since conversion ratios between methadone and other opiates vary widely depending on extent of prior methadone exposure and because methadone has a long half-life and tends to accumulate in plasma.²⁹⁰

Patients receiving fentanyl transdermal systems may receive extended-release tablets beginning 18 hours after removal of the transdermal system.²⁹⁰ Use a conservative initial dosage of approximately 10 mg every 12 hours as extended-release tablets for each 25-mcg/hour increment in fentanyl transdermal system dosage.²⁹⁰ Monitor closely; experience with this dosage conversion is limited.²⁹⁰

Dosage Adjustment to Achieve Adequate Analgesia

Oral

May adjust dosage every 1–2 days, generally in increments of 25–50% of the current total daily dosage, to provide adequate analgesia and acceptable adverse effects; provide supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for patients experiencing breakthrough pain.²⁹⁰

Safety and efficacy of dosing intervals <12 hours not established.²⁹⁰

If level of pain increases after dosage stabilization, attempt to identify cause of increased pain before increasing dosage of the extended-release tablets.²⁹⁰

Frequent communication among the prescriber, other members of the healthcare team, the patient, and the patient's caregiver or family is important during periods of changing analgesic requirements, including the initial dosage titration period.²⁹⁰

Maintenance Therapy

Oral

Continually assess adequacy of pain control and reevaluate for adverse effects, as well as for development of addiction, abuse, or misuse.²⁹⁰

During long-term therapy, periodically reevaluate need for continued opiate therapy.²⁹⁰

Discontinuance of Therapy

Oral

Discontinue therapy gradually to avoid precipitation of withdrawal symptoms.²⁹⁰

Pain (Oxycodone Myristate Extended-release Capsules)

Oral

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.²⁹¹ Individualize initial dosage based on patient's prior analgesic use, response, pain severity, and risk factors for addiction, abuse, and misuse.²⁹¹

Only use single oxycodone doses >36 mg (equivalent to 40 mg of oxycodone hydrochloride) or total daily dosages >72 mg (equivalent to 80 mg of oxycodone hydrochloride) in patients with established tolerance to opiates of comparable potency.²⁹¹

Supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for breakthrough pain may be necessary during therapy with extended-release capsules; discontinue any other existing around-the-clock opiates when therapy with oxycodone myristate extended-release capsules is initiated.²⁹¹

Patients are considered opiate tolerant if they have been receiving at least 60 mg of oral morphine sulfate daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone hydrochloride daily, 8 mg of oral hydromorphone hydrochloride daily, 25 mg of oral oxymorphone hydrochloride daily, 60 mg of oral hydrocodone bitartrate daily, or an equianalgesic dose of another opiate daily for at least 1 week.²⁹¹

Initial Therapy with Extended-release Capsules in Opiate-naive or Nontolerant Patients

Oral

Initially, 9 mg (equivalent to 10 mg of oxycodone hydrochloride) every 12 hours.²⁹¹ Higher initial dosages in patients who are not opiate tolerant may result in fatal respiratory depression.²⁹¹

Switching from Conventional Oxycodone Preparations to Extended-release Capsules

Oral

Calculate the total daily dosage of the conventional preparation and give as extended-release capsules in 2 divided doses at 12-hour intervals.²⁹¹

Dosage adjustment may be necessary; oxycodone myristate extended-release capsules are not bioequivalent to other oxycodone extended-release preparations.²⁹¹

Switching from Other Opiates to Extended-release Capsules

Oral

Manufacturer states that no equianalgesic conversion ratios have been established in clinical trials for transferring patients from other opiate analgesics to oxycodone myristate extended-release capsules.²⁹¹

Because of substantial interpatient variability in relative potency of opiate analgesics and analgesic formulations, it is preferable to underestimate the patient's 24-hour opiate requirements and provide “rescue” therapy with an immediate-release opiate analgesic than to overestimate the requirements and manage an adverse reaction.²⁹¹

Carefully individualize dosage; overestimation of the initial dosage in opiate-tolerant patients can result in fatal overdosage.²⁹¹

Manufacturer recommends initial dosage of 9 mg (equivalent to 10 mg of oxycodone hydrochloride) every 12 hours; administer supplemental analgesics (i.e., “rescue” therapy with an immediate-release analgesic) if necessary.²⁹¹

Particularly close monitoring required following switch from methadone, since conversion ratios between methadone and other opiates vary widely depending on extent of prior methadone exposure and because methadone has a long half-life and tends to accumulate in plasma.²⁹¹

Patients receiving fentanyl transdermal systems may receive extended-release capsules beginning 18 hours after removal of the transdermal system.²⁹¹ Use a conservative initial dosage of approximately 9 mg (equivalent to 10 mg of oxycodone hydrochloride) every 12 hours as extended-release capsules for each 25-mcg/hour increment in fentanyl transdermal system dosage.²⁹¹ Monitor closely; experience with this dosage conversion is limited.²⁹¹

Dosage Adjustment to Achieve Adequate Analgesia

Oral

May adjust dosage every 1–2 days, generally in increments of 25–50% of the current total daily dosage, to provide adequate analgesia and acceptable adverse effects; provide supplemental analgesia (i.e., “rescue” therapy with an immediate-release analgesic) for patients experiencing breakthrough pain.²⁹¹ Do not exceed 288 mg (eight 36-mg capsules) daily.²⁹¹

Safety and efficacy of dosing intervals <12 hours not established.²⁹¹

If level of pain increases after dosage stabilization, attempt to identify cause of increased pain before increasing dosage of the extended-release capsules.²⁹¹

Frequent communication among the prescriber, other members of the healthcare team, the patient, and the patient's caregiver or family is important during periods of changing analgesic requirements, including the initial dosage titration period.²⁹¹

Maintenance Therapy

Oral

Continually assess adequacy of pain control and reevaluate for adverse effects, as well as for development of addiction, abuse, or misuse.²⁹¹

During long-term therapy, periodically reevaluate need for continued opiate therapy.²⁹¹

Discontinuance of Therapy

Oral

Discontinue therapy gradually to avoid precipitation of withdrawal symptoms.²⁹¹

Prescribing Limits

Adults

Acute Pain

Oral

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435}

Chronic Pain

Oral

CDC recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥33 mg of oxycodone hydrochloride daily) for chronic pain and avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥60 mg of oxycodone hydrochloride daily) or carefully justify their decision to prescribe such dosages.⁴¹¹ Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.^{423 431}

Some states have set prescribing limits (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).^{411 420 421 423}

Pain (Oxycodone Myristate Extended-release Capsules)

Oral

Maximum 288 mg of oxycodone daily (eight 36-mg capsules); safety of excipients at dosages >288 mg daily not established.²⁹¹

Special Populations

Hepatic Impairment

Conventional Preparations

Use conservative initial dosage; adjust dosage based on the clinical situation.^{299 302}

Oxycodone Hydrochloride/Acetaminophen Extended-release Tablets

Initial oxycodone hydrochloride dose of 7.5 mg (in fixed combination with acetaminophen 325 mg).³⁰⁵ Monitor for respiratory depression and adjust dosage as needed.³⁰⁵

Oxycodone Hydrochloride Extended-release Tablets

Initially, 33–50% of the usual dosage; titrate dosage carefully.²⁹⁰

Oxycodone Myristate Extended-release Capsules

Initially, 33–50% of the usual dosage; titrate dosage carefully.²⁹¹ Use alternative analgesic if required oxycodone dose is <9 mg.²⁹¹

Renal Impairment

Conventional and Extended-release Preparations

Use conservative initial dosage in patients with Cl_cr <60 mL/minute; adjust dosage based on the clinical situation.^{290 291 299 302}

Oxycodone hydrochloride/acetaminophen extended-release tablets in patients with Cl_cr <60 mL/minute: Initial oxycodone hydrochloride dose of 7.5 mg (in fixed combination with acetaminophen 325 mg).³⁰⁵ Monitor for respiratory depression and adjust dosage as needed.³⁰⁵

Oxycodone myristate extended-release capsules: Do not use if required oxycodone dose is <9 mg.²⁹¹

Geriatric Patients

Conventional Preparations

Select dosage with caution, usually starting at the low end of the dosage range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{299 302 303}

Oxycodone Hydrochloride Extended-release Tablets

Manufacturer states that usual doses and dosing intervals may be appropriate for geriatric patients; however, reduced initial dosage of 33–50% of the usual dosage recommended in geriatric patients who are debilitated and non-opiate-tolerant; adjust dosage carefully.²⁹⁰

Oxycodone Myristate Extended-release Capsules

Manufacturer states that usual doses and dosing intervals may be appropriate for geriatric patients; nevertheless, select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.²⁹¹ Titrate dosage slowly.²⁹¹

Use alternative analgesic if required oxycodone dose is <9 mg.²⁹¹

Cautions for Oxycodone

Contraindications

• Substantial respiratory depression, hypercarbia, or acute or severe bronchial asthma in unmonitored settings or in the absence of resuscitative equipment.^{290 291 299 302 303}

• Known or suspected paralytic ileus and GI obstruction.^{290 291 299 302 303}

• Known hypersensitivity to oxycodone or any ingredient in the formulation.^{290 291 299 302 303}

Warnings/Precautions

Warnings

Addiction, Abuse, and Misuse

Risk of addiction, abuse, and misuse.^{290 291 303} Addiction can occur with appropriately prescribed or illicitly obtained opiates, and at recommended dosages or with misuse or abuse.^{290 291 303}

Assess each patient’s risk for addiction, abuse, and misuse prior to prescribing; monitor all patients for development of these behaviors or conditions.^{290 291 303} Personal or family history of substance abuse (drug or alcohol addiction or abuse) or mental illness (e.g., major depression) increases risk.^{290 291 303} The potential for addiction, abuse, and misuse should not prevent opiate prescribing for appropriate pain management,^{290 291 299 302 303} but does necessitate intensive counseling about risks and proper use and intensive monitoring for signs of addiction, abuse, and misuse.^{290 291 303}

Modified-release (e.g., extended-release) opiates are associated with a greater risk of overdose and death because of the larger amount of drug contained in each dosage unit.^{290 291}

Abuse or misuse of extended-release tablets containing oxycodone by crushing, cutting, breaking, or chewing the tablets, snorting the contents, or injecting the dissolved contents will result in uncontrolled delivery of oxycodone and can result in a fatal overdose.^{290 305} Snorting or injecting the dissolved contents of oxycodone myristate extended-release capsules also can result in a fatal overdose.²⁹¹ The risk of toxicity is increased when used concomitantly with alcohol or other CNS depressants, including other opiates.^{290 291 303}

OxyContin extended-release tablets and Xtampza ER extended-release capsules are formulated with physical and chemical properties intended to make these dosage forms more difficult to manipulate for IV or intranasal abuse and misuse.^{290 291} However, abuse by these routes, as well as by the oral route, is still possible.^{290 291}

Prescribe in smallest appropriate quantity and instruct patients on secure storage and proper disposal to prevent theft.^{290 291 303}

Respiratory Depression

Serious, life-threatening, or fatal respiratory depression reported with use of opiates, even when used as recommended; can occur at any time during therapy, but risk is greatest during initiation of therapy and following dosage increases.^{290 291 303} Monitor for respiratory depression, especially during first 24–72 hours of therapy and following any dosage increase.^{290 291 303}

Carbon dioxide retention from opiate-induced respiratory depression can exacerbate the drug's sedative effects.^{290 291 303}

Geriatric, cachectic, or debilitated patients are at increased risk of life-threatening respiratory depression.^{290 291 299 302 303} Closely monitor such patients, particularly following initiation of therapy, during dosage titration, and during concomitant therapy with other respiratory depressants.^{290 291 303} Consider use of nonopiate analgesics.^{291 303}

Even recommended doses of oxycodone may decrease respiratory drive to the point of apnea in patients with COPD or cor pulmonale, substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression.^{290 291 299 302 303} Closely monitor such patients, particularly following initiation of therapy, during dosage titration, and during concomitant therapy with other respiratory depressants.^{290 291 303} Consider use of nonopiate analgesics.^{290 291 299 302 303}

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.^{290 291 303} Overestimation of the dosage when transferring patients from another opiate analgesic can result in fatal overdosage with the first dose;^{290 291 303} large initial doses in nontolerant patients also can result in fatal overdosage.^{290 291 299 302}

Accidental ingestion of even 1 dose, especially by a child, can result in respiratory depression and fatal overdose.^{290 291 303}

Routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics, including oxycodone.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of OUD, those who have experienced a prior opiate overdose).⁷⁵⁰

Medication Errors with Oral Solutions

Use caution when prescribing, dispensing, and administering oral solutions of oxycodone to avoid dosing errors due to confusion between mg and mL or between oxycodone hydrochloride solution (5 mg/5 mL) and oxycodone hydrochloride concentrate solution (100 mg/5 mL).^{299 304} (See Medication Errors with Oral Solutions in Boxed Warning and see Oral Administration under Dosage and Administration.)

Use the oral concentrate solution only in opiate-tolerant patients.³⁰⁴

Interactions with Drugs that Affect CYP3A4

Concomitant use of CYP3A4 inhibitors may increase plasma oxycodone concentrations, increasing or prolonging opiate effects and potentially resulting in fatal respiratory depression.^{290 291 299 302 303}

Concomitant use of CYP3A4 inducers may result in decreased plasma oxycodone concentrations, lack of efficacy, or manifestations of withdrawal.^{290 291 299 302 303} (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiates, including oxycodone, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.^{416 417 418 700 701 702 703} Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{416 417 418 435 700 701}

Reserve concomitant use of oxycodone and other CNS depressants for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs under Interactions.)

Sensitivity Reactions

Cross-sensitivity to Codeine

Anaphylactic reactions reported in patients with known sensitivity to codeine (structurally similar opiate).³⁰³ Frequency of this possible cross-sensitivity unknown.³⁰³

Sulfite Sensitivity

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^a

Other Warnings and Precautions

Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.^a

Only clinicians who are knowledgeable in the use of potent opiates for the management of chronic pain should prescribe oxycodone hydrochloride extended-release tablets or oxycodone myristate extended-release capsules.^{290 291}

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.^{290 291 299 302 303}

Concurrent use with other CNS depressants may result in profound sedation, coma, respiratory depression, or death.^{290 291 299 302 303 700 703} (See Interactions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.^{291 303 400} Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.^{291 303 400}

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.^{291 303 400} If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.^{291 303 400} In some patients, switching to a different opiate improved symptoms.^{291 303 400}

Hypotension

May cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients, especially in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant use of certain drugs that compromise vasomotor tone (e.g., phenothiazines, general anesthetics).^{290 291 299 302 303} (See Interactions.)

Vasodilation produced by the drug may further reduce cardiac output and BP in patients with circulatory shock.^{290 291 299 302 303} Use oxycodone with caution in such patients;^{299 302 303 305} manufacturers recommend avoiding use of oxycodone hydrochloride extended-release tablets and oxycodone myristate extended-release capsules.^{290 291}

Increased Intracranial Pressure or Head Trauma

May reduce respiratory drive and further increase intracranial pressure in patients with increased intracranial pressure, head injuries, brain tumors, or other intracranial lesions.^{291 299 302 303} Monitor for sedation and respiratory depression, particularly during initiation of therapy.^{290 291}

May obscure the clinical course in patients with head injuries.^{290 291 299 302 303}

Avoid use of oxycodone hydrochloride extended-release tablets and oxycodone myristate extended-release capsules in patients with impaired consciousness or coma.^{290 291}

GI Complications with Extended-release Tablets

Some patients report difficulty in swallowing oxycodone hydrochloride extended-release tablets (e.g., choking, gagging, regurgitation, tablet stuck in throat).²⁹⁰ (See Oral Administration under Dosage and Administration.)

Intestinal obstruction and exacerbation of diverticulitis reported rarely; sometimes requires medical intervention to remove the tablet.²⁹⁰ Risk increased in patients with underlying GI disorders (e.g., esophageal or colon cancer) associated with narrow GI lumen.²⁹⁰

Consider using an alternative analgesic in patients who have difficulty swallowing and in those at risk for underlying GI disorders associated with narrow GI lumen.²⁹⁰

Same precautions also apply to oxycodone hydrochloride/acetaminophen extended-release tablets since these tablets swell and become sticky when wet.³⁰⁵

Acute Abdominal Conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.^{299 302 303}

Obstructive Bowel Disease

Diminishes propulsive peristaltic waves in GI tract and decreases bowel motility; may prolong GI obstructions.^{299 302 303}

Contraindicated in patients with GI obstruction, including paralytic ileus.^{290 291 299 302 303}

Monitor postoperative patients receiving opiates for decreased bowel motility.³⁰³

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi and increase serum amylase concentrations; monitor patients with biliary disease, including acute pancreatitis.^{290 291 302 303}

Seizure Disorders

May aggravate preexisting seizure disorder.^{290 291 299 302 303} Monitor for worsened seizure control.^{290 291}

May induce or aggravate seizures in other settings associated with seizures.^{290 291 299 302 303}

Debilitated and Special Risk Patients

Increased risk of life-threatening respiratory depression in geriatric, cachectic, or debilitated patients and in patients with chronic pulmonary disease.^{290 291 299 303} (See Respiratory Depression under Cautions.)

Use with caution and in reduced dosage in patients with hypothyroidism, Addison’s disease, prostatic hypertrophy, or urethral stricture.^{299 302 303} Also use with caution in those with toxic psychosis, acute alcoholism, or delirium tremens.^{299 302 303}

Urine Testing for Opiates

Presence of oxycodone not reliably detected by all urine drug tests for opiates, especially those designed for in-office use; urine drug concentrations below a specified value may be reported as negative results.^{290 291} If urine testing for oxycodone is used in patient management, consider the limitations of testing and ensure appropriate assay sensitivity and specificity.^{290 291}

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;^{291 303 400 401 402 403 404} causality not established.^{291 303 400} Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.^{291 303 400} Perform appropriate laboratory testing in patients with manifestations of hypogonadism.^{303 400}

Fixed-Combination Preparations

When used in fixed combination with other drugs, consider the cautions, precautions, and contraindications associated with the other drug.^{303 305 a}

Specific Populations

Pregnancy

Category B^{299 302} or C.^{290 303}

Analysis of data from the National Birth Defects Prevention Study (large population-based, case-control study) suggests therapeutic use of opiates in pregnant women during organogenesis is associated with a low absolute risk of birth defects, including heart defects, spina bifida, and gastroschisis.^{295 301}

Use of opiates in pregnant women during labor can result in neonatal respiratory depression.^{290 291 295 299 302 303}

Prolonged maternal use of opiates during pregnancy can result in neonatal opiate withdrawal syndrome; in contrast to adults, withdrawal syndrome in neonates may be life-threatening and requires management according to protocols developed by neonatology experts.^{290 291 303} Syndrome presents with irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.^{290 291 303} Onset, duration, and severity vary depending on the specific opiate used, duration of use, timing and amount of last maternal use, and rate of drug elimination by the neonate.^{290 291 303}

Lactation

Distributed into milk.^{290 291 295 299 302}

Avoid use in nursing women.^{290 291 299 302} If used, observe infant for GI effects, sedation, respiratory depression, and changes in feeding patterns.^{291 295 303}

Symptoms of withdrawal can occur in opiate-dependent breast-fed infants upon cessation of breast-feeding by women receiving oxycodone.^{290 291 303}

Pediatric Use

Safety and efficacy of oxycodone hydrochloride extended-release tablets not established in children <11 years of age.²⁹⁰

Safety and efficacy of other preparations not established in children;^{291 299 302 303 305} however, the drug is recommended for use in pediatric patients.^{296 298 a f g h} (See Pediatric Dosage under Dosage and Administration.)

Geriatric Use

Possible increased sensitivity to the drug's effects.^{299 302 303} Increased risk of respiratory depression.^{290 291 299 302 303}

Clearance may be slightly reduced in geriatric patients.^{290 291} (See Absorption: Special Populations, under Pharmacokinetics.)

Select dosage with caution.^{290 291 299 302 303} (See Geriatric Patients under Dosage and Administration.) Monitor closely for adverse effects, especially during initiation of therapy and dosage titration and when used concomitantly with other respiratory depressants.^{290 291 303}

Hepatic Impairment

Increased systemic exposure;^{290 291} drug effects may be increased.²⁹⁰ (See Absorption: Special Populations, under Pharmacokinetics.)

Use with caution.^{299 303} Use conservative initial dosage, monitor closely, and adjust dosage based on response.^{290 291 299 302} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Increased systemic exposure^{290 291 302} with increased sedation reported.^{290 291} (See Absorption: Special Populations, under Pharmacokinetics.)

Use with caution.^{299 303} Use conservative initial dosage, monitor closely, and adjust dosage based on response.^{290 291 299 302} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Constipation,^{290 291 299 302} nausea,^{290 291 299 302 303} sedation/somnolence,^{290 291 299 302 303} dizziness,^{290 291 299 302 303} lightheadedness,³⁰³ vomiting,^{290 291 299 302 303} pruritus,^{290 291 299 302} headache,^{290 291 299 302} insomnia,^{299 302} dry mouth,²⁹⁰ sweating,²⁹⁰ asthenia.^{290 299 302}

Drug Interactions

Metabolized by CYP3A4 and to a lesser extent by CYP2D6.^{290 291 299 302}

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Possible decreased clearance and increased plasma concentrations of oxycodone; may result in increased or prolonged opiate effects, including potentially fatal respiratory depression.^{290 291 299 302 303} These effects may be more pronounced with concomitant use of CYP2D6 and 3A4 inhibitors.^{290 291} If concomitant use of oxycodone and CYP3A4 inhibitor is necessary, monitor frequently for respiratory depression and sedation; consider dosage adjustments until drug effects are stable.^{290 291 299 302 303} If CYP3A4 inhibitor is discontinued, monitor frequently for withdrawal symptoms and/or reduced analgesic efficacy and adjust oxycodone dosage as needed.^{291 303}

CYP3A4 inducers: Possible increased clearance and decreased plasma concentrations of oxycodone; may result in decreased analgesic efficacy and/or development of opiate withdrawal.^{290 291 299 302 303} If concomitant use is necessary, monitor for opiate withdrawal; consider dosage adjustments until drug effects are stable.^{290 291 299 302 303} If CYP3A4 inducer is discontinued, oxycodone concentrations may increase, potentially resulting in increased or prolonged therapeutic or adverse effects, including potentially fatal respiratory depression.^{290 291 303} If CYP3A4 inducer is discontinued, monitor for increased opiate effects and adjust oxycodone dosage as needed.^{291 303}

CYP2D6 inhibitors: Clinically important effects on oxycodone metabolism not demonstrated.^{290 291 299 303}

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.^{291 303 400} May occur at usual dosages.⁴⁰⁰ Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.⁴⁰⁰ (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.^{291 303 400}

If serotonin syndrome is suspected, discontinue oxycodone, other opiate therapy, and/or any concurrently administered serotonergic agents.^{291 303 400}

Specific Drugs

Oxycodone Pharmacokinetics

Absorption

Bioavailability

Following oral administration, about 60–87% of an oral dose reaches the systemic circulation.^{290 299 302 303 g}

Oxycodone hydrochloride/acetaminophen extended-release tablets: Bilayer formulation that contains a portion of the labeled doses of the 2 drugs in an immediate-release layer and the remaining portion in an extended-release layer.³⁰⁵ Bioavailability (dose-normalized AUC and peak plasma concentration) of oxycodone is comparable to that of conventional preparations.³⁰⁵

Relative oral bioavailability of oxycodone hydrochloride extended-release tablets to conventional oral dosage forms is the same.²⁹⁰

Relative oral bioavailability of oxycodone myristate extended-release capsules to an oral solution of the drug is lower in the fasting state (75%) but comparable in the fed state (114%).²⁹¹ Mean peak serum concentrations are lower (73 and 43% lower under fasting and fed conditions, respectively) and peak concentrations occur about 3 hours later with the extended-release capsules compared with oral solution in the fasting state.²⁹¹

Oxycodone myristate extended-release capsules are not bioequivalent to oxycodone hydrochloride extended-release tablets.²⁹¹ Under fasting conditions, peak serum concentration and AUC are lower for extended-release capsules; under fed conditions, peak serum concentrations are lower, but AUC is similar to values for extended-release tablets.²⁹¹

Peak plasma concentrations occur within 1.2–1.4 hours for conventional oral dosage forms.³⁰²

Peak oxycodone concentrations occur in 3–4 hours for extended-release oxycodone hydrochloride/acetaminophen tablets.³⁰⁵

Peak concentrations occur in approximately 4.5 hours for oxycodone myristate extended-release capsules under fed conditions.²⁹¹

Onset

Conventional preparations: Analgesia within 10–15 minutes; peak at about 1 hour.^{a g}

Oxycodone hydrochloride extended-release tablets: Analgesia within 1 hour; peak effect also may occur at this time but persists.^{g 300}

Duration

Conventional preparations: Analgesia persists for 3–6 hours.^a

Food

Oxycodone hydrochloride tablets and oral solution: Effects of food on rate or extent of absorption not expected to be clinically important.^{299 302}

Oxycodone hydrochloride/acetaminophen extended-release tablets: Low-fat or high-fat meal delays peak oxycodone concentrations by 1 or 2 hours, respectively; increases mean AUC by 15–16%; and increases peak concentrations by 12–25%.³⁰⁵

Oxycodone hydrochloride extended-release tablets: Food does not affect extent of absorption.²⁹⁰

Oxycodone myristate extended-release capsules: Food increases bioavailability; effect is dependent on content of meal.²⁹¹ High-fat, high-calorie meal increases peak concentration and AUC by 100–150 and 50–60%, respectively; medium-fat, medium-calorie meal increases peak concentration and AUC by 84 and 28%, respectively; low-fat, low-calorie meal increases peak concentration by 19% but does not affect AUC.²⁹¹

Pharmacokinetic profile for contents of extended-release capsule sprinkled on food is equivalent to that for intact capsule administered with food.²⁹¹

Special Populations

Mild to moderate hepatic impairment: Peak plasma concentrations of oxycodone and noroxycodone increased by 50 and 20%, respectively, and AUCs increased by 95 and 65%, respectively.^{290 291} Peak concentrations and AUCs of oxymorphone decreased by 30 and 40%, respectively.^{290 291}

Renal impairment (Cl_cr <60 mL/minute): Peak concentrations of oxycodone and noroxycodone increased by 50 and 20%, respectively; AUCs for oxycodone, noroxycodone, and oxymorphone increased by 60, 50, and 40%, respectively.^{290 291}

Geriatric patients: Plasma concentrations not increased or increased only minimally (by 15%).^{290 291 299 302}

Pediatric patients ≥11 years of age: Systemic exposure to oxycodone (administered as oxycodone hydrochloride extended-release tablets) expected to be similar to that in adults at any given dosage.²⁹⁰

Females: Plasma concentrations following administration of oxycodone hydrochloride extended-release tablets or oxycodone myristate extended-release capsules reportedly up to 20–25% higher than in males (after accounting for differences in body weight and/or body mass index).^{290 291} Gender apparently does not affect pharmacokinetics of the immediate-release tablets.^{299 302}

Distribution

Extent

Distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain.^{290 291}

Readily crosses the placenta.^{290 291 299 302 303 e}

Distributes into milk.^{290 291 295 299 302}

Plasma Protein Binding

About 45%.^{290 291 299 302 303 g}

Elimination

Metabolism

Extensively metabolized in the liver to noroxycodone, oxymorphone, and noroxymorphone, and their glucuronide conjugates.^{290 291 299 302}

Metabolized by CYP3A to noroxycodone and, to a lesser extent, by CYP2D6 to oxymorphone.^{290 291 299 302 g} Oxymorphone is present in low concentrations following oxycodone administration and not thought to contribute substantially to analgesic effects.^{290 291 299 302}

Elimination Route

Oxycodone and its metabolites excreted principally in urine.^{290 291 299 302}

Half-life

Conventional preparations: 3–5 hours.^{290 291 299 302 303 g}

Oxycodone hydrochloride/acetaminophen extended-release tablets: 4.5 hours.³⁰⁵

Oxycodone hydrochloride extended-release tablets: 4.5 hours.²⁹⁰

Oxycodone myristate extended-release capsules (under fed conditions): 5.6 hours.²⁹¹

Special Populations

Renal impairment: Elimination half-life increased by 1 hour compared with normal renal function.^{290 291 g} Exposure to the drug increased substantially.^g (See Special Populations, under Cautions.)

Mild to moderate hepatic impairment: Elimination half-life increased by 2.3 hours compared with normal hepatic function.^{290 291 g 290} Exposure to oxycodone and noroxycodone increased.^g (See Special Populations, under Cautions.)

Stability

Storage

Oral

Conventional or Extended-release Preparations

Room temperature; consult manufacturer's labeling for specific storage recommendations.^{290 291 299 302 303}

Actions

• Principal pharmacologic effects are on CNS and intestines.^e

• Acts at several sites within the CNS involving several systems of neurotransmitters to produce analgesia; precise mechanism of action not fully elucidated.^e

Advice to Patients

• Importance of reading the manufacturer’s patient information (e.g., medication guide) each time the drug is dispensed.^{290 291}

• Potential for addiction, abuse, and misuse, which can lead to overdosage or death, even when used as recommended.^{290 291 303} Protect from theft or misuse; properly dispose of any unused drug.^{290 291 299 302 303} Do not share oxycodone with others.^{290 291 299 302 303}

• Risk of potentially fatal respiratory depression; most likely to occur following initiation of therapy or increase in dosage; may occur at recommended dosages.^{290 291 303} Importance of seeking immediate medical attention if signs or symptoms of respiratory depression (e.g., difficulty breathing; slow, shallow breathing; extreme drowsiness with slowed breathing; feelings of faintness, dizziness, or confusion) occur.^{290 291 299 303} Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.⁷⁵⁰

• Importance of strictly adhering to recommended dosing of oxycodone hydrochloride extended-release tablets in pediatric patients.²⁹⁰

• Accidental ingestion, especially by a child, may result in respiratory depression or death.^{290 291 299 303} Instruct patient to keep oxycodone out of reach of children.^{290 291 299 302 303}

• Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.^{290 291 299 302 303}

• Importance of not breaking, crushing, or chewing extended-release tablets; potentially fatal overdose can occur.^{290 305} Swallow tablets whole, one at a time, with enough water to ensure complete swallowing of the tablet immediately after it is placed in the mouth.^{290 305} Do not wet the tablet (e.g., by soaking, licking) before placing it in the mouth; wetting can lead to difficulty in swallowing the tablet.^{290 305}

• Importance of always using the calibrated measuring device provided with the particular oxycodone hydrochloride oral solution to accurately measure and administer the dose.^{299 304} Advise patient that the oral concentrate solution should be used only in opiate-tolerant patients;³⁰⁴ inform patient if the concentration of the solution will be changed.^{299 304}

• Importance of taking each dose of oxycodone myristate extended-release capsules with food and with approximately the same amount of food to ensure consistent plasma concentrations are achieved.²⁹¹ Follow manufacturer's administration instructions if the capsules will be opened and sprinkled on food or administered directly into the mouth or via a feeding tube.²⁹¹ (See Oral Administration under Dosage and Administration.)

• Importance of adhering to any additional preparation-specific administration instructions.³⁰² (See Oral Administration under Dosage and Administration.)

• Advise patient that extended-release tablets of oxycodone hydrochloride/acetaminophen are not interchangeable with immediate-release formulations of this drug combination.³⁰⁵

• Importance of informing clinicians of breakthrough pain or adverse effects.^{290 291 303}

• Importance of taking exactly as prescribed; do not increase dosage or abruptly discontinue without consulting a clinician.^{290 291 299 302 303}

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.^{290 291 299 302 303 700 703} Importance of informing patients that oxycodone should not be combined with alcohol.^{290 291 299 302 303 700 703}

• Potential risk of serotonin syndrome with concurrent use of oxycodone and other serotonergic agents.^{291 303 400} Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.^{291 303 400}

• Potential risk of adrenal insufficiency.^{291 303 400} Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.^{291 303 400}

• Potential for severe constipation.^{290 291 299 302} Advise patients on appropriate management of constipation.^{290 291 299 302}

• Risk of orthostatic hypotension and syncope.^{290 291 299}

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.⁴⁰⁰ Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.⁴⁰⁰

• Importance of seeking medical attention if symptoms of severe hypersensitivity (e.g., anaphylaxis) occur.^{290 291 303}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{290 291 299 302 303}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{290 291 299 302 303} Importance of informing women that chronic use during pregnancy may result in neonatal opiate withdrawal syndrome, which can be life-threatening if not recognized and treated.^{290 291 303}

• Importance of informing patients of other important precautionary information.^{290 291 299 302 303} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Oxycodone preparations are subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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