Opioid Indications and Prescribing Guidelines

Comprehensive Assessment and Management

• Biopsychosocial-Based Assessment: Conduct thorough biopsychosocial assessments.
• Diagnosis: Establish a clear diagnosis.
• Consideration: Evaluate the likely benefits and risks of opioids and non-drug alternatives.
• Management Plan: Develop a plan through shared decision making (SDM) and continual clinical monitoring.

Awareness of Risks

• Dependence and Withdrawal: Understand the potential for opioid dependence and withdrawal.
• Problematic Drug Use: Be aware of diversion and misuse.
• Harmful Effects: Discuss risks such as falls, cognitive effects, and motor vehicle accidents with patients.

Opioid Indications

• Strong Evidence:
  • Acute Pain: Effective for managing short-term severe pain.
  • Cancer Pain: Essential for pain control in cancer patients.
  • Palliation Toward End of Life: Critical for providing comfort in end-of-life care.
  • Opioid Dependency: Used in opioid replacement therapy.
• Limited Evidence:
  • Chronic Non-Cancer Pain: Limited evidence supports the long-term effectiveness of opioids for chronic non-cancer pain.

Opioid Prescribing Guidelines

Non-Cancer Pain

• Treatment Duration: Maximum 90 days.
• Dosage: ≤ 40 mg daily oral morphine equivalent.

Cancer Pain

• Dosage: ≤ 300 mg daily oral morphine equivalent.

Minimize Risks: Prescribe opioids at the lowest effective dose for the shortest timeframe.

Comorbidities: Avoid prescribing opioids to patients with alcohol or substance use disorders or polydrug use. Seek specialist opinion for these patients.

Short-Term Use: Generally, use opioids as a short-term therapeutic option.

Long-Term Use: If alternatives fail, supervised long-term opioid treatment may be acceptable. Regular attempts at dose reduction should be scheduled, with continued monitoring of health outcomes.

SAFE LIMITS FOR OPIOID PRESCRIBING

A diagnosis of the source of the pain must be made.

• Simple analgesia and other appropriate treatments should have been trialled.
• An opioid-risk tool should be used to determine if the patient is at risk of opioid misuse.
• A contract defining treatment goals, length of treatment and an exit strategy should be signed with the patient.
• There should be regular assessment of the patient using the 5As

Choice of Opioid

• Acute Pain or Cancer Breakthrough Pain: Use short-acting agents.
• Chronic Non-Cancer Pain: Use long-acting agents.
• Long-Term Use: Injectable opioids are not recommended.
• Dose Adjustments:
  • Elderly and Comorbidities: Start with a lower dose and increase slowly (“start low and go slow”).
  • Hepatic Impairment: Increased opioid sensitivity requires careful dosing.
  • Renal Impairment: Risk of metabolite accumulation; fentanyl is preferred as it has no active metabolites, while oxycodone has only weakly active metabolites.

Patient Selection/Exclusion Process

• Use for Acute Pain Only: When non-opioid medications have failed or are contraindicated.
• Avoid in High-Risk Groups: Patients with polydrug use, alcohol, or substance use disorders.

• Patient Groups Requiring Caution:
  • Pregnancy and lactation
  • Workers’ compensation injuries
  • Patients who drive
  • Patients with sleep apnoea or disordered breathing
  • Patients over 65 years of age
  • Patients with renal or hepatic disease
  • Aboriginal and Torres Strait Islander patients or culturally diverse populations
  • Patients with comorbid mental health disorders
• Methadone: Use with caution due to its long half-life and frequent drug interactions.

Strategies to Address Risk with Opioid Prescriptions

Comprehensive Assessment

• Risk Screening: While recommended, there is limited evidence on the effectiveness of screening for opioid risk.
  • Higher Risk Patients
    • Younger Patients: Substance use issues often begin before age 35.
    • No Definite Diagnosis: Higher risk if there is no clear diagnosis or pathology.
    • Active Substance Use: Increased risk if patients have substance use problems or contact with such individuals.
    • Psychiatric Problems: Active psychiatric problems increase risk.
    • Benzodiazepine Use: Concomitant use increases risks, particularly cognitive impairment, sedation, and respiratory depression.
    • Socioenvironmental Problems: Patients with social and environmental issues are at higher risk.
• Treatment Agreements and Urine Testing: Recommended but do not significantly reduce opioid misuse or overdose rates.

Monitoring and Referral

• Prescription Monitoring: Use state-based systems to check for substance use history.
• Urine Drug Screen: Routine screening can reveal unknown substance use; refer to specialists if illicit or unprescribed substances are found.
• Negative Results: Indicate possible diversion; requires further investigation.

Baseline Urine Drug Test (UDT) for Opioid Therapy

Initial Visit

• Perform Baseline UDT: Include detection of oxycodone and other drugs not usually recognized by immunoassay (fentanyl, tramadol, methadone, buprenorphine).
• Additional Costs: These tests will incur extra costs to the patient.

Screening and Testing

Onsite Urine Testing Strips

• Immediate Results: Provide a basic guide to the drugs being used within a couple of minutes.
• Screening Tool: Not confirmatory and should be used with clinical signs and history.
• False Positives/Negatives: Can occur but are rare.

Laboratory Testing

• Gas Chromatography: Most urinalysis procedures are conducted in specialist laboratories.
• Result Delay: There is usually a delay in receiving results.
• Presence vs. Quantity: Tests confirm the presence of drugs but do not measure the amounts taken.

Detection Time

• Length of Detection: Different drugs have varying detection times in urine (refer to Table E1.1 for specific times).

Interpreting Urine Drug Tests

Unexpected Results

• Limitations: Results should be interpreted considering the limitations of the tests.
• Additional Tests: Fentanyl, buprenorphine, synthetic drugs, anabolic steroids, and usually oxycodone are not routinely detected and must be requested separately (at extra cost).

Manipulation of Results

• Sample Switching: Drug misusers may attempt to influence results by switching urine samples or other methods.

Prescribing Practices to Minimise Risks

Dose and Duration Management

• Lowest Effective Dose: Prescribe for the shortest clinical timeframe.
• Manageable Pill Load: Dispense only the amount needed for a defined interval.
• Frequent Dispensing: Reduce misuse risk by dispensing smaller quantities more frequently (weekly, twice weekly, or daily).
• Do Not Fill Until Date: Instructions to control dispensing without requiring frequent visits.

Legislative Restriction

Information Needed for an S8 Prescription to Comply with State and Territory Standards

• Prescriber Information: Full name, address, and prescriber number.
• Date: The date the prescription was written.
• Patient Information: Full name, address, and date of birth.
• Medication Details: Description and quantity of the drug of addiction to be dispensed.
• Usage Directions: Precise directions for use.
• Repeats: Number of repeats (if any) and intervals at which they may be dispensed.
• Signature: Signature of the prescriber.
• Handwritten Requirements: For computer-generated S8 prescriptions, the information highlighted above must be written in the doctor’s own handwriting.

Pharmaceutical Benefits Scheme (PBS) Requirements for Opioid Prescriptions

PBS Amendments (Effective June 1, 2020)

• Reducing Pack Sizes: For acute pain use.
• Changes to Indications: Specific indications for different opioid categories.
• Authority Process Changes: Revised authority process for prescribing opioids subsidised through the PBS.

Opioid Categories and Restrictions

1. First-Line Treatments for Acute Severe Pain:
   • Codeine tablets, codeine + paracetamol tablets, tramadol capsules, injections, and oral drops.
   • Restricted benefits for severe, postoperative, or cancer-related pain when non-opioid analgesics are inadequate.
   • Reduced pack sizes intended for use beyond 2–3 days.
2. Second-Line Treatments for Acute Severe Pain:
   • Hydromorphone tablets, injections, and oral solutions; morphine tablets, oral solutions, and injections.
   • Restricted benefits for severe or cancer-related pain, preoperative care, or adjunct to general anesthesia.
   • Reduced pack sizes intended for use beyond 2–3 days.
3. First-Line Treatments for Chronic Severe Pain:
   • Buprenorphine transdermal patches, morphine capsules, tablets, granules, oxycodone tablets, oxycodone + naloxone tablets, tapentadol tablets, and tramadol tablets.
   • Authority-required (STREAMLINED) benefits for patients needing daily, continuous, long-term therapy where non-opioid analgesics are inadequate.
4. Second-Line Treatments for Chronic Severe Pain:
   • Hydromorphone tablets, methadone tablets and injection, fentanyl transdermal patches.
   • Authority-required (STREAMLINED) benefits for non-opioid-naïve patients needing daily, continuous, long-term therapy.

Increased Quantities and Repeats

• Secondary Reviews: Required for patients whose opioid treatment exceeds 12 months. Conducted by a second medical practitioner or palliative care nurse practitioners (for palliative care patients).
• Online Authority Approval: Real-time approval through the Online PBS Authorities (OPA) system for up to three months’ treatment.
• Telephone and Written Requests: Up to one month’s treatment via telephone and up to three months’ treatment in writing.

Authority-Required (STREAMLINED) Benefits

• Streamlined Process: Specific conditions only, using a four-digit streamlined authority code from the PBS website.

Review of Therapy

• The 4 A’s:
  • Analgesia: Assess pain relief.
  • Activity: Monitor improvements in function.
  • Adverse Effects: Evaluate side effects.
  • Aberrant Behavior: Watch for signs of misuse or abuse.

Opioid Rotation

Definition: Opioid rotation involves switching a patient from one opioid to another to reduce the opioid morphine equivalent daily dose (OMEDD) while maintaining analgesic efficacy.

Validation: Canadian guidance supports opioid rotation as a method to facilitate dose reduction in chronic non-cancer pain (CNCP).

Mechanism: The reduction in OMEDD during rotation is based on the lack of cross-tolerance between different opioids.

Process

• Conversion and Dose Reduction:
  • When converting from one opioid to another, the calculated equianalgesic dose of the new opioid should be reduced to avoid side effects such as respiratory depression and overdose.
  • Typical Reduction: Prescribe 50-75% of the calculated equianalgesic dose of the new opioid.
  • Considerations: Special care is needed for the elderly and patients with hepatic or renal impairment to prevent accidental overdose.
  • Drug Interactions: Be aware of potential drug-drug interactions that could affect serum levels of the new opioid.

Example Calculation

• Current Prescription:
  • Morphine solution: 20 mg three times daily.
  • Morphine sulfate controlled-release: 60 mg twice daily.
  • Total OMEDD: 180 mg.
• Conversion to Oxycodone:
  • 180 mg morphine is approximately equivalent to 120 mg oxycodone.
  • Reduced Dose: To avoid side effects, prescribe 50-75% of the calculated dose:
    • Equivalent Dose: 30-45 mg oxycodone twice daily (60-90 mg per day).
    • Final Equivalent:
      • 60 mg oxycodone = 90 mg morphine.
      • 90 mg oxycodone = 135 mg morphine.
  • Result: The rotation from morphine to oxycodone results in a final daily dose of 50-75% of the original dose, effectively reducing the total OMEDD.

Key Points

• Safety: Always reduce the dose of the new opioid to accommodate individual patient factors and avoid overdose risks.
• Clinical Monitoring: Continuous monitoring and reassessment are essential to ensure safe and effective pain management during and after opioid rotation.
• Documentation: Maintain clear documentation of the rationale, calculations, and adjustments made during opioid rotation to ensure continuity of care.

Weaning Maintenance Opioids

• Negotiation: Agree on an appropriate time frame to limit withdrawal symptoms and minimize patient distress.
• Reduction Plan: Typically reduce the opioid dose by 10-25% of the starting dose each month.
• Duration: This gradual tapering can achieve cessation within 3-9 months.

Reduction (Tapering) of Oral morphine equivalent daily dose (OMEDD)

Opioid Tapering

• Method: Gradual reduction in dose over weeks to months.
• High-Dose Opioids: May require opioid rotation before tapering.
• Reduction Rate: Approximately 10% of the starting dose per week.

Opioid Taper

• Convert all opioids to one long-acting opioid (may involve opioid rotation).
• Decrease dose of the long-acting opioid at a rate of 10% of the starting dose per week or fortnight.
• Strictly limit the use of short-acting opioids or as-needed doses.
• Use non-opioid analgesics to manage pain flares.
• Manage opioid withdrawal symptoms by reducing the taper rate.

Key Considerations

• Patient Cooperation: Essential for successful tapering.
• Explanation: Careful explanation of indications, benefits, contraindications, and risks is needed.
• Indications for Tapering: Mainly for patient safety and to reduce the risk of death from high OMEDDs (>100 mg).
• Side Effects: Consider long-term opioid side effects like opioid-induced hyperalgesia and opioid-induced hypogonadism.
• Review of Long-Term Opioid Use: Recent evidence suggests opioids may cause more harm and provide less effective analgesia than non-opioid options for osteoarthritis pain.
• Evidence of Benefits: Weak evidence suggests benefits in terms of pain reduction, improved function, and quality of life.

Special Considerations

• Specialist Input: Necessary for conditions such as cancer pain, acute pain, and new or ongoing tissue damage.
• OUD: Opioid tapering is not an alternative to opioid agonist therapy (OAT).
• Pregnancy: Tapering is not recommended due to the risks of opioid withdrawal.
• Psychological Symptoms: Monitor for emergence or exacerbation of psychiatric conditions. Provide psychosocial support.

Managing Patient Distress

• Chronic Opioid Withdrawal: Consider if symptoms of dysphoria, fatigue, or sleep disturbance emerge.
• Therapeutic Relationship: Manage symptoms within a caring therapeutic relationship.
• Speed of Taper: May need to reduce speed if significant distress occurs.
• Benzodiazepines: Not recommended for managing anxiety during a taper.
• Specialist Advice: Recommended for managing psychological symptoms; persisting with tapering is often worthwhile given the risks of high opioid doses.

Replacement Pharmacotherapy (Opioid Agonist Therapy)

• Aberrant Behaviors: Up to 30% of patients on long-term opioids develop behaviors such as unsanctioned use, dose escalation, lost prescriptions, or prescription forgery.
• Diagnosis of OUD: Important to consider if aberrant behaviors are present. Use the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
• Opioid Agonist Therapy (OAT):
  • Buprenorphine or Methadone: Beneficial for patients with OUD.
  • Refusal of OAT: Seek addiction specialist advice.
• Accredited Training: Each state and territory in Australia offers pharmacotherapy prescribing training for clinicians, covering clinical issues, practical considerations, and local regulations.

Reversal with Naloxone

• Overdose Risk: High-dose opioids carry a risk of overdose and respiratory depression.
• Community Overdose Prevention Education: Provides training on harm reduction, including naloxone use.
• Naloxone: A mu-opioid receptor antagonist that reverses opioid overdose effects.
  • Availability: In Australia, available as a vial, prefilled syringe, or nasal spray.
  • Patient Education: Offer naloxone and training on its administration to all patients at risk of opioid overdose.
• Threshold for Consideration: Naloxone supply should be considered for patients on 50 mg or more OMEDD.
• Training: Basic training includes identifying toxicity features and administering intranasal or intramuscular naloxone.

Discontinuing Opioids

Managing Opioid Discontinuation

Where There Is Evidence of Substance Use Disorder (SUD)

• Legislative Requirements: Vary by state and territory but generally require permits or approvals from the relevant health department’s pharmaceutical services unit for prescribing S8 drugs to patients with SUD.
• Opioid Dependency: If opioid dependency is identified during weaning, GPs should offer or arrange evidence-based treatment, usually medication-assisted treatment with buprenorphine-naloxone or methadone, combined with behavioral therapies.
• Complex Comorbidities: Referral to an addiction or pain specialist is advised.

Where There Is No Evidence of Substance Use Disorder

• Gradual Dose Reduction:
  • Decrease the original dose by 10% every five to seven days until 30% of the original dose is reached.
  • Then, decrease the remaining dose by 10% each week.
  • This approach minimizes withdrawal symptoms and improves adherence.
• Short-Term Opioid Therapy: If discontinuation is required after a shorter period of therapy, a faster weaning rate may be appropriate:
  • Reduce the daily opioid dose each week by 10–25% of the starting dose.

Refer to a Specialist

Joint Management for High-Risk Patients

• Complex Cases: High-risk patients need joint management between primary care and specialized services.
• Initial Evaluation: Referral may be needed for a comprehensive evaluation or to determine optimal strategies.

Indications for Referral

• Higher Risk or Complex Needs:
  • Young patients (<35 years).
  • Comorbid psychiatric or psychological disorders.
  • Previous or current opioid (or other) SUDs.
  • Indeterminate pathology.
• Monitoring and Management Issues:
  • Unexpected drug dose escalation.
  • Ceiling drug dosages reached.
  • Suspected abuse or misuse.
  • Change in risk category.
  • High levels of patient distress.
  • Unusual opioid requirements or suspected drug diversion.
  • Poorly controlled comorbid psychiatric or psychological disorder.