Validation and Counseling of
Prescriptions for Controlled
Substances and Opioids Course

The goals of this learning experience are to ensure that all patients with valid prescriptions have access to controlled substances, to use the database of the Prescription Drug Monitoring Program, to evaluate prescriptions for their appropriate therapeutic value, to identify prescriptions that are not based on a legitimate medical purpose, to understand the laws and regulations related to prescribing and dispensing controlled substances, to properly store and dispose of controlled substances, to establish protocols for addressing and resolving issues identified during drug utilization review, to provide education on emergency treatment for suspected opioid overdose, to offer pharmacist-initiated counseling to patients with opioid prescriptions, and to identify available treatment resources for physical dependence, addiction, misuse, or abuse of opioids.

Controlled substances have important medical uses, but they also trigger the brain's reward center, which can lead to misuse and other negative effects. Pharmacists may feel hesitant to fill prescriptions for controlled substances, but it is crucial for them to fill all valid prescriptions for controlled substances that are prescribed for legitimate medical purposes.

To assist Florida pharmacists in verifying a prescription's legitimacy, the Florida Board of Pharmacy has established general standards in Rule 64B16-27.81.

1. General standards for validating a prescription:
   1. Definition: The process that pharmacists implement to determine if the prescription was issued for a valid medical purpose.
   2. Pharmacists must ensure that all communication with the patient is private and not overheard by others. No one, including other licensees, should interfere with the pharmacist's independent professional judgment. If33 at any time, the pharmacist feels that concerns with the validity of the prescription cannot be resolved, the pharmacist should refuse to fill or dispense the prescription.
   3. Each prescription may require a different validation process, and there is no one-size-fits-all approach. There are situations that may cause a pharmacist to question the validity of a prescription for a controlled substance; however, such concerns do not necessarily mean the prescription should not be filled. Instead, when a pharmacist is presented with a prescription for a controlled substance, the pharmacist should try to determine its validity and resolve any concerns about its validity by using their independent professional judgment.
   4. The Board of Pharmacy understands that it is important for patients in Florida to be able to fill valid prescriptions for controlled substances. While filling these prescriptions, the Board does not expect pharmacists to take any specific action beyond using sound professional judgment. Pharmacists should not be afraid of disciplinary action from the Board or other enforcement agencies for dispensing controlled substances for legitimate medical purposes in the usual course of professional practice. Every patient situation is unique, and prescriptions for controlled substances should be reviewed with each patient's unique situation in mind. Pharmacists should attempt to work with the patient and the prescriber to determine the validity of the prescription.

During the validation process, pharmacists must conduct a Prospective Drug Use Review of the patient's prescription record for each new and refill prescription. This is to promote therapeutic appropriateness by identifying the following potential problems:

(a) Over-utilization or under-utilization;

(b) Therapeutic duplication;

(c) Drug-disease contraindications;

(d) Drug-drug interactions;

(e) Incorrect drug dosage or duration of drug treatment;

(f) Drug-allergy interactions;

(g) Clinical abuse/misuse.

If any of these issues are recognized, the pharmacist must take appropriate steps to avoid or resolve them, which may include consulting with the prescriber if necessary.

During the validation process, pharmacists should also be on the lookout for any red flags. A red flag is anything that may indicate a problem with a prescription, such as a prescription that was not written for a legitimate medical purpose. Examples of red flags include:

• changes made to the original prescription,
• patients who only bring in prescriptions for controlled substances,
• individuals who bring in prescriptions for multiple people,
• patients who travel great distances to your pharmacy,
• unusual behavior,
• patients who only pay cash despite having insurance,
• practitioners who issue prescriptions outside of their scope of practice.

When assessing potential red flags, it is crucial to take certain precautions. First, confirm that the prescription is valid and intended for a legitimate purpose. Always prioritize the patient's well-being by verifying that they truly require the medication. Has the patient previously been prescribed controlled substances, and what is their diagnosis? Additionally, consider the patient-physician relationship. Is the prescriber local? Are you familiar with the prescriber? Are they associated with pain management or mental health?

Pharmacists play an important role in identifying and resolving all potential issues with prescriptions, documenting them for future reference. If a pharmacist knowingly ignores a questionable prescription, it may be considered intentional distribution of a controlled substance and lead to prosecution, along with the prescribing practitioner. Additionally, if a pharmacist suspects a prescriber of diverting controlled substances, they are obligated to report it to the Department of Health.

It is necessary for healthcare practitioners that are licensed to prescribe medicinal drugs ensure that written prescriptions are legibly printed or typed, so that pharmacists who fill the prescription can understand it. The prescription must include the prescribing practitioner's name, the name and strength of the drug prescribed, the quantity of the drug prescribed, and the directions for use of the drug. If the prescription is written, the month and quantity must be written out. Additionally, the prescription must be dated and signed by the prescribing practitioner on the day of issue. It is worth noting that electronic prescribing of controlled substances is also permitted.

To ensure that a prescription for a controlled substance is legitimate, pharmacists can refer to the Code of Federal Regulations 1306.04. The prescription must be based on a relationship between the doctor and patient, and it must be prescribed for a legitimate medical purpose, meeting four criteria:

• Must be based on sound clinical judgment,
• Must follow current best practices,
• Must be appropriately documented,
• Must demonstrate a benefit to the patient.

As pharmacists, it is our responsibility to ensure that the controlled substance prescription is legitimate by verifying that these criteria are met.

Pharmacists should confirm that the prescription is being used for a suitable diagnosis, duration, and dose, based on their clinical expertise. Pharmacists may also refer to current guidelines, such as the CDC guidelines for prescribing opioids for pain, to ensure that the latest best practices are being followed. Moreover, pharmacists should make sure that the prescription is properly documented and inquire about the effectiveness of the medication.

Essential Fact: The process a pharmacist uses to determine that a prescription was issued for a legitimate medical purpose is known as validating a prescription.

All pharmacists should be able to explain the process they use to validate a prescription. This process may include checking the PDMP, resolving red flags, and talking with the patient or provider. All steps should be documented.

Before a pharmacist can refuse to fill a prescription based solely upon a concern with the validity of the prescription, the pharmacist must attempt to resolve those concerns and validate the prescription by taking the following steps:

1. Initiate communication with the patient or their representative to obtain relevant information about the prescription's validity concerns.
2. Initiate communication with the prescriber or their agent to obtain relevant information about the prescription's validity.

If a pharmacist cannot perform either step 1 or 2, the pharmacist may access the Prescription Drug Monitoring Program's database to acquire relevant information. If a pharmacist is unable to comply due to a refusal to cooperate, the pharmacist is not required to follow the minimum standards for refusing to fill a prescription.

The Electronic Florida Online Reporting of Controlled Substances Evaluation (EFORCSE) was established by the Florida legislature in 2009 to combat drug abuse and diversion in the state. EFORCSE is a Prescription Drug Monitoring Program (PDMP) that tracks data related to the prescription and dispensing of schedule II, III, IV, and certain schedule V drugs. These records help guide prescribing and dispensing decisions for controlled substances. Records are automatically generated when these schedules are filled and sold and are typically uploaded by the end of the next business day. The records are stored for 4 years.

To use EFORCSE, one must register online as a prescriber, pharmacist, or other authorized user. Delegates of authorized users can also register and use EFORCSE if approved by the authorized user. To search for fill history, patient information such as name and date of birth is required. Users can choose to check other states that share information with EFORCSE by scrolling down on the same page. EFORCSE allows users to view the medication name, fill date, quantity dispensed, prescribing physician, and pharmacy where the medication was filled. Searches cannot go back more than 2 years from the current date. Records will not show for prescriptions dispensed within the Department of Corrections, or if the controlled substance was directly administered to a patient.

EFORCSE also provides clinical information, such as Morphine Milligram Equivalent (MME) values of the patient's picked-up medications. Caution should be exercised when interpreting buprenorphine or pregabalin MME values. Additionally, an overdose risk score is provided. Individual patient characteristics should be considered, and this score should not be used as a substitute for clinical decision making.

Prescribers or their delegates must check the PDMP each time they write a prescription for a controlled substance for any patient aged 16 or older, including any schedule II-IV substance and certain schedule V substances (non-opioids are excluded). Similarly, pharmacists must review the PDMP before dispensing any new prescriptions or refills for these same controlled substances. When one of these controlled substances is picked up, the telephone number of the patient and the identification of the person picking up the prescription shall be reported. If technical difficulties arise and prescribers/pharmacists cannot consult the PDMP, prescribers may write for no more than a 3-day supply of any controlled substance and must document the reason. Pharmacists may dispense no more than a 3-day supply of any controlled substance as well.

It is important for all pharmacists to realize that refusing to fill a controlled substance prescription may have serious consequences for their patients, including suicide, withdrawal from prescribed medications, taking street drugs, or even death. The Centers for Disease Control and Prevention (CDC) recommends against abruptly discontinuing or tapering opioid medications.

Scenario: Joe, a 45-year-old male, presents a prescription for methadone 10mg, take 2 tablets three times daily. He is new to your pharmacy and explains that his normal pharmacy does not have the medication in stock. The prescription is written by a local pain management provider. Joe's PDMP history is appropriate, and he is due to fill the prescription today. He has been on this dose of methadone for months. You evaluate the prescription, and the only red flag is the high dose of methadone. You have the medication in stock; however, you are worried about the high dose of methadone.

As pharmacists, our oath states that the relief of suffering should be our primary concern. If we refuse to fill this prescription, Joe will experience withdrawal symptoms and suffer. Therefore, in this scenario, the pharmacist should document the validation steps taken (PDMP review, discussion with the patient, continuation of therapy) and fill the prescription.

It is important to note that refusing to fill a prescription can have negative consequences for the patient, including worsening of their condition or seeking out medication through other means. By filling the prescription and documenting the steps taken to ensure its appropriateness, the pharmacist is providing Joe with the best possible care.

When it comes to drug overdoses, opioids are responsible for more than 60% of overdose deaths. However, opioids are not the only prescription drugs that are abused. CNS depressants (sedatives) and stimulants are also commonly abused, according to the National Institute on Drug Abuse.

To aid healthcare providers in prescribing opioid pain medications, the CDC released the CDC Clinical Practice Guideline for Prescribing Opioids for Pain in 2016. The guideline was updated in 2022 and can be divided into four parts:

1. Deciding whether or not to start using opioids for pain
2. Selecting opioids and determining dosage
3. Deciding duration of initial opioid prescription and conducting follow-up
4. Assessing risk and addressing potential harms of opioid use

Deciding Whether Or Not To Start Using Opioids For Pain

This section of the 2022 CDC Clinical Practice Guidelines discusses whether to start opioids for acute and nonacute pain (subacute and chronic). Acute pain is pain lasting less than a month, subacute pain lasts 1-3 months, and chronic pain lasts more than 3 months. Nonopioid medications are often just as effective as opioids for acute pain. Clinicians should utilize both nonopioid and nonpharmacologic treatments, if appropriate for the condition being treated, before considering opioid therapy. It is important to weigh the risks and benefits before deciding between nonopioid or opioid therapy for acute pain.

For many types of acute pain conditions (musculoskeletal injuries, lower back pain, neck pain, dental pain, mild post-op pain, and headaches), nonopioid measures have been shown to be at least as effective as opioids. In a systematic review, it was shown that for minor musculoskeletal injuries, such as sprains, strains, and whiplash, topical NSAIDs had the best benefit to harm ratio, with oral NSAIDs or acetaminophen with and without diclofenac coming next. Opioid use caused the most harm and adverse events, including nausea, dizziness, and somnolence. Opioid use for lower back pain and postoperative pain has been associated with an increased chance of long-term opioid use. The American College of Physicians (ACP) recommends NSAIDs and skeletal muscle relaxants for lower back pain, and the American Academy of Family Physicians (AAFP) and ACP recommend topical NSAIDs (with or without menthol gel) as first-line for musculoskeletal injuries, with oral NSAIDs or acetaminophen being used to reduce pain if needed. Both organizations recommend against using opioids (including tramadol) for musculoskeletal injuries. Similarly, for kidney stone pain and dental pain, NSAIDs have been shown to be more effective for management than opioids while being on par with opioids for lower back pain. NSAIDs can reduce smooth muscle tone and reduce spasms in the ureters, potentially further reducing kidney stone pain. For episodic migraines, other treatments have been shown to have improved pain and functioning, all the while having lesser adverse events. These treatments include triptans, dihydroergotamine, NSAIDs, antiemetics, and newer therapies such as the gepants (Ubrogepant and Rimegepant) and Lasmiditan. Opioids and medications containing butalbital had a two-fold increased risk for developing medication overuse headache when compared to those listed. For the conditions detailed above, NSAIDs should be the therapy of choice (alongside the therapies listed for episodic migraine) when no contraindications are present. Risks and benefits must be considered when treating patients with hypertension, renal insufficiency, heart failure, peptic ulcer disease, and cardiovascular disease before initiating an NSAID. Similarly, risks/benefits for patients with cardiovascular risk factors should be analyzed before treating with triptans or ergotamines.

For pregnant and postpartum persons, ACOG recommends using acetaminophen or NSAIDs as first-line for pain after vaginal delivery, followed by an opioid if needed. After cesarean delivery, oral and parental medications such as NSAIDs, acetaminophen, and opioids can be considered. For both situations, opioids should be used at the lowest effective dose and should be short-acting. These patients should be counseled on adverse effects of opioids, especially if a codeine containing opioid is given due to its risk for the fetus/newborn.

In addition to nonopioid therapy, nonpharmacologic therapy should also be considered. For acute low back pain, the American College of Physicians (ACP) recommends using heat, massage therapy, acupuncture, and spinal manipulation as adjuncts to pharmacologic therapy if pharmacologic therapy is needed. Similarly, for acute musculoskeletal pain, it is recommended to use acupressure and a TENS unit to reduce pain and to apply ice alongside elevation. These measures are typically not covered by insurance, so access may be difficult for some patients. Nonetheless, these nonpharmacologic measures should be used where appropriate.

Opioid therapy still has an important place in acute pain conditions, including severe traumatic injuries and surgeries where there is likely to be moderate/severe postoperative pain. When opioids are needed, best practice dictates that immediate release formulations should be prescribed at the lowest effective dose for the shortest time necessary.

Nonopioid therapies are also preferred for subacute and chronic pain. Nonopioid and nonpharmacologic measures should be maximized for these patients, and goals of therapy alongside benefits of therapy should be discussed with patients prior to initiation of an opioid. Patient preferences should be assessed, and patients should be educated on the risks of and alternatives to opioid therapy prior to initiation. If goals are not met or if benefits do not outweigh the risks, opioid discontinuation should be discussed with patients. For patients with subacute pain who have been on opioids for more than 30 days, underlying factors of pain should be assessed and reversed if possible so that long-term therapy can potentially be avoided. However, if long-term opioid therapy is done, it should only be the result of an intentional decision that considers the risks/benefits, not an unintentional continuation of medication without reassessment. Prior to initiation of any therapy, the diagnosis should be confirmed and should consider a detailed evaluation, including things such as the history and characteristics of the pain, aggravating and remitting factors, and imaging if necessary. For complex pain cases, referral to a pain specialist may be indicated. Proper diagnosis can help identify underlying factors that may be specific to a disease state (i.e diabetic neuropathy, rheumatoid arthritis). If diagnosed and treated properly, this alone can slow, ease or even reverse symptoms of pain.

Nonpharmacologic therapies play a big role in the treatment of chronic pain. Exercise is commonly used for back pain, fibromyalgia, and hip/knee osteoarthritis. Other nonpharmacological options include weight loss, psychological therapy, spinal manipulation, stress reduction, cognitive behavioral therapy, mind-body techniques (yoga/tai chi), massage, and acupuncture. Exercise therapy is prominent in the management of back pain, fibromyalgia, and hip/knee osteoarthritis, as benefits in pain and function are seen immediately and are sustained for 2-6 months as shown by high-quality evidence. Other nonpharmacologic modalities detailed above can improve pain/function for at least 1 month. Active approaches such as exercise, cognitive behavioral therapy, and mind-body practices help involve the patient in the care plan and have a bit more evidence for continued improvement as compared to more passive approaches. Nonpharmacologic options are often not covered by insurance, so patients with limited income may struggle to gain access. Use of public facilities can help these patients, and clinicians should be aware of low-cost options within their communities to recommend to patients.

For osteoarthritis patients who have had less than ideal relief from nonpharmacological options, topical NSAIDs can be considered for shallow osteoarthritis of a single/few joints (i.e knee). For osteoarthritis of many joints and low back pain, or if not controlled by topical NSAIDs, systemic NSAIDs or duloxetine can be used. NSAIDs should be used at the lowest effective dose and for the shortest duration to avoid adverse effects, and care should be taken if used in elderly patients, and those with previous GI bleeding, renal insufficiency, and cardiovascular issues. COX-2 inhibitors or NSAIDs with PPIs can be used to minimize GI risk compared to NSAIDs alone, if there is no history of GI bleeding. Acetaminophen is not effective for osteoarthritis and is no longer recommended. Similarly, in patients with chronic low back pain who have had little relief from exercise, NSAIDs and duloxetine can be recommended if no contraindications exist, as there is moderate-quality evidence that small improvements can be gained.

Tricyclic antidepressants, SNRIs, capsaicin, and certain anticonvulsant drugs can be used for neuropathic pain. Tricyclic antidepressants should be used with caution in the elderly and in those predisposed to falling. Some anticonvulsants, gabapentin and pregabalin, have been associated with blurred vision, cognitive effects, weight gain, and sedation, while the SNRIs have been more so associated with nausea and sedation. As a reminder, TCAs in patients over 65 should be carefully considered because of their anticholinergic effects. Some of these medications are commonly used in fibromyalgia. SNRIs (duloxetine and milnacipran), NSAIDs (topical diclofenac), gabapentin, and pregabalin are associated with modest improvements in pain and quality of life when it comes to fibromyalgia. TCAs (amitriptyline) are commonly used for this condition but with little evidence. Several of these medications are also approved to treat other neuropathic pain disorders such as diabetic neuropathy (duloxetine and pregabalin) and postherpetic neuralgia (gabapentin and pregabalin).

Opioids should not be used first-line for subacute or chronic pain. Clinical reviews have found scant evidence for the long-term benefits of opioids and found an increased risk for harms, which appear to be dose dependent. Opioid use was associated with an increased risk of GI side effects, drowsiness, dizziness, itching, opioid use disorder, falls/fractures, overdose, all-cause death, and myocardial infarction. In the short term (1-6 months), opioids had a small mean improvement in pain; however, no studies have assessed their effectiveness beyond 6 months. Some evidence also suggests that improvement in pain is reduced with longer durations of opioid therapy. However, this does not mean that step therapy must be failed with other agents/nonpharmacological measures for an opioid to be started. Each situation must be thought about, as in the case of a terminally ill patient whose desire is comfort, opioids may be appropriate regardless of what was used before. In other situations, such as headache or neuropathic pain, the benefits of starting an opioid are unlikely to outweigh the risks. If an opioid is being considered, patient-specific goals should be discussed as well as an exit strategy should the opioid not work. Furthermore, education about the following should be provided:

• Low-cost alternatives/nonpharmacologic therapy
• Elimination of pain is unlikely and that there is limited evidence that opioids improve pain with long-term use
• Improvement in function should be the main goal
• Opioids carry serious side effects such as respiratory depression, which is worsened when combined with benzodiazepines, alcohol, sedatives, and other opioids, and can affect their activities of daily living
• Common side effects include constipation, dry mouth, vomiting/nausea, confusion, tolerance, and physical dependence alongside withdrawal if abruptly stopped
• Patients should increase their hydration, exercise, and fiber intake while also using a stimulant laxative (with or without a stool softener) to avoid opioid-induced constipation
• Advise on the risks of taking additional acetaminophen-containing medications should the opioid be co-formulated with acetaminophen
• Storage in a secure area to prevent accidental ingestion by someone else, options for safe disposal, and use of naloxone to prevent an overdose from occurring.
• Periodic reassessment is important to address goals and potential tapering/discontinuation if needed

For subacute and chronic pain, there also exist interventional approaches such glucocorticoid injections, nerve ablation, and neurostimulation procedures. Much of these interventional approaches provide short-term relief, often to supplement exercise or physical therapy. Evidence of effectiveness varies by procedure, and little evidence exists on the benefits/risks of these approaches compared to the risks of opioids and other pharmacologic options. If these are to be considered, clinicians should consult with pain management and should follow strict infection control measures. Multimodal pain management is also an option for subacute and chronic pain. This often includes mixing pharmacological, psychosocial, and other nonpharmacological measures for the best outcome. For example, combining psychological therapy with exercise reduces long-term pain and disability compared to exercise alone. When possible, medications should be combined with nonpharmacologic measures to improve outcomes. Furthermore, medications with different mechanisms of action can be considered to provide synergistic benefit; however, some combinations can cause an increased risk of side effects, such as sedation and respiratory depression when using concurrent gabapentin and opioids.

Selecting Opioids and Determining Dosage

When prescribing opioids, immediate-release formulations should be preferred over extended-release and long-acting formulations. These formulations should be reserved for severe, continuous pain for opioid-tolerant patients, and should not be prescribed for “as needed” use. Clinical reviews have shown that pain levels were relatively consistent across opioids with differing durations of action (short and long-acting) and opioid type (full vs partial agonist vs mixed action). Other trials that directly compared opioids to one another found that mixed-action opioids resulted in greater pain relief and had fewer serious adverse events. When considering extended release/long acting (ER/LA) opioids, it is important to know that studies have shown increased risk of overdose when compared to immediate release (IR) formulations in the short term (<2 weeks) and that there is no evidence that scheduled ER/LA opioids are more effective than IR formulations. Interestingly, no evidence was found for ER/LA opioids to reduce the risk of opioid use disorder.

Furthermore, if changing from an immediate-release formulation to an ER/LA formulation, product labeling should be consulted, and incomplete cross-tolerance should be considered. Product labeling should also be consulted whenever there is concern about whether an opioid should only be used for an opioid-tolerant patient, defined as >60 MME/day for 1 week. When using these ER/LA formulations, patient comorbidities should be considered, especially if decreased clearance is present, as this can lead to accumulation and toxic levels. Certain LA opioids, such as methadone and transdermal fentanyl, should only be used by clinicians who are well-versed in their side effects, dosing, and monitoring parameters. For example, absorption of transdermal fentanyl must be understood and patients on methadone will require QT monitoring. Methadone should not be the first choice if considering an ER/LA opioid, as it is associated with a disproportionate number of overdoses compared to its frequency of use, as well as being associated with cardiac arrhythmias and variable pharmacokinetics. Ideally, if prescribing an opioid, one with predictable kinetics should be preferred. It should be noted that opioids that come formulated with abuse deterrents do not fully deter abuse, as oral abuse is the most common way of misusing opioids, though nonoral abuse is still possible. No studies were found assessing the abuse deterrents effectiveness on misuse or overdose.

If an opioid is to be prescribed for a naïve patient, the lowest effective dosage should be used. This lowest effective dose can be determined using product labeling and should be used in conjunction with clinical reasoning that considers pain severity and patient comorbidities. Generally, starting doses for naïve patients is a total daily dose of 20-30 MME, with single doses being 5-10 MME. Dose increases are generally unnecessary for naïve patients if being treated for a few days or less, and should not be attempted without monitoring. If opioids are to be continued for subacute/chronic pain, caution should be used when continuing opioids and dose increases should be avoided if possible. Patients do not often see increased benefits over 50 MME/day but instead see increased risk of side effects, overdose, and even tolerance to the opioid resulting in lessened benefits for pain and function. Instead of increasing beyond this amount, clinicians should reassess diagnosis, consider alternative options, and discuss with the patient about their goals and preferences.

In patients that are receiving opioid therapy, changing opioid dosage should be done with caution. If the benefits of the opioid outweigh the risks, nonopioid measures should also be optimized while still on opioids. If the risks outweigh the benefits, other therapies should be maximized while working to taper to lower dosages or even discontinue the opioid. Opioid tapers should be considered if the patient requests a dose reduction or discontinuation, the underlying cause of pain has been fixed, the opioid has not resulted in pain relief, risk/benefit if unclear for the patient, side effects reduce quality of life/function, evidence of misuse is present, the patient has an overdose, or if the patient has concomitant medical conditions/medications that predispose them to serious adverse effects. Opioids should not be abruptly stopped, except in the cases of life-threatening circumstances (overdose) and should not be quickly reduced from higher doses. Discontinuation is associated with higher risks when done over a shorter time span. The FDA has warned that quickly tapering/abrupt discontinuation risks acute withdrawal symptoms, worsening pain, extreme distress, and suicidal thoughts.

Shared-decision making is important when having conversations about the benefits/risks of opioids and tapering, and treatment changes should be made in a patient-centered manner while attempting to avoid abandonment. In a systematic review, it was shown that when patients agreed to taper, dose reduction was associated with better pain, function, and quality of life. Clinicians should not insist on tapering when opioid therapy is indicated. Clinicians should follow-up at least monthly with patients undergoing an opioid taper, and patient education on how long/how quick the taper will occur should happen. Opioid tapers can take a while, months to years, depending on the dose/how the patient tolerates the taper. Tapers should be individualized per patient, but in general, tapers of 10% per month are likely to be better tolerated than faster tapers and may need to be slower depending on the occurrence of withdrawal symptoms. Patients may struggle with a taper, and as such, nonopioid measures should be maximized to ameliorate these struggles. Similarly, patients may need to stop a taper and restart when the patient is ready, especially as the taper reaches low doses. Clinicians should utilize caution before deciding to reverse a taper and should educate patients on the risks of returning to higher dosages, including overdose and offer naloxone. After determining patient goals, if the patient wants to eventually discontinue opioids, the dosing interval can be extended once the lowest dose is reached and can be stopped when taken less frequently than once a day.

If a patient does not want to taper or cannot taper, proper education and monitoring should be done for those remaining on high doses/high-risk regimens (benzodiazepine + opioid), including providing naloxone. If on another sedative such as a benzodiazepine, this should also be tapered to reduce the risk of withdrawal symptoms (anxiety, seizure, hallucinations, delirium tremens). If considering a taper for a pregnant patient, medications for tapering are preferred, however proper expertise should be consulted to reduce risk for the fetus and patient should the patient go into withdrawal. Patients should be educated that in the short term, it is possible to experience insomnia, anxiety, depression, and increased pain, but that overall, most patients report improved anxiety/mood/function without worsening pain or even decreased pain levels. Mental health specialists should be utilized to help patients during their taper, and clinicians should continue to monitor for anxiety/depression/opioid abuse and disorder during the tapering process.

For the management of withdrawal symptoms during a taper, the first approach should be to slow or pause the taper. If needed, the alpha-2 antagonists clonidine and lofexidine can help with withdrawal symptoms after abrupt discontinuation (tachycardia/sweating). No evidence could be found for the use of these medications for a patient experiencing symptoms while tapering from long-term opioid treatment for pain, however, tizanidine has been used for this. Undiagnosed opioid use disorder is another complication of tapering, especially if tapering is unsuccessful in the face of harm to the patient. In this situation, evidence-based treatment and naloxone should be offered.

If a patient does not meet the criteria for opioid use disorder and who are unable to taper, evidence suggests there might be benefit for transition to buprenorphine. Buprenorphine is a partial agonist and has less risk for respiratory depression, however, requires specific timing for initiation depending on the opioid the patient is currently on. To avoid withdrawal symptoms, buprenorphine should be started 8-12 hours after a short-acting full agonist and 12-24 hours after an ER/LA full agonist, and even longer after a dose of methadone. If used for analgesia, buprenorphine will require multiple daily dosing due to its shorter duration of action for analgesia as compared to its duration of action for opioid withdrawal.

Deciding Duration of Initial Opioid Prescription and Conducting Follow-up

To start, acute pain caused by non-traumatic and non-surgical factors can usually be managed without opioids. However, if opioids are necessary for acute pain, opioids should be prescribed for the shortest duration possible, often a few days or less (i.e., 4-7 days), tailored to the individual patient. For postoperative pain, specific opioid prescribing recommendations exist for different procedures. Prescribing opioids for longer than expected should be avoided. If continued opioid therapy is required for acute pain, therapy should be reassessed at least every 2 weeks. If the opioid is used around the clock for acute pain, a brief taper is recommended to reduce the likelihood of withdrawal symptoms. If a patient on chronic opioid therapy experiences superimposed acute pain, additional opioids should be continued for the shortest possible duration, and the patient should be returned to their maintenance dose of opioids. A taper should be used if additional opioids were taken around the clock for more than a few days.

If starting opioid therapy for subacute or chronic pain, patients should be reassessed after 1-4 weeks of starting or increasing the dose to evaluate the risks and benefits. If starting an extended-release/long-acting opioid, follow-up should be on the shorter end of this range, as there is an increased risk of overdose, especially within the first two weeks. For methadone, follow-up intervals should be every 2-3 days for the first week due to its erratic pharmacokinetics. All patients on long-term opioid therapy should be reassessed at least every 3 months, with their perspectives and goals reviewed, and should be screened for adverse effects and opioid use disorder. Patients at particular risk of overdose or opioid use disorder (with a history of abuse, depression, mental health conditions, taking >50MME/day, history of overdose, or taking concomitant sedatives) should be reassessed more often than every 3 months.

Assessing Risk and Addressing Potential Harms of Opioid Use

Before and during opioid therapy, clinicians should assess opioid-related risks and discuss them with patients. Clinicians should also mitigate risks where possible, including offering naloxone. This includes discussing drug and alcohol use and using proper tools to screen for mental health and substance use disorders. If possible, clinicians should manage depression and other mental health issues prior to initiating long-term opioid therapy. Patients who are at an increased risk of overdose or developing opioid use disorder, including those with depression or other mental health issues, should be offered naloxone and counseled on how to use it. Naloxone can be prescribed through clinics, collaborative practice agreements with pharmacists, and standing orders/protocols at pharmacies.

To reduce the risk of respiratory depression, opioids should not be prescribed to people with moderate to severe sleep-disordered breathing. Dose titration should also be done with caution in this population.

For pregnant patients, opioids should be balanced with the need to treat pain. Pregnancy is not an exclusion for treating acute pain, but there are risks to the fetus, including stillbirth, poor growth, and preterm delivery, as well as neonatal abstinence syndrome in some cases. The American College of Obstetricians and Gynecologists recommends that pain be treated in pregnant patients, as neonatal abstinence syndrome is treatable. If opioid use disorder (OUD) is a concern, methadone or buprenorphine should be initiated as early as possible in pregnancy to prevent harm. Shared decision-making about goals and pregnancy intentions, as well as counseling about potential side effects and alternative treatments to opioids, should be discussed and reviewed. If an opioid taper is necessary in a pregnant patient, appropriate expertise should be consulted to minimize the risk of withdrawal symptoms. Newborns should be monitored for withdrawal for at least 72 hours if exposed to immediate-release opioids, 4-7 days if exposed to buprenorphine or extended-release/long-acting opioids, and 5-7 days if exposed to methadone.

Other at-risk populations include patients with renal and hepatic insufficiency and patients over 65 years old, as opioids can accumulate and lead to adverse events. Regular risk assessments for falls, cognitive impairment, and proper bowel regimens should be conducted. These populations should be monitored more closely, and clinicians should assess pain control and minimize risks where possible. For patients with jobs where safety is important, clinicians should regularly evaluate the patient's ability to perform job duties. Patients with mental health disorders and substance abuse disorders are also at increased risk. Patients with mental health conditions should be optimized, especially if depression or anxiety is present, because depression is associated with an increased risk of opioid use disorder and overdose. Depression that is managed can reduce pain symptoms and overdose risk. TCAs or SNRIs should be considered for dual management of neuropathic pain and depression if this comorbidity is present. Screening tools, such as the drug abuse screening test, the Tobacco, Alcohol, Prescription medication, and other Substance use tool, and the Alcohol Use Disorders Identification Test, can be used to screen for substance use disorders and risk of overdose. In patients with prior overdose, methadone and buprenorphine are associated with reduced all-cause mortality, and counseling on risk mitigation/use of naloxone should be given.

Using the PDMP prior to prescribing/dispensing opioids is another risk mitigation tool. This should be done before all opioid prescriptions to assess for additional sedatives or opioids from other prescribers. PDMP reported overdose risk scores have not been validated, and clinicians should not dismiss patients based on PDMP information.

Toxicology testing is an important risk mitigation tool and should be considered before starting opioid therapy and at least annually thereafter. It should be explained to patients that the testing is for their own safety, and they should be counseled on expected results and asked questions about substance use in a nonjudgmental manner. Toxicology panels are generally performed as a nonspecific immunoassay at first that screens for drug classes but can be narrowed down to specific confirmatory testing if a result was unexpected. Unexpected results should be discussed with patients and used to improve patient safety, whether that be through more frequent evaluation or reducing/discontinuing the opioid.

Reducing the frequency at which opioids and other central nervous system depressants (primarily benzodiazepines) are co-prescribed is another method of risk mitigation. Caution should also be taken with other CNS depressants (muscle relaxers, gabapentin/pregabalin, and other sedatives). Patients with opioid use disorder should not have methadone or buprenorphine withheld if they are on a benzodiazepine. Risks, benefits, and goals of therapy should be assessed if a patient is on both therapies. If a benzodiazepine is stopped abruptly, withdrawal symptoms can be precipitated, so tapers should be individualized. If the benzodiazepine was being used for anxiety, alternative nonpharmacological therapies, such as cognitive behavioral therapy, should be offered to the patient.

If a patient has or develops opioid use disorder, evidence-based treatment should be offered. Opioid detoxification alone is associated with increased risk of relapse, overdose, and death from overdose. Buprenorphine, methadone, and naltrexone are current medications used to treat opioid use disorder. Naltrexone is an opioid antagonist, whereas buprenorphine and methadone are a partial agonist and full agonist, respectively. Buprenorphine and methadone are preferred over naltrexone because naltrexone requires abstinence, has stronger evidence for better outcomes, is used more often, and has fewer issues with initiation. Naltrexone must be started after a full withdrawal from opioids (~7-10 days after the last dose) and is typically administered as an injection which lasts for 1 month, although an oral formulation is also available. Importantly, this medication can be stopped abruptly without risk of withdrawal since it is an antagonist, and patients should be counseled about overdose risk if relapse occurs because of the loss of previous tolerance. Though for patients who can tolerate and complete naltrexone, it has similar effectiveness as buprenorphine for relapse rates. Buprenorphine is commonly co-formulated with naloxone, an abuse deterrent, which is inactive if taken orally but can cause withdrawal if injected. In general, buprenorphine should not be started until the patient has objective signs of withdrawal to avoid precipitating further withdrawal. Evidence regarding a low-dose strategy for patients not currently in withdrawal is lacking, but this is a strategy that has also been used. For normal dose buprenorphine, doses should be titrated at 2-hour intervals, under clinical supervision, after objective signs of withdrawal have been seen. Of note, dosage thresholds for buprenorphine and methadone for pain do not apply when these agents are used for opioid use disorder, and no duration exists for the duration of treatment, as discontinuation is associated with relapse and overdose. If discontinued, buprenorphine should be tapered over several months. Psychosocial treatment alongside pharmacological therapy should be utilized for opioid use disorder where possible.

For pregnant patients with opioid use disorder, buprenorphine and methadone are preferred, as these have been associated with improved maternal outcomes and should be offered early in pregnancy. Transmucosal buprenorphine (without naloxone) is preferred to prevent fetal exposure to naloxone, though systematic reviews have not noted any adverse effects of the combination product. For patients taking naltrexone, consideration should be given to its lack of data in pregnancy and the potential for relapse upon discontinuation of naltrexone. The American Academy of Pediatrics recommends breastfeeding if there has been no drug use for at least 90 days, considered if there has been drug use within 30-90 days, and avoided if drug use has occurred within 30 days.

For patients with opioid use disorder who also require pain management, nonpharmacologic and nonopioid measures should be used where possible. For patients who are treated with buprenorphine and require additional management, an increase in the frequency of buprenorphine can be considered, as well as doses of a short-acting full agonist without discontinuing the patient's buprenorphine. In these patients, careful monitoring should be done, especially if it is decided that buprenorphine should be stopped, because of the increased risk of respiratory depression. Patients on naltrexone should receive higher doses of nonopioid therapies for severe pain. Patients taking methadone who need additional doses of short-acting opioids should be monitored closely as well.

There are a variety of resources available to assist individuals seeking treatment for substance abuse. These resources include inpatient rehabilitation centers, outpatient programs, support groups, and individual therapy. Inpatient rehabilitation centers can provide a highly structured environment for individuals to focus solely on their recovery, while outpatient programs allow individuals to receive treatment while still managing their daily responsibilities. Support groups, such as Alcoholics Anonymous or Narcotics Anonymous, can provide a sense of community and accountability for those in recovery. Individual therapy can also be beneficial in addressing underlying mental health issues that may be contributing to substance abuse. It is important for individuals to seek out the resources that best fit their individual needs and circumstances to achieve long-term success in their recovery. For a list of available providers, please visit the Substance Abuse and Mental Health Services Administration website at www.samhsa.gov.

Many states have recently implemented new rules regarding the prescription of opioids for both acute and chronic pain. In Florida, for example, House Bill 21 came into effect on July 1, 2018, and mandates the following changes:

• All practitioners authorized to prescribe controlled substances must complete a two-hour training course on the safe and effective prescribing of controlled substances prior to licensure renewal.
• "Acute pain" is defined as the normal, predicted, physiological, and time-limited response to an adverse chemical, thermal, or mechanical stimulus associated with surgery, trauma, or acute illness. However, pain related to cancer, a terminal condition, palliative care to relieve symptoms of an incurable, progressive illness or injury, or a serious traumatic injury with an Injury Severity Score of 9 or greater is specifically excluded from this definition.
• A prescription for Schedule II opioids for treating acute pain is limited to no more than three days unless deemed medically necessary by the prescribing practitioner and properly documented. In such cases, this limit may be increased to seven days. The prescriber must document the medical condition and lack of treatment alternatives that justify providing up to a 7-day supply for a Schedule II opioid prescription. The prescription must also have the "Acute pain exception" printed or written on it.
• A prescription for Schedule II opioids for treating chronic pain must have "non-acute pain" printed or written on it.
• Pharmacists and dispensing practitioners must verify a patient's identity before dispensing controlled substances. Electronic prescriptions for controlled substances are explicitly authorized.

Essential Fact: Only scheduled two (CII) opioid medications require “Acute pain exception” or “non-acute pain” written or printed on the face of the prescription. Non-scheduled two opioids such as tramadol, buprenorphine, or APAP/codeine do not require the annotation.  

Proper storage and disposal are important considerations when patients are prescribed medications, especially controlled substances. According to the CDC, around 55% of controlled medications are obtained for free from friends or relatives. Proper storage and disposal can help reduce this statistic.

Patients can take several steps to properly store their medication. Patients should keep all opioids in the original packaging so that the directions, prescription information, and expiration date are available. Patients should store opioids in a secure place away from household members and guests. Patients should also monitor the medications consumed to ensure that none are missing. For patches, patients should ensure that the patches are covered and regularly check that they have not fallen off.

There are three main methods for disposing of medication.

1. The first is through Drug Take Back Days, which are events where patients can dispose of unwanted medications. These events can usually be found easily online.
2. The second method is to use a designated medication drop box in the community, which can often be found at community pharmacies.
3. The final method is to dispose of the medication at home. Patients can either destroy the drugs or flush them down the toilet. To destroy medications, patients should remove the drugs from their original packaging and mix them with something undesirable, such as coffee grounds, dirt, or cat litter. Patients should then put the drug in something that can be sealed to prevent leakage and throw it away. There are also drug disposal kits, such as Deterra, that can make this process simpler. Flushing medication is recommended by the FDA, as the risk of harm from having access to these medications far outweighs the potential risk to the environment or humans from flushing. Patients can access a list of medications that can be flushed on the FDA website, called the FDA Flush List. For patches, patients should fold them in half with the sticky side together and flush them down the toilet.

Naloxone is a medication that rapidly counteracts the effects of opioids, reversing opioid overdoses. Opioid overdoses can be fatal as they overwhelm the brain and disrupt the body's natural drive to breathe. Naloxone temporarily displaces the drug from receptors, restoring breathing and preventing death. The FDA recommends that anyone with a risk of overdosing, including those prescribed opioids, those with a history of substance abuse, or those with household members at risk for accidental ingestion, should have access to naloxone. Naloxone is available as a 2-pack intranasal spray, which should be administered by tilting the patient's head back and administering the spray quickly before placing the patient on their side. If the patient is not arousable within three minutes, the second dose should be administered in the opposite nostril. It's important to note that there is only one dose in each blister, so the spray should not be primed. In case of an overdose, always call 911 as naloxone has a short half-life, and the patient may return to an overdose state without appropriate medical attention.

In Florida, pharmacists have been able to dispense naloxone with a valid prescription and in emergency situations to emergency responders. However, with the new SB 544 amendment, which went into effect on July 1st, 2022, pharmacists can now prescribe naloxone directly to a patient upon request, expanding access to this life-saving drug to a wider population.

Pharmacists play a vital role in combatting the opioid epidemic. Pharmacists can safely dispense controlled substance medications to help avoid misuse and abuse. Pharmacists are frontline healthcare professionals who can counsel patients on proper use of controlled substances and are able to provide resources for those who may need assistance with misuse and abuse.