Opioid Equivalents and Conversions

A thorough pain assessment is vital to the initial evaluation of a patient and must be performed to guide treatment decisions. ^{[1, 2, 3, 4, 5]}

Dosing may be done incrementally and titrated to analgesic effect. Particularly in those without prior analgesic use, effects are variable and overdosing in these patients can result in adverse events.

Individualize doses based on risk for adverse outcomes, prior effective doses, comorbidities, concomitant medications, and response to therapy.

Immediate-release opioids are recommended for breakthrough pain.

When possible, use the same class of opioid analgesic for long-acting (ie, 24-hour scheduled doses) and short-acting (ie, PRN doses for breakthrough pain) pain relief.

Dosing charts are guidelines only.

Most data are reported for opioid-tolerant patients so must be used with caution.

Cross-tolerance

Reduce opioid dose by 30-50% to accommodate for unknown cross-tolerance and titrate to goal.

The wide variation among individuals is multifactorial and poorly understood.

Incomplete cross-tolerance can lead to greater than anticipated potency in a new opioid, even in the same class of analgesic.

Monitor clinical response and adverse effects.

Warning

Respiratory depression risk is highest in opioid-naïve patients.

Methadone and fentanyl are generally safe and considered good options in patients with renal insufficiency.

Acute pain

Assess the pain level before initiating therapy.

For mild pain, the starting regimen should be a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen.

For moderate pain, an opioid agonist (eg, hydrocodone, oxycodone) can be used. An NSAID or acetaminophen may be used in conjunction, when appropriate.

For severe pain, a higher potency opioid agonist (eg, hydromorphone, morphine, fentanyl) can be used.

Chronic nonmalignant pain

Assess the underlying cause.

Prescribe acetaminophen or NSAIDs.

Opioids may be used, but long-acting formulations are recommended in place of prn dosing. Select formulation based on previous response, adverse effects, and comorbid conditions.

In 2016, the Centers for Disease Control and Prevention (CDC) issued recommendations for prescribing opioids for chronic pain. The recommendations included the following ^{[6, 7]} :

• Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate.

• Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and should consider how opioid therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety.

• Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy.

• When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids.

• When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing the dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing the dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day.

• Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than 7 days will rarely be needed.

• Clinicians should evaluate benefits and harms with patients within 1-4 wk of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every 3 mo or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids.

• Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate, into the management plan, strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use, are present.

• Clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose. Clinicians should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 mo.

• When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.

• Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.

• Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.

In 2022, the CDC published updated guidelines for prescribing opioids for adults with acute and chronic pain. Highlights of the guidelines are as follows ^[8] :

• Before initiating opioid therapy, clinicians should discuss with patients the realistic benefits and known risks of opioid therapy.
• Clinicians should maximize use of nondrug and nonopioid drug therapies, as these are at least as effective as opioids for many common types of acute pain and are preferred for subacute and chronic pain.
• When initiating opioid therapy for acute, subacute, or chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release and long-acting opioids.
• Clinicians should prescribe the lowest effective dosage when opioids are initiated for opioid-naïve patients with acute, subacute, or chronic pain.
• When opioids are needed for acute pain, clinicians should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids.
• Clinicians should evaluate benefits and risks with patients within 1-4 weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation.
• Clinicians should evaluate risk for opioid-related harms and discuss risk with patients before starting and periodically during continuation of opioid therapy.
• When prescribing initial opioid therapy for pain, clinicians should review the patient’s history of controlled substance prescriptions to determine whether the patient is receiving opioid dosages or combinations that put the patient at high risk for overdose.
• For patients with opioid use disorder, clinicians should offer or arrange treatment with evidence-based medications.

Steps for converting or rotating between opioids

See the list below:

1. Calculate total mg dose taken in past 24-hours.

2. Determine equi-analgesic dose (Table 1).

3. If pain is controlled on current opioid, reduce the new opioid daily dose by 25-50% to account for cross-tolerance, dosing ratio variation, and interpatient variability.

4. If pain is uncontrolled on the current opioid, increase opioid daily dose by up to 100-125%.

5. Titrate liberally and rapidly to analgesic effect during first 24 hours.

6. Monitor for adverse events and effectiveness.

7. Reassess the analgesic effect every 2-3 days.

Table 1. Opioid Equi-analgesic Doses

Table. (Open Table in a new window)

Transdermal fentanyl

Conversion from morphine (or equivalent) to fentanyl transdermal:

1. Calculate the total 24-hour morphine dose (or morphine-equivalent).

2. Select microgram per hour dose of transdermal fentanyl based on Table 2.

3. Decrease new dose 30-50% to allow for incomplete cross-tolerance.

4. Manage breakthrough pain with morphine/short-acting opioid PRN.

5. Titrate patch to effect every 72 hours.

Table 2. Conversion of Opioid Analgesics to Fentanyl Transdermal

Table. (Open Table in a new window)

Fentanyl transdermal cautions

See the list below:

• Transdermal fentanyl is NOT recommended for breakthrough or unstable pain requiring frequent dosage adjustments.

• Patches MUST NOT be used in opioid-naïve patients; they are indicated only for patients who are opioid tolerant.

• Do not apply any external heat to patch; heat may increase absorption and increase risk of overdose.

PRN dosing for breakthrough pain

See the list below:

• Augment around-the-clock scheduled opioid doses with PRN doses of short-acting opioids for acute exacerbation of chronic pain.

• Short-acting opioid doses are approximately 10-20% of total 24-hour scheduled opioid dose (eg, 24-hour scheduled morphine totals 150 mg, therefore give short-acting morphine 15 mg PO q1h PRN for breakthrough pain).

• Reassess efficacy and adverse effects at 60 minutes.

  • If the pain score is unchanged or increased, increase PRN dose 50-100%.

  • If the pain score is decreased, continue current effective PRN dose.

Fentanyl transmucosal or intranasal spray for breakthrough cancer pain

See the list below:

• Transmucosal or intranasal spray fentanyl should not be used in opioid-naïve patients.

• Initiate dosing cautiously in the chosen formulation and titrate to effect.

• Do not exceed more than 2 doses per breakthrough episode.

• Consider increasing 24-hour scheduled opioid therapy if more than 4 breakthrough episodes occur in a day.

Opioid rotation

Introduction

• Of cancer patients receiving active cancer treatment, 33% experience severe pain but 30% do not receive adequate pain treatment.

• Opioids do not have a ceiling effect or uniform plasma levels, so individual titration required.

• Intolerable side effects along with inadequate analgesia contribute in 10-30% of patients treated with oral morphine for pain.

• After initiation and titration, the initial clinical efficacy may gradually decline. Then higher doses may have undesirable side-effects, and rotation can be considered.

Indications

• Unmanageable side effects during dose titration

• Poor analgesia despite dose titration

• Alternate route of administration needed

• Change in clinical status requires different pharmacokinetics (eg, renal insufficiency or hepatic dysfunction)

• Cost or financial considerations

• Drug availability issues

• Interactions between drugs

• Most commonly done for poor opioid responsiveness

• Specific mechanisms by which it improves overall response is unknown; likely from large individual variation to different agents and the phenomenon of incomplete cross-tolerance

Equianalgesic dose tables

• Opioid dose requirements can vary in the clinical setting as much as 40-fold.

• Equianalgesic dose defined as the dose in steady state providing the same analgesic response. This has been standardized to 10 mg of parental morphine in most studies.

• First equianalgesic dose table published more than 40 years ago, and remain with little variation.

• Items that may influence relative potencies:

  • Major organ dysfunction, particularly renal and hepatic impairment, but also adrenal insufficiency, hypothyroidism, and abnormal levels of protein binding

  • Demography, including race, age, and gender

  • Most trials were short term trials of acute postoperative pain or in cancer pain with low dose opioids

  • All new treatment should be considered a trial until it is found to be analgesically effective with acceptable side-effect profile.

  • No evidence-based guidelines for opioid choices with rotation.

  • Rotation in cancer patients regains satisfactory pain control and/or reduced side effects in 50-70% of patients.

  • In cancer population, 80% of patients required one switch, 44% 2 or more, 20% 3 or more.

Conversion from oral or transdermal to parenteral route results in more rapid analgesic effects. In cancer patients this is successful 75-95% of the time.