Class: Opiate Antagonists
VA Class: CN102
Chemical Name: 17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one
Molecular Formula: C20H23NO4C20H23NO4•HCl
CAS Number: 16590-41-3
Brands: ReVia, Vivitrol
- Hepatic Effects
Possible dose-related hepatotoxicity.1 102 226 228 247 Margin between therapeutic and hepatotoxic dosages may be less than fivefold; hepatotoxicity not apparent at usual dosages.1 102 247 (See Hepatic Effects under Cautions.)
FDA approved a REMS for naltrexone to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of naltrexone and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().
Uses for Naltrexone
Used as an adjunct to a medically supervised behavior modification program1 35 99 102 147 160 161 162 163 164 165 166 170 in the maintenance of opiate cessation (opiate-free state) in individuals who were formerly physically dependent on opiates and who have successfully undergone detoxification1 14 35 102 143 147 158 162 163 164 165 (designated an orphan drug by FDA for this use).217
Behavior modification is an integral component in maintaining opiate cessation; behavior modification programs involve supervised programs of counseling, psychologic support and therapy, education, and changes in life-style (social rehabilitation).1 2 35 37 102 143 147 159 160 162 170 189 192 193 204
May diminish or eliminate opiate-seeking behavior by blocking opiate euphoria and by preventing the conditioned abstinence syndrome (i.e., heightened sensitivity to stimuli, abnormal autonomic responses, dysphoria, intense opiate craving) that occurs following opiate withdrawal.1 2 27 102 158 190 191
Efficacy in maintaining long-term cessation appears to be low;2 11 14 15 42 123 125 135 161 182 203 poor compliance appears to be the major limiting factor.1 2 8 13 42 99 182 204 Because noncompliance with naltrexone is not associated with unpleasant symptoms of withdrawal, compliance depends more on voluntary efforts; successful cessation may be more likely in highly motivated individuals.1 2 8 13 15 35 36 99 102 130 147 162 163 167 172
Rapid opiate detoxification involves the administration of opiate antagonists (e.g., naltrexone and/or naloxone) to shorten the time period of detoxification.246
Ultrarapid detoxification is similar but involves the administration of opiate antagonists while the patient is sedated or under general anesthesia.246 Consider the risk of adverse respiratory and cardiovascular effects associated with this procedure, as well as the costs of general anesthesia and hospitalization.246
Management of alcohol dependence in conjunction with a behavior modification program1 232 233 234 235 236 237 247 involving supervised programs of counseling, psychologic support and therapy, and education and changes in life-style (social rehabilitation).1 232 238
Behavior modification is an integral component in maintaining alcohol cessation; naltrexone has not been shown to provide any therapeutic benefit except as part of an appropriate plan of addiction management.1 232 234 237 239 245
When used in conjunction with behavior modification, naltrexone reportedly decreases alcohol craving, reduces alcohol consumption, decreases the number of drinking days, maintains abstinence from alcohol ingestion, and prevents, decreases, or ameliorates the severity of relapse.1 232 235 237 238
Naltrexone Dosage and Administration
REMS for Parenteral Naltrexone
FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for parenteral naltrexone.259
The REMS requires that a medication guide be given to the patient each time parenteral naltrexone is dispensed;259 260 the goal is to inform patients about serious risks associated with parenteral naltrexone.259 (See Advice to Patients and also see Cautions.)
Verification of Opiate Abstinence Prior to Initiation of Therapy
Manufacturers recommend that at least 7–10 days elapse between discontinuance of opiates and initiation of naltrexone therapy because of the risk of precipitating opiate withdrawal (see Accidental Precipitation of Withdrawal under Cautions.)1 102 This waiting period may vary depending on the dose and duration of action of the opiate;1 102 121 162 allow at least 7 days in patients using relatively short-acting opiates (e.g., heroin, hydromorphone, meperidine, morphine) and at least 10–14 days in those using longer-acting opiates (e.g., methadone).237
Some clinicians have cautiously precipitated withdrawal using repeated naloxone injections and then rapidly initiated naltrexone therapy with incremental doses of the drug; this procedure can reduce the transition period from opiate dependence to naltrexone maintenance and generally is well accepted by patients.14 41 196 207
In addition to patient verification of abstinence from opiates, perform urinalysis after the minimum 7- to 10-day waiting period, but prior to administration of naltrexone, to confirm the absence of opiates.1 102 If it is uncertain whether the patient is opiate free, perform a naloxone challenge test prior to administering naltrexone.1 102 247
Naloxone Challenge Test
Perform test prior to induction of naltrexone therapy in patients formerly physically dependent on opiates who have completed detoxification and in those suspected of having been dependent on opiates.1 2 14 15 41 102 162 237
Test should not be performed in patients who are exhibiting signs and/or symptoms of opiate withdrawal, those whose urine shows evidence of opiates, or those in whom there is a high degree of suspicion that opiates are still being used, since naloxone may precipitate potentially severe opiate withdrawal.1 102
Do not attempt naltrexone therapy if signs and/or symptoms of opiate withdrawal (e.g., nasal stuffiness, rhinorrhea, lacrimation, yawning, sweating, tremor, abdominal cramps, vomiting, piloerection, myalgia, skin crawling) are evident following administration of the naloxone challenge test;1 102 instead, repeat the naloxone challenge test in 24 hours.1
Naloxone may be administered IV or sub-Q in the challenge test.1
IV challenge test: Draw 0.8 mg of naloxone hydrochloride into a syringe.1 Administer 0.2 mg initially; while the needle remains in the vein observe the patient for 30 seconds196 for evidence of opiate withdrawal.1 Alternatively, some clinicians recommend 15 minutes for the period of observation. If no evidence of withdrawal is observed, inject the remaining 0.6-mg dose and observe the patient for an additional 20 minutes for evidence of withdrawal.1
If evidence of opiate withdrawal is present, delay naltrexone therapy and repeat the naloxone challenge test in 24 hours with the 0.8-mg dose; repeat the test every 24 hours until results are negative.1 196
If it is uncertain whether the patient is opiate free or is undergoing opiate withdrawal following an initial test, repeat the naloxone challenge test with a 1.6-mg IV dose.1
Patients should take naltrexone as directed and not attempt self-administration of opiates during therapy with the drug.1 102 (See Risks Associated with Self-administration of Opiates During Naltrexone Therapy under Cautions.)
Administer by deep IM injection into the upper outer quadrant of the gluteal muscle every 4 weeks (or once a month); alternate buttocks for subsequent injections.247
Administer only with needle and other components of dose pack supplied by manufacturer.247
Do not administer by IV or sub-Q injection; do not inadvertently administer into fatty tissue.247 257 Inadvertent sub-Q injection may increase likelihood of severe injection site reactions.247 (See Local Reactions under Cautions.)
Evaluate the patient's body habitus prior to each injection to ensure that the 1.5-inch needle supplied by the manufacturer is adequate for gluteal IM injection in that patient.247 Consider alternative treatment for any patient whose body habitus (i.e., gluteal fat thickness) precludes IM injection with the provided needle.247 261
Consult manufacturer’s labeling for instructions for using components of dose pack for reconstitution.247
Allow dose pack to reach room temperature before reconstituting.247
Reconstitute vial labeled as containing 380 mg of naltrexone extended-release microspheres with 3.4 mL of diluent; shake vigorously for 1 minute.247 Use only the diluent supplied by the manufacturer.247 Administer immediately.247
Available for oral administration as naltrexone hydrochloride; dosage expressed in terms of the salt.1
Available for IM administration as naltrexone.247
Induction of Therapy for Opiate CessationOral
Initiate induction regimen following completion of opiate detoxification and verification that the patient is free of opiates.102 (See General under Dosage and Administration.)
Initially, 25 mg; if no evidence of withdrawal is present, begin 50 mg daily.1
Maintenance Therapy for Opiate CessationOral
Alternatively, flexible dosing schedules have been suggested in an attempt to improve compliance.1 2 35 62 99 102 122 138 157 158 161 164 196 Administration of larger doses at longer intervals (e.g., 48–72 hours) may reduce opiate antagonist activity somewhat, but may improve compliance.1 102 121 Single doses >50 mg may increase risk of hepatic injury; weigh possible risks against probable benefits of flexible dosing.1
- Flexible Naltrexone Hydrochloride Dosing Schedules for Maintenance Therapy for Opiate Cessation
150 mg on Monday and 200 mg on Thursday196
Ingestion of the naltrexone dose generally should be observed in a clinic setting or by a responsible family member to ensure compliance, in which case, regimens requiring less frequent visits may be more acceptable to the patient.8 99 102 182 194 196
In patients who discontinue naltrexone prematurely and then desire to resume therapy following a relapse to opiate abuse, perform urinalysis for the presence of opiates and, if necessary, a naloxone challenge test prior to resuming therapy.161 196 If there is evidence of opiate dependence, conduct detoxification prior to reinitiation of naltrexone therapy.102 161
The following regimen of naltrexone, given in conjunction with clonidine to attenuate withdrawal manifestations, has been studied.38
Day of Detoxification Therapy
Administered every 4 hours to attenuate the withdrawal induced by naltrexone38
Administered every 4 hours; 1 mg initially; then increased in 1-mg increments during the daytime on day 2 38
Administered every 4 hours to attenuate the withdrawal induced by naltrexone; highest mean dosage was 2.3 mg daily on day 338
Administered every 4 hours; dosage increased in 2-mg increments during the daytime on day 338
Administered only as needed to reduce signs and symptoms of withdrawal38
10 mg 3 times daily38
Administered only as needed to reduce signs and symptoms of withdrawal38
380 mg every 4 weeks or once a month following verification that the patient is free of opiates. 247 (See General under Dosage and Administration.)
If a dose is missed, reschedule administration with a health-care professional as soon as possible.247
Therapy may be initiated with parenteral preparation; not necessary to initiate therapy with oral naltrexone and then switch to parenteral preparation.247
Dosage adjustment not needed in patients with mild to moderate (Child-Pugh class A or B) hepatic impairment.247
Dosage adjustment not needed in patients with mild renal impairment (Clcr of 50–80 mL/minute).247
Cautions for Naltrexone
Patients with known hypersensitivity to the drug or any ingredient in the formulation.1 247 Not known whether cross-sensitivity exists between naltrexone and naloxone or phenanthrene-derivative opiate agonists (e.g., codeine, morphine, oxymorphone).1
Manufacturers state that naltrexone-induced hepatocellular injury appears to be a direct toxic rather than an idiosyncratic effect.1 Some clinicians suggest that liver function abnormalities may be caused by noroxymorphone, a minor metabolite of naltrexone that has opiate agonist activity.196 206
Manufacturer of oral naltrexone recommends monitoring liver function at intervals deemed appropriate for the naltrexone dosage employed and the clinical status of the patient.1
IM injection associated with injection site reactions (e.g., tenderness, induration, pain, pruritus, ecchymosis, nodules, swelling) in most patients.247 Cellulitis,247 hematoma,247 abscess,247 sterile abscess,247 and necrosis247 also reported.247 Injection site reactions occur predominantly in females.247
Some reactions may be very severe, result in substantial scarring, or require surgery, including debridement of necrotic tissue.247 Inadvertent sub-Q injection may increase likelihood of a severe injection reaction.247
Patients should monitor the injection site and contact clinician if injection site reactions worsen or persist.257 258 (See Advice to Patients.) Promptly evaluate patients with signs of abscess, cellulitis, necrosis, or extensive swelling to determine if referral to a surgeon is warranted.247
Verification of Opiate Abstinence Prior to Initiation of Therapy
To minimize the risk of precipitating signs and symptoms of withdrawal, instruct opiate-dependent individuals who are candidates for naltrexone therapy to remain free of opiates for a minimum of 7–10 days prior to initiating therapy with the drug.1 102 247
Absence of opiates in urine is frequently insufficient evidence that a patient is free of opiates.1 102 247 If it is uncertain whether the patient is opiate free, perform a naloxone challenge test prior to administering naltrexone.1 102 247 (See Naloxone Challenge Test under Dosage and Administration.)
Risks Associated with Self-administration of Opiates During Naltrexone Therapy
Self-administration of large doses of opiates in an attempt to overcome the antagonist activity of naltrexone may produce signs and symptoms of acute opiate overdosage (e.g., respiratory arrest, circulatory collapse, death).1 247
Signs and symptoms of opiate overdosage also may occur following administration of smaller doses of opiate agonists relatively long after the last naltrexone dose or in an amount that results in a longer duration of agonist activity than the antagonist activity of naltrexone and its metabolites.1 247
Therapeutic Use of Opiates in Naltrexone-treated Patients
In an emergency situation when adequate analgesia can be achieved only by administration of an opiate agonist in naltrexone-treated patients, cautious administration of an opiate may afford adequate analgesia, but higher than usual dosages may be required.1 102 Whenever possible, use nonopiate analgesics, regional analgesia, conscious sedation with a benzodiazepine, or general anesthesia.1 102 247
If an opiate is required as a component of anesthesia or analgesia, the patient should be continuously monitored in an anesthesia care setting by individuals who are trained in the use of anesthetic agents and in the management of respiratory depressant effects of potent opiates and who are not involved in the conduct of the surgical or diagnostic procedure.247
Respiratory depression produced by the opiate may be deeper and more prolonged.1 102 Patients may experience apparent nonopiate receptor-induced effects such as facial swelling, pruritus, generalized erythema, or bronchoconstriction that are probably caused by opiate-induced histamine release and/or other mechanisms.1
Use of a short-acting opiate with minimal respiratory depression is preferable; adjust dosage of the opiate agonist carefully according to individual requirements and response.1 102 Closely monitor the patient in a setting equipped and staffed by health-care personnel appropriately trained in CPR.1 247
Discontinue oral naltrexone ≥48 hours prior to elective surgical procedures requiring opiate analgesia.121
Avoid use of other opiate-agonist-containing preparations (e.g., those used for the management of cough or diarrhea) when alternative nonopiate therapy is available, since adequate therapeutic benefit may be difficult to achieve with an opiate.1 102
Accidental Precipitation of Withdrawal
Accidental ingestion of naltrexone has precipitated severe withdrawal in some patients physically dependent on opiates; signs and symptoms of withdrawal usually appeared within 5 minutes of naltrexone ingestion and continued for up to 48 hours.1 31 102 124
Individuals with Bleeding Disorders
Use IM preparation with caution in individuals with thrombocytopenia or a coagulation disorder (e.g., hemophilia).247
Common Adverse Effects
Interactions for Naltrexone
Specific Drugs and Laboratory Tests
Drug or Test
Both drugs are potentially hepatotoxic1
Manufacturers recommend concomitant use only if the potential benefits justify the possible risks1
Avoid use of opiate-containing preparations during naltrexone therapy when alternative nonopiate therapy is available1
Tests, urinary opiates
No interference reported with thin-layer (TLC), gas-liquid (GLC), or high-performance liquid (HPLC) chromatography assays for methadone or morphine1
Tests, urinary quinine
No interference reported with TLC, GLC, or HPLC methods1
Rapidly and almost completely (about 96%) absorbed following oral administration,1 2 3 22 67 71 72 100 102 105 but undergoes extensive first-pass metabolism in the liver;1 2 3 33 62 71 102 only 5–40% reaches systemic circulation unchanged.1 2 67 71 72 74 102
Following IM administration of the extended-release injection, naltrexone is released slowly and gradually from the microspheres by diffusion and erosion as the polylactide co-glycolide polymer degrades.247 249 251 252 Peak plasma concentrations of naltrexone and the active metabolite (6-β-naltrexol) occur in about 2–3 days; 247 251 252 steady-state plasma concentrations of naltrexone and 6-β-naltrexol are attained by the end of the dosing interval after the first injection.247 251
Following administration of a single IM dose of naltrexone 380 mg, total naltrexone exposure is three- to fourfold higher and 6-β-naltrexol exposure is 3.4-fold lower than exposure following oral administration of naltrexone 50 mg daily for 28 days.247 251
Onset of opiate antagonism occurred 15–30 minutes following oral administration in a limited number of patients who had been receiving morphine chronically.25
Decreases opiate craving within 3–5 weeks after start of oral naltrexone in individuals formerly dependent on opiates;42 66 158 160 reduction in opiate craving has occurred during the first week of therapy in some individuals, with further decreases occurring in subsequent weeks.102 182
Following IM administration, plasma concentrations of naltrexone and 6-β-naltrexol in individuals with mild to moderate hepatic impairment (Child-Pugh class A and B) are similar to those in healthy individuals with normal hepatic function.247 252
Plasma Protein Binding
Metabolized in the liver principally by reduction of the 6-keto group of naltrexone to an active metabolite, 6-β-naltrexol (6-β-hydroxynaltrexone); 1 2 33 62 67 72 84 100 101 102 103 104 105 106 107 109 112 113 115 116 117 118 other minor metabolites are formed.1 2 62 67 72 84 100 101 102 103 105 107 108 111 114 117 118
Because oral but not IM administration of naltrexone results in substantial first-pass hepatic metabolism, 6-β-naltrexol concentrations following IM administration are substantially lower than concentrations achieved following oral administration.247 251 252
Following IM administration, pharmacokinetics not altered in patients with mild renal impairment (Clcr of 50–80 mL/minute).247
After mixing with diluent, use immediately.247
In patients who have received single or repeated large doses of opiate agonists, naltrexone attenuates or produces a complete but reversible block of the pharmacologic effects (e.g., physical dependence, analgesia, euphoria, tolerance) of the opiate.1 3 13 14 22 23 25 31
Antagonizes most of the subjective and objective effects of opiates,3 14 25 102 103 including respiratory depression,72 102 103 miosis,14 25 72 102 103 euphoria,14 72 102 103 and drug craving.3 25 72 102 103
Because the duration of action of naltrexone may be shorter than that of the opiate, the effects of the opiate may return as the effects of naltrexone dissipate.15 33 36 Degree of opiate antagonism produced by naltrexone depends on the dose and the time elapsed since the last dose of naltrexone and the dose of the opiate.1 11 32 102 122
Does not produce physical or psychologic dependence, and tolerance to the drug’s opiate antagonist activity reportedly does not develop.1 7 8 11 13 22 27 33 39 40 79 May precipitate mild to potentially severe withdrawal in individuals physically dependent on opiates1 2 7 11 15 31 35 38 42 82 or pentazocine.196
Alcohol ingestion stimulates release of endogenous opiate agonists,1 235 237 238 239 242 which may increase some of the rewarding effects associated with alcohol ingestion through agonist activity at opiate (e.g., μ) receptors.237 238 By competitively binding to opiate receptors, naltrexone may reduce alcohol consumption by blocking the effects of endogenous opiates and thus making alcohol ingestion less pleasurable.1 232 233 235 236 237 238 241 247
Advice to Patients
Importance of patient reading the medication guide prior to initiating parenteral naltrexone therapy and before each injection of the drug.258 Importance of ensuring that patient understands risks.260
Importance of patients informing clinicians that they are taking naltrexone.1 247 258 Advise patients to carry a medical identification card that can alert clinicians to this fact in an emergency situation.1 247 258
Importance of contacting a clinician if manifestations of acute hepatitis (e.g., abdominal pain lasting more than a few days, light-colored [e.g., white] stools, dark urine, yellowing of the eyes) occur.1 247 258 Discontinue oral naltrexone.1
Importance of not self-administering opiates (e.g., heroin) during naltrexone therapy, since self-administration of small doses of opiates in an attempt to overcome the antagonist activity of naltrexone will not result in any pharmacologic effect and large doses may result in serious consequences (e.g., coma, death).1 102 247 258
Advise patients receiving parenteral naltrexone to monitor the injection site and to contact clinician if injection site reactions (i.e., pain, swelling, tenderness, induration, bruising, pruritus, redness) worsen or if they do not improve within 2 weeks following injection.257 258 Advise patients to notify clinician promptly if intense or prolonged pain, swelling, skin color changes, or signs of necrosis (e.g., hard nodule, blistering, open wound, dark scab) are present at the injection site.247 258
Advise patients that they may need to be referred to a surgeon for worsening injection site reactions.257
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
For injectable suspension, extended-release, for IM use
Vivitrol (available as a dose pack containing naltrexone microspheres, diluent, needles)
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Embeda 20-0.8MG Controlled-release Capsules (KING PHARMA): 20/$96.99 or 30/$144.98
Embeda 50-2MG Controlled-release Capsules (KING PHARMA): 30/$239.98 or 90/$699.99
Naltrexone HCl 50MG Tablets (MALLINCKRODT PHARM): 30/$103.99 or 90/$308.95
ReVia 50MG Tablets (TEVA/WOMENS HEALTH): 30/$275.32 or 90/$794.22
Vivitrol 380MG Suspension (ALKERMES): 1/$1,101.94 or 3/$3,263.83
AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions October 3, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Mallinckrodt. Naltrexone hydrochloride tablets prescribing information. Hazelwood, MO; 2009 Feb 5.
2. Crabtree BL. Review of naltrexone, a long-acting opiate antagonist. Clin Pharm. 1984; 3:273-80. [IDIS 185528] [PubMed 6329589]
3. Anon. Naltrexone—an investigational narcotic antagonist. Hosp Pharm. 1982; 17:687-8.
4. Lehman TM, Pyati P, Peterson GR. Inhibition of drug metabolism by chronically administered naltrexone. Life Sci. 1979; 25:1591-1600. [PubMed 522615]
5. Benson DW, Kaufman JJ, Koski WS. Theoretic significance of pH dependence of narcotics and narcotic antagonists in clinical anesthesia. Anesth Analg. 1976; 55:253-6. [IDIS 69574] [PubMed 3994]
6. Endo Pharmaceuticals. Narcan injection, Narcan neonatal injection prescribing information. Manati, PR; 1982 Sep.
7. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In: Gilman AG, Goodman L, Gilman A, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 6th ed. New York: The Macmillan Company; 1980:494-534.
8. Renault PF. Treatment of heroin-dependent persons with antagonists: current status. Bull Narc. 1978; 30:22-9.
9. Anon. Naltrexone. Natl Clgh Drug Abuse Inf. 1978; 38:1-7.
10. Braude MC, Morrison JM. Preclinical toxicity studies of naltrexone. NIDA Res Monogr. 1976; 9:16-26. [PubMed 826824]
11. Resnick RB, Volavka J, Freedman AM et al. Studies of EN-1639A (naltrexone): a new narcotic antagonist. Am J Psychiatry. 1974; 131:646-50. [PubMed 4827793]
12. Resnick RB. Prospects, problems, side effects, and safety of narcotic antagonists. Int J Addict. 1977; 12:863-7. [IDIS 85686] [PubMed 591144]
13. Renault PF. The future of naltrexone. NIDA Res Monogr. 1978; 19:340-5. [IDIS 190265] [PubMed 106298]
14. Resnick RB, Washton AM, Thomas MA et al. Naltrexone in the treatment of opiate dependence. NIDA Res Monogr. 1978; 19:321-32. [IDIS 190263] [PubMed 218108]
15. Greenstein RA, O’Brien CP, McLellan AT et al. Naltrexone: a short-term treatment for opiate dependence. Am J Drug Alcohol Abuse. 1981; 8:291-300. [IDIS 190287] [PubMed 7340503]
16. Martin W, Bell J, Gilbert P et al. The effects of naltrexone in the chronic spinal dog and acute spinal cat; possible interaction with naturally-occurring morphine-like agonists. NIDA Res Monogr. 1976; 9:27-30. [PubMed 187942]
17. Kaim SC. Evolution of the National Academy of Sciences study of naltrexone. NIDA Res Monogr. 1976; 9:37-44. [PubMed 794719]
18. Brahen L, Wiechert V, Capone T. Narcotic antagonist treatment of the criminal justice patient—institutional vs outpatient—including a 24 hour detox naltrexone induction regimen with oral medication. NIDA Res Monogr. 1976; 9:93-8. [IDIS 190293] [PubMed 794727]
19. Copolov DL, Helme RD. Enkephalins and endorphins: clinical, pharmacological and therapeutic implications. Drugs. 1983; 26:503-19. [IDIS 178952] [PubMed 6360635]
20. Gold MS, Pottash ALC, Extein I et al. Anti-endorphin effects of methadone. Lancet. 1980; 2:972-3. [IDIS 125530] [PubMed 6107608]
21. Smith TC. Comparison of naltrexone and naloxone in man. Anesthesiology. 1979; 51:S373.
22. Weintraub M, Evans P. Naltrexone: a potent oral narcotic antagonist for opiate addiction. Hosp Formul. 1983; 19:449-53.
23. Martin WR. Pharmacology of opioids. Pharmacol Rev. 1983; 35:283-323. [IDIS 182771] [PubMed 6144112]
24. Mielke DH, Gallant DM. An oral opiate antagonist in chronic schizophrenia: a pilot study. Am J Psychiatry. 1977; 134:1430-1. [IDIS 83364] [PubMed 920847]
25. Martin WR, Jasinski DR, Mansky PA et al. Naltrexone, an antagonist for the treatment of heroin dependence. Arch Gen Psychiatry. 1973; 28:784-91. [PubMed 4707988]
26. Mendelson JH, Ellingboe J, Kuehnle JC et al. Effects of naltrexone on mood and neuroendocrine function in normal adult males. Psychoneuroendocrinology. 1979; 3:231-6.
27. Resnick RB, Schuyten-Resnick E, Washton AM. Narcotic antagonists in the treatment of opioid dependence: review and commentary. Compr Psychiatr. 1979; 20:116-25.
28. Schecter A. The role of narcotic antagonists in the rehabilitation of opiate addicts: a review of naltrexone. Am J Drug Alcohol Abuse. 1980; 7:1-18. [IDIS 190266] [PubMed 6254356]
29. Gritz ER, Shiffman SM, Jarvik ME et al. Naltrexone: physiological and psychological effects of single doses. Clin Pharmacol Ther. 1976; 19:773-6. [IDIS 73576] [PubMed 773586]
30. Davis GC, Buchsbaum MS, van Kammen DP et al. Analgesia to pain stimuli in schizophrenics and its reversal by naltrexone. Psychiatry Res. 1979; 1:61-9. [IDIS 189591] [PubMed 298339]
31. Tornabene VW. Narcotic withdrawal syndrome caused by naltrexone. Ann Intern Med. 1974; 81:785-7. [IDIS 48497] [PubMed 4433085]
32. Volavka J, Resnick RB, Kestenbaum RS et al. Short-term effects of naltrexone in 155 heroin ex-addicts. Biol Psychiatry. 1976; 11:679-85. [IDIS 190253] [PubMed 999987]
33. Verebey K, Mulé SJ. Naltrexone pharmacology, pharmacokinetics, and metabolism: current status. Am J Drug Alcohol Abuse. 1975; 2:357-63. [IDIS 190257] [PubMed 1227297]
34. Davis GC, Buchsbaum MS, Bunney WE. Research in endorphins and schizophrenia. Schizophr Bull. 1979; 5:244-50. [PubMed 37596]
35. Greenstein R, O’Brien C, Mintz J et al. Clinical experience with naltrexone in a behavioral research study: an interim report. NIDA Res Monogr. 1976; 9:141-9. [IDIS 190250] [PubMed 794715]
36. Goldstein A. Naltrexone in the management of heroin addiction: critique of the rationale. NIDA Res Monogr. 1976; 9:158-61. [PubMed 187941]
37. Schecter AJ, Friedman JG, Grossman DJ. Clinical use of naltrexone (EN-1639A): part 1: safety and efficacy in pilot studies. Am J Drug Alcohol Abuse. 1974; 1:253-69. [IDIS 190254] [PubMed 4467728]
38. Charney DS, Riordan CE, Kleber HD et al. Clonidine and naltrexone: a safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy. Arch Gen Psychiatry. 1982; 39:1327-32. [IDIS 160676] [PubMed 7138234]
39. Mello NK, Mendelson JH, Kuehnle JC. Buprenorphine effects on human heroin self-administration: an operant analysis. J Pharmacol Exp Ther. 1982; 233:30-9.
40. Mello NK, Mendelson JH, Kuehnle JC et al. Operant analysis of human heroin self-administration and the effects of naltrexone. J Pharmacol Exp Ther. 1981; 216:45-54. [IDIS 130484] [PubMed 7452507]
41. Resnick RB, Kestenbaum RS, Washton A et al. Naloxone-precipitated withdrawal: a method for rapid induction onto naltrexone. Clin Pharmacol Ther. 1977; 21:409-13. [IDIS 88195] [PubMed 849672]
42. National Research Council Committee on Clinical Evaluation of Narcotic Antagonists. Clinical evaluation of naltrexone treatment of opiate-dependent individuals. Arch Gen Psychiatry. 1978; 35:335-40. [IDIS 102993] [PubMed 365122]
43. O’Brien CP, Greenstein R, Ternes J et al. Clinical pharmacology of narcotic antagonists. Ann NY Acad Sci. 1978; 311:232-40. [PubMed 369432]
44. Buchsbaum MS, Reus VI, Davis GC et al. Role of opioid peptides in disorders of attention in psychopathology. Ann NY Acad Sci. 1982; 398:352-65. [IDIS 190259] [PubMed 6297359]
45. Christian MS. Reproductive toxicity and teratology evaluations of naltrexone. J Clin Psychiatry. 1984; 45(9 Section 2):7-10. [PubMed 6469938]
46. Sternbach HA, Annitto W, Pottash ALC et al. Anorexic effects of naltrexone in man. Lancet. 1982; 1:388-9.
47. Atkinson RL. Endocrine and metabolic effects of opiate antagonists. J Clin Psychiatry. 1984; 45(9:Section 2):20-4.
48. Janowsky D, Judd L, Huey L et al. Naloxone effects on serum growth hormone and prolactin in man. Psychopharmacology (Berl). 1979; 65:95-7. [PubMed 116298]
49. Rubin P, Swezey S, Blaschke T. Naloxone lowers plasma-prolactin in man. Lancet. 1979; 1:1293. [PubMed 87748]
50. Gold MS, Redmond DE, Donabedian RK. Prolactin secretion, a measurable central effect of opiate-receptor antagonists. Lancet. 1978; 1:323-4. [PubMed 75353]
51. Mirin SM, Mendelson JH, Ellingboe J et al. Acute effects of heroin and naltrexone on testosterone and gonadotropin secretion: a pilot study. Psychoneuroendocrinology. 1976; 1:359-69.
52. Abel EL. Opiates and sex. J Psychoact Drugs. 1984; 16:205-16.
53. Mirin SM, Meyer RE, Mendelson JH et al. Opiate use and sexual function. Am J Psychiatry. 1980; 137:909-15. [IDIS 119772] [PubMed 6774622]
54. Veldhuis JD, Rogol AD, Samojlik E et al. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man. J Clin Invest. 1984; 74:47-55. [IDIS 186844] [PubMed 6429197]
55. Veldhuis JD, Rogol AD, Williams FA et al. Do α-adrenergic mechanisms regulate spontaneous or opiate-modulated pulsatile luteinizing hormone secretion in man? J Clin Endocrinol Metab. 1983; 57:1292-6. (IDIS 178715)
56. Veldhuis JD, Rogol AD, Johnson ML et al. Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man. J Clin Invest. 1983; 72:2031-40. [IDIS 179482] [PubMed 6315775]
57. Ellingboe J, Veldhuis JD, Mendelson JH et al. Effect of endogenous opioid blockade on the amplitude and frequency of pulsatile luteinizing hormone secretion in normal men. J Clin Endocrinol Metab. 1982; 54:854-7. [IDIS 150223] [PubMed 7061693]
58. Mendelson JH, Ellingboe J, Kuehnle JC et al. Heroin and naltrexone effects on pituitary-gonadal hormones in man: interaction of steroid feedback effects, tolerance and supersensitivity. J Pharmacol Exp Ther. 1980; 214:503-6. [IDIS 125357] [PubMed 7400959]
59. Ellingboe J, Mendelson JH, Kuehnle JC. Effects of heroin and naltrexone on plasma prolactin levels in man. Pharmacol Biochem Behav. 1980; 12:163-5. [IDIS 190248] [PubMed 7367458]
60. Gold MS, Pottash AC, Extein I et al. Methadone-induced endorphin dysfunction in addicts. NIDA Res Monogr. 1982; 41:476-82. [IDIS 190262] [PubMed 6289119]
61. Mendelson JH, Ellingboe J, Kuehnle J et al. Heroin and naltrexone effects on pituitary-gonadal hormones in man: tolerance and supersensitivity. NIDA Res Monogr. 1979; 27:302-8. [IDIS 190256] [PubMed 121347]
62. Gold MS, Dackis CA, Pottash ALC et al. Naltrexone, opiate addiction, and endorphins. Med Res Rev. 1982; 2:211-46. [PubMed 6289026]
63. Morley JE, Baranetsky NG, Wingert TD et al. Endocrine effects of naloxone-induced opiate receptor blockade. J Clin Endocrinol Metab. 1980; 50:251-7. [IDIS 111845] [PubMed 6243662]
64. Gambert SR, Gorthwaite TL, Pontzer CH et al. Fasting associated with decrease in hypothalamic β-endorphin. Science. 1980; 210:1271-2. [PubMed 6254156]
65. Volavka J, Cho D, Mallya A et al. Naloxone increases ACTH and cortisol levels in man. N Engl J Med. 1979; 300:1056-7. [PubMed 219337]
66. Meyer R, Mirin SM, Altman JL. The clinical usefulness of narcotic antagonists: implications of behavioral research. Am J Drug Alcohol Abuse. 1975; 2:417-32. [PubMed 179316]
67. Bullingham RES, McQuay HJ, Moore RA. Clinical pharmacokinetics of narcotic agonist-antagonist drugs. Clin Pharmacokinet. 1983; 8:332-43. [IDIS 173933] [PubMed 6352139]
68. Maugh TH. Narcotic antagonists: the search accelerates. Science. 1972; 177:249-50. [IDIS 32474] [PubMed 5041023]
69. Rosenkrantz H. Physiologic and morphologic changes and incidence of neoplasms in mice and rats fed naltrexone HCl for 24 months. J Clin Psychiatry. 1984; 45(9 Section 2):11-4. [PubMed 6469931]
70. Verebey K, Kogan MJ, DePace A et al. Quantitative determination of naltrexone and beta-naltrexol in human plasma using electron capture detection. J Chromatogr. 1976; 118:331-5. [PubMed 1254668]
71. Meyer MC, Straughn AB, Lo MW et al. Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry. 1984; 45(9 Section 2):15-9. [IDIS 190715] [PubMed 6469932]
72. Verebey K, Volavka J, Mule SJ et al. Naltrexone: disposition, metabolism, and effects after acute and chronic dosing. Clin Pharmacol Ther. 1976; 20:315-28. [IDIS 75286] [PubMed 954353]
73. Jasinski DR, Martin WR, Haertzen CA. The human pharmacology and abuse potential of N-allylnoroxymorphone (naloxone). J Pharmacol Exp Ther. 1967; 157:420-6. [PubMed 6039832]
74. Kogan MJ, Verebey K, Mulé SJ. Estimation of the systemic availability and other pharmacokinetic parameters of naltrexone in man after acute and chronic oral administration. Res Commun Chem Pathol Pharmacol. 1977; 18:29-34. [IDIS 189587] [PubMed 905632]
75. Misra AL, Bloch R, Vardy J et al. Disposition of [15,16-3H] naltrexone in the central nervous system of the rat. Drug Metab Dispos. 1976; 4:276-80. [PubMed 6233]
76. Derendorf H, El-Kaussi ALA, Garrett ER. Electrochemical chromatographic determinations of morphine antagonists in biological fluids, with applications. J Pharm Sci. 1984; 73:621-4. [IDIS 185658] [PubMed 6737235]
77. Ludden TM, Malspeis L, Baggot JD et al. Tritiated naltrexone binding in plasma from several species and tissue distribution in mice. J Pharm Sci. 1976; 65:712-6. [PubMed 819644]
78. Tempel A, Gardner EL, Zukin RS. Neurochemical and functional correlates of naltrexone-induced opiate receptor up-regulation. J Pharmacol Exp Ther. 1985; 232:439-44. [PubMed 2982011]
79. Kleber HD, Kosten TR, Gaspari J et al. Nontolerance to the opioid antagonism of naltrexone. Biol Psychiatry. 1985; 20:66-72. [PubMed 2981129]
80. Horita A, Carino MA, Fatherazi S et al. Naloxone and naltrexone block the gastrointestinal effects of TRH and MK-212. Proc West Pharmacol Soc. 1984; 27:385-6. [PubMed 6436825]
81. Briski K, Quigley K, Meites J. Counteraction by naltrexone of stress-induced inhibition of TSH release: role of noradrenergic system (41956). Proc Soc Exp Biol Med. 1984; 177:354-9. [PubMed 6091150]
82. Charney DS, Redmond DE, Galloway MP et al. Naltrexone precipitated opiate withdrawal in methadone addicted human subjects: evidence for noradrenergic hyperactivity. Life Sci. 1984; 35:1263-72. [PubMed 6482651]
83. Rosella-Dampman LM, Keil LC, Chee O et al. Naltrexone effects on plasma vasopressin concentration elevated and lowered by various stimuli. J Pharmacol Exp Ther. 1983; 226:373-81. [PubMed 6875851]
84. Verebey K, DePace A, Jukofsky D et al. Quantitative determination of 2-hydroxy-3-methoxy-6β-naltrexol (HMN), naltrexone, and 6β-naltrexol in human plasma, red blood cells, saliva, and urine by gas liquid chromatography. J Anal Toxicol. 1980: 4:33-7.
85. Cicero TJ, Wilcox CE, Bell RD et al. Naloxone-induced increases in serum luteinizing hormone in the male: mechanisms of action. J Pharmacol Exp Ther. 1980; 212:573-8. [PubMed 6244390]
86. Verebey K, Mulé SJ. Naltrexone and β-naltrexol plasma levels in schizophrenic patients after large oral doses of naltrexone. Res Commun Psychol Psychiatry Behav. 1979: 4:311-7.
87. Strahlendorf JC, Strahlendorf HK, McKown-Pulliam R et al. Chronic administration of naltrexone alters central catecholamine levels but not the development of hypertension in spontaneously hypertensive rats. Neuropharmacology. 1982; 21:1195-8. [PubMed 7177344]
88. Tempel A, Zukin S, Gardner EL. Supersensitivity of brain opiate receptor subtypes after chronic naltrexone treatment. Life Sci. 1982; 31:1401-4. [PubMed 6292636]
89. Vargish T, Reynolds DG, Gurll NJ et al. Naloxone reversal of hemorrhagic shock in dogs. Circ Shock. 1980; 7:31-8. [PubMed 6248264]
90. Gurll NJ, Reynolds DG, Vargish T et al. Naltrexone improves survival rate and cardiovascular function in canine hemorrhagic shock. J Pharmacol Exp Ther. 1982; 220:625-8. [PubMed 6278127]
91. Grandison L, Buchweitz E, Weiss HR. Effect of naltrexone on regional brain oxygen consumption in the cat. Brain Res. 1982: 233:369-79.
92. Wassef NM, Smith AA. Inhibition of growth in young mice treated with pentazocine: reversal by naltrexone. Eur J Pharmacol. 1980; 155-60.
93. Freye E, Hartung E, Schenk GK. Effects of three narcotic antagonists (naltrexone, diprenorphine, and S-20682) on blood pressure, heart rate and electrical cortical activity. Pharmacology. 1983; 26:110-6. [PubMed 6133288]
94. Volavka J, James B, Reker D et al. EEG and other effects of naltrexone and heroin in man. Pharmakopsychiatr Neuro Psychopharmakol. 1979; 12:79-85.
95. Jhamandas K, Sutak M. Stereospecific enhancement of evoked release of brain acetylcholine by narcotic antagonists. Br J Pharmacol. 1983; 78:433-40. [PubMed 6831119]
96. Sanger DJ, McCarthy PS, Lord JAH et al. The anorectic properties of opiate antagonists. Drug Dev Res. 1983; 3:137-142.
97. Reisberg A, Ferris SH, Anand R et al. Effects of naloxone in senile dementia: a double-blind trial. N Engl J Med. 1983; 308:721-2. [IDIS 167362] [PubMed 6338389]
98. Foldes FF. The human pharmacology and clinical use of narcotic antagonists. Med Clin North Am. 1964; 48:421-43. [PubMed 14151252]
99. Renault PF. Treatment of heroin-dependent persons with antagonists: current status. NIDA Res Monogr. 1981; 28:11-22. [PubMed 6791000]
100. Wall ME, Brine DR, Perez-Reyes M. The metabolism of naltrexone in man. NIDA Res Monogr. 1981; 28:105-31. [PubMed 6790999]
101. Misra AL. Current status of preclinical research on disposition, pharmacokinetics, and metabolism of naltrexone. NIDA Res Monogr. 1981; 28:132-46. [PubMed 6267469]
102. DuPont Pharmaceuticals. Trexan (naltrexone hydrochloride) in opioid addiction: a comprehensive product monograph. Wilmington, DE; 1985 March.
103. Verebey K. The clinical pharmacology of naltrexone: pharmacology and pharmacodynamics. NIDA Res Monogr. 1981; 28:147-58. [PubMed 6791001]
104. Cone EJ, Gorodetzky CW, Yeh SY. The urinary excretion profile of naltrexone and metabolites in man. Drug Metab Dispos. 1974; 2:506-12. [PubMed 4156313]
105. Wall ME, Brine DR, Perez-Reyes M. Metabolism and disposition of naltrexone in man after oral and intravenous administration. Drug Metab Dispos. 1981; 9:369-75. [IDIS 136706] [PubMed 6114837]
106. Blumberg H, Ikeda C. Comparison of naltrexone and beta-naltrexol for narcotic antagonist action in rats and mice. Fed Proc. 1976; 35:469.
107. Wall ME, Perez-Reyes M, Brine DR et al. Naltrexone disposition in man after subcutaneous administration. Drug Metab Dispos. 1984; 12:677-82. [IDIS 192979] [PubMed 6150815]
108. Cone EJ, Gorodetzky CW, Darwin WD et al. The identification and measurement of two new metabolites of naltrexone in human urine. Res Commun Chem Pathol Pharmacol. 1978; 20:413-33. [IDIS 189590] [PubMed 674824]
109. Dayton HE, Inturrisi CE. The urinary excretion profiles of naltrexone in man, monkey, rabbit, and rat. Drug Metab Dispos. 1976; 4:474-8. [IDIS 76649] [PubMed 10147]
110. Inturrisi CE. Disposition of narcotics and narcotic antagonists. Ann NY Acad Sci. 1976; 281:273-87. [IDIS 189588] [PubMed 828465]
111. Brine GA, Brine DR, Welch CD et al. Carbon-13 nuclear magnetic resonance identification of 2-hydroxy-3-O-methyl-6β-naltrexol as a minor naltrexone metabolite. Res Commun Chem Pathol Pharmacol. 1978; 22:455-64. [IDIS 189589] [PubMed 734225]
112. Drayer DE. Active drug metabolites and renal failure. Am J Med. 1977; 62:486-9. [IDIS 88801] [PubMed 851118]
113. Malspeis L, Bathala MS, Ludden TM et al. Metabolic reduction of naltrexone. I. Synthesis, separation and characterization of naloxone and naltrexone reduction products and qualitative assay of urine and bile following administration of naltrexone, α-naltrexol, or β-naltrexol. Res Commun Chem Pathol Pharmacol. 1975; 12:43-65. [IDIS 189592] [PubMed 810832]
114. Verebely, Chedekel MA, Mulé SJ et al. Isolation and identification of a new metabolite of naltrexone in human blood and urine. Res Commun Chem Pathol Pharmacol. 1975; 12:67-84. [PubMed 1188187]
115. Chatterjie N, Fujimoto JM, Inturrisi CE et al. Isolation and stereochemical identification of a metabolite of naltrexone from human urine. Drug Metab Dispos. 1974; 2:401-5. [IDIS 46124] [PubMed 4156301]
116. Verebely K, Mulé SJ, Jukofsky D. A gas-liquid chromatographic method for the determination of naltrexone and beta-naltrexol in human urine. J Chromatogr. 1975; 111:141-8. [PubMed 239958]
117. Verebey K. Quantitative determination of naltrexone, 6β-naltrexol and 2-hydroxy-3-methoxy-6β-naltrexol (HMN) in human plasma, red blood cells, saliva and urine by gas liquid chromatography. NIDA Res Monogr. 1981; 28:36-51. [PubMed 6791012]
118. Wall ME, Brine DR. Analytical methods for quantitative and qualitative analysis of naltrexone and metabolites in biological fluids. NIDA Res Monogr. 1981; 28:52-65. [PubMed 6791013]
119. Perez-Reyes M, Wall ME. A comparative study of the oral, intravenous, and subcutaneous administration of 3H-naltrexone to normal male volunteers. NIDA Res Monogr. 1981; 28:93-101. [PubMed 6791016]
120. Licko V. Overview of human pharmacokinetics of naltrexone. NIDA Res Monogr. 1981; 28:161-71. [PubMed 6791002]
121. Anon. Naltrexone for opioid addiction. Med Lett Drugs Ther. 1985; 27:11-2. [PubMed 3969057]
122. O’Brien CP, Greenstein RA, Mintz J et al. Clinical experience with naltrexone. Am J Drug Alcohol Abuse. 1975; 2:365-77. [PubMed 1227298]
123. Taintor Z, Landsberg R, Wicks N et al. Experiences with naltrexone in Buffalo. Am J Drug Alcohol Abuse. 1975; 2:391-401. [IDIS 190299] [PubMed 775969]
124. Volavka J, Resnick RB. Treatment of accidental naltrexone-induced withdrawal. Am J Psychiatry. 1976; 133:233. [IDIS 58138] [PubMed 56139]
125. Schecter A. Clinical use of naltrexone (EN 1639 A). Part II: Experience with the first 50 patients in a New York city treatment clinic. Am J Drug Alcohol Abuse. 1975; 2:433-42. [IDIS 190301] [PubMed 1227301]
126. Julius DA. Withdrawal from endogenous opiates. Am J Psychiatry. 1979; 136:358. [IDIS 112676] [PubMed 420348]
127. Hurzeler M, Gerwirtz D, Kleber H. Varying clinical contexts for administering naltrexone. NIDA Res Monogr. 1976; 9:48-66. [IDIS 190281] [PubMed 794721]
128. Haas N, Ling W, Holmes E et al. Naltrexone in methadone maintenance patients electing to become “drug free.” NIDA Res Monogr. 1976; 9:70-3. (IDIS 190283)
129. Bradford A, Hurley F, Golondzowski O et al. Interim report on clinic intake and safety data collected from 17 NIDA-funded naltrexone studies. NIDA Res Monogr. 1976; 9:163-70. [IDIS 190289] [PubMed 794717]
130. Landsberg R, Taintor Z, Plumb M et al. An analysis of naltrexone use—its efficacy, safety and potential. NIDA Res Monogr. 1976; 9:106-13. [IDIS 190291] [PubMed 1004529]
131. Thomas M, Kauders F, Harris M et al. Clinical experiences with naltrexone in 370 detoxified addicts. NIDA Res Monogr. 1976; 9:88-92. [IDIS 190292] [PubMed 794726]
132. Judson BA, Goldstein A. Symptom complaints of patients maintained on methadone, LAAM (methadyl acetate), and naltrexone at different times in their addiction careers. Drug Alcohol Depend. 1982; 10:269-82. [PubMed 7166139]
133. Wikler A. Methadone maintenance and narcotic blocking drugs. Int J Addict. 1977; 12:869-81. [IDIS 85687] [PubMed 338517]
134. Renault PF. Narcotic antagonists: naltrexone. Introduction. NIDA Res Monogr. 1976; 9:1-3. [PubMed 794713]
135. Lewis DC, Mayer J, Hersch RG et al. Narcotic antagonist treatment: clinical experience with naltrexone. Int J Addict. 1978; 13:961-73. [IDIS 116532] [PubMed 730406]
136. Wettstein JG, Kamerling SG, Martin WR. Pharmacological comparison of naltrexone and naloxone in the dog. Fed Proc. 1983; 42:632.
137. Curran S, Savage C. Patient response to naltrexone: issues of acceptance, treatment effects, and frequency of administration. NIDA Res Monogr. 1976; 9:67-9. [PubMed 794722]
138. Hollister LE, Johnson K, Boukhabza D et al. Aversive effects of naltrexone in subjects not dependent on opiates. Drug Alcohol Depend. 1981; 8:37-41. [PubMed 7297411]
139. Lewis DC. The clinical usefulness of narcotic antagonists: preliminary findings on the use of naltrexone. Am J Drug Alcohol Abuse. 1975; 2:403-15. [IDIS 190298] [PubMed 1227300]
140. Schecter A, Kauders F. Patient deaths in a narcotic antagonist (naltrexone) and l-β-acetylmethadol program. Am J Drug Alcohol Abuse. 1975; 2:443-9. [IDIS 190297] [PubMed 1227302]
141. Brahen LS, Capone T, Wiechert V et al. Naltrexone and cyclazocine: a controlled treatment study. Arch Gen Psychiatry. 1977; 34:1181-4. [IDIS 94440] [PubMed 911218]
142. Simpson GM, Branchey MH, Lee JH. A trial of naltrexone in chronic schizophrenia. Curr Ther Res. 1977; 22:909-13.
143. Callahan E, Rawson R, Glazer M et al. Comparison of two naltrexone treatment programs: naltrexone alone versus naltrexone plus behavior therapy. NIDA Res Monogr. 1976: 9:150-7.
144. Gitlin M, Rosenblatt M. Possible withdrawal from endogenous opiates in schizophrenics. Am J Psychiatry. 1978; 135:377-8. [IDIS 102731] [PubMed 626239]
145. Ragheb M, Berney S, Ban T. Naltrexone in chronic schizophrenia: results of a clinical trial. Int Pharmacopsychiatry. 1980; 15:1-5. [PubMed 6993401]
146. Volavka J. Action of naloxone and naltrexone in different types of psychoses. Mod Probl Pharmacopsychiatry. 1981; 17:202-12. [PubMed 6276726]
147. Ling W, Wesson DR. Naltrexone treatment for addicted health-care professionals: a collaborative private practice experience. J Clin Psychiatry. 1984; 45:46-8. [IDIS 190721] [PubMed 6469936]
148. Henrich RT, Jayaraman J, Morishima A et al. Induction of segregational errors of chromosomes by naltrexone. Mamm Chromosomes Newsl. 1978; 19:26.
149. Coutino R, Meyne J, Legator MS. Cytogenetic studies in Chinese hamster ovary cells with the narcotic antagonistic naltrexone. Mutat Res. 1978; 53:80.
150. Zimmering S. Evidence for a mutagenic effect of the narcotic antagonist, naltrexone, in germ cells of Drosophila. Mutat Res. 1979; 66:129-31. [PubMed 107446]
151. Brusick D, Matheson D, Jagannath D et al. Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride. Drug Chem Toxicol. 1978; 1:103-35. [PubMed 158518]
152. Ginzburg HM, Glass WJ. The role of the National Institute on Drug Abuse in the development of naltrexone. J Clin Psychiatry. 1984; 45(9 Section 2):4-6. [IDIS 190714] [PubMed 6088469]
153. Nuite JA, Kennedy GL, Smith S et al. Reproductive and teratogenic studies with naltrexone in rats and rabbits. Toxicol Appl Pharmacol. 1975; 33:173.
154. Nieder GL, Corder CN. Effects of opiate antagonists on early pregnancy and pseudopregnancy in mice. J Reprod Fertil. 1982; 65:341-6. [PubMed 7097642]
155. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983: 912.
156. Maickel RP, Lambert CS, Zabik JE et al. Interactions of psychoactive drugs with narcotic agonists and antagonists. Ann NY Acad Sci. 1976; 281:321-30. [PubMed 1071367]
157. Brahen LS, Capone T, Heller RC et al. Controlled clinical study of naltrexone side effects comparing first-day doses and maintenance regimens. Am J Drug Alcohol Abuse. 1978; 5:235-45. [IDIS 189895] [PubMed 747177]
158. Sideroff SI, Charuvastra VC, Jarvik ME et al. Craving in heroin addicts maintained on the opiate antagonist naltrexone. Am J Drug Alcohol Abuse. 1978; 5:415-23. [IDIS 189894] [PubMed 755381]
159. Callahan EJ, Rawson RA, McCleave B et al. The treatment of heroin addiction: naltrexone alone and with behavior therapy. Int J Addict. 1980; 15:795-807. [IDIS 129172] [PubMed 7461877]
160. Meyer RE, Mirin SM, Altman JL et al. A behavioral paradigm for the evaluation of narcotic antagonists. Arch Gen Psychiatry. 1976; 33:371-7. [IDIS 70391] [PubMed 944026]
161. Greenstein RA, Arndt IC, McLellan AT et al. Naltrexone: a clinical perspective. J Clin Psychiatry. 1984; 45(9 Section 2):25-8. [IDIS 190717] [PubMed 6469933]
162. Kleber HD, Kosten TR. Naltrexone induction: psychologic and pharmacologic strategies. J Clin Psychiatry. 1984; 45(9 Section 2):29-38. [IDIS 190718] [PubMed 6469934]
163. Washton AM, Pottash AC, Gold MS. Naltrexone in addicted business executives and physicians. J Clin Psychiatry. 1984; 45(9 Section 2):39-41. [IDIS 190719] [PubMed 6088468]
164. Tennant FS, Rawson RA, Cohen AJ et al. Clinical experience with naltrexone in suburban opioid addicts. J Clin Psychiatry. 1984; 45(9 Section 2):42-5. [IDIS 190720] [PubMed 6469935]
165. Brahen LS, Henderson RK, Capone T et al. Naltrexone treatment in a jail work-release program. J Clin Psychiatry. 1984; 45(9 Section 2):49-52. [IDIS 190722] [PubMed 6469937]
166. Lewis D, Hersch R, Black R et al. Use of narcotic antagonists (naltrexone) in an addiction treatment program. NIDA Res Monogr. 1976; 9:99-105. [PubMed 794728]
167. Greenstein RA, Evans BD, McLellan AT et al. Predictors of favorable outcome following naltrexone treatment. Drug Alcohol Depend. 1983; 12:173-80. [PubMed 6653389]
168. Gold MS, Dackis CA, Washton AM. The sequential use of clonidine and naltrexone in the treatment of opiate addicts. Adv Alcohol Subst Abuse. 1984; 3:19-39. [PubMed 6388273]
169. Rawson RA, Washton AM, Resnick RB et al. Clonidine hydrochloride detoxification from methadone treatment—the value of naltrexone aftercare. Adv Alcohol Subst Abuse. 1984; 3:41-9. [PubMed 6093484]
170. Anton RF, Hogan I, Jalali B et al. Multiple family therapy and naltrexone in the treatment of opiate dependence. Drug Alcohol Depend. 1981; 8:157-68. [PubMed 7318681]
171. Gitlin MJ, Gerner RH, Rosenblatt M. Assessment of naltrexone in the treatment of schizophrenia. Psychopharmacology. 1981; 74:51-3. [IDIS 190247] [PubMed 6791204]
172. Resnick RB, Washton AM. Clinical outcome with naltrexone. Ann NY Acad Sci. 1978; 311:241-6. [PubMed 283722]
173. Ketchum JS, Jarvik ME. Pharmacotherapy for the opioid addict: agonists or antagonists? Ration Drug Ther. 1979; 13:1-5. (IDIS 120679)
174. Washton AM, Resnick RB, Perzel JF et al. Lofexidine, a clonidine analogue effective in opiate withdrawal. Lancet. 1981; 1:991-2. [IDIS 130897] [PubMed 6112397]
175. Blumberg H, Dayton HB, Wolf PS. Analgesic and narcotic antagonist properties of noroxymorphone derivatives. Toxicol Appl Pharmacol. 1967; 10:406.
176. Goldstein DJ, Keiser HR. A case of episodic flushing and organic psychosis: reversal by opiate antagonists. Ann Intern Med. 1983; 98:30-4. [IDIS 162788] [PubMed 6184003]
177. Rathmann KL, Conner CS. Alzheimer’s disease: clinical features, pathogenesis, and treatment. Drug Intell Clin Pharm. 1984; 18:684-91. [IDIS 190037] [PubMed 6383752]
178. Volavka J, Mallya A, Bauman J et al. Hormonal and other effects of naltrexone in normal men. Adv Exp Med Biol. 1979; 116:291-305. [PubMed 224675]
179. Serri O, Rasio E, Somma M. Effects of naloxone on insulin-induced release of pituitary hormones. J Clin Endocrinol Metab. 1981; 53:206-8. [IDIS 135253] [PubMed 6263936]
180. Grossman A, Rees LH. The neuroendocrinology of opioid peptides. BMJ. 1983; 39:83-8.
181. Morley JE. The endocrinology of the opiates and opioid peptides. Metabolism. 1981; 30:195-209. [PubMed 6258010]
182. Judson BA, Carney TM, Goldstein A. Naltrexone treatment of heroin addiction: efficacy and safety in a double-blind dosage comparison. Drug Alcohol Depend. 1981; 7:325-46. [PubMed 7023894]
183. Hollister LE, Schwin RL, Kasper P. Naltrexone treatment of opiate-dependent persons. Drug Alcohol Depend. 1977; 2:203-9. [PubMed 880876]
184. Gold MS, Pottash AC, Sweeney DR et al. Opiate withdrawal using clonidine: a safe, effective, and rapid nonopiate treatment. JAMA. 1980; 243:343-6. [IDIS 106365] [PubMed 7351747]
185. Gold MS, Redmond DE, Kleber HD. Noradrenergic hyperactivity in opiate withdrawal supported by clonidine reversal of opiate withdrawal. Am J Psychiatry. 1979; 136:100-2. [IDIS 120397] [PubMed 364997]
186. Zlotkin SH, Fettes I, Stallings VA. The anorectic effects of naltrexone in children with the Prader Willi syndrome. Fed Proc. 1985; 44:1550.
187. Reisberg B, London E, Ferris SH et al. Novel pharmacologic approaches to the treatment of senile dementia of the Alzheimer’s type (SDAT). Psychopharmacol Bull. 1983; 19:220-5. [PubMed 6346374]
188. Reisberg B, Ferris SH, Anand R et al. Naloxone effects on primary degenerative dementia. Psychopharmacol Bull. 1983; 19:45-7.
189. Goldstein A. Heroin addiction: sequential treatment employing pharmacologic supports. Arch Gen Psychiatry. 1976; 33:353-8. [PubMed 1259524]
190. Wikler A. The theoretical basis of narcotic addiction treatment with narcotic antagonists. NIDA Res Monogr. 1976; 9:119-22. [PubMed 1004530]
191. Wikler A. Dynamics of drug dependence: implications of a conditioning theory for research and treatment. Arch Gen Psychiatry. 1973; 28:611-6. [PubMed 4700675]
192. Stone-Washton N, Resnick RB, Washton AM. Naltrexone and psychotherapy. NIDA Res Monogr. 1981; 41:505-7.
193. Resnick RB, Washton AM, Stone-Washton N. Psychotherapy and naltrexone in opioid dependence. NIDA Res Monogr. 1980; 34:109-15.
194. O’Brien CP. A new approach to the management of opioid dependence: naltrexone, an oral antagonist. Summary. J Clin Psychiatry. 1984; 45(9 Section 2):57-8.
195. Zaks A, Jones T, Fink M et al. Naloxone treatment of opiate dependence. JAMA. 1971; 215:2108-10. [IDIS 21537] [PubMed 5108223]
196. Reviewers’ comments (personal observations); 1985 Oct.
197. Atkinson RL, Berke LK, Drake CR et al. Effects of long-term therapy with naltrexone on body weight in obesity. Clin Pharmacol Ther. 1985; 38:419-22. [IDIS 206890] [PubMed 4042525]
198. Russ CS, Ciavarella PA, Kaiser DL et al. Effects of naltrexone on food intake and selection in obese humans. Fed Proc. 1984; 43:1060.
199. Vaupel DB. Naltrexone fails to antagonize the βIGMA/ effects of PCP and SKF 10,047 in the dog. Eur J Pharmacol. 1983; 92:269-74. [PubMed 6313397]
200. Amir S. Morphine exacerbates anaphylactic shock in mice by stimulating central opiate receptors. Neurosci Lett. 1983; 40:169-74. [PubMed 6314208]
201. Maggio CA, Presta E, Bracco EF et al. Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men. Brain Res Bull. 1985; 14:657-61. [PubMed 3896411]
202. Serby M, Resnick R, Jordan B et al. Naltrexone in Alzheimer’s disease. Paper presented at the American College of Neuropsychopharmacology meeting. Kaanapali Shores, HI: 1985 Dec 12.
203. Resnick R, Aronoff M, Lonborg G et al. Clinical efficacy of naltrexone: a one year follow up. NIDA Res Monogr. 1976; 9:114-7. [PubMed 1088899]
204. Greenstein RA, Resnick RB, Resnick E. Methadone and naltrexone in the treatment of heroin dependence. Psychiatr Clin North Am. 1984; 7:671-9. [PubMed 6522309]
205. Cherubin CE, Kane S, Weinberger DR. Persistence of transaminase abnormalities in former drug addicts. Ann Intern Med. 1972; 76:385-9. [PubMed 5015913]
206. Verebey K, Mulé SJ. Naltrexone (Trexan): a review of hepatotoxicity issues. In: Harris LS, ed. Problems of drug dependence 1985: proceedings of the 47th annual scientific meeting, the Committee on Problems of Drug Dependence, Inc. Rockville, MD: National Institute of Drug Abuse. (in press)
207. Resnick R. Critique: uses of naloxone in the diagnosis and treatment of heroin addiction. In: Cooper JR, Altman F, Brown BS et al, eds. Research on the treatment of narcotic addiction: state of the art. Rockville, MD: National Institute of Drug Abuse; 1983: 14-7.
208. Laursen T, Schmidt A. Increase in serum-GPT and serum-LDH after administration of morphine to patients suffering from bile-duct dyskinesia. Scand J Clin Lab Invest. 1967; 18:175-7.
209. Foulk WT, Fleisher GA. The effect of opiates on the activity of serum transaminase. Proc Staff Meet Mayo Clin. 1957; 32:405-10. [PubMed 13465819]
210. McNeely MDD. Serum transaminases (SGOT, SGPT). Drug Ther (Hosp). 1978; 3:79-84.
211. Needham WP, Shuster L, Kanel GC et al. Liver damage from narcotics in mice. Toxicol Appl Pharmacol. 1981; 58:157-70. [PubMed 6166089]
212. James RC, Goodman DR, Harbison RD. Hepatic glutathione and hepatotoxicity: changes induced by selected narcotics. J Pharmacol Exp Ther. 1982; 221:708-14. [PubMed 7086683]
213. Correia MA, Wong JS, Soliven E. Morphine metabolism revisited: I. Metabolic activation of morphine to a reactive species in rats. Chem Biol Interact. 1984; 49:255-68. [PubMed 6327094]
214. Chang YYH, Ho IK. Effects of acute and continuous morphine administration on serum glutamate oxalacetate transaminase and glutamate pyruvate transaminase activities in the mouse. Biochem Pharmacol. 1979; 28:1373-7. [PubMed 444304]
215. Andersen T, Christoffersen P, Gluud C. The liver in consecutive patients with morbid obesity: a clinical, morphological, and biochemical study. Int J Obes. 1984; 8:107-15. [PubMed 6724792]
216. Andersen T, Gluud C. Liver morphology in morbid obesity: a literature study. Int J Obes. 1984; 8:97-106. [PubMed 6373641]
217. Wallner JN (Du Pont, Wilmington, DE): Personal communication; 1986 Jan 6.
218. Schmidt WK, Tam SW, Shotzberger GS et al. Nalbuphine. Drug Alcohol Depend. 1985; 14:339-62. [PubMed 2986929]
219. Malcolm R, Gabel T, Morton A. Idiosyncratic reaction to naltrexone augmented by thioridazine. Am J Psychiatry. 1988; 145:773-4. [IDIS 242586] [PubMed 3369583]
220. Malcolm R, Gabel T, Morton A. More on idiosyncratic reaction to naltrexone. Am J Psychiatry. 1989; 146:124-5. [PubMed 2912237]
221. Maany I, O’Brien CP, Woody G. Interaction between thioridazine and naltrexone. Am J Psychiatry. 1987; 144:966. [IDIS 231311] [PubMed 3605414]
222. Maany I, O’Brien CP. Drs. Maany and O’Brien reply. Am J Psychiatry. 1988; 145:774. [IDIS 242587] [PubMed 3369584]
223. Jonas JM, Gold MS. Naltrexone reverses bulimic symptoms. Lancet. 1986; 1:807. [IDIS 213932] [PubMed 2870306]
224. Igoin-Apfelbaum L, Apfelbaum M. Naltrexone and bulimic symptoms. Lancet. 1987; 2:1087-8. [IDIS 235720] [PubMed 2889994]
225. Mitchell JE, Christenson G, Jennings J et al. A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia. J Clin Psychopharmacol. 1989; 9:94-7. [IDIS 253431] [PubMed 2656781]
226. Mitchell JE. Naltrexone and hepatotoxicity. Lancet. 1986; 1:1215. [IDIS 216491] [PubMed 2871452]
227. Childs A. Naltrexone in organic bulimia: a preliminary report. Brain Inj. 1987; 1:49-55. [PubMed 3454671]
228. Mitchell JE, Morley JE, Levine AS et al. High-dose naltrexone therapy and dietary counseling for obesity. Biol Psychiatry. 1987; 22:35-42. [PubMed 3790639]
229. Brahen LS, Capone TJ, Capone DM. Naltrexone: lack of effect on hepatic enzymes. J Clin Pharmacol. 1988; 28:64-70. [IDIS 238442] [PubMed 3350993]
230. Charney DS, Heninger GR, Kleber HD. The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry. 1986; 143:831-7. [IDIS 217884] [PubMed 3717421]
231. O’Mara NB. Wesley LC. Naltrexone in the treatment of alcohol dependence. Ann Pharmacother. 1994; 28: 210-1.
232. Volpicelli JR. Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992; 49: 876-80. [IDIS 305457] [PubMed 1345133]
233. O’Malley SS, Jaffe AJ, Chang G et al. Naltrexone and coping skills therapy for alcohol dependence. Arch Gen Psychiatry. 1994; 49: 881-7.
234. Anon. DuPont Merck Revis approval for alcoholism adjunctive therapy includes Phase IV commitments based on product sales: SNDA approved on Dec. 30. F-D-C Rep. 1995 Jan 9: 3-4.
235. Swift RW, Whelihan W, Kuznetsov O et al. Naltrexone-induced alterations in human ethanol intoxication. Am J Psychiatry. 1994; 151:1463-67. [IDIS 336231] [PubMed 8092339]
236. Volpicelli JR, Watson NT, King AC et al. Effect of naltrexone on alcohol ″high″ in alcoholics. Am J Psychiatry. 1995; 152:613-5. [IDIS 344645] [PubMed 7694913]
237. Anon. Naltrexone for alcohol dependence. Med Lett Drugs Ther. 1995; 37:64-6. [PubMed 7603392]
238. O’Brien CP. Treatment of alcoholism as a chronic disorder. Experientia, Suppl. 1994; 71:349-59.
239. Volpicelli JR. Naltrexone in alcohol dependence. Lancet. 1995; 346:456. [IDIS 353145] [PubMed 7637475]
240. Gordis E. Dear colleague letter regarding the use of naltrexone for alcoholism. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 1995 Feb 6.
241. National Institute on Alcohol Abuse and Alcoholism. Naltrexone approved for alcoholism treatment. Bethesda, MD; 1995 Jan 17. Press release.
242. DuPont Merck Pharmaceutical Co. DuPont Merck introduces a new medication for the treatment of alcohol dependence. Wilmington, DE; 1995 Jan 17. Press release.
243. Mastrangelo L. (DuPont Merck Pharmaceutical Co., Wilmington, DE): Personal communication; 1995 Oct. 19.
244. Krystal JH, Cramer JA, Krol WF et al. Naltrexone in the treatment of alcohol dependence. N Engl J Med. 2001; 345:1734-9. [IDIS 481448] [PubMed 11742047]
245. Fuller RK, Gordis E. Naltrexone treatment for alcohol dependence. N Engl J Med. 2001; 345:1770-1. [IDIS 481451] [PubMed 11742054]
246. O’Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA. 1998; 279:229-34. [IDIS 398211] [PubMed 9438745]
247. Alkermes. Vivitrol (naltrexone for extended-release injectable suspension) prescribing information. Cambridge, MA; 2009 May.
248. Garbutt JC, Kranzler HR, O’Malley SS et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005; 293:1617-25. [PubMed 15811981]
249. Anon. Naltrexone (Vivitrol)--a once-monthly injection for alcoholism. Med Lett Drugs Ther. 2006; 48:63-4. [PubMed 16874283]
250. Starosta AN, Leeman RF, Volpicelli JR. The BRENDA model: integrating psychosocial treatment and pharmacotherapy for the treatment of alcohol use disorders. J Psychiatr Pract. 2006; 12:80-9. [PubMed 16728904]
251. Dunbar JL, Turncliff RZ, Dong Q et al. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Alcohol Clin Exp Res. 2006; 30:480-90. [PubMed 16499489]
252. Turncliff RZ, Dunbar JL, Dong Q et al. Pharmacokinetics of long-acting naltrexone in subjects with mild to moderate hepatic impairment. J Clin Pharmacol. 2005; 45:1259-67. [PubMed 16239359]
253. Bertolotti M, Ferrari A, Vitale G et al. Effect of liver cirrhosis on the systemic availability of naltrexone in humans. J Hepatol. 1997; 27:505-11. [PubMed 9314128]
254. Chan CF, Page-Sharp M, Kristensen JH et al. Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk. J Hum Lact. 2004; 20:322-6. [PubMed 15296587]
255. Kambia NK, Dine T, Odou P et al. Pharmacokinetics and dialysability of naltrexone in patients undergoing hemodialysis. Eur J Drug Metab Pharmacokinet. 2004; 29:225-30. [PubMed 15726882]
256. Mason BJ, Goodman AM, Dixon RM et al. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology. 2002; 27:596-606. [IDIS 519891] [PubMed 12377396]
257. Food and Drug Administration. MedWatch-Safety-related drug labeling changes. Vivitrol (naltrexone) [August 2008]. From FDA website.
258. Alkermes, Inc. Vivitrol (naltrexone for extended-release injectable suspension) medication guide. Waltham, MA; 2010 Mar.
259. Vivitrol (naltrexone for extended-release injectable suspension) risk evaluation and mitigation strategy (REMS). From FDA website. Accessed 2010 Jun 29.
260. Food and Drug Administration. Vivitrol (naltrexone for extended-release injectable suspension): medication guide required for patients. Rockville, MD; 2010 May 4. From FDA website.
261. Food and Drug Administration. Information for healthcare professionals: naltrexone injection site reactions [naltrexone for extended-release injectable suspension (marketed as Vivitrol)]. 2008 Aug 12. From FDA website.
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