Dosing and uses of OxyContin, Xtampza ER (oxycodone)
Adult dosage forms and strengths
capsule, immediate-release: Schedule II
- 5mg
tablet, immediate-release: Schedule II
- 5mg
- 10mg
- 15mg
- 20mg
- 30mg
abuse deterrent tablet, immediate-release (Oxaydo): Schedule II
- 5mg
- 7.5mg
abuse deterrent tablet, controlled-release (OxyContin): Schedule II
- 10mg
- 15mg
- 20mg
- 30mg
- 40mg
- 60mg
- 80mg
abuse deterrent capsule, controlled-release (Xtampza): Schedule II
- 9mg (equivalent to 10 mg oxycodone HCl)
- 13.5mg (equivalent to 15 mg oxycodone HCl)
- 18mg (equivalent to 20 mg oxycodone HCl)
- 27mg (equivalent to 30 mg oxycodone HCl)
- 36mg (equivalent to 40 mg oxycodone HCl)
- Abuse-deterrent capsule utilizing DETERx technology platform to maintain its extended-release profile after being subjected to common methods of tampering
oral concentrate: Schedule II
- 20mg/mL
oral solution: Schedule II
- 5mg/5mL
Moderate-to-Severe Pain
Immediate-release
- Opioid-tolerant:: 10-30 mg PO q4-6hr
- Opioid-naïve: 5-15 mg PO q4-6hr
Chronic Severe Pain
Controlled-release products (eg, OxyContin, Xtampza ER) are indicated 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
Also see Administration
Initial dosing
- OxyContin
- Opioid-naïve patients: 10 mg PO q12hr initially; titrate gradually every 1-2 days, increasing by 25-50% increments, with q12hr dosing interval maintained
- A single dose >40 mg ER or total dose >80 mg ER are for use only in opioid-tolerant patients
- Xtampza ER
- Opioid-naïve patients: 9 mg PO q12hr with food
Conversion from other opioids to OxyContin or Xtampza Er
- Provide immediate-release opioids for breakthrough pain
- Monitor patient closely for adverse effects or breakthrough pain during conversion and for several days following
- Also see reference topic - Opioid Equivalents
- OxyContin
- Conversion from other oral oxycodone formulations: Administer one-half of the patient's total daily PO oxycodone dose as q12hr
- Conversion from fentanyl transdermal: Wait 18 hr after patch removed, then initiate conservative dose of ~10 mg q12hr oxycodone controlled-release for each 25 mcg/hr fentanyl transdermal patch
- Xtampza ER
- Conversion from other oral oxycodone formulations: Administer one-half of the patient's total daily PO oxycodone dose as q12hr with food; because Xtampza ER is not bioequivalent to other oxycodone extended-release products, monitor patients for possible dosage adjustment
- Conversion from other opioids: Discontinue all other around-the clock opioid drugs; there are no established conversion ratios for conversion from other opioids to Xtampza ER defined by clinical trials; initiate dosing using 9 mg PO q12hr with food and provide immediate-release rescue medication while stabilizing patient on Xtampza ER
- Conversion from methadone: Close monitoring is of particular importance when converting from methadone to other opioid agonists; the ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure and methadone has a long half-life and can accumulate in the plasma
- Conversion from fentanyl transdermal: 18 hr following the removal of the transdermal fentanyl patch, initiate Xtampza ER; there has been no systematic assessment of such conversion, a conservative oxycodone dose, ~9 mg (equivalent to 10 mg oxycodone HCl) q12hr should be initially substituted for each 25 mcg/hr fentanyl transdermal patch
Opioid-tolerant definition
- Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
- Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
Limitations of use
- Because of the risks 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, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
- Long-acting opioids are not indicated as a PRN analgesic
Dosage modifications
Renal impairment (CrCl <60 mL/min): Serum concentration may increase by 50%; adjust dosage to response
Hepatic impairment: Reduce dosage in liver disease; decrease dosage of extended-release form to one third or one half of usual starting dosage; titrate to response
Coadministration with other CNS depressants: Initiate long-acting oxycodone with one-third to one-half the recommended starting dose; monitor for signs of respiratory depression, sedation, and hypotension
Pediatric dosage forms and strengths
tablet, immediate release: Schedule II
- 5mg
- 10mg
- 15mg
- 20mg
- 30mg
capsule, immediate-release: Schedule II
- 5mg
oral concentrate: Schedule II
- 20mg/mL
oral solution: Schedule II
- 5mg/5mL
abuse deterrent tablet, controlled-release (OxyContin): Schedule II
- 10mg
- 15mg
- 20mg
- 30mg
- 40mg
- 60mg
- 80mg
Moderate-to-Severe Pain
Immediate-release: 0.05-0.15 mg/kg PO q4-6hr PRn
Chronic Severe Pain
Controlled-release (ie, OxyContin) is indicated 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 in opioid-tolerant pediatric patients aged ≥11 yr who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent
Note: Xtampza ER is not approved for children or adolescents younger than 18 yr
Initial dose
- Dosing information is only for children ≥11 yr who are already receiving and tolerating opioids for at least 5 consecutive days, and for the 2 days immediately preceding dosing with OxyContin, patients must be taking a minimum of 20 mg/day of oxycodone or its equivalent
- Not appropriate for use in pediatric patients requiring <20 mg/day
- Discontinue all other around-the-clock opioid drugs when OxyContin is initiated
- Also see Administration
Converting to OxyContin in children ≥11 yr
- Although tables of oral and parenteral equivalents are readily available, there is substantial interpatient variability in the relative potency of different opioid drugs and formulations
- As such, it is preferable to underestimate a patient’s 24-hr oral oxycodone requirements and provide rescue medication (eg, immediate-release opioid) than to overestimate the 24-hr oral oxycodone requirements and manage adverse effects
- Conversion factors of prior opioid
- Oxycodone PO: 1
- Hydrocodone PO: 0.9
- Hydromorphone PO: 4
- Hydromorphone parenteral: 20
- Morphine PO: 0.5
- Morphine parenteral: 3
- Tramadol PO 0.17
- Tramadol parenteral: 0.2
- NOTE: For patients receiving high-dose parenteral opioids, a more conservative conversion is warranted; for example, for high-dose parenteral morphine, use 1.5 instead of 3 as a multiplication factor
Conversion steps to OxyContin
- Use the conversions listed above
- Step 1 – calculate daily opioid dose(s)
- Pediatric patients taking a single opioid: Add the current total daily dosage of the opioid and then multiply the total daily dosage by the approximate conversion factor to calculate the estimated OxyContin daily dose
- Pediatric patients on a regimen of >1 opioid: Calculate the approximate oxycodone daily dose for each opioid and add the daily totals to obtain the approximate OxyContin dose/day
- Pediatric patients on a regimen of fixed-ratio opioid/nonopioid analgesic products: Use only the opioid component of these products in the conversion
- Step 2 – round dose down
- If rounding is necessary, always round the dosage down to the nearest tablet strength available and initiate OxyContin therapy with that dose
- If the calculated oxycodone daily dosage is <20 mg, there is no safe strength for conversion and do not initiate
- Example: Conversion from a single opioid (eg, hydrocodone) to OxyContin; using the conversion factor of 0.9 for oral hydrocodone, a total daily hydrocodone dosage of 50 mg is converted to 45 mg/day of oxycodone or 22.5 mg q12hr of OxyContin
- After rounding down to the nearest strength available, the recommended OxyContin starting dosage is 20 mg q12hr
- Step 3 – closely observe and titrate
- Following conversion, observation and titration are warranted until pain management is stable
- Monitor for signs and symptoms of opioid withdrawal or for signs of oversedation/toxicity
OxyContin titration and maintenance
- Individually titrate to a dosage that provides adequate analgesia and minimizes adverse reactions
- Continually re-evaluate pain control, signs and symptoms of opioid withdrawal, and adverse reactions, as well as monitoring for the development of addiction, abuse and misuse
- If breakthrough pain occurs, may require a dosage increase of OxyContin or a short-acting rescue analgesic
- If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OxyContin
- Because steady-state plasma concentrations are approximated in 1 day, may adjust OxyContin dose every 1-2 days
- As a guideline for children ≥11 yr, the total daily oxycodone dosage usually can be increased by 25% of the current total daily dosage
Dosage modifications
Coadministration with other CNS depressants: Initiate OxyContin with one-third to one-half the recommended starting dose; monitor for signs of respiratory depression, sedation, and hypotension
Dosing Considerations
Long-acting or controlled-release oxycodone is not indicated for PRN analgesic dosing
Geriatric dosage forms and strengths
Reduce starting dose to one-third to one-half of usual starting dosage; titrate cautiously
OxyContin, Xtampza ER (oxycodone) adverse (side) effects
Frequency not defined
Agitation
Angina pectoris
Anticholinergic effects (dry mouth, palpitation, tachycardia)
Bradycardia
Cardiac arrest
Coma
Constipation
Dizziness
Dysphoria
Euphoria
Faintness
Mental clouding/depression
Myocardial infarction
Nausea
Nervousness
Pruritus, urticaria
QT-interval prolongation
Respiratory arrest
Respiratory/circulatory depression
Restlessness
Sedation
Seizures
Severe cardiac arrhythmias
Shock
ST-segment elevation
Sweating, flushing, warmness of face/neck/upper thorax
Syncope
Urinary retention, oliguria
Ventricular tachycardia
Visual disturbances
Vomiting
Weakness
Warnings
Black box warnings
Addiction, abuse, and misuse
- Risk 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
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 tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal dose
Accidental exposure
- Accidental of even 1 dose, 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
- Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
- Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Cytochrome P450 3A4 interaction
- Concomitant use of oxycodone ER with all cytochrome P450 (CYP-450) 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
Oral solutions
- Concentrated oral solution is available as a 20 mg/mL concentration is indicated for use in opioid-tolerant patients only
- Take care when prescribing and administering oxycodone oral solution to avoid dosing errors due to confusion between milligrams and milliliter, and other oxycodone solutions with different concentrations
Contraindications
Known or suspected GI obstruction, including paralytic ileus
Hypersensitivity (eg, anaphylaxis) to oxycodone
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Cautions
Use caution in patients with anemia, cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, gout, head injury, renal/hepatic disease or impairment, hypoprothrombinemia, toxic psychosis, hypothyroidism, increased intracranial pressure, prostatic hypertrophy, renal impairment, seizures with epilepsy, thyrotoxicosis, urethral stricture, urinary tract surgery, vitamin K deficiency, anoxia, central nervous system (CNS) depression, hypercapmia, respiratory depression or disease, hypersensitivity to phenantrene-derivative opioid agonists, morbid obesity, untreated myxedema, adrenocrotical insufficiency including Addison disease
If crushed, extended-release preparation (OxyContin) can deliver large opiate dose with potential for abuse or overdose; OxyContin reformulated in April 2010 to prevent tablet from being cut, broken, crushed, or dissolved to release more medication; inability to tamper with product reduces potential for abuse
Caution with OxyContin in patients who have difficulty swallowing or have underlying GI disorders that may predispose to obstruction
May obscure diagnosis of acute abdominal conditions
Withdrawal symptoms may develop following abrupt discontinuation or with concurrent administration of opioid antagonists
May cause severe hypotension; use caution in patients with hypovolemia, cardiovascular disease or drugs that may exaggerate hypotensive hypotensive effects
A single dose >40 mg or total dose >80 mg are for use only in opioid-tolerant patients
May cause constipation, which may be problematic in patients with unstable angina and patients post-myocardial infarction; reduce potential for constipation by administering stool softener or increasing fiber in diet in patients following myocaridal infarction and unstable angina
Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi
Use cuation in patients who re morbidly obese
Use caution in patients with thyroid dysfunction
Dose adjustment required when initiating extended release therapy in patients taking other CNS depressants
Use with caution in perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics
Some dosage forms may contain sodium benzoic acid (benzoate), a metabolite of benzyl alcohol; large amounts of benzyl alcohol have been associated with potentially fatal toxicity (gasping syndrome) in neonates
Extended release tablets may be difficult to swallow and could become lodged in throat; patients with swallowing difficulties may be at risk; intestinal obstruction or diverticulitis exacerbation also reported
Long-acting opioids
- Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black box warnings)
- Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black box warnings)
- Serious, life-threatening, or fatal respiratory depression reported (see Black box warnings)
- Accidental exposure reported, including fatalities (see Black box warnings)
- Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black box warnings)
- Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension
- Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
Pregnancy and lactation
Pregnancy category: B; D if used for prolonged periods or near term
Lactation: Drug excreted in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of OxyContin, Xtampza ER (oxycodone)
Mechanism of action
Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation
Absorption
Bioavailability: 60-87%
Onset:10-15 min (immediate-release); controlled-release designed to consistently deliver drug over 12 hr
Duration: 3-6 hr (immediate release); ≤12 hr (controlled release)
Peak plasma time: 1.5-1.9 hr (immediate-release); 4-5 hr (OxyContin 10-80 mg)
Distribution
Protein bound: 45%
Vd: 2.6 L/kg
Metabolism
Metabolized in liver by CYP3A mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with a lower contribution from CYP2D6 mediated O-demethylation to oxymorphone
Metabolites: Noroxycodone, oxymorphone (and glucuronide conjugates)
CYP2D6 poor metabolizers may not achieve adequate analgesia; ultra-rapid metabolizers (≤7% of Caucasians and ≤30% of Asian and African populations) may have increased toxicity as consequence of rapid conversion
Elimination
Half-life: 2-4 hr; 4.5 hr (OxyContin)
Excretion: Urine (83%)
Administration
Oral Administration, Controlled-release
Do not discontinue abruptly, use gradually downward titration
OxyContin
- May take with or without food
- Swallow whole, do not chew, crush, dissolve, or break
- OxyContin is manufactured with abuse deterrence ingredients
- The abuse-deterrent formulation is an immediate-release preparation with "abuse aversion" technology (if crushed, crumbles into chunks instead of powder and foams if mixed with liquid)
Xtampza Er
- Must be taken with food in order to ensure consistent plasma levels are achieved
- Xtampza ER utilizing DETERx technology platform to maintain its extended-release profile after being subjected to common methods of tampering
- Difficulty swallowing: Sprinkle capsule contents on soft foods or into a cup, and then administer directly into the mouth; alternatively, may be given through a gastrostomy or nasogastric feeding tube
