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Introduction

Opioid use disorder continues to be a significant public health crisis. Based on 2016 National Survey on Drug Use and Health (NSDUH) data, 692,000 adults received treatment for prescription pain reliever abuse and 636,000 adults for heroin abuse.¹ Survey data suggests that 7.3 million adults aged 18 or older needed treatment for an illicit substance use problem, which represents 3% of the United States (US) adult population. Of particular concern, 6.0 million (81.6%) of those adults aged 18 or older requiring treatment for illicit substance use did not receive specialty treatment in the past year.¹

Opioid use disorder is a chronic, relapsing disease. Treatment should be patient- centered and made with patient input. The evidence-based treatment for opioid use disorder is medication assisted treatment (MAT) combined with psychosocial treatment.^2,3 Medically supervised withdrawal or detoxification is when opioid dependent patients receive medications, such as opioid agonists or alpha 2 adrenergic agonists, in a taper to reduce the severity of withdrawal symptoms or assist in induction. Supervised withdrawal is not the treatment of choice for opioid use disorder and should only occur in conjunction with a comprehensive treatment plan.^2,4 When patients receive detoxification treatment alone, the rate of relapse is high.⁴ In the US, methadone, buprenorphine/naloxone, and naltrexone are the available MAT treatment alternatives. Medication selection should be based on willingness to receive pharmacotherapy, preferred/available treatment setting, prior history of response, medication efficacy and safety, and patient comorbidity.^2,5

Methadone

Methadone is a full mu opioid agonist used both for detoxification and the treatment of opioid use disorder. It is a long acting opioid, which is slowly absorbed.

Practice Setting

Methadone can be prescribed for pain and the management of detoxification within various settings. However federal law mandates that methadone can only be prescribed and dispensed for the treatment of opioid use disorder within a licensed opioid treatment program (OTP). There are 1500 licensed OTPs within the United States (US).³ Patients initially receive daily doses of medication at their treatment program. With progressive treatment, demonstration of response, and low risk of diversion, patients work towards receiving take home doses of methadone, which no longer necessitate daily clinic visits. Many OTPs also offer buprenorphine/naloxone, which does not require that the prescriber have a federal waiver, and naltrexone. These medications are generally dispensed and administered using the same OTP regulations and procedure as methadone.³ Since daily visits to an OTP program can be time intensive, there are often limited treatment slots and long waits for this type of program. The practice setting may not be necessary for all patients with opioid use disorder. Treatment is recommended for those with history of OUD, who meet federal OTP criteria, are able to provide consent, and have no contraindications.^2,3 However, patients with history of prior response or who have failed other treatment options may be preferred.

Efficacy

Methadone has been shown to be efficacious in decreasing mortality and opioid use and improving treatment retention compared with drug-free treatment.^2,3 Methadone is associated with superior treatment retention compared with buprenorphine.⁵ Methadone has specifically been shown to decrease overdose-related deaths, improve morbidity by reducing risk of HIV, hepatitis C, and cellulitis, and decrease criminal activity.³ The goals of treatment include preventing opioid withdrawal symptoms, blocking the intoxicating effects of illicit opioids, eliminating opioid craving, and encouraging adherence with psychosocial interventions.²

Dosing

Medication induction involves starting a patient's medication at a low dose and slowly increasing to produce efficacy without causing side effects. The initial methadone dose is selected based on the degree of physical dependence, which is affected by the type, amount, and frequency of opioid abuse. However, dosing should not be determined based on opioid equivalence.³ Methadone must be started low and increase slowly to prevent intoxication and opioid overdose symptoms such as respiratory depression. The American Society of Addiction Medicine's (ASAM) Methadone Action Group recommends a starting dose of 10-30 mg/day with reassessment in 2-4 hours.² Patients who should be started at lower doses include older adults (60 years and older), those with lower opioid tolerance, those taking sedating or interacting prescriptions, and individuals with comorbid alcohol use disorder, respiratory disorders (asthma, chronic obstructive pulmonary disorder, kyphoscoliosis), cardiac arrhythmias, sleep apnea, electrolyte disturbances, and obesity.³ Federal law requires that the initial dose be no greater than 30 mg and not exceed 40 mg in the first day.⁶ Patient doses may be increased in 5-10 mg increments every seven days. Methadone has a long half-life. The full effect of a dose increase may not be apparent to a patient for at least 4 days.³ Most patients will be maintained on doses of 60-120 mg/d. However, the dose should be titrated to the minimum necessary to prevent craving, withdrawal, and illicit opioid effects and can vary substantially among patients. The data sugge that patients demonstrate improved efficacy on higher doses of methadone.² Because of the increasing potency of illicit/street opioids, some patients require methadone doses greater than 120mg/d. While methadone serum levels are not generally monitored to assess efficacy, they can be used to evaluate metabolism (rapid, slow) and toxicity.²

Side effects/Toxicity and Drug Interactions

Side effects commonly attributed to methadone include constipation, nausea, vomiting, hypotension, hyperhidrosis, sexual dysfunction, weight gain, edema, dizziness, and sedation. Methadone can produce dose-related cardiac arrhythmias including QTc prolongation and torsades de pointes. Before initiating methadone, patients should receive a medical work up to assess for structural heart disease, arrhythmia, or syncope. Electrocardiogram (EKG) monitoring should be ordered for patients receiving high methadone doses (>120 mg/d), having a history of QTc prolongation, or receiving other medications which may prolong QTc interval.² QTc prolongation greater than 500 milliseconds is associated with increased risk for lethal ventricular arrhythmias.³ Safer treatment alternatives such as buprenorphine or naltrexone may need to be considered for those with significant cardiac dysfunction.²

Compared with other MAT alternatives, methadone is associated with the greatest amount and most significant drug-drug interactions. This agent is metabolized primarily by the CYP450 3A4 system. Medications that significantly affect this enzyme system can produce methadone drug interactions. However, other CYP450 enzymes such as CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6 also affect methadone's metabolism to a lesser degree.⁷ Enzyme inducers, particularly CYP450 3A4 inducers, or medications that may decrease methadone levels can cause opioid withdrawal symptoms and increase risk for relapse, while medications which increase methadone such as inhibitors produce toxicity such as sedation, respiratory depression, severe constipation/bowel impaction, and QTc prolongation.⁷ Nelfinavir, efavirenz, nevirapine, rifampin, ritonavir, carbamazepine, phenytoin, and phenobarbital are all examples of medications that may decrease levels.^3,8 Amiodarone, cannabinoids, ciprofloxacin, clarithromycin, erythromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, fluconazole, metronidazole, miconazole, norfloxacin, omeprazole (slight), cimetidine, quinine, saquinavir, zafirlukast, fluvoxamine, fluoxetine, sertraline, paroxetine may increase methadone levels.^3,8 Medications with similar pharmacodynamics effects may exacerbate methadone side effects. For instance, combining benzodiazepines and/or alcohol with methadone can worsen respiratory depression. Anticholinergic medications exacerbate constipation. Antipsychotics, tricyclic antidepressants, and calcium channel blockers are associated with QTc prolongation.

Treatment Duration

The duration of treatment remains unclear. However, the risk for relapse with medication discontinuation is significant.^2,3 Patients may require extended treatment. The decision to discontinue should be made with the patient. Methadone should be restarted in patients who relapse upon discontinuation. Patients who discontinue treatment and then relapse are at greater risk for opioid overdose-related death and should be counseled accordingly.

Switching from Methadone to Buprenorphine/Naloxone

Patients who are experiencing significant side effects or prefer a treatment-setting alternative may be candidates for switching to buprenorphine/naloxone. Because methadone is a full opioid agonist and buprenorphine/naloxone is only a partial agonist, care must be taken to prevent inducing withdrawal symptoms. Patients should also be closely monitored for risk of relapse. The methadone dose should be slowly tapered to 30-40mg/d and then discontinued. Once mild to moderate withdrawal symptoms develop, buprenorphine may be administered to prevent naloxone-induced withdrawal symptoms.² It usually takes at least 24 hours opioid-free for symptoms to develop. Patients may be less likely to experience precipitated withdrawal after 36 hours. The Clinical Opiate Withdrawal Scale (COWS) has been validated as an objective tool for monitoring acute opioid withdrawal severity.^9,10 Buprenorphine should not be started until patient has a COWS score of at least 12. ASAM recommends the patient should receive an initial buprenorphine dose of 2 to 4 mg and then be observed for one hour. However, other guidelines suggest the combined buprenorphine/naloxone product can be initiated safely.³ If opioid withdrawal symptoms persist, one to two additional doses of 2 mg can be dispensed to be taken as needed.^2,3

Buprenorphine/Naloxone

Buprenorphine is a partial mu-agonist. In the absence of a full agonist, buprenorphine produces agonist effects. However, when administered with a full agonist, buprenorphine has strong binding capacity and can displace the full agonist from opioid receptors resulting in precipitated withdrawal symptoms. A combination buprenorphine/naloxone product is often preferred for the treatment of opioid use disorder. Naloxone is an opioid antagonist, which is added to the formulation solely to prevent diversion. Naloxone has poor oral and sublingual bioavailability. Consequently, very little is absorbed when the patient administers the product as directed by the manufacturer. However, if buprenorphine/naloxone is injected, naloxone becomes systemically bioavailable and can produce precipitated withdrawal.

Practice Setting

The Drug Addiction Treatment Act of 2000 (DATA 2000) expanded access to opioid use disorder treatment by allowing specially waivered physicians to prescribe medication outside of a licensed OTP.^2,3 This is known as office based opioid treatment or (OBOT). DATA 2000 allows for opioid medications scheduled III through V with a Food and Drug Administration (FDA) indication for the treatment of opioid dependence to be prescribed. The prescriber can treat patients directly within the outpatient office or clinic and the medications can be dispensed within a local pharmacy. The only medications which currently meet DATA 2000 requirements are buprenorphine and buprenorphine/naloxone. In order to obtain a waiver, the physician must be licensed under state law, registered to prescribe controlled substances with the Drug Enforcement Administration (DEA), and qualified by training in addiction medicine or completion of an eight-hour certification program.² Initially, prescribers are limited to treat no more than 30 patients. However, after one year, the prescriber can apply to have the waiver capacity expanded.³ Prescribers are assigned a unique DEA number which starts with a "X" and is often known as a "X license". In 2017, the Comprehensive Addiction Recovery Act (CARA) was passed, which further expanded treatment of opioid use disorder to allow waivered nurse practitioners and physicians assistants to also prescribe buprenorphine within an office setting for the treatment of opioid dependence and expanded the maximum number of patients that can be treated by a physician from 100 to 275.³ Patients can be referred to Substance Abuse and Mental Health Services Administration's (SAMHSA) website to locate a waivered prescriber (https://www.samhsa.gov/medication-assisted-treatment/physician-program-data/treatment-physician-locator). However, participation with this list is voluntary and not all prescribers choose to be included. The National Alliance of Advocates for Buprenorphine Treatment (www.treatment match.org/TM_index.php) also offers free assistance finding providers.

Efficacy

Buprenorphine/naloxone has been shown to be effective in treating opioid use disorder compared with placebo and reduces HIV transmission risk and opioid overdose related deaths.³ While methadone appears to be associated with better treatment retention compared with buprenorphine/naloxone, the latter is equally effective in reducing opioid use evidenced by negative urine drug screens and is considered as effective as lower dose methadone.⁵ Because buprenorphine/naloxone can be prescribed in a community setting with less restrictions, it may be preferred for some patients. The treatment goals are similar to methadone, which are to prevent opioid withdrawal, avoid opioid intoxicating effects, reduce craving, and enhance psychosocial interventions.²

Dosing

Since buprenorphine is a partial agonist, initiating treatment can sometimes be difficult. There are three phases to dosing: induction, stabilization and maintenance. The patient must be opioid-free long enough to produce mild to moderate withdrawal symptoms before initiating the medication. Otherwise, buprenorphine will displace the full agonist from the opioid receptors and precipitate withdrawal.³ Withdrawal symptoms can be measured using an objective rating scale such as Clinical Opioid Withdrawal Scale (COWS).^9,10 A COWS score of up to 12 is associated with mild withdrawal, while 13-24 is considered moderate withdrawal. Buprenorphine should not be initiated for at least 6 to 12 hours after last use of a short-acting opioid, such as heroin, and 24 to 72 hours after a long-acting opioid such as methadone with a COWS score of at least 11-12.²

Guidelines recommend buprenorphine induction be observed by a clinician. The patient is provided an initial buprenorphine/naloxone dose of 2/0.5 to 4/1 mg and can receive additional doses of up to 8/2 mg total in the first day, based on response (relief of opioid cravings and withdrawal, absence of precipitated withdrawal or other side effects). Patients, recently incarcerated or at significant risk for relapse, may be treated with buprenorphine/naloxone despite the fact that they are not currently opioid dependent.³ These individuals should be started on lower doses.

After the first day, the buprenorphine/naloxone dose is further titrated over a one to three day period. Newer literature suggests that patients may successfully complete unobserved induction in a home setting with proper education.^3,12,13,14 Home-based induction should be reserved for buprenorphine-experienced patients and providers.²

Once the patient reaches a stabilizing dose, the individual can return for less frequent appointments. Most patients are monitored initially every seven days, which is when they will receive the next medication refill. The frequency of monitoring is reduced as the patient successfully progresses through treatment with most stable patients returning only monthly. Once the optimal dose is determined, there is usually little fluctuation, unless there is a change in medical or medication history. Most patients will respond to a dose between 8 and 16 mg/d, with some needing up to 24 mg/d.² Doses above 24 mg are not associated with increased efficacy and may increase risk for diversion. Buprenorphine/naloxone can be legally refilled in many states. However, the patient will continue to require close monitoring for relapse and diversion.

Newer formulations of buprenorphine/naloxone have higher bioavailability allowing for even lower dosing (Table 1). In addition, there are two injectable formulations (implant, long acting injectable), which were developed to improve adherence and reduce diversion. The buprenorphine implant and long-acting injectable formulations do not contain naloxone, since risk for diversion is lower and systemic exposure to naloxone would produce precipitated withdrawal. The implant must be inserted through a minor surgical procedure within a prescriber's office and delivers the equivalent of 8 mg or less of buprenorphine per day. The plasma concentrations start 12 hours after insertion and reach steady state in four weeks. The implants should be replaced after 6 months. The long acting buprenorphine injectable must be administered by a healthcare provider and should be started only after at least seven days of sublingual buprenorphine/naloxone administration.³ The patient should receive 300mg once a month for 2 months and then a maintenance dose of 100mg per month. The maintenance dose can be further increased to 300mg per month, if warranted. Healthcare providers and pharmacies must have special certification to order and dispense this product as part of the Sublocade Risk Evaluation and Mitigation Strategy (REMS) program. Pharmacies must ensure that the prodcut is dispensed directly to healthcare providers only.

Side Effects/Toxicity and Drug Interactions

Common buprenorphine-associated side effects include headache, gastrointestinal upset, constipation, anxiety, lower extremity edema, sweating, and sleep disturbance. Compared with methadone, buprenorphine/naloxone is less likely to cause severe opioid overdose symptoms like respiratory depression.²¹ The risk is greatest when buprenorphine is injected and/or combined with respiratory depressants, such as benzodiazepines or alcohol.²² Buprenorphine does not produce significant QTc prolongation and may be a safer alternative compared to methadone for opioid use disorder patients with a history of cardiac arrhythmias.²³ Buprenorphine is primarily metabolized by CYP3A4 but is associated with significantly less serious drug-drug interactions compared with methadone. Rifampin is a CYP3A4 inducer, which has been shown to affect buprenorphine and increase risk for opioid withdrawal. Reports suggest that atazanavir can increase buprenorphine resulting in increased sedation.⁷ There are FDA-approved REMS for all buprenorphine formulations.

Treatment Duration

As is the case with methadone, the exact duration of treatment remains unclear and the decision to taper should made based on patient input with consideration of risks versus benefits . When the medication is to be discontinued, the dose is generally slowly tapered over months to prevent relapse.² Characteristics associated with effective medication discontinuation include employment, sustained abstinence, positive psychosocial environment and supports, and sustained treatment engagement.² Psychotherapy should continue after medication discontinuation. Patients should be educated about risk for overdose-related death with relapse. Buprenorphine/naloxone should be restarted in patients who relapse.

Switching from Buprenorphine/Naloxone to Naltrexone

Buprenorphine/naloxone should be discontinued for 7 to 14 days before starting naltrexone to prevent precipitated withdrawal.² A naloxone challenge can be administered to ensure the pateint is no longer opioid dependent before starting naltrexone.

Switching from Buprenorphine/Naloxone to Methadone

Because this is a switch from partial to full opioid agonist, no delay in therapy is necessary.²

Naltrexone

Naltrexone is a long-acting, opioid antagonist. Naltrexone reduces the intoxicating effects associated with opioid use.

Practice Setting

Naltrexone has no regulatory restrictions for prescribing. It is sometimes offered as a treatment option within licensed OTPs. However, it can be prescribed within an outpatient setting by any healthcare professional licensed to prescribe medications including physicians, nurse practitioners, physician assistants, and pharmacists under collaborative drug therapy management agreements. Depending on the formulation prescribed, there are administration issues, which may limit the practice setting.

Efficacy

Naltrexone has been available in an oral formulation for many years. However, data suggest that the oral formulation was only efficacious in managing opioid use disorder in patients who were highly motivated or received mandated/supervised administration.² To improve adherence, a monthly injectable was developed. Studies comparing naltrexone extended release injectable to placebo found reduction in opioid use and improved treatment retention.^3,24,25 Recently published Norwegian and US trials comparing extended release naltrexone injectable and sublingual buprenorphine/naloxone found that both agents had similar effectiveness and retention, once a patient was successfully induced.^26,27 However, the US trial had significantly more patients who were successfully induced on buprenorphine/naloxone. Treatment goals should include preventing relapse in those who are no longer opioid dependent, blocking the effects of opioids, managing opioid craving, and enhancing treatment recovery.² Naltrexone is preferred by some patients, since it is not an opioid.³ In addition, it may be a good alternative for patients who do not have access to opioid agonist treatment due to limited treatment options or incarceration. Naltrexone is also indicated for alcohol use disorder and may be beneficial for patients with this comorbidity.

Dosing

Patient must be opioid-free for at least 7 days before initiating and should have an opioid negative urine screen. While not required, a naloxone challenge can be administered to assess for opioid dependence before starting naltrexone.^2,3 Oral naltrexone can be dosed daily (50 mg/d) or three times per week (two 100 mg doses, followed by one 150mg). The extended release formulation is administered with manufacturer-provided customized needles as 380 mg once per month intramuscularly to gluteal muscle. Patients who are obese may require longer needles.²² With each injection, the buttocks administration site should be alternated. Oral administration is not required, and there is no available data on switching from the oral to extended release injectable formulation. To improve comfort with administration, allow the medication to come to room temperature for 45 minutes.²² As of 2018, 40 states have legislation allowing pharmacists to administer injectables other than immunizations to patients.²⁸ Extended-release naltrexone administration within a pharmacy setting could allow patients more flexibility and expand access to treatment.

Side effects/Toxicity and Drug-Drug Interactions

Naltrexone has few serious side effects. The most common side effects include insomnia, dizziness, sedation, anxiety, gastrointestinal effects (nausea, vomiting, abdominal pain), headache, anorexia, precipitated withdrawal, and muscle cramps.^2,29 The injection is associated with site-specific irritation. Hepatoxicity and hepatitis have occurred. Hepatitis C is a frequent comorbidity for patients with opioid use disorder but is not an absolute contraindication. Data suggest that patients with hepatitis C can be safely treated with extended-release injectable naltrexone.³⁰ The risk and benefit of using naltrexone should be considered, when deciding whether to treat with this medication. Patients who recently discontinued opioid use and relapse are at greater risk for overdose-related death. Of particular concern with naltrexone, patients must remain opioid-free for 7 days or more before the medication can be initiated. Naltrexone is not associated with significant drug-drug interactions beyond the blockade of opioid analgesia.

Treatment Duration

The optimal treatment duration is unclear and should be based on patient response and preference, as well as clinical judgement.² Medication can be discontinued without taper as there is no risk for withdrawal.

Switching from Methadone or Buprenorphine/Naloxone to Naltrexone

Patients switching to naltrexone must be completely opioid-free before starting this medication. In most cases, this may take 7 days but can be up to 14 days, especially with longer acting opioids such as methadone. Since naloxone is a shorter acting opioid antagonist, patients may receive a naloxone challenge dose followed by monitoring for precipitated withdrawal before starting naltrexone.²

Switching from Naltrexone to Opioid Agonists

Patients are not at risk for opioid withdrawal. Methadone or buprenorphine/naloxone can be initiated once most of the naltrexone is out of the patient's system (24 hours for oral, 30 days for injection). However, patients may require lower starting doses than those used with individuals who are currently opioid dependent to prevent intoxication or opioid overdose symptoms.²

Patient Monitoring with MAT^2,3

Upon initiation of MAT, patients should be offered screening for HIV and hepatitis. Patients should receive routine monitoring for efficacy, toxicity, and diversion. Many patients will benefit from weekly or more frequent monitoring during treatment initiation. Urine drug testing (routine and random) can be utilized to determine, if the patient is continuing to abuse opioids or other illicit substances and is adherent with some medications such as buprenorphine. However, the pharmacist must be familiar with the specific urine drug analysis. Some tests do not screen for synthetic opioids such as buprenorphine or fentanyl. Patients who continue to abuse opioids may require higher doses of MAT and/or increased level of treatment as opposed to treatment discontinuation. The pharmacist can assist in monitoring by ensuring that a patient is regularly and timely filling prescriptions. Internationally, pharmacists are responsible for monitoring observed dosing within the pharmacy and may partner with treatment programs in future in the US. In addition, pharmacists should routinely review the state Prescription Drug Monitoring Program (PDMP). Methadone is often excluded from PDMP data. Pharmacists and technicians should be familiar with state PDMP law, which can vary. Pharmacists should encourage patients to obtain their MAT prescriptions from the same pharmacy to allow for better patient care. When possible, pharmacists should routinely stock MAT and encourage patients to fill prescriptions early enough before they run out to prevent risk for opioid withdrawal and relapse. Diversion has been reported with buprenorphine and buprenorphine/naloxone. However, patient surveys suggest that buprenorphine monotherapy has more abuse potential and that the combination product is often diverted for self-medication.^31,32,33,34 Diversion can be reduced by regular monitoring, urine drug testing, observed dosing, and pill counts. Patients treated with buprenorphine/naloxone should be educated to secure medications to prevent theft and to properly dispose of unused doses.

MAT and Pregnancy/Breastfeeding

Ideally, pregnant women should be managed by a treatment team that includes an obstetrician and an addiction psychiatrist. Opioid agonist treatment is preferred in many pregnant women, since the long-term risk of continued opioid use outweighs the minimal risk of developmental effects.^1,35 Opioid withdrawal is associated with significant risk for OUD relapse and neonatal abstinence syndrome (NAS) and is not considered the treatment of choice in managing opioid use disorder in pregnant women. Data supports treatment with opioid agonist therapy (methadone or buprenorphine).³ Methadone metabolism can increase during pregnancy. Pregnant women who are started on methadone should have their dose titrated to efficacy (amelioration of craving and withdrawal).³⁵ Methadone dosing may need to be adjusted (dosed more frequently than once per day and/or dose increased) throughout pregnancy, but particularly during the third trimester to prevent withdrawal, due to altered pharmacokinetics and physiologic changes.³⁵ Lower doses of methadone are not associated with less NAS.³⁵ There is conflicting information as to whether to treat with buprenorphine monotherapy or buprenorphine/naloxone. Many references suggest the former to prevent NAS. However, the American College of Obstetricians and Gynecologists note that recent data suggest there is no increased risk with the combination product and that the standard for treatment is likely to change as more data becomes available.³⁵ The buprenorphine dose does not generally need to be increased throughout pregnancy. Patients stabilized on methadone should not transition to buprenorphine or buprenorphine/naloxone during pregnancy in order to prevent precipitated withdrawal. During labor, methadone or buprenorphine should be continued along with the additional pain relief as preferred by the patient.³⁵ Patients may require higher opioid doses due to tolerance. Naltrexone has not been well studied and is not recommended for initiation during pregnancy. The risks versus benefits of treatment should be discussed with women who were stabilized on naltrexone before becoming pregnant. It is unclear if naltrexone should be continued.³ Patients who discontinue naltrexone and return to opioid use should receive buprenorphine or methadone. Women may breastfeed while taking methadone or buprenorphine/naloxone as little passes into the breastmilk.³⁵

Summary

MAT has been shown to be more effective than placebo or no medication in reducing illicit opioid use and risk of opioid overdose and improving treatment retention. Patients with untreated opioid use disorder should be referred for treatment including MAT. Pharmacists can assist in the optimizing patient care by assisting in medication management and monitoring, and patient education. Table 2 provides a comparator summary of MAT and Table 3 offers a general cost comparison for medications most commonly seen in community pharmacies.

References

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