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Medications for Opioid Use Disorder: For Healthcare and Addiction Professionals, Policymakers, Patients, and Families: Updated 2021 [Internet]. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2018. (Treatment Improvement Protocol (TIP) Series, No. 63.)

Cover of Medications for Opioid Use Disorder

Medications for Opioid Use Disorder: For Healthcare and Addiction Professionals, Policymakers, Patients, and Families: Updated 2021 [Internet].

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Chapter 3C: Naltrexone

Chapter 3C gives an overview of naltrexone pharmacology and specific guidance on dosing for oral and injectable naltrexone.

The opioid receptor antagonist naltrexone was synthesized in the 1960s to block the euphoric effects of morphine.162 Oral naltrexone was approved by the Food and Drug Administration (FDA) in 1984 for the blockade of the effects of exogenously administered opioids. Long-acting, sustained-release opioid agonist preparations have been investigated since the 1970s to improve adherence over oral medications. In 2010, FDA approved injectable extended-release naltrexone (XR-NTX) for preventing return to opioid dependence after medically supervised withdrawal.

Despite its potential advantages (e.g., no abuse liability, no special regulatory requirements), oral naltrexone is not widely used to treat opioid use disorder (OUD) because of low rates of patient acceptance, difficulty in achieving abstinence for the necessary time before initiation of treatment, and high rates of medication nonadherence.163

Before initiating either formulation of naltrexone, patients must be opioid abstinent for an adequate period of time after completing opioid withdrawal. Medically supervised opioid withdrawal can be conducted on an outpatient or inpatient basis. The latter is often reserved for patients with co-occurring substance use disorders (SUDs) or medical or psychiatric illness.

There are several pharmacological approaches to medically supervised withdrawal. Methadone can be used for this purpose in opioid treatment programs (OTPs) and hospital settings. Patients in opioid withdrawal typically receive an individualized dose between 20 mg and 30 mg per day, gradually reduced over 6 days or more. Buprenorphine can be used in an adequate dose to lessen withdrawal symptoms and then reduced gradually over several days or more. If an opioid agonist is used for medically supervised withdrawal, an adequate interval of time following the last dose must occur before naltrexone induction. When it is not possible to use opioid agonists, alpha-2 adrenergic agonists such as clonidine can be used off label at doses from 0.1 mg to 0.3 mg every 6 to 8 hours to treat symptoms.164

Formulations

Oral: Oral naltrexone is a 50 mg tablet of naltrexone hydrochloride. It was approved by FDA in 1984 for blockade of the effects of exogenously administered opioids and in 1994 for alcohol dependence treatment. A Cochrane review examined 13 randomized trials among 1,158 patients who were opioid dependent and provided counseling. They were treated with or without oral naltrexone. The review concluded that oral naltrexone was not superior to placebo or to no medication in treatment retention or illicit opioid use reduction.165

XR-NTX: In 2006, FDA approved XR-NTX as an intramuscular (IM) injection every 4 weeks or once a month for the treatment of alcohol dependence. In 2010, FDA approved XR-NTX for the prevention of return to opioid dependence following medically supervised withdrawal. XR-NTX is a suspension of 380 mg naltrexone embedded in microspheres made from a biodegradable copolymer that undergoes hydrolysis as it absorbs water. XR-NTX requires refrigeration and is supplied as a vial of dry powder along with a separate vial of an aqueous diluent, which providers combine just before use.166

XR-NTX is more effective than placebo167 or no medication168 in reducing risk of return to opioid use.169 A multisite randomized trial in the United States started in residential treatment programs found that buprenorphine treatment was associated with lower rates of return to use during 24 weeks of postdischarge outpatient treatment compared with XR-NTX,170 given the significant proportion of patients who did not actually receive XR-NTX because of challenges related to XR-NTX induction. The same study found no significant between-group differences in rates of return to use when data were analyzed based solely on patients who did begin assigned medications. Study findings may not generalize to outpatient settings, where XR-NTX induction may be more difficult than in residential treatment settings.

One additional study merits mention. A 12-week trial was conducted in Norway with 159 participants who, at the time of random assignment to XR-NTX or buprenorphine, had completed medically supervised withdrawal or were already opioid abstinent. XR-NTX was found to be noninferior to buprenorphine in terms of treatment retention or reduction in illicit opioid use.171

Pharmacology

Naltrexone is a competitive mu-opioid receptor antagonist with strong receptor affinity. Naltrexone does not activate the mu-opioid receptor and exerts no opioid effects. Unlike opioid agonists, naltrexone will not alleviate withdrawal symptoms, will not cause withdrawal when stopped, and cannot be diverted.

If patients maintained on naltrexone use opioid agonists, naltrexone can block their effects—a key feature of its therapeutic efficacy. However, because the interaction at the receptor is competitive, the blockade can potentially be overridden with high doses of opioids.

Taking naltrexone after recent use of opioids can precipitate opioid withdrawal. Given its strong affinity, naltrexone can displace other opioids from the receptor. Patients must typically wait 7 to 10 days after their last use of short-acting opioids and 10 to 14 days after their last use of long-acting opioids before taking their first dose of naltrexone.

Bioavailability

Oral: The gastrointestinal tract readily absorbs oral naltrexone. Peak concentrations occur in 1 to 2 hours.172

XR-NTX: IM injection causes a transient peak blood concentration 2 hours after injection and another at 2 to 3 days after injection.173 About 14 days after injection, concentrations gradually diminish, with measurable blood levels for more than 1 month.

Both formulations are extensively metabolized by the kidneys and liver, but without CYP450 enzyme system involvement. Unlike methadone and buprenorphine, naltrexone has limited potential drug–drug interactions. Its major metabolite, 6-beta naltrexol, is also a mu-opioid receptor antagonist. It is eliminated primarily by the kidneys in the urine.174

Orally administered naltrexone has a half-life of approximately 4 hours. Its primary metabolite, 6-beta-naltrexol, is a weak mu-opioid receptor antagonist with a half-life of approximately 12 hours.175

XR-NTX, or “depot naltrexone,” is encapsulated in biodegradable polymer microspheres. It provides opioid blockade by delivering steady naltrexone concentrations for about 1 month.176 Elimination half-life is 5 to 10 days. Repeated administration causes no accumulation of naltrexone or its metabolites.

Dosing Considerations

XR-NTX

XR-NTX is indicated for the prevention of return to opioid dependence following medically supervised opioid withdrawal. Appropriate patients should have an adequate period of abstinence with no signs of opioid withdrawal before XR-NTX administration. Patients must be willing to receive monthly IM injections. Become acquainted with the FDA label for XR-NTX, which is available online (https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd11c435-b0f0-4bb9-ae78-60f101f3703f).

Contraindications

Contraindications to receiving XR-NTX (as well as to receiving oral naltrexone, with the exception of hypersensitivity to the XR-NTX suspension and diluent) include: 177

Current pain treatment with opioid analgesics.

Current physiological opioid dependence.

Current acute opioid withdrawal.

Severe hepatic impairment.

Naloxone challenge (Exhibit 3C.1) or oral naltrexone dose causing opioid withdrawal symptoms.

History of hypersensitivity to naltrexone, polylactide-co-glycolide, carboxymethylcellulose, or any other components of the diluent.

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EXHIBIT 3C.1. Naloxone Challenge.

Research suggests that patients who test positive for current opioid use are not contraindicated for XR-NTX induction as long as they pass the naloxone challenge, indicating they are not opioid dependent.178 In one study, patients being transitioned to XR-NTX using a 7-day detoxification protocol could safely begin receiving XR-NTX as long as they passed a naloxone challenge on Day 8 of the protocol, even if they were unable to completely refrain from using opioids during the transition period.179,180 Patients who tested positive for either methadone or buprenorphine were excluded from enrollment in the study, however.

Precautions and warnings

Discuss the risks and benefits of continuing naltrexone with patients who become pregnant while receiving naltrexone treatment and whose OUD is in remission. Unlike methadone and buprenorphine, naltrexone has been little researched in pregnant populations.181,182

Patients are vulnerable to opioid overdose death after completing the every-4-weeks or once-monthly dosing period, missing a dose, or stopping treatment. Trying to override opioid blockade with high opioid doses may cause overdose.

Patients may experience injection site reactions including pain, tenderness, induration, swelling, erythema, bruising, or pruritus. Severe injection site reactions may occur (e.g., cellulitis, hematoma, abscess, sterile abscess, necrosis). Some cases may require surgical intervention and may result in significant scarring. (See the Chapter 3C Appendix for techniques to reduce injection site reactions.) As with any IM injection, use caution in patients with thrombocytopenia or a coagulation disorder.

Precipitated opioid withdrawal can occur in patients who used illicit opioids recently or switched from an opioid agonist medication. Symptoms may be severe enough for hospitalization. To avoid precipitated withdrawal from either formulation, patients should typically stop use of short-acting opioid agonists for 7 to 10 days and long-acting agonists for 10 to 14 days.183 There is also research on approaches to initiate XR-NTX more quickly for patients physically dependent on opioid agonists.184,185,186

Hepatitis has been associated with XR-NTX, often in the presence of other potential causes of hepatic toxicity (e.g., alcohol liver disease, viral hepatitis). Monitor liver function tests during treatment. Discontinue treatment in the presence of acute hepatitis and severe liver disease.187 Initiate or refer patients to treatment for hepatitis.

Use cautiously in patients with moderate-to-severe renal impairment, because the medication is eliminated primarily through the kidneys.

Hypersensitivity reactions can occur, including rash, urticaria, angioedema, and anaphylaxis.

Monitor patients with OUD for depression and suicidal ideation. Oral naltrexone use has been occasionally associated with dysphoria,188 although it's unclear whether this is a side effect of the medication or a manifestation of underlying depression or depressed mood related to OUD.189 Monitor patients for depression, which is common with OUD.

If a patient needs emergency pain treatment, regional anesthesia or nonopioid analgesics are alternatives to opioid analgesics. A patient who must have opioids for pain treatment or anesthesia requires continuous monitoring in an anesthesia care setting.

Side effects

Possible side effects of XR-NTX include (see the FDA label for a complete list https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd11c435-b0f0-4bb9-ae78-60f101f3703f):192

Insomnia.

Injection site pain.

Hepatic enzyme abnormalities.

Nasopharyngitis.

Assessment

Thorough assessment helps determine whether naltrexone treatment is appropriate for a patient. (Part 2 of this Treatment Improvement Protocol [TIP] covers screening and assessment in more detail.)

Patients who have been abstinent from short-acting opioids (including tramadol) for 7 to 10 days or long-acting opioids (e.g., methadone, buprenorphine) for 10 to 14 days can initiate naltrexone following assessment that includes:

Checking the state prescription drug monitoring program database.

Taking the patient's history.

-

Conduct a medical, psychiatric, substance use, and substance use treatment history.

-

Assess recent opioid use, including frequency, quantity, type, route, and last day of use. Confirm an adequate opioid abstinence period.

-

Establish OUD diagnosis.

-

Assess for other SUDs, including those that involve alcohol, benzodiazepines, or stimulants.

Conducting a physical exam.

-

Assess for signs and symptoms of intoxication. Do not give a first dose to a patient who is sedated or intoxicated. Assess and treat him or her appropriately.

-

Assess for evidence of opioid withdrawal and physiological dependence. The Clinical Opioid Withdrawal Scale (COWS) or the Clinical Institute Narcotic Assessment (CINA) Scale for Withdrawal Symptoms can be used to assess withdrawal signs (see “Resource Alert: Opioid Withdrawal Scales”). The patient should not exhibit any signs of opioid withdrawal before taking the first dose of naltrexone, to avoid precipitated withdrawal.

Obtaining laboratory tests.

-

Conduct drug and alcohol tests. Use reliable urine tests for opioids (including morphine, methadone, buprenorphine, and oxycodone), benzodiazepines, cocaine, and other drugs commonly used in the area. Use a breathalyzer to estimate the patient's blood alcohol content.

-

Conduct a pregnancy test. Naltrexone is not recommended for OUD treatment in pregnancy. Refer pregnant patients to prenatal care.193

-

Assess liver function. Obtain liver function tests followed by periodic monitoring at 6- or 12-month intervals during treatment.194

-

Obtain kidney function tests (e.g., creatinine) for people who inject drugs.

-

Conduct hepatitis and HIV tests. Hepatitis B and C are common among patients entering naltrexone treatment. HIV infection is also prevalent. Everyone ages 15 to 65 should be tested at least once for HIV. Persons at higher risk, such as people who use drugs by injection, should be tested annually.195 Anyone who is injecting or has ever injected drugs, even once, no matter how long ago, should be tested for hepatitis C, regardless of their intention to seek treatment for SUD.196 The Centers for Disease Control and Prevention recommends hepatitis B vaccine for individuals seeking treatment for SUDs.197

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RESOURCE ALERT.

During assessment, discuss with patients the risks and benefits of naltrexone and alternative treatment approaches. Explore patients' motivation to initiate medication treatment and to adhere to the dosing regimen. Start naltrexone if the patient:

Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for OUD.

Understands risks and benefits.

Reports opioid abstinence for 7 to 10 days (short acting) or 10 to 14 days (long acting).

Reports no allergies to naltrexone or the components of the XR-NTX preparation.

Does not have a coagulation disorder.

Will not soon require opioid analgesia.

Has a negative pregnancy test.

Has a negative urine opioid screen for morphine, methadone, buprenorphine, oxycodone, and other opioids.

Is free of current opioid withdrawal signs and symptoms (Exhibit 3C.2).

Has liver function test results that do not indicate acute hepatitis or liver failure.

Has a negative naloxone challenge result (Exhibit 3C.1).

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EXHIBIT 3C.2. Signs and Symptoms of Opioid Withdrawal.

Patient selection

No evidence clearly predicts which patients are best treated with XR-NTX versus other OUD medications. A secondary analysis of the data from a randomized trial of XR-NTX versus placebo conducted in Russia found no significant baseline predictors of successes among the 25 variables examined, including demographics, clinical severity, level of functioning, craving, and HIV serostatus.198

Inform patients of all their treatment options and the settings in which they are available. OTPs may be best for patients needing more structure. Tailor decisions about which medication to use to patients' medical and substance use histories, patient preferences, and treatment availability.

Pregnant women are not appropriate candidates for XR-NTX treatment.

Potentially suitable candidates for XR-NTX treatment include patients who: 199

Do not wish to take opioid agonists.

Have been opioid abstinent for at least 1 week, have recently been or will soon be released from controlled environments (e.g., incarceration, residential addiction treatment), and do not wish to initiate (or are not able to access) opioid agonist treatment. For patients requesting opioid agonist treatment, methadone or buprenorphine must be started at much lower doses and increased much more slowly than for opioid-tolerant patients (see sections on methadone and buprenorphine dosing).

Have not responded well to prior adequate treatment with opioid agonist therapy.200

Are part of an overall program with external monitoring and significant, immediate external consequences for lack of adherence (because these patients [e.g., healthcare professionals, pilots, probationers, parolees] may show higher rates of retention with XR-NTX because of required external monitoring).201

Have home locations or work schedules making daily or almost-daily OTP visits impossible or risky (e.g., job loss).

One study demonstrated that stable patients who were able to taper to 8 mg or less of buprenorphine may be successfully started on XR-NTX using a regimen consisting of a buprenorphine taper and ancillary medications to palliate withdrawal symptoms.202 The study employed a hybrid outpatient and residential care model and excluded patients who consistently tested positive for illicit or nonprescribed opioids.

Informed consent

Inform all patients of the following basic information:

Their OUD diagnosis and the nature of the disorder

Risks and benefits of XR-NTX and other OUD medications

Risks and benefits of nonmedication treatments

Consider asking patients to sign a treatment agreement form before starting treatment. (See Appendix 3C for a sample treatment agreement.) Document informed consent discussions in the medical record.

Educate patients and their families about what to expect from XR-NTX treatment (Exhibit 3C.3). A naltrexone medication guide should be dispensed to patients with each injection. Caution them about increased risk of overdose if they stop treatment and return to illicit opioid use or attempt to override the receptor blockade of XR-NTX. Document education in the medical record. Chapter 3C Appendix has a patient education counseling tool for XR-NTX.

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EXHIBIT 3C.3. Key Points of Patient Education for XR-NTX.

Use language and written materials appropriate to each patient's comprehension level to ensure that he or she understands the options and can make informed decisions.

Initiating XR-NTX treatment

Storage and preparation

A pharmacy will send XR-NTX and its diluent in a refrigerated package with two sets of administration needles (1.5 and 2 inches), a 1-inch preparation needle, and a needle protection device.

The XR-NTX microspheres are temperature sensitive. When the carton arrives from the pharmacy, store it in a refrigerator at 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius). The refrigerator should have a working thermometer; check the temperature regularly.

Do not freeze the carton or expose it to temperatures above 77 degrees Fahrenheit (25 degrees Celsius). XR-NTX can be stored unrefrigerated for up to 7 days before administration.

Before preparing XR-NTX for administration, keep it at room temperature for about 45 minutes. Examine the microspheres and diluent to ensure that no particulate matter or discoloration are present. Mix following FDA-approved package insert directions, using the 1-inch preparation needle. Resulting suspension should be milky white, without clumps, and able to move freely down the wall of the vial.

Two sets of needles of two different lengths are shipped with the medication in case the first needle clogs before injection. Use the 1.5-inch needle for lean patients and the 2-inch needle for patients with more subcutaneous tissue overlying the gluteal muscle. The longer needle helps ensure that the injection reaches the muscle. Inject patients with average body habitus with either needle.

Administration

Administer XR-NTX every 4 weeks or once a month as a 380 mg IM gluteal injection. Alternate buttocks for each 4-week injection. Given the risk of severe injection site reactions, FDA requires a risk evaluation and mitigation strategy (www.vivitrolrems.com) for XR-NTX including a patient counseling tool, a patient medication guide, and a visual aid to reinforce proper XR-NTX injection technique.

Follow-up care after first dose

Examine patients within a week of administering their first XR-NTX dose. It can be clinically beneficial to maintain weekly contact in the first month to:

Provide supportive counseling.

Assess ongoing drug or alcohol use.

Monitor side effects.

Obtain drug testing.

Follow up on status of referrals to counseling or other services.

Patients who test the opioid blockade of XR-NTX may discontinue use because of the blocking of the euphoric effects of illicit opioids.203 Patients who miss a dose can restart medication (use procedures outlined earlier in this section) after an adequate period of opioid abstinence (7 to 14 days).

The TIP expert panel cautions that, based on current data, arbitrary time limits on XR-NTX are inappropriate.

See Chapter 3E for information on the management of patients taking naltrexone in office-based treatment settings.

Duration of treatment

Barring contraindications, patients should continue taking XR-NTX as long as they benefit from it and want to continue. Data are limited on the long-term effectiveness of XR-NTX compared with methadone or buprenorphine.

Treatment discontinuation

When patients wish to discontinue naltrexone, engage in shared decision making and explore:

Their reasons for wanting to discontinue.

The risks and benefits of discontinuing.

Problem-solving strategies that can help them make an informed choice.

Their appropriateness for buprenorphine or methadone treatment.

Discourage patients who are not yet stable from discontinuing treatment, because of the high rate of return to illicit opioid use and the increased chance of overdose death.

Signs that a patient may be ready to discontinue medication include:204

Sustaining illicit drug abstinence over time.

Having stable housing and income.

Having no legal problems.

Having substantially reduced craving.

Attending counseling or mutual-help groups.

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RESOURCE ALERT.

Patients who discontinue should have a recovery plan that may include monitoring as well as adjunctive counseling and recovery support. If they return to opioid use, encourage them to return for assessment and reentry into treatment.

Given the high risk of return to illicit opioid use, offer patients information about opioid overdose prevention and a naloxone prescription they can use in case of overdose. When patients stop using naltrexone, they will have no tolerance for opioids. Their risk of overdose is very high if they use again. For more information, see the SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/product/Opioid-Overdose-Prevention-Toolkit/SMA18-4742).

Rapid naltrexone induction

Patients with OUD need to discontinue opioids and wait 7 to 14 days after last opioid use (including any given for withdrawal treatment) before receiving XR-NTX. As described above, they can do so through medically supervised withdrawal in a controlled environment, such as an inpatient unit, residential addiction treatment program, correctional facility, or hospital, or on an outpatient basis.

Financial issues and managed care constraints may influence patients' access to controlled treatment environments. The alternative—abstaining long enough after outpatient medically supervised withdrawal—is challenging. Thus, various approaches to rapid naltrexone induction have been developed205 and more recently refined in research settings.206,207,208

Consider rapid induction in specialty addiction treatment programs, not general medical settings. It may be hard for providers in general medical settings to start XR-NTX successfully with patients who need medically supervised opioid withdrawal. Rapid induction approaches are likely beyond the scope of general outpatient settings. However, patients can successfully initiate XR-NTX in a general outpatient medical setting if they:

Have been abstinent for sufficient time and pass the naloxone challenge.

Started taking XR-NTX elsewhere and are due for the next injection.

One randomized trial compared two approaches to starting XR-NTX on an outpatient basis. This study assigned adults dependent on opioids to either a standard 14-day buprenorphine-assisted opioid withdrawal or more rapid 7-day oral naltrexone-assisted opioid withdrawal.209 Naltrexone-assisted withdrawal was conducted over 7 days. It included 1 day of buprenorphine administration; 1 day with ancillary medications including clonidine and clonazepam but no buprenorphine; followed by 4 days of ancillary medications and increasing daily doses of oral naltrexone (starting with 1 mg, 3 mg, 12 mg, and 25 mg); and concluding on day 7 with XR-NTX administration. Buprenorphine-assisted withdrawal consisted of a 7-day buprenorphine taper followed by the recommended 7 days without opioids. The naltrexone-assisted withdrawal group was significantly more likely to begin XR-NTX compared with the buprenorphine-assisted withdrawal group (56.1 percent versus 32.7 percent, respectively). This type of approach, which must be conducted with careful daily monitoring, is used in some residential programs and may prove to be a useful approach to outpatient XR-NTX induction in specialty programs. More discussion on rapid induction approaches is available in Implementing Antagonist-Based Relapse Prevention Treatment for Buprenorphine-Treated Individuals,210 available online (http://pcssmat.org/wp-content/uploads/2015/02/PCSSMAT-Implementing-Antagonist-with-Case.Bisaga.CME_.pdf).

Oral Naltrexone

The effectiveness of oral naltrexone is limited, given poor adherence and the requirement of 7 to 14 days of opioid abstinence before initiation. During this waiting period, patients may drop out of care. One study found significantly lower patient retention in treatment after incarceration for patients treated with oral naltrexone compared with methadone.211

Oral naltrexone blocks opioid-induced euphoria for only a day or two. When patients stop taking it, risks of return to opioid use and overdose increase.

The TIP expert panel doesn't recommend using oral naltrexone except in the limited circumstances described in the following sections. This view is in keeping with expert reviews for the United Kingdom's National Health Service,212 a clinical practice guideline published by the Department of Veterans Affairs and Department of Defense,213 and a Cochrane review.214

Indications and contraindications, precautions and warnings, side effects, and assessment.

All are similar to those for XR-NTX, save issues specific to suspension/diluent contents and the injection itself.

Patient Selection

In limited circumstances, oral naltrexone may be considered after the risks and benefits, as well as alternative treatments, are discussed with the patient. Examples include:

Patients who cannot afford XR-NTX but wish to take an opioid receptor antagonist.

Patients with high levels of monitoring and negative consequences for nonadherence, such as healthcare professionals who may not be permitted to have opioid agonist treatment.215,216

Patients leaving controlled environments (e.g., prisons, hospitals, inpatient addiction rehabilitation) who may benefit from medication to prevent return to illicit drug use but cannot or will not take XR-NTX and do not wish to be treated with (or do not have access to) opioid agonists.

The TIP expert panel does not recommend that payers require patients to fail oral naltrexone before providing access to XR-NTX, given the risk of unintentional overdose death if the patient returns to illicit opioid use.

Patients who have taken methadone or extensively used heroin are especially poor oral naltrexone candidates.217

Dosing

Following a negative naloxone challenge, the first oral dose of naltrexone can be 25 mg (half of the usual daily naltrexone maintenance dose). This reduces risk of a more severe precipitated opioid withdrawal than could occur with a full 50 mg dose. This lower dose may also reduce nausea associated with the first oral naltrexone dose. The dose can be increased to 50 mg daily on the second day.

To increase adherence, arrange for directly observed administration of oral naltrexone. This is more feasible if patients who tolerate a daily dose of 50 mg are switched to a 3-days-per-week regimen for a total weekly dose of 350 mg (e.g., administer 100 mg on Monday and Wednesday and 150 mg on Friday). A member of the patient's social network (e.g., spouse) may also directly observe therapy.

Duration of treatment

The optimal length of treatment with oral naltrexone is not known. In general, the longer patients take an effective medication, the better their outcomes.

Use of illicit opioids during treatment with oral naltrexone is a cause of concern and may be a precursor to treatment discontinuation.218 Some patients will initially test the opioid blockade with illicit opioids and then discontinue opioid use. However, others will continue using illicit opioids.219

If patients continue to test the blockade, immediately discuss alternative treatment plans that include:

Increased counseling.

Switching to XR-NTX.

Closer monitoring.

Directly observed oral naltrexone therapy.

Residential treatment.

Assessment for the appropriateness of buprenorphine or methadone.

Naltrexone Dosing Summary

XR-NTX

Before administering XR-NTX, keep it at room temperature for about 45 minutes.

Use the correct needle length to ensure the injection is in the gluteal muscle.

-

Use the 2-inch needle for patients with more subcutaneous tissue and the 1.5-inch needle for patients with less adipose tissue.

-

Use either length in patients with normal body habitus.

Use proper aseptic technique.

Use proper gluteal IM injection technique.

Never inject intravenously or subcutaneously.

Repeat the injection every 4 weeks or once per month.

Oral Naltrexone

Use in limited circumstances after discussing risks and benefits, as well as alternative treatment options, with the patient.

Do the naloxone challenge.

The first oral naltrexone dose should be 25 mg.

The dose can be increased on the second day to 50 mg daily if necessary.

If desired, switch patients who tolerate a daily dose of 50 mg to a 3-days-per-week regimen for a total weekly dose of 350 mg.

Chapter 3C Appendix

Key Techniques for Reducing Injection Site Reactions222

To reduce severe injection site reactions when administering XR-NTX via intramuscular injection, use the following techniques:

Use one of the administration needles provided with the XR-NTX kit to ensure that the injection reaches the gluteal muscle. Use the 2-inch needle for patients who have more subcutaneous adipose tissue. Use the 1.5-inch needle for patients with less subcutaneous adipose tissue. Either needle is appropriate for use with patients who have average amounts of subcutaneous adipose tissue.

Use aseptic technique when administering intramuscularly. Using a circular motion, clean the injection site with an alcohol swab. Let the area dry before administering the injection. Do not touch this area again before administration.

Use proper deep intramuscular injection technique into the gluteal muscle. XR-NTX must not be injected intravenously, subcutaneously, or into adipose tissue. Accidental subcutaneous injection may increase the risk of severe injection site reactions.

-

Administer the suspension by deep intramuscular injection into the upper outer quadrant of gluteal muscle, alternating buttocks per monthly injection.

-

Remember to aspirate for blood before injection. If blood aspirates or the needle clogs, do not inject. Change to the spare needle provided in the package and administer into an adjacent site in the same gluteal region, again aspirating for blood before injection.

-

Inject the suspension in a smooth, continuous motion.

A patient counseling tool is available to help you counsel your patients before administration about the serious risks associated with XR-NTX.

The above information is a selection of key safety information about the XR-NTX injection. For complete safety information, refer to the directions for use and the prescribing information provided in the medication kit. You can also obtain this information online (www.vivitrolrems.com) or by calling 1-800-VIVITROL.

Available online (www.vivitrolrems.com/content/pdf/patinfo-injection-poster.pdf).

Copyright Notice

This is an open-access report distributed under the terms of the Creative Commons Public Domain License. You can copy, modify, distribute and perform the work, even for commercial purposes, all without asking permission.

Bookshelf ID: NBK574913

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