Morphine / Naltrexone Dosage

Usual Adult Dose for Chronic Pain

The following dosing recommendations can be considered approaches to what is actually a series of clinical decisions over time in the management of the pain of an individual patient.

All doses expressed as MORPHINE/NALTREXONE

Use as the FIRST OPIOID ANALGESIC or those who are not opioid tolerant:
Initial dose: 20 mg/0.8 mg orally every 24 hours

CONVERSION FROM OTHER OPIOIDS:

• Discontinue all other around-the-clock opioids
• Initiate at 30 mg/1.2 mg orally every 24 hours

CONVERSION FROM OTHER ORAL MORPHINE FORMULATIONS:

• Give one-half of the patient's total daily morphine dose orally every 12 hours OR give the total daily morphine dose orally once daily

CONVERSION FROM PARENTERAL MORPHINE OR OTHER OPIOIDS:

• When converting from parenteral morphine: 1 mg of parenteral morphine is equivalent to approximately 2 to 6 mg of oral morphine; typically the dose of oral morphine is 3 times the daily parenteral morphine dose.
• When converting from other opioids (parenteral or oral): The initial morphine-naltrexone dose should be one-half of the estimated daily morphine requirement; manage inadequate analgesia by supplementing with immediate-release morphine.

CONVERSION FROM METHADONE:

• Methadone has a long half-life and can accumulate in the plasma; the ratio of other opioid agonists to methadone may vary widely. Close monitoring will be of particular importance.

MAINTENANCE DOSE: Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions; dose adjustments may be made every 1 to 2 days.
BREAKTHROUGH PAIN: If the level of pain increases after dose stabilization, attempt to identify the source before increasing dose

• Rescue medication with an appropriate immediate-release analgesia may be helpful
• For patients experiencing inadequate analgesia with once-daily dosing, a twice daily regimen may be considered.

Comments:

• An opioid tolerant patient is one who has been receiving for 1-week or longer at least: oral morphine 60 mg/day, transdermal fentanyl patch 25 mcg per hour, oral oxycodone 30 mg/day, oral hydromorphone 8 mg/day, oral oxymorphone 25 mg/day, or an equianalgesic dose of another opioid.
• The 100 mg/4 mg capsules are reserved for use in opioid-tolerant patients only.
• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy.
• The first dose of this drug may be taken with the last dose of any immediate-release opioid due to its extended-release characteristics.

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.

Liver Dose Adjustments

Use with caution.

Dose Adjustments

Do not abruptly discontinue; use a gradual downward titration every 2 to 4 days to prevent withdrawal in the physically-dependent patient.

If coadministration with a CNS depressant is necessary, start with morphine 20 mg-naltrexone 0.8 mg orally once daily, consider dose reduction of 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; INTERACTION WITH ALCOHOL; 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.
REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation or following a dose increase. Instruct patients to swallow capsule whole or to sprinkle the contents of the capsule on applesauce and swallow immediately without chewing. Crushing, chewing or dissolving this drug can cause rapid release and absorption of a potentially fatal dose of morphine.
ACCIDENTAL INGESTION: Accidental ingestion of even 1 dose of this drug, especially by children, can result in a fatal overdose of morphine.
NEONATAL OPIOID WITHDRAWAL SYNDROME: Prolonged use of this drug 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 during pregnancy, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
INTERACTION WITH ALCOHOL: Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking this drug. The co-ingestion of alcohol with this drug may result in increased plasma levels and a potentially fatal overdose of morphine.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: 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:

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected paralytic ileus
• Hypersensitivity (e.g., anaphylaxis) to either component of this drug

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:

• Swallow capsules whole; do not crush, chew, or dissolve
• If unable to swallow whole, may sprinkle the capsule contents on applesauce and immediately swallow without chewing; rinse mouth to ensure all pellets have been swallowed
• Do NOT administer pellets through a nasogastric or gastric tube
• Use of the morphine 100 mg-naltrexone 4 mg capsule is reserved for those patients who are opioid-tolerant.

General:

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

Monitoring:

• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dose increases.
• Monitor all patients regularly for the development of addiction, abuse, and misuse.
• Monitor patients for signs of hypotension upon initiating therapy and following dose increases, especially those whose blood pressure is compromised.

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.
• Advise patients 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.
• Instruct patients not to consume alcoholic beverages, or prescription and non-prescription products that contain alcohol as this may result in increased morphine levels.
• 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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer