Naloxone / 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/naloxone

All doses expressed as oxycodone/naloxone

OPIOID-NAIVE and OPIOID NON-TOLERANT patients:
Initial dose: 10 mg/5 mg orally every 12 hours

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression with first dose.

CONVERSIONS From Other Oral Oxycodone Formulations:

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

CONVERSIONS From Other Opioids:

Dose conversions should be done carefully and with close monitoring due to large patient variability in opioid analgesic response; see dose adjustment section.

MAINTENANCE DOSE:

Adjust by 10 mg/5 mg every 12 hours every 1 to 2 days as needed based on efficacy, safety, and tolerability; 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

Maximum single dose: 40 mg/20 mg
Maximum daily dose: 80 mg/40 mg

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.
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following all dose increases.

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

Mild to Severe Renal Impairment: Reduce initial dose by one-half usual starting dose, titrate carefully; monitor for signs of respiratory depression, sedation, and hypotension

Liver Dose Adjustments

Mild hepatic impairment: Reduce initial dose by one-third to one-half of usual starting dose, titrate carefully; monitor for signs of respiratory depression, sedation, and hypotension
Moderate or severe hepatic impairment: Contraindicated

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; discontinue all other around the clock opioid drugs when initiating therapy with this drug

Dose conversion is a 2-step process:

First, calculate the equivalent daily oral morphine dose by multiplying the current total daily dose of each opioid by the appropriate Conversion Factor (CF); morphine CF=1; codeine CF=0.3; hydrocodone CF=1.8; hydromorphone CF=8; Oxycodone CF=2; Oxymorphone CF=4; Tapentadol CF=0.3; Methadone CF=3
Then, using the calculated equivalent daily oral morphine dose, choose the recommended starting oxycodone/naloxone dose; if rounding is necessary, round down
Daily oral morphine dose of 20 to less than 70 mg: Oxycodone 10 mg/naloxone 5 mg orally every 12 hours
Daily oral morphine dose of 70 to less than 110 mg: Oxycodone 20 mg/naloxone 10 mg orally every 12 hours
Daily oral morphine dose of 110 to less than 150 mg: Oxycodone 30 mg/naloxone 15 mg orally every 12 hours
Daily oral morphine dose of 150 to 160 mg: Oxycodone 40 mg/naloxone 20 mg orally every 12 hours

CONVERSION FROM TRAMADOL: Oxycodone 10 mg/naloxone 5 mg orally 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.
CONVERSION FROM TRANSDERMAL FENTANYL: Remove transdermal fentanyl patch at least 18 hours prior to initiating therapy with oxycodone/naloxone; substitute oxycodone 10 mg/naloxone 5 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: For patients receiving buprenorphine 20 mcg/hr or less: Initiate with oxycodone 10 mg/naloxone 5 mg every 12 hours; monitor closely as there is limited experience with this conversion

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. Manufacture product information may be consulted for a suggested taper schedule.

Concomitant Use of CNS Depressants:

Initiate this drug at one-third to one-half the recommended starting dose; consider lowering the dose of the concomitant CNS depressant

Precautions

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

US BOXED WARNINGS: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYP450 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.
Opioid Analgesic REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dose increase. Patients should be monitored closely. Instruct patients to swallow tablets whole without crushing, chewing, or dissolving as this may cause a rapid release and absorption of a potentially fatal dose of oxycodone.
Accidental Ingestion: Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose of oxycodone.
Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, the patient should be advised of the risk of neonatal opioid withdrawal syndrome and ensure appropriate treatment will be available.
CYP450 3A4 Interaction: Concomitant use of CYP450 3A4 inhibitors may result in increased oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used CYP450 3A4 inducer may result in increased oxycodone plasma concentrations. Monitor patients concomitantly receiving 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.

CONTRAINDICATIONS:

Hypersensitivity to the active substances or any product ingredients
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Severe respiratory depression
Known or suspected gastrointestinal obstruction, including paralytic ileus
Moderate to severe liver dysfunction

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 tablets whole; do not crush chew, or dissolve as this will result in uncontrolled delivery of oxycodone which can lead to overdose

Missed dose: If a dose is missed, take next dose as scheduled, unless it is more than 8 hours to next regularly scheduled dose in which case, take the missed dose and return to their original schedule; patients should not double up or take extra tablets to make up for missed dose.

Storage requirements:

Protect from moisture

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:

Patients should be instructed to read the US FDA-approved Medication Guide each time this drug is dispensed; they should understand the safe use, serious risks, and proper storage and disposal of this drug.
Advise patients to store this drug safely out of the sight and reach of children; accidental use by a child is a medical emergency and can result in death.
Patients should understand that 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.