Naltrexone / Oxycodone Dosage

Usual Adult Dose for:

Chronic Pain

Additional dosage information:

Renal Dose Adjustments
Liver Dose Adjustments
Dose Adjustments
Precautions
Dialysis
Other Comments

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 in the management of the pain of each individual patient. Discontinue all other around the clock opioid drugs when initiating therapy with extended-release oxycodone/naltrexone

All doses expressed as oxycodone/naltrexone

Extended-release (ER) capsule strengths of 60 mg/7.2 mg and 80 mg/9.6 mg, single doses greater than 40 mg/4.8 mg, or total daily doses greater than 80 mg/9.6 mg should only be used in patients who are opioid tolerant.

OPIOID-NAIVE and OPIOID NON-TOLERANT patients:
Initial dose: 10 mg/1.2 mg orally every 12 hours

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.

DOSE CONVERSIONS

From Other Oral Oxycodone Hydrochloride Formulations:

Initial dose: One-half of the total daily oral oxycodone dose as oxycodone/naltrexone orally every 12 hours

From Other Opioid Formulations: Dose conversions should be done carefully and with close monitoring due to large patient variability in regards to opioid analgesic response. See dose adjustment section or manufacturer's product information and/or local protocol for guidance.

MAINTENANCE DOSE:

Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; close observation and frequent titration are warranted until pain management is stable; once stable, periodically reassess for continued need
May adjust by 20 mg/2.4 mg every 2 to 3 days as needed based on efficacy, safety, and tolerability

Comments:

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, oral hydrocodone 60 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.

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.

Renal Dose Adjustments

Use with caution; monitor closely for CNS or respiratory depression and for signs of withdrawal

Liver Dose Adjustments

Use with caution; monitor closely for CNS or respiratory depression and for signs of withdrawal

Dose Adjustments

Elderly, Cachectic, or Debilitated Patients:

Start at the low end of the dosing range; monitor closely for respiratory depression
Consider use of non-opioid analgesic, especially among patients concomitantly receiving other drugs that depress respiration.

DOSE CONVERSIONS:

It is important to account for inter-patient variability in the potency of opioid drugs and their formulations when switching opioids; it is always best to underestimate a patient's oral oxycodone requirement and provide rescue medication than to overestimate and manage an overdose.
The following Conversion Factors (CF) are provided to estimate conversion to oxycodone/naltrexone; these CFs should not be used to convert oxycodone/naltrexone to the oral opioid as doing so may result in overdose. The approximate CF for conversion from codeine is 0.1; from hydrocodone it is 0.67; from hydromorphone it is 2.67; and from oxycodone it is 1.
To calculate the oxycodone/naltrexone dose: (1) Sum the total daily dose of the current oral opioid and multiply by the appropriate CF to arrive at the approximate total daily oral oxycodone dose (2) Reduce the daily oxycodone dose by 50% to obtain the total daily oxycodone/naltrexone dose (3) Divide the total daily oxycodone/naltrexone dose in half to obtain the every 12 hour dose (4) Always round down to the available strength (5) Provide rescue medication as necessary.
Formula: mg/day prior opioid x conversion factor (CF) = mg/day oxycodone/naltrexone

CONVERSION FROM TRANSDERMAL FENTANYL: Remove transdermal fentanyl patch and 18 hours later substitute oxycodone 10 mg/naltrexone 1.2 mg every 12 hours for each 25 mcg/hr fentanyl transdermal patch; monitor closely as there is limited experience with this conversion
CONVERSION FROM TRANSDERMAL BUPRENORPHINE: Initiate with oxycodone 10 mg/naltrexone 1.2 mg every 12 hours
CONVERSION FROM TRAMADOL: Initiate with oxycodone 10 mg/naltrexone 1.2 mg every 12 hours
CONVERSION FROM METHADONE: When converting from methadone, close monitoring is of particular importance due to methadone's long half-life and unpredictable pharmacokinetics.

Therapy Discontinuation:

Abrupt discontinuation is not recommended
Taper dose gradually by 25% to 50% every 2 to 4 days; if signs or symptoms of withdrawal occur, may raise the dose to previous level and taper more slowly.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for extended-release and long-acting opioid analgesics. The REMS consists of a medication guide and elements to assure safe use. Additional information is available at REMS@FDA

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse: This drug 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.
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, 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 should be available.
Cytochrome P450 3A4 Interaction: 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. Additionally, 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 use in 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.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule II

Dialysis

Data not available

Other Comments

Administration advice:

Take orally every 12 hours
Swallow capsules whole; do not crush, chew, or dissolve the pellets as this will result in uncontrolled delivery of oxycodone which can lead to overdose
For patients unable to swallow capsules whole, may open capsule and sprinkle capsule contents on applesauce and immediately swallow without chewing

General:

This drug should be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
Because of the risks of addiction, abuse and misuse, the lowest dose for the shortest duration consistent with individual patient treatment goals should be used.
Frequent communication between members of the healthcare team, patients, and their caregiver/family is important during periods of changing analgesic requirements; if the level of pain increases after dose stabilization, an attempt should be made to identify the source of increased pain before increasing the dose of pain medication.
For patients receiving other opioid analgesics and switching to 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.

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 the development of behaviors indicative of addiction, abuse, or misuse

Patient advice:

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 this drug, even when taken as recommended can 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 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 seek medical advice for signs and symptoms of opioid withdrawal such as tremors, chills, diarrhea, irritability, and yawning.
Patients should be instructed to check with their healthcare provider before taking any new medications, including alcohol, herbal supplements and over the counter products
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.
Patients should be instructed in proper disposal.