#45122: Strategies for Appropriate Opioid Prescribing: The Florida Requirement

In Florida, misuse of prescription opioids became a serious problem in the 1990s and 2000s, but efforts to stem the problem appear to be working. The rate of drug overdose deaths increased 58.9% during 2003–2010, and in 2009, one in eight deaths in Florida was attributable to drug overdose [35,36]. In 2022, opioids accounted for 79% of fatal drug overdoses in the state [35]. In 2015, Florida experienced an increase in oxycodone-caused deaths, the first in six years [27]. These trends resulted in the enactment of several measures to address prescribing that was inconsistent with best practices, and partnership with the U.S. Drug Enforcement Administration (DEA) to close and prevent "pill mills" from introducing millions of opioid dose units into illicit markets [37,38]. In May 2017, Governor Rick Scott signed an executive order declaring the opioid epidemic a public health emergency, providing additional funding and empowering state health professions to take steps to address this pressing issue [38]. As part of this order, the State Health Officer has issued a standing order for opioid antagonists to ensure emergency responders have access [38]. In 2022, the Florida Department of Health issued a statewide Standing Order for Naloxone, which authorizes pharmacists to dispense certain naloxone formulations to emergency responders for administration to persons exhibiting signs of opioid overdose [24].

An influx of clandestine fentanyl into Florida in early 2014, and several fentanyl analogs and other novel non-pharmaceutical opioids more recently, has largely driven the increases in opioid overdose fatalities. Analyses of data from 2013–2015 indicate sharp increases in overdose fatalities in Florida linked to counterfeit alprazolam, oxycodone, and hydrocodone tablets that contained fentanyl [39]. The decrease in prescription opioid fatalities, offset by increasing overdose fatalities from other opioid and non-opioid agents, reflects the intervention focus on the supply side ("pill mill laws") and neglect of treatment funding that would address the demand side of problematic drug use [40].

In Florida, fatalities with benzodiazepines present peaked in 2010 with 6,188, falling to 1,761 in 2023 (32% were alprazolam) [41]. Other primary contributors to opioid analgesic-related fatalities include alcohol and prescribed methadone [30,42].

In addition to the executive order issued in 2017, several new state laws were passed in 2018 to impose additional legal requirements on controlled substance prescribers [43]. These laws will be discussed in detail later in this course.

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 in a quantity no greater than that needed for the expected duration of severe pain. In most cases, three days or less will be sufficient; more than seven days will rarely be needed [44]. However, payers and health systems should not use the 2022 guideline to set rigid standards related to dosage or duration of opioid therapy. The guideline is not a replacement for clinical judgment or individualized, patient-centered care [5].

Florida law dictates that, for the treatment of acute pain, a prescription for an opioid drug may not exceed a three-day supply; an exception may be made for a seven-day supply if [54]:

With postoperative, acute, or intermittent pain, analgesia often requires frequent titration, and the two- to four-hour analgesic duration with short-acting hydrocodone, morphine, and oxycodone is more effective than extended-release formulations. Short-acting opioids are also recommended in patients who are medically unstable or with highly variable pain intensity [55,56,57].

As part of House Bill 21, passed in 2018, the Florida Board of Medicine and the Board of Osteopathic Medicine are required to establish guidelines for prescribing controlled substances for acute pain; these guidelines are forthcoming [54].

Information obtained by patient history, physical examination, and interview, from family members, a spouse, or state prescription drug monitoring program (PDMP), and from the use of screening and assessment tools can help the clinician to stratify the patient according to level of risk for developing problematic opioid behavioral responses (Table 1). Low-risk patients receive the standard level of monitoring, vigilance, and care. Moderate-risk patients should be considered for an additional level of monitoring and provider contact, and high-risk patients are likely to require intensive and structured monitoring and follow-up contact, additional consultation with psychiatric and addiction medicine specialists, and limited supplies of short-acting opioid formulations [44,58].

Anxiety disorders, major depressive disorder, and intense emotional distress alter pain perception and response. Intensity and perception of reported pain is also influenced by factors such as mood, cultural background, social supports, and financial resources. A biopsychosocial model is required to inform pain assessment in order to address the biologic basis of pain and presence of social and psychologic contributors [51].

Before deciding to prescribe an opioid analgesic, clinicians should perform and document a detailed patient assessment that includes [1]:

Depression is perhaps the single most important comorbidity in patients with chronic pain and is vastly underdiagnosed and untreated. Patients with unrecognized and untreated depression are unlikely to respond to opioids and other pain therapies, but successful treatment of depression can promote analgesia [62].

If substance abuse is active, in remission, or in the patient's history, consult an addiction specialist before starting opioids [1]. In active substance abuse, do not prescribe opioids until the patient is engaged in a treatment/recovery program or other arrangements made, such as addiction professional co-management and additional monitoring. When considering an opioid analgesic (particularly those that are extended-release or long-acting), one must always weigh the benefits against the risks of overdose, abuse, addiction, physical dependence and tolerance, adverse drug interactions, and accidental exposure by children [44,63].

Screening and assessment tools can help guide patient stratification according to risk level and inform the appropriate degree of structure and monitoring in the treatment plan. It should be noted that despite widespread endorsement of screening tool use to help determine patient risk level, most tools have not been extensively evaluated, validated, or compared to each other, and evidence of their reliability is poor [64].

Opioid therapy should be presented as a trial for a pre-defined period (e.g., ≤30 days). The goals of treatment should be established with all patients prior to the initiation of opioid therapy, including reasonable improvements in pain, function, depression, anxiety, and avoidance of unnecessary or excessive medication use [1,44]. The treatment plan should describe therapy selection, measures of progress, and other diagnostic evaluations, consultations, referrals, and therapies. All patients prescribed an opioid for pain related to a traumatic injury (severity score ≥9) should be concurrently prescribed an antagonist (e.g., naloxone) [54].

In opioid-naïve patients, start at the lowest possible dose and titrate to effect. Dosages for opioid-tolerant patients should always be individualized and titrated by efficacy and tolerability [1]. The need for frequent progress and benefit/risk assessments during the trial should be included in patient education. Patients should also have full knowledge of the warning signs and symptoms of respiratory depression.

Prescribers should be knowledgeable of federal and state opioid prescribing regulations. Issues of equianalgesic dosing, close patient monitoring during all dose changes, and incomplete cross-tolerance with opioid conversion should be considered. If necessary, treatment may be augmented, with preference for nonopioid and immediate-release opioids over long-acting/extended-release opioids. Taper opioid dose when no longer needed [63].

The CDC recommends that clinicians should evaluate benefits and risks with patients within one to four weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation. Clinicians should regularly re-evaluate benefits and risks of continued opioid therapy with patients.

(https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm Last Accessed: August 23, 2024)

Strength of Recommendation/Level of Evidence: A4 (Most patients should receive based on clinical experience and observations, observational studies with important limitations, or randomized clinical trials with several major limitations)

When implementing a chronic pain treatment plan that involves the use of opioids, the patient should be frequently reassessed for changes in pain origin, health, and function [1]. This can include input from family members and/or the state PDMP. During the initiation phase and during any changes to the dosage or agent used, patient contact should be increased. At every visit, chronic opioid response may be monitored according to the "5 A's" [1,75]:

Signs and symptoms that, if present, may suggest a problematic response to the opioid and interference with the goal of functional improvement include [76]:

The decision to continue, change, or terminate opioid therapy is based on progress toward treatment objectives and absence of concerning adverse effects and risks of overdose or diversion [1]. Satisfactory therapy is indicated by improvements in pain, function, and quality of life. It is important to remember that for some patients with severe chronic pain, improved function may take longer than pain control or either pain or function (not both) will improve. In some cases, preventing worsening pain/functional impairment is the best achievable outcome. Brief assessment tools to assess pain and function may be useful, as may UDTs. Treatment plans may include periodic pill counts to confirm adherence and minimize diversion.

In 2021, nearly 14% of persons who died of an opioid overdose also tested positive for benzodiazepines, a class of sedative medication commonly prescribed for anxiety, insomnia, panic attack, and muscle spasm [8]. Benzodiazepines work by raising the level of the neurotransmitter gamma-aminobutyric acid (GABA) in the brain. Common formulations include diazepam, alprazolam, and clonazepam. Combining benzodiazepines with opioids is unsafe because both classes of drug cause central nervous system depression and sedation and can decrease respiratory drive—the usual cause of overdose fatality. Both classes have the potential for drug dependence and addiction.

The CDC recommends that healthcare providers use caution when prescribing benzodiazepines concurrently with opioids whenever possible [4]. If a benzodiazepine is to be discontinued, the clinician should taper the medication gradually, because abrupt withdrawal can lead to rebound anxiety and complications such as hallucinations, seizures, delirium tremens, and, in rare instances, death. The rate of tapering should be individualized [4].

It is important to seek consultation or patient referral when input or care from a pain, psychiatry, addiction, or mental health specialist is necessary. Clinicians who prescribe opioids should become familiar with opioid addiction treatment options (including licensed opioid treatment programs for methadone and office-based opioid treatment for buprenorphine) if referral is needed [1].

Ideally, providers should be able to refer patients with active substance abuse who require pain treatment to an addiction professional or specialized program. In reality, these specialized resources are scarce or non-existent in many areas [1]. Therefore, each provider will need to decide whether the risks of continuing opioid treatment while a patient is using illicit drugs outweigh the benefits to the patient in terms of pain control and improved function [82].

As noted, documentation is a necessary aspect of all patient care, but it is of particular importance when opioid prescribing is involved. All clinicians should maintain accurate, complete, and up-to-date medical records, including all written or telephoned prescription orders for opioid analgesics and other controlled substances, all written instructions to the patient for medication use, and the name, telephone number, and address of the patient's pharmacy [1]. Good medical records demonstrate that a service was provided to the patient and that the service was medically necessary. Regardless of the treatment outcome, thorough medical records protect the prescriber.

Patients and caregivers should be counseled regarding the safe use and disposal of opioids. As part of its mandatory Risk Evaluation and Mitigation Strategy (REMS) for extended-release/long-acting opioids, the FDA has developed a patient counseling guide with information on the patient's specific medications, instructions for emergency situations and incomplete pain control, and warnings not to share medications or take them unprescribed [63]. A copy of this form may be accessed online at https://www.accessdata.fda.gov/drugsatfda_docs/rems/ERLA_opioids_2016-04-26_Patient_Counseling_Document.pdf[83].

When prescribing opioids, clinicians should provide patients with the following information [63]:

There are no universal recommendations for the proper disposal of unused opioids, and patients are rarely advised of what to do with unused or expired medications [84]. According to the Office of National Drug Control Policy, most medications that are no longer necessary or have expired should be removed from their containers, mixed with undesirable substances (e.g., cat litter, used coffee grounds), and put into an impermeable, nondescript container (e.g., disposable container with a lid or a sealed bag) before throwing in the trash [85]. Any personal information should be obscured or destroyed. The FDA recommends that certain medications, including oxycodone/acetaminophen (Percocet), oxycodone (OxyContin tablets), and transdermal fentanyl (Duragesic Transdermal System), be flushed down the toilet instead of thrown in the trash [85]. The FDA provides a free toolkit of materials (e.g., social media images, fact sheets, posters) to raise awareness of the serious dangers of keeping unused opioid pain medicines in the home and with information about safe disposal of these medicines. The Remove the Risk Outreach toolkit is updated regularly and can be found at https://www.fda.gov/drugs/ensuring-safe-use-medicine/safe-opioid-disposal-remove-risk-outreach-toolkit[86]. Patients should be advised to flush prescription drugs down the toilet only if the label or accompanying patient information specifically instructs doing so and no other disposal method is appropriate. In 2023, the FDA issued a letter requiring all manufacturers of opioid analgesics dispensed in outpatient settings to submit a proposed modification to the Opioid Analgesic REMS. The modification requires manufacturers to make available prepaid mail-back envelopes to outpatient pharmacies and other opioid dispensers as an opioid analgesic disposal option for patients [9].

The American College of Preventive Medicine has established best practices to avoid diversion of unused drugs and educate patients regarding drug disposal [84]:

The decision to continue or end opioid prescribing should be based on a physician-patient discussion of the anticipated benefits and risks. An opioid should be discontinued with resolution of the pain condition, intolerable side effects, inadequate analgesia, lack of improvement in quality of life despite dose titration, deteriorating function, or significant aberrant medication use [1,44].

Clinicians should provide physically dependent patients with a safely structured tapering protocol. Withdrawal is managed by the prescribing physician or referral to an addiction specialist. Patients should be reassured that opioid discontinuation is not the end of treatment; continuation of pain management will be undertaken with other modalities through direct care or referral.

As a side note, cannabis use by patients with chronic pain receiving opioid therapy has traditionally been viewed as a treatment agreement violation that is grounds for termination of opioid therapy. However, some now argue against cannabis use as a rationale for termination or substantial treatment and monitoring changes, especially considering the increasing legalization of medical use at the state level [82].

For patients who are not proficient in English, it is important that information regarding the risks associated with the use of opioids and available resources be provided in their native language, if possible. When there is an obvious disconnect in the communication process between the practitioner and patient due to the patient's lack of proficiency in the English language, an interpreter is required. Interpreters can be a valuable resource to help bridge the communication and cultural gap between patients and practitioners. Interpreters are more than passive agents who translate and transmit information back and forth from party to party. When they are enlisted and treated as part of the interdisciplinary clinical team, they serve as cultural brokers who ultimately enhance the clinical encounter. In any case in which information regarding treatment options and medication/treatment measures are being provided, the use of an interpreter should be considered. Print materials are also available in many languages, and these should be offered whenever necessary.

Relatively minor changes in the structure of an opioid can convert an agonist drug into one with antagonistic actions at one or more opioid receptor types. Opioid antagonists include naloxone, naltrexone, and nalmefene. Interestingly, naloxone also appears to block the analgesic effects of placebo medications and acupuncture. These agents have no abuse potential [89].

In response to acute overdose, the short-acting opioid antagonist naloxone is considered the gold standard, and it remains the most widely used opioid antagonist for the reversal of overdose and opioid-related respiratory depression. It acts by competing with opioids at receptor sites in the brain stem, reversing desensitization to carbon dioxide, and reversing or preventing respiratory failure and coma. There is no evidence that subcutaneous or intramuscular use is inferior to intravenous naloxone. This has prompted some states to pass laws allowing opioid antagonists to be available to the general public for administration outside the healthcare setting to treat acute opioid overdose [90]. In 2014, the FDA approved naloxone as an autoinjector dosage form for home use by family members or caregivers, and in 2015, the agency approved intranasal naloxone after a fast-track designation and priority review. Intranasal naloxone is indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression [91,92].

When used for opioid overdose, a dose of 0.4–2 mg of naloxone is administered intravenously, intramuscularly, or subcutaneously [93]. If necessary, the dose may be repeated every two to three minutes for full reversal. For ease of use, naloxone is also available in a pre-filled auto-injection device. The intranasal formulation is available in doses of 2 mg, 4 mg, or 8 mg [93]. In 2023, the FDA approved Narcan, the first over-the-counter naloxone nasal spray [69]. Narcan is available as a 3-, 4-, or 8 -mg single dose, administered in one nostril [93]. It is important that standard Advanced Cardiac Life Support (ACLS) protocols be continued while naloxone is being administered and that medical treatment (at a healthcare facility) be given immediately.

The DEA is responsible for formulating federal standards for the handling of controlled substances. In 2011, the DEA began requiring every state to implement electronic databases that track prescribing habits, referred to as PDMPs. Specific policies regarding controlled substances are administered at the state level [95].

According to the DEA, drugs, substances, and certain chemicals used to make drugs are classified into five distinct categories or schedules depending upon the drug's acceptable medical use and the drug's abuse or dependency potential [96]. The abuse rate is a determinate factor in the scheduling of the drug; for example, Schedule I drugs are considered the most dangerous class of drugs with a high potential for abuse and potentially severe psychologic and/or physical dependence.

In Florida, the prescribing, dispensing, and consumption of certain controlled substances are governed by Chapter 893 of the Florida Statutes [97]. This law establishes the standards for controlled substance prescribing, including reporting system requirements, for prescribers and pharmacists in Florida. At the time of publication of this course, the Florida schedule of controlled substances aligns with the DEA schedule [43].

Emerging trends and patterns of prescription opioid abuse, addiction, and overdose are monitored by several industry and government agencies through data collection from a variety of sources. These include health insurance claims; the Automation of Reports and Consolidated Orders System, a DEA-run program that monitors the flow of controlled substances from manufacturing through distribution to retail sale or dispensing; the Treatment Episode Data Set, which monitors treatment admissions; the National Center for Health Statistics state mortality data; and the Researched Abuse, Diversion, and Addiction-Related Surveillance System, which monitors prescription drug abuse, misuse, and diversion [98].

Almost all states, including Florida, have enacted PDMPs to facilitate the collection, analysis, and reporting of information on controlled substances prescribing and dispensing [1]. All prescribers must consult the Electronic Florida Online Reporting of Controlled Substances Evaluation (E-FORCSE) to review a patient's controlled substance dispensing history before prescribing or dispensing a controlled substance to a patient 16 years of age or older [99]. This is mandated even for existing patients and should be done each time a controlled substance is prescribed or dispensed [43]. If the system is nonoperational or cannot be accessed due to a temporary technologic or electrical failure, the prescription may be issued (with documentation of the exception) for up to a maximum three-day supply.

All clinicians who dispense controlled substances are required to report the action to E-FORCSE as soon as possible, but no later than the close of the next business day [99]. This should be repeated each time the substance is dispensed. This reporting requirement is waived in certain circumstances, including for [99]:

A full evaluation, including radiographic studies and consultation with psychiatry and physical therapy, is completed. The working diagnosis for the patient's acute illness is toxic encephalopathy caused by the sedative side effects of opioid medication on the CNS. It is explained that the combination of his advancing age and diabetes likely reduced the efficiency of his kidneys in clearing the medication and its metabolites, making him more susceptible to CNS sedation. It is noted that the patient and his wife have little understanding of the rationale, proper use and safeguards, potential side effects, and limited effectiveness of opioid use for chronic pain.

In addition, the patient is diagnosed with poorly controlled chronic pain syndrome secondary to osteoarthritis and degenerative disc disease; exacerbating factors include deconditioning and reactive depression. The use of an opioid analgesic, at least for the near term, is considered appropriate, if dosed properly, monitored closely, and integrated into a comprehensive, multidisciplinary plan that includes treatment of depression and the use of adjunctive, nonpharmacologic modalities of care. In the setting of possible early diabetic nephropathy, the option of utilizing an NSAID, except for very brief periods of break-through pain, is not considered to be a safe option.

At discharge, and in consultation with his primary care physician, a written treatment and management plan addressing all aspects of the patient's care is presented to the patient and his wife for discussion and consent. Among the key issues addressed are:

On follow-up six weeks after discharge, the patient is noticeably improved. He reports that he feels stronger and is sleeping better. His affect is brighter, and he is getting out more. He has maintained his physical therapy and exercise routine and is compliant with his medication. Though he still has pain, it is noticeably less and he is coping better. He and his wife are encouraged by his progress, particularly in regard to his improved functional status.