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Learning Objectives:

• Describe morphine equivalent daily dose (MEDD) and how it is being used to indicate potential dose-related risk for prescription opioid overdose.
• Summarize best practices for prescribing opioids.
• Identify resources available that promote responsible opioid prescribing, including online and mobile applications for calculation of morphine milligram equivalency.
• Describe recent legislation in California related to prescription opioids.

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Key Points:

• While there is no completely safe dose of opioids, MEDD can be used as an indicator of potential dose-related risk for adverse drug reactions, including overdose.
• The Medical Board of California (MBC) recommends proceeding cautiously at 80 mg MEDD. Referral to an appropriate specialist should be considered when higher doses are contemplated.
• In the Medi-Cal fee-for-service population, the vast majority (97.4%) of paid claims for opioids were well under the 80 mg MEDD threshold recommended by the MBC for a yellow flag warning.
• Online and mobile application calculators are available to help clinicians determine morphine milligram equivalency. These calculators are not intended for dosage conversion from one product to another, but can be used to assess the comparative potency of opioids using a morphine equivalency standard.
• In order to be most effective, MEDD calculations need to include all opioid prescriptions written for a patient, including those written by other providers. Effective October 2, 2018, it is mandatory to consult the Controlled Substance Utilization Review and Evaluation System (CURES) 2.0 database prior to prescribing, ordering, administering, or furnishing a Schedule II – IV controlled substance.
• Effective January 1, 2019, California prescribers are now required to offer a prescription to a patient for either naloxone or another drug approved by the U.S. Food and Drug Administration (FDA) for the complete or partial reversal of opioid-induced respiratory depression when certain conditions are present, including when the prescription dosage for the patient is ≥90 mg MEDD.

Background
Each day in the United States, 46 people die from an overdose of prescription opioid or narcotic pain relievers.1 While the amount of opioids prescribed in the United States began to decrease in 2011,2 in 2017, prescription opioids were still involved in more than 35% of all opioid overdose deaths.1 The Centers for Disease Control and Prevention (CDC) describes the following groups as particularly vulnerable to prescription opioid overdose: 1) people who obtain multiple controlled substance prescriptions from multiple providers and pharmacies; 2) people who take high daily dosages of prescription painkillers and those who misuse multiple abuse-prone prescription drugs, especially other central nervous system (CNS) depressants, such as benzodiazepines, carisoprodol, or other sedatives; 3) people with a low income who live in rural areas; and 4) people with mental illness and/or those with a history of alcohol or other substance abuse.3

Morphine Equivalent Daily Dose (MEDD)
While there is no completely safe opioid dose, a patient’s cumulative MEDD is one indicator of potential dose-related risk for adverse drug reactions to opioids, including overdose.4 – 6 The terminology for daily morphine equivalency may vary depending on the resource used and may be described as MEDD, morphine equivalent dose (MED), or morphine milligram equivalent (MME). Daily morphine milligram equivalents are used to assess comparative potency but not to convert a particular opioid dosage from one product to another.

The calculation to determine morphine milligram equivalents includes drug strength, quantity, days’ supply, and a defined conversion factor unique to each drug. By converting the dose of an opioid to a morphine equivalent dose, a clinician can determine whether a cumulative daily dose of opioids approaches an amount associated with increased risk. Equianalgesic dose ratios are only approximations and do not account for genetic factors, incomplete cross-tolerance between various opioids, and variable pharmacokinetics that may affect relative potency. If used to estimate a conversion, it is recommended that after calculating the appropriate conversion dose, the prescribed dose be reduced by 25 – 50% to ensure patient safety.4 – 6

Compared with patients receiving an MEDD of 1 – 20 mg, who had a 0.2% annual overdose rate, patients receiving an MEDD of 100 mg or more had almost nine times as much risk of overdose and a 1.8% annual overdose rate as compared to the lowest doses.4 The CDC review of opioid prescribing and overdose found that among patients who are prescribed opioids, an estimated 80% are prescribed low doses (<100 mg MEDD) by a single provider, and these patients account for an estimated 20% of all prescription drug overdoses. Another 10% of patients are prescribed high doses (≥100 mg MEDD) of opioids by single prescribers and account for an estimated 40% of prescription opioid overdoses. The remaining 10% of patients seek care from multiple doctors, are prescribed high daily doses, and account for another 40% of opioid overdoses.6
 
Online and mobile application calculators are available to estimate MEDD. It should be noted again that these calculators are not intended for dosage conversion from one product to another but only to assess the comparative potency of opioids. Furthermore, calculated morphine equivalency may vary between tools for certain drugs, depending on the algorithm used. Web-based calculators are offered by several agencies, including the Washington State Agency Medical Directors’ Group and the Oregon Health Authority.

The CDC also offers the CDC Opioid Guideline application, which is available for free download on Google Play (Android devices) and in the Apple Store (iOS devices). This mobile application is designed to help providers apply the recommendations of CDC’s Guideline for Prescribing Opioids for Chronic Pain and includes an MEDD calculator, summaries of key recommendations and a link to the full Guideline, and an interactive motivational interviewing feature to help providers practice effective communications skills and prescribe with confidence.

While there are differing opinions among experts and organizations regarding the maximum MEDD threshold that should trigger additional action by clinicians (Table 1), the MBC recommends proceeding cautiously (a yellow flag warning) once the MEDD reaches 80 mg.7 In addition, effective January 1, 2019, California prescribers are now required to offer a prescription to a patient for either naloxone or another drug approved by the FDA for the complete or partial reversal of opioid-induced respiratory depression when the following conditions are met:

• The prescription dosage for the patient is ≥90 mg MEDD.
• An opioid medication is prescribed concurrently with a prescription for a benzodiazepine.
• The patient presents with an increased risk for overdose, including a patient with a history of overdose, a patient with a history of substance use disorder, or a patient at risk for returning to a high dose of opioid medication to which the patient is no longer tolerant.