Naltrexone is an oral opiate receptor antagonist. It is derived from thebaine and is very similar in structure to oxymorphone. Like parenteral naloxone, naltrexone is a pure antagonist (i.e., agonist actions are not apparent), but naltrexone has better oral bioavailability and a much longer duration of action than naloxone. Clinically, naltrexone is used to help maintain an opiate-free state in patients who are known opiate abusers. Naltrexone is of the greatest benefit in patients who take the drug as part of a comprehensive occupational rehabilitative program or other compliance-enhancing program. Unlike methadone or LAAM, naltrexone does not reinforce medication compliance and will not prevent withdrawal. Naltrexone has been used as part of rapid and ultrarapid detoxification techniques. These techniques are designed to precipitate withdrawal by administering opiate antagonists. These approaches are thought to minimize the risk of relapse and allow quick initiation of naltrexone maintenance and psychosocial supports. Ultrarapid detoxification is performed under general anesthesia or heavy sedation. While numerous studies have been performed examining the role of these detoxification techniques, a standardized procedure including appropriate medications and dose, safety, and effectiveness have not been determined in relation to standard detoxification techniques. Naltrexone supports abstinence, prevents relapse, and decreases alcohol consumption in patients treated for alcohol dependence. Naltrexone is not beneficial in all patients with alcohol dependence and may only provide a small improvement in outcome when added to conventional therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Administer tablets by mouth with food to decrease nausea. Tablets are scored for splitting, if needed.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-For deep gluteal intramuscular injection only. Do not administer by any other routes.
-To reduce the risk of a clogged needle, administer the injection immediately after preparation and only use the needles supplied by the manufacturer.
Intramuscular Administration
Naltrexone extended-release injection (i.e., Vivitrol)
-Must be administered by a health care professional only.
-Proper administration is imperative to reduce the likelihood of a severe injection site reaction.
-Use only the provided needle and only give as a deep intramuscular (IM) gluteal injection.
-The risk of serious injection site reactions may be increased when Vivitrol is deposited in subcutaneous or fatty tissue.
--Body habitus (physical build) should be assessed prior to each injection for each patient to assure that the proper needle is selected and that the needle length is adequate for intramuscular administration.
-The needles provided are customized needles. Vivitrol must not be injected using any other needle.
-Consider alternate treatment for those patients whose body conditions preclude a deep IM gluteal injection with one of the provided needles.
Preparation:
-Take the carton out of the refrigerator for about 45 minutes before preparation to allow the product to reach room temperature.
-Firmly tap the bottom of the vial on a hard surface to ensure that the powder moves freely. Remove the flip caps off the drug and diluent vials.
-Using aseptic technique, place the 1-inch preparation needle on the syringe and withdraw 3.4 mL diluent from diluent vial; inject the 3.4 mL diluent into naltrexone microsphere vial. Do not use any other diluent or needle.
-Vigorously shake the vial for 1 minute. A properly mixed suspension will be milky white, will not contain clumps, and will move freely down the wall of the vial. If these conditions do not exist, do not administer.
-Immediately after suspension, withdraw 4.2 mL of the suspension into the syringe using the same preparation needle.
-Select the appropriate needle for deep IM injection based on patient's body conditions:
--1.5-inch needle for very lean patients
-2-inch needle for patients with larger amount of subcutaneous tissue overlying the gluteal muscle
-Either of the provided needles may be used in patients with average body conditions
Intramuscular injection:
-Hold the syringe with the needle pointing upward and tap the syringe. Expel the syringe contents to get rid of any air bubbles and until only 4 mL remains in the syringe.
-Insert the needle deep into the gluteal muscle, and aspirate before injection to avoid injection into a blood vessel. If blood aspirates or the needle clogs, remove the needle and replace with the supplied spare administration needle. Repeat the procedure at an adjacent site in the same gluteal muscle. If no blood appears, inject the medicine using a slow and continuous delivery.
-Alternate the right and left buttock for the injection site each month.
Cases of hepatotoxicity, such as hepatitis and clinically significant liver dysfunction have been observed in association with naltrexone exposure. Transient, asymptomatic hepatic transaminase elevations have also been observed. Studies have shown that naltrexone causes hepatocellular injury in a substantial proportion of patients exposed to doses higher than the usual dose of 50 mg/day orally. In a placebo-controlled study in which naltrexone was administered to obese subjects at a dose approximately 5-fold that recommended for the blockade of opiate receptors (300 mg/day orally), 19% of naltrexone recipients and 0% of placebo-treated patients developed elevations of elevated hepatic enzymes (i.e., peak ALT values 3 to 19 times their baseline values) after 3 to 8 weeks of treatment. All patients were asymptomatic, and transaminase levels returned to baseline or decreased in a matter of weeks. There may also be a higher risk of hepatocellular injury with single doses above 50 mg, including those used for approved alternate day dosing schedules used for supervised administration (e.g., 100 mg orally every other day or 150 mg orally every third day). Clinical trial data indicate that 7% to 13% of study patients receiving 380 mg/month of naltrexone extended-release intramuscular injection experienced elevated hepatic enzymes compared to 2% to 6% of those on placebo. Drug-induced hepatitis, elevated hepatic enzymes, and hyperbilirubinemia have been reported postmarketing with naltrexone. When naltrexone-treated patients presented with elevated transaminases, there were often other potential causative or contributory etiologies identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Patients should seek immediate medical attention if they experience symptoms of acute hepatitis. Discontinue naltrexone if symptoms and/or signs of acute hepatitis develop.
Central nervous system (CNS) effects occurring during clinical trials of oral naltrexone for alcohol or opiate dependence and at greater incidence than with placebo included headache (7% or more), dizziness (4% to 9%), nervousness (4% or more), insomnia (3% or more), anxiety (2% or more), fatigue (4% or more), drowsiness (2% or less), increased energy (less than 10%), irritability (less than 10%). Events occurring in less than 1% of treated patients included paranoia, restlessness, confusion, disorientation, hallucinations, nightmares, yawning, and hot flashes. During clinical trials of extended-release naltrexone (380 mg/month) intramuscular injection for alcohol opioid dependence, the following effects were reported more frequently than with placebo: dizziness (sometimes with syncope) (13%), insomnia (6% to 14%), headache (3% to 25%), drowsiness (4%), and anxiety (12%). Cerebral arterial aneurysm, seizures, mental impairment, dysgeusia, euphoric mood (euphoria), migraine, ischemic stroke, irritability, disturbance in attention, abnormal dreams, agitation, delirium, hot flashes, and paresthesias were also reported during clinical trials of intramuscular naltrexone. CNS effects reported postmarketing with naltrexone use include abnormal thinking, agitation, anxiety, headache, fatigue, confusion, euphoria, hallucinations, insomnia, nervousness, drowsiness, hot flashes, dizziness, and hyperkinesis. It is not always possible to distinguish these occurrences from signs and symptoms of naltrexone-induced opiate discontinuation syndrome.
Depression, suicidal ideation, and attempted suicide have been reported in individuals receiving oral naltrexone, placebo, and in concurrent control groups undergoing treatment for alcoholism or opiate dependence and during postmarketing experience. No causal relationship to naltrexone has been demonstrated or suspected. The incidence ranges for these events range from 0% to 15% for depressed mood and 0% to 1% for suicidal ideation; the rates are similar to placebo. In a 24-week, placebo-controlled, pivotal trial of extended-release naltrexone intramuscular injection for alcohol dependence, adverse events involving depressed mood were reported by 10% of patients treated with naltrexone versus 5% of patients treated with placebo; 1% of treated patients discontinued naltrexone due to depression-related symptoms. Suicidal ideation, suicide attempts, or completed suicides occurred in 1% of treated individuals versus 0% placebo. In an open-label, long-term safety study in the U.S., adverse events of a suicidal nature (depressed mood, suicidal ideation, suicide attempt) were reported by 5% of opioid-dependent patients treated with naltrexone extended-release injection and 10% of those receiving oral naltrexone. In a 24-week, placebo-controlled pivotal trial conducted for opioid-dependent patients, adverse events involving depressed mood or suicidal thinking were not reported by any patient in either the naltrexone extended-release injection or placebo treatment groups. Monitor patients for the development of depression or suicidal thinking. Families and caregivers of treated patients should be aware of the symptoms of depression or suicidality and should report such symptoms to the patient's health care provider. Prescribers should be aware that treatment with naltrexone does not reduce the risk of suicide in these patients.
In clinical trials of the extended-release naltrexone intramuscular injection, patients who received naltrexone had increases in eosinophil counts (eosinophilia) relative to patients taking placebo, but eosinophil counts returned to normal over a period of several months in the naltrexone-treated individuals. One diagnosed case and one suspected case of eosinophilic pneumonia occurred; the pneumonia in the diagnosed case resolved with antibiotics and corticosteroids. Consider the possibility of eosinophilic pneumonia if progressive shortness of breath and hypoxemia develop. Consider eosinophilic pneumonia in patients who do not respond to antibiotics.
Patients treated with naltrexone 380 mg IM experienced a mean maximal decrease in platelet count of 17,800/mm3 as compared with 2600/mm3 in placebo patients. In randomized controlled trials, naltrexone administration was not associated with an increase in bleeding related adverse events. Idiopathic thrombocytopenic purpura was reported in one patient who may have been sensitized to naltrexone in a previous course of treatment with naltrexone. The condition cleared without sequelae after discontinuation of naltrexone and corticosteroid treatment. In addition, deep vein thrombosis and pulmonary embolism were reported as treatment-emergent adverse reactions during clinical trials of naltrexone suspension for injection; the incidences are unknown.
Gastrointestinal (GI) effects occurring during clinical trials of oral naltrexone for alcohol or opiate dependence include nausea (10% or more), vomiting (3% or more), abdominal pain (more than 10%), anorexia (less than 10%), diarrhea (less than 10%), and constipation (less than 10%). GI side effects reported in less than 1% of naltrexone-treated patients included appetite stimulation, weight loss, weight gain, xerostomia, flatulence, hemorrhoids, and peptic ulcer. During controlled trials of oral naltrexone 50 mg/day for alcohol dependence, approximately 5% of patients discontinued naltrexone due to nausea. During clinical trials of extended-release naltrexone intramuscular injection (380 mg/month) for alcohol or opioid dependence, the following GI effects were reported more frequently than with placebo: nausea (33%), vomiting (14%), diarrhea (13%), abdominal pain (11%), xerostomia (5%), dental pain (toothache; 4%), and anorexia (14%). Weight loss, weight gain, abdominal discomfort, colitis, constipation, flatulence, appetite stimulation, gastroenteritis, gastroesophageal reflux disease (GERD), GI bleeding, hemorrhoids, acute pancreatitis, paralytic ileus, and perirectal abscess were also reported. In postmarketing experience with oral naltrexone, GI effects including anorexia, nausea, vomiting, abdominal pain, and diarrhea have been reported. It is not always possible to distinguish these occurrences from signs and symptoms of naltrexone-induced opiate discontinuation syndrome.
Injection site reactions have been precipitated following self-administration of the naltrexone extended-release intramuscular injection suspension; the injection must be prepared and administered by a health care professional. Naltrexone extended-release injectable suspension should only be administered intramuscularly (IM); the risk of serious injection site reactions may be increased when the injection is deposited in subcutaneous or fatty tissue. Of 440 patients who received extended-release naltrexone intramuscular injection (380 mg/month) in clinical trials for alcohol dependence, 69% had an injection site reaction (pain, tenderness, induration, swelling, or itching) versus 50% of those receiving a placebo injection. Specific injection site reactions that occurred more frequently with naltrexone than the placebo group included injection site tenderness (45%), injection site induration (35%), injection site pain (5% to 17%), nodules/swelling (15%), itching at the injection site (10%), and injection site ecchymosis (7%). One patient developed an area of induration at the injection site that continued to enlarge after 4 weeks and eventually, necrotic tissue developed that required surgical excision. The FDA has received 196 reports of injection site reactions including cellulitis, induration, hematoma, abscess, sterile abscess, and tissue necrosis. Sixteen patients required surgical intervention ranging from incision and drainage for abscesses to extensive surgical debridement for tissue necrosis. Instruct patients to monitor the injection site and to seek medical care if they develop pain, swelling, tenderness, induration, bruising, itching, or redness at the injection site that does not improve or that worsens within 2 weeks. Promptly refer patients with worsening injection site reactions to a surgeon.
Urticaria, angioedema, and anaphylactoid reactions (anaphylaxis) have occurred in association with naltrexone administration in both clinical trials and during postmarketing use. Patients should be advised of the potential for serious hypersensitivity reactions while using naltrexone and instructed to seek immediate medical attention in the event of such a reaction.
During clinical trials using the naltrexone extended-release intramuscular injection, infections reported more frequently within the active drug group than the placebo group included naso-pharyngitis (7%) and influenza (5%). Other respiratory or related effects that were reported included upper respiratory tract infection, advanced HIV disease in HIV-infected patients, bronchitis, chronic obstructive pulmonary disease, dyspnea, laryngitis, pharyngolaryngeal pain, pneumonia, sinus congestion, and sinusitis. Respiratory effects or symptoms of infection occurring in less than 1% of patients during clinical trials of oral naltrexone for opiate dependence included nasal congestion, rhinorrhea, sneezing, sore throat, excess mucus, sinus trouble, hoarseness, cough, fever, and dyspnea.
In clinical trials of naltrexone extended-release intramuscular injection (380 mg/month) in patients with opioid dependence, hypertension occurred 5% of naltrexone-treated patients and at a higher incidence than with placebo. Other cardiovascular effects observed included angina, atrial fibrillation, congestive heart failure, coronary artery atherosclerosis, myocardial infarction, and palpitations. Cardiac and vascular effects occurring in less than 1% of patients receiving oral naltrexone for opiate dependence included epistaxis, phlebitis, edema, increased blood pressure, unspecified ECG changes, palpitations, and sinus tachycardia. Cardiovascular effects reported during postmarketing use of naltrexone include chest pain (unspecified), palpitations, and changes in blood pressure. It is not always possible to distinguish these occurrences from signs and symptoms of naltrexone-induced opiate discontinuation syndrome.
During clinical trials of naltrexone extended-release intramuscular injection (380 mg/month) for opioid dependence, the following musculoskeletal effects or pain symptoms were reported more frequently with naltrexone than placebo: arthralgia (12%), back pain (6%), and muscle cramps (8%). Myalgia, joint stiffness, limb pain, and muscle spasms have also been reported. Musculoskeletal effects or pain symptoms occurring during clinical trials of oral naltrexone for opiate dependence included arthralgia and myalgia (more than 10%), shoulder pain (less than 1%), knee or leg pain (less than 1%), tremor (less than 1%), twitching (less than 1%), inguinal pain (less than 1%), and side pain. Tremor and myalgia have been reported during postmarketing use of naltrexone. It is not always possible to distinguish these occurrences from signs and symptoms of naltrexone-induced opiate discontinuation syndrome. Increased creatinine phosphokinase (CPK) concentrations have been associated with naltrexone use. In open-label trials, 16% of patients dosed for more than 6 months had increases in CPK. Increases in 1 to 2 times the upper limit of normal (ULN) were most common with both oral and intramuscular naltrexone. Elevations as high as 4 times ULN for the oral naltrexone group and 35 times ULN for the intramuscular naltrexone group were also noted; there was no difference with placebo with respect to the proportions of patients with a CPK value at least 3 times ULN. No factors other than naltrexone exposure were associated with the CPK elevations.
Dermatologic or related effects occurring during clinical trials of oral naltrexone for opiate dependence included rash (less than 10%), oily skin (less than 1%), pruritus (less than 1%), acne vulgaris (less than 1%), tinea pedis (less than 1%), cold sores (less than 1%), and alopecia (less than 1%). During clinical trials of naltrexone extended-release intramuscular injection, rash (6%) occurred more frequently than with placebo; night sweats, pruritus, heat exhaustion, and hyperhidrosis (increased sweating) also occurred. Rash and increased sweating have also been reported during postmarketing use of naltrexone. It is not always possible to distinguish these occurrences from signs and symptoms of naltrexone-induced opiate discontinuation syndrome.
Genitourinary (GU) effects occurring during clinical trials of oral naltrexone included ejaculation dysfunction (delayed ejaculation; less than 10%), dysuria (less than 1%), increased urinary frequency (less than 1%), and libido increase or libido decrease (less than 1%). Decreased libido and urinary tract infection have also been reported with the use of naltrexone extended-release intramuscular injection.
Special senses effects (otic, ophthalmic) occurring in less than 1% of patients during clinical trials of oral naltrexone included blurred vision, ocular irritation (burning), light sensitivity (photophobia), eye swelling/ache (ocular inflammation), otalgia, and tinnitus. Unspecified visual impairment has been reported during postmarketing use of oral naltrexone. Conjunctivitis and blurred vision have also been reported with the use of naltrexone extended-release intramuscular injection; no cases of retinal artery occlusion have been reported during clinical trials or postmarketing use. Retinal artery occlusion has rarely been reported after injection with another drug product containing polylactide-co-glycolide (PLG) microspheres and in the presence of abnormal arteriovenous anastomosis.
Lymphadenopathy and increased white blood cell count have been reported with the use of naltrexone extended-release suspension for injection during clinical trials.
Acute cholecystitis and cholelithiasis have been reported as treatment-emergent adverse effects in patients who received naltrexone extended-release suspension for injection for alcohol and/or opioid dependence; the incidence of these effects is unknown.
General effects occurring during clinical trials of oral naltrexone for opiate dependence included increased thirst (polydipsia) (less than 10%), chills (less than 10%), swollen glands (less than 1%), and cold feet (less than 1%). During clinical trials of naltrexone extended-release intramuscular injection for opioid dependence, asthenia was reported more frequently in the active treatment group (23%) than with placebo. Other general events observed during clinical trial evaluation of intramuscular naltrexone included chest tightness, chills, face edema, pyrexia, rigors, and lethargy. Malaise and asthenia have been reported during postmarketing use of oral naltrexone.
During clinical trial evaluation of intramuscular naltrexone suspension, metabolic or nutritional effects including dehydration and hypercholesterolemia were observed; however, the frequencies are unknown. In some individuals, the use of opiate antagonists has been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones. The clinical significance of these changes is not fully understood.
Abrupt withdrawal precipitated by administration of an opioid antagonist to an opioid-dependent patient may result in a withdrawal syndrome severe enough to require hospitalization, and in some cases management in the intensive care unit. Opioid withdrawal has been precipitated following self-administration of the naltrexone extended-release suspension (e.g., Vivitrol). Inform patients that the injection must be prepared by and administered by a healthcare professional. To prevent precipitation of withdrawal, patients should be opioid-free for a minimum of 7 to 10 days prior to initiation of naltrexone. When transitioning from buprenorphine or methadone, patients may be vulnerable to precipitation of withdrawal symptoms for up to two weeks. Precipitated opioid withdrawal has also been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids. Make patients aware of the risks associated with precipitated withdrawal and the need to give an accurate account of last opioid use. Studies of naltrexone in alcoholic populations and in volunteers in clinical pharmacology studies have suggested that a small fraction of patients may experience an opioid discontinuation-like symptom complex including, but not limited to, tearfulness, abdominal cramps, bone, muscle, or joint pain, nasal symptoms, and feeling restless. These symptoms may represent the unmasking of occult opioid use or it may represent symptoms attributable to naltrexone. Patients treated for alcohol dependence with naltrexone should be assessed for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment. Because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period, prescribers should always be prepared to manage withdrawal symptomatically with non-opioid medications. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Withdrawal symptoms and death have been reported during the use of naltrexone in ultra rapid detoxification programs; the causes of death are not known. If rapid transition from agonist to antagonist therapy is considered necessary and appropriate by the healthcare provider, patients should be closely monitored in an appropriate medical setting where precipitated withdrawal can be managed.
Naltrexone is contraindicated in patients with hypersensitivity to naltrexone or any components of the commercially available product. Naltrexone is incorporated in 75:25 polylactide-co-glycolide (PLG) at a concentration of 337 mg of naltrexone per gram of microspheres. The diluent is composed of carboxymethylcellulose sodium salt, polysorbate 20, sodium chloride, and water for injection. Naltrexone should also not be used in patients with a known hypersensitivity to naloxone or nalmefene because these three drugs are all structurally similar.
The use of naltrexone in patients with hepatic disease should be carefully considered due to the hepatotoxic effects of naltrexone and the potential for decreased clearance of naltrexone. Naltrexone does not appear to be hepatotoxic at recommended doses. However, the margin between a safe dose and a hepatotoxic dose appears to be five-fold or less. There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits. There are reports of hepatitis and significant hepatic dysfunction in association with exposure to naltrexone oral tablets and parenteral naltrexone. In patients treated with naltrexone tablets or injection who presented with elevated transaminases, other potential causes were often identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Opioid withdrawal does not typically manifest as clinically significant hepatic dysfunction, however, abruptly precipitated opioid withdrawal may lead to systemic sequelae including acute liver injury. Warn patients of the potential risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue use of naltrexone if signs/symptoms of acute hepatitis occur.
Depression, suicide, attempted suicide and suicidal ideation have been reported in patients receiving naltrexone for the treatment of opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. Monitor alcohol and opioid dependent patients, including those taking naltrexone, for the development of depression or suicidal thinking. Inform families and caregivers of patients being treated with naltrexone to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient's healthcare provider.
Naltrexone is contraindicated in patients who are receiving opioid analgesics, partial opiate agonists (e.g., buprenorphine), those with current physiologic opioid dependence, and those in acute opioid withdrawal. Administration of naltrexone to these patients may precipitate an abrupt withdrawal severe enough to require hospitalization, and in some cases management in the intensive care unit. To prevent precipitation of withdrawal, patients should be opioid-free (including tramadol) for a minimum of 7 to 10 days prior to initiation of naltrexone. When transitioning from buprenorphine or methadone, patients may be vulnerable to precipitation of withdrawal symptoms for up to two weeks. In every case, be prepared to manage withdrawal symptomatically with non-opioid medications because there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. Since the absence of an opiate drug in the urine is often not sufficient proof that a patient is opiate-free, a naloxone challenge should be done if there is any question of occult opioid dependence. A naloxone challenge test may be helpful; however, a few case reports have indicated that patients may experience precipitated withdrawal despite having a negative urine toxicology screen or tolerating a naloxone challenge test (usually in the setting of transitioning from buprenorphine treatment). Make patients aware of the risks associated with precipitated withdrawal and the need to give an accurate account of last opioid use. A positive reaction to the naloxone challenge predicts a similar response to naltrexone. Use of naltrexone is contraindicated in an individual who fails the naloxone challenge test or who has a positive urine test for opioids. The naloxone challenge can be repeated in 24 hours. Assess patients treated for alcohol dependence for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with naltrexone. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or co-dependence on opioids.
If a painful procedure such as surgery is planned and opiate therapy is required, oral naltrexone may be discontinued 72 hours prior to the procedure. During this time, patients should be monitored for risk of relapse. Patients who have received intramuscular naltrexone prior to an emergent procedure should be considered for regional analgesia or use of non-opioid analgesics. If opiate therapy is required for anesthesia or analgesia in a patient currently receiving naltrexone, the patient should be continuously monitored in an anesthesia care setting. Opiates should be provided by individuals specifically trained in the use of anesthetic drugs and the management of respiratory effects of potent opioids, specifically establishment and maintenance of a patent airway and assisted ventilation. The amount of opioid required may be greater than usual and should be titrated to the needs of the patient. The resulting respiratory depression may also be deeper and more prolonged. If an opioid analgesic is required, a rapid-acting medication that minimizes the duration of respiratory depression is preferred. Patients should be abstinent from opiate analgesia for at least 7 days before restarting naltrexone to avoid precipitating withdrawal.
Naltrexone treated patients who require emergent opiate analgesia may require the administration of large opiate doses to provide adequate pain control, which may increase the risk of deep or prolonged respiratory depression. A rapidly acting opiate agonist is preferred for emergent analgesia to limit the duration of respiratory depression. Non-opiate receptor mediated actions (i.e., histamine-mediated) may occur with the use of opiates and should be expected (e.g., facial swelling, itching, generalized erythema or bronchoconstriction). Other alternatives for emergent analgesia in patients taking naltrexone include the use of regional analgesia, conscious sedation, non-opiate analgesics, or general anesthetics.
Attempts to overcome the antagonistic effects of naltrexone with large doses of an opioid agonist by patients maintained on naltrexone may result in potential for overdose or poisoning that may be fatal; cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment. Despite a prolonged pharmacologic effect, the blockade produced by naltrexone is surmountable. As the naltrexone blockade wanes and eventually dissipates, patients may respond to lower doses of opioids than previously used, potentially resulting in life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Patients are at particular risk at the end of the dosing interval, after missing a scheduled dose or after discontinuing naltrexone treatment. Patients should be informed of the serious consequences of attempting to overcome the opioid blockade and that they may be more sensitive to lower doses of opioid agonists once naltrexone therapy is stopped. Advise patients to inform family members and those closest to them of this increased sensitivity and risk of overdose. Discuss the availability of naloxone with all patients and strongly consider prescribing it in patients treated for opioid use disorder (OUD) because of the potential for relapse. Inform patients and caregivers of their options for obtaining naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).
The major active metabolite of naltrexone is excreted primarily by the kidney via active tubular secretion. Use caution in administering naltrexone to patients with moderate to severe renal impairment as the disposition of naltrexone in patients with moderate to severe renal impairment (CrCl less than 50 mL/minute) has not been evaluated.
The use of naltrexone for a substance abuse disorder during pregnancy should be considered only if supportive substance abuse prevention measures are ineffective. There are no adequate and well-controlled studies of naltrexone use in pregnant women to be informative of any drug-associated risks for birth defects or miscarriage, adverse maternal outcomes, or fetal outcomes. A retrospective analysis compared the outcomes of pregnant patients who chose oral naltrexone treatment (following full detoxification from opiates) with those patients who opted for opioid agonist pharmacotherapy. Of the 121 infants born to mothers on naltrexone, there were 23 first-trimester exposures (11 patients taking naltrexone at conception and 12 patients started in the first trimester). No fetal anomalies occurred and no spontaneous abortions or intrauterine fetal deaths were reported in these first trimester exposures. There were 2 neonates with anomalies in both the naltrexone and opioid agonist groups. Rates of neonatal abstinence syndrome were significantly lower in the naltrexone group than in patients taking opioid agonists (8.4% vs 75.2%); there was no difference in mean birthweight between study groups. However, additional studies are needed to replicate these findings and further identify any potential risks associated with in utero exposure to naltrexone. If treatment with naltrexone is selected, the potential benefit to the mother versus the potential risk to the fetus should be evaluated. There are known risks of opiate and alcohol addiction to the fetus. Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use. Published studies have also demonstrated that alcohol is associated with fetal harm including growth restriction, facial abnormalities, central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Daily oral administration of naltrexone to female rats and rabbits increased the incidence of early fetal loss at exposures 11 times or more and 2 times or more the human exposure, respectively. Daily oral administration of naltrexone to pregnant rats and rabbits during the period of organogenesis did not induce malformation at exposures up to 175 times and 14 times the human exposure, respectively. The effects of naltrexone during labor and delivery are unknown.
Naltrexone and its metabolite 6-beta-naltrexol are present in human breast milk. There are no data on the effects on the breastfed infant or the effects on milk production. The developmental health benefits of breast-feeding should be considered along with the mother's clinical need for naltrexone and any potential adverse effects on the breastfed infant from naltrexone or the mother's underlying maternal condition. Alcohol dependence and opiate addiction are known to have potential adverse drug risks to the nursing infant; alcohol and many opiates are excreted in breast milk.
Naltrexone may cause dizziness. Tell patients about the importance of not driving or operating machinery, or performing other potentially hazardous tasks, until they know how this medicine will affect them.
Naltrexone extended-release (ER) injectable suspension (e.g., Vivitrol) is for deep intramuscular gluteal administration only; inadvertent subcutaneous administration may increase the likelihood of severe injection site reactions. Proper administration technique and patient selection are imperative. Consider alternate treatment for patients whose body composition precludes a gluteal intramuscular injection with one of the provided needles. Naltrexone ER injections may be followed by pain, tenderness, induration, swelling, erythema, bruising, or pruritus; however, in some cases injection site reactions may be very severe. In the clinical trials, one patient developed an area of induration that continued to enlarge after 4 weeks, with subsequent development of tissue necrosis that required surgical excision. In the postmarketing period, additional cases have been reported. Some cases required surgical intervention, including debridement of necrotic tissue. Some cases resulted in significant scarring. The reported cases occurred primarily in females. Evaluate patients reporting signs of abscess, cellulitis, tissue necrosis to determine if referral to a surgeon is warranted. As with any intramuscular injection, naltrexone ER injectable suspension should be administered with caution to patients with thrombocytopenia or coagulopathy (e.g., hemophilia and severe hepatic failure) due to the risk for hematoma or bleeding.
Naltrexone use may cause laboratory test interference for selected drug detection methods. Naltrexone does not interfere with thin-layer, gas-liquid, and high pressure liquid chromatographic methods which may be used for the separation and detection of morphine, methadone or quinine in the urine. Naltrexone may be cross-reactive with certain immunoassay methods for the detection of drugs of abuse (specifically opioids) in urine. Naltrexone may or may not interfere with enzymatic methods for the detection of opioids depending on the specificity of the test. For further information, reference to the specific test/assay instructions is recommended.
For the maintenance treatment of alcohol dependence:
Oral dosage:
Adults: 50 mg PO once daily with food for 12 weeks has been shown to be effective. Other regimens or durations have not been evaluated in placebo-controlled trials, but include 50 mg PO once daily on weekdays and 100 mg PO on Saturdays; 100 mg PO every other day; or 150 mg PO every third day. A consensus panel recommends naltrexone treatment be individualized to meet the patient's needs. Some patients may require naltrexone doses of 100 mg/day PO. Initially, patients may require 3 to 6 months of naltrexone treatment. Certain patients may benefit from up to 1 year of treatment. To decrease gastrointestinal side effects, start with 12.5 mg to 25 mg PO once daily and gradually titrate the dose, split the daily dose, or adjust the administration times. Pharmacotherapy should be used as a part of a comprehensive management program that includes psychosocial support and treatment. Naltrexone does not eliminate or reduce alcohol withdrawal symptoms. If naltrexone is initiated early in the abstinence process, it will not prevent signs and symptoms that would be experienced if the drug had not been started.
Intramuscular dosage:
Adults: 380 mg IM as deep gluteal injection every 4 weeks. Use is indicated in patients who are able to abstain from alcohol in an outpatient setting. Patients should not be actively drinking alcohol at the time of initial IM dose. Pretreatment with oral naltrexone is not required. LIMIT OF USE: There are no data to specifically address re-initiation in patients who discontinue naltrexone use. There are no systematic data that specifically address switching from oral naltrexone to IM naltrexone.
For prevention of relapse to opiate agonist dependence after opioid detoxification:
Oral dosage:
Adults: 25 mg PO once daily, initially. Increase the dose to 50 mg PO once daily if no withdrawal signs occur. An opioid-free interval of a minimum of 7 to 10 days is recommended before starting naltrexone to avoid precipitation of opioid withdrawal.
Intramuscular dosage:
Adults: 380 mg IM every 4 weeks or once monthly. Pretreatment with oral naltrexone is not required before use. An opioid-free interval of a minimum of 7 to 10 days is recommended before starting naltrexone to avoid precipitation of opioid withdrawal. There are no data to specifically address treatment re-initiation in persons who stopped therapy. There are no systematically collected data that specifically address the switch from oral naltrexone or other medications for opioid use disorder to IM naltrexone. Persons transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks and management of withdrawal symptomatically with non-opioid medications may be required.
For the opiate agonist withdrawal induction* during detoxification:
NOTE: Rapid and ultrarapid opiate detoxification should only be done in a controlled setting under the supervision of a physician experienced in the management of opiate withdrawal. Severe withdrawal symptoms and death have been reported in patients undergoing ultrarapid opiate detoxification.
-for rapid opiate detoxification*:
Oral dosage:
Adults: Various titration regimens leading up to a full dose of naltrexone 50 mg PO once daily have been used during rapid opiate detoxification. In some cases patients have been treated with naloxone prior to naltrexone. Many studies also use concomitant adjuvant medications to decrease withdrawal symptoms including phenothiazines, benzodiazepines, and non-opiate analgesics (NSAIDs).
-for ultrarapid opiate detoxification*:
Oral dosage:
Adults: Naltrexone with or without naloxone has been given during ultrarapid opiate detoxification. In a study using naltrexone alone, 50 mg PO was given prior to sedation with midazolam. Other medications used in ultrarapid detoxification include clonidine, benzodiazepines, antiemetic agents (e.g., metoclopramide and ondansetron), and general anesthesia.
For the treatment of pruritus*:
-due to cholestatic liver disease:
Oral dosage:
Adults: 50 mg PO once daily for 7 days to 4 weeks resulted in significant improvement in itching and sleep in patients with pruritus resistant to cholestyramine or ursodiol. Nausea may be limited by using an initial dose of naltrexone 25 mg PO once daily, followed by subsequent titration.
-due to systemic or dermatologic disease:
Oral dosage:
Adults: Limited data suggest 50 mg PO once daily may be effective. In an open-label pilot study of 50 patients with severe pruritus, naltrexone for up to 20 months significantly reduced symptoms in 35 patients, with 13 patients experiencing complete resolution. Six patients experienced tachyphylaxis within 1-9 months of treatment; 2 patients with chronic prurigo nodularis overcame tachyphylaxis by administration of 50 mg twice a day. Adverse effects, including fatigue, dizziness, heartburn, and diarrhea were rare and were restricted to the first 2 weeks of treatment. Nausea, which occurred in 11 patients, was generally controlled by metoclopramide; however, 2 patients required discontinuation of therapy.
-for uremic pruritus*:
Oral dosage:
Adults: Limited data suggest 50 mg PO once daily may be effective. In a randomized, double-blind, placebo-controlled crossover trial of 15 hemodialysis patients with severe resistant pruritus, treatment with naltrexone for 7 days resulted in a significant reduction in pruritus compared to placebo. Relief from pruritus occurred within the first 48 hours of treatment. Adverse reactions were reported by a total of 5 patients and included heartburn and upper abdominal discomfort.
For use as an adjunct to psychosocial interventions for tobacco cessation* (smoking cessation*):
Oral dosage:
Adults: Limited data are available. Naltrexone 50 mg PO once daily has been used alone or in combination with nicotine transdermal patches as a treatment or adjuvant therapy in patients attempting to stop smoking. In a trial comparing nicotine patches alone or with naltrexone, the results showed a decreased urge to smoke in response to smoking cues, a decrease in withdrawal scored, and reduced negative effects following exposure to smoking cues in patients treated with the combination. The conclusions of this study are considered preliminary and require more extensive follow-up.
For the treatment of amphetamine-type stimulant use disorder (in combination with bupropion)*:
Intramuscular dosage:
Adults: 380 mg extended IM every 3 to 4 weeks in combination with bupropion (450 mg/day extended-release) appears to promote a reduction in the use of amphetamine-type stimulants. This combination may be particularly helpful for individuals with concomitant alcohol use disorder, as naltrexone has been shown to be helpful in reducing alcohol consumption (moderate certainty, conditional recommendation).
Maximum Dosage Limits:
-Adults
150 mg/day PO; 380 mg/dose IM.
-Elderly
150 mg/day PO; 380 mg/dose IM.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Naltrexone undergoes significant liver metabolism. In patients with severe hepatic dysfunction, up to a 10-fold increase in naltrexone AUC may be observed. Dosage adjustment may be necessary in patients with hepatic impairment. However, specific guidelines for dosage adjustments in patients with hepatic dysfunction are not available.
Patients with Renal Impairment Dosing
Both naltrexone and its active metabolite are excreted renally, and naltrexone doses may need adjustment for patients with renal impairment. However, specific guidelines for dosage adjustment in patients with renal impairment are not available.
*non-FDA-approved indication
Acamprosate: (Minor) The administration of naltrexone with acamprosate results in an increase in acamprosate exposure (AUC) by 25% and in peak concentration (Cmax) by 33%. However, acamprosate dosage adjustments are not required.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Acetaminophen; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Acetaminophen; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
Acetaminophen; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Alfentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of alfentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from alfentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Aspirin, ASA; Carisoprodol; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Aspirin, ASA; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Atropine; Difenoxin: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Bremelanotide: (Major) Avoid using bremelanotide with an orally-administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the severe consequence of naltrexone treatment failure. In pharmacokinetic studies, bremelanotide significantly affected the oral absorption of naltrexone.
Buprenorphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Buprenorphine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Butalbital; Aspirin; Caffeine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Butorphanol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Chlorpheniramine; Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Chlorpheniramine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
Chlorpromazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Codeine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Codeine; Guaifenesin: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Codeine; Guaifenesin; Pseudoephedrine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Codeine; Phenylephrine; Promethazine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Codeine; Promethazine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. An opiate antagonist should only be administered to a patient taking codeine with clinically significant respiratory or cardiovascular depression. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Diphenoxylate; Atropine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Disulfiram: (Major) The safety and efficacy of concomitant use of naltrexone and disulfiram is unknown. There is the possibility of additive hepatotoxicity and concurrent use of these agents is not recommended. If concomitant use of naltrexone and disulfiram is required, liver function tests should be performed prior to beginning combination therapy, then they should be repeated every 2 weeks for 1 to 2 months. Continue monitoring LFTs monthly after the third month of combined use.
Dronabinol: (Moderate) Concomitant administration of naltrexone and oral THC like dronabinol enhances the positive subjective effects of oral THC. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Fentanyl: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Fluphenazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Homatropine; Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
Hydrocodone: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
Hydrocodone; Ibuprofen: (Major) The opiate antagonists naloxone and naltrexone are pharmacologic opposites of hydrocodone. These drugs can block the actions of hydrocodone and, if administered to patients who have received chronic hydrocodone, can produce acute withdrawal and/or reduce the analgesic effect of hydrocodone.
Hydromorphone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Opiate antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Ibuprofen; Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Levorphanol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Lofexidine: (Major) Separate administration of lofexidine and oral naltrexone by 2 hours as simultaneous administration may reduce the efficacy of naltrexone. Coadministration of lofexidine and oral naltrexone resulted in statistically significant differences in the steady state pharmacokinetics of naltrexone. This interaction is not expected if naltrexone is administered by non-oral routes.
Meperidine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Methadone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Methylnaltrexone: (Major) Avoid concomitant use of methylnaltrexone with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Morphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Morphine; Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Nabilone: (Moderate) Concomitant administration of naltrexone and nabilone enhances the 'positive' subjective effects of nabilone. Data from separate investigations demonstrate that pretreatment with an opioid receptor blocker such as naltrexone significantly increases many of the euphoric effects of oral THC in heavy marijuana smokers.
Nalbuphine: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Naldemedine: (Major) Avoid concomitant use of naldemedine with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Naloxegol: (Major) Avoid concomitant use of naloxegol with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.
Opiate Agonists-Antagonists: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Oxycodone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Oxymorphone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Naltrexone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxymorphone overdose. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Pentazocine; Naloxone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving mixed opiate agonists/antagonists. Naltrexone will antagonize the therapeutic benefits of mixed opiate agonists/antagonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Perphenazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Perphenazine; Amitriptyline: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Phenothiazines: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Prochlorperazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Promethazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Promethazine; Dextromethorphan: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Promethazine; Phenylephrine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Remifentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of remifentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from remifentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Sufentanil: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. The usual doses of sufentanil will be ineffective in patients receiving naltrexone. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. However, respiratory depression from sufentanil is not expected to last longer than the effect of a single naloxone dose. Other non-opioid medications should be used prior to, during, and after surgery as increased doses of opiate agonists are required to override the antagonistic effects of naltrexone and may induce prolonged and more severe adverse effects. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Tapentadol: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects (respiratory insufficiency or arrest or circulatory collapse) with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
Thioridazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Trifluoperazine: (Moderate) Patients receiving phenothiazines and naltrexone concomitantly have had symptoms of somnolence and lethargy.
Naltrexone is a competitive antagonist at opiate receptors mu, kappa, and delta. Opiate receptors have been reclassified by an International Union of Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and OP3 (mu). Naltrexone can either displace opiate agonists from binding at these receptors or prevent opiate binding. Naltrexone does not antagonize the effects of non-opiates such as cocaine, ethanol, amphetamines, barbiturates, or benzodiazepines. Blockade of opiate receptors by naltrexone is a competitive phenomenon and results in elimination of the euphoric effect of opiates. At usual opiate concentrations, naltrexone's greater affinity for the receptor prevents the binding of the opiate agonist to the receptor. However, when opiate concentrations are extremely high, the opiate can displace naltrexone, and respiratory depression and/or death is possible. Although naltrexone itself may possess some agonistic properties, these are minor compared to its potent antagonistic actions. Naltrexone is 17-times more potent than nalmorphine and twice as potent as naloxone. In patients who are physically dependent on opiates, naltrexone will precipitate an opiate withdrawal syndrome. Naltrexone use is not associated with tolerance or dependence, therefore, withdrawal from naltrexone does not occur. When co-administered with opiate agonists, naltrexone blocks the physical dependence to morphine, heroin, and other opiate agonists. Depending on the dose, the clinical effects of naltrexone can persist for up to 72 hours.
Endogenous opioids such as beta-endorphins and enkephalins may play an important role in alcohol dependence. An opioid reward system mediated by mu- and delta-receptors and an opposing aversion system mediated by kappa-receptors must be in balance to maintain a neutral state with regard to the development of addiction. Several theories regarding alcohol dependence and the function of endogenous opioids exist. All of these theories are based on an imbalance in favor of the endogenous reward pathways due to alcohol. Naltrexone inhibits the effects of endogenous opioids and decreases the positive or reward pathways associated with alcoholism. Naltrexone is not aversive therapy and will not produce a disulfiram-like reaction if opiates or ethanol are ingested while receiving naltrexone.
Naltrexone is administered orally or intramuscularly (IM). Naltrexone is widely distributed throughout the body, and antagonistic activity appears to be related to plasma and tissue concentrations.CSF concentrations are not known. Protein binding is roughly 21% to 28%. Naltrexone is metabolized to 6-beta-naltrexol, which also has antagonistic activity but is less potent than its parent. Significantly less 6-beta-naltrexol is generated following IM administration of naltrexone compared to administration of oral naltrexone due to a reduction in first-pass hepatic metabolism. Two other minor metabolites have been identified: 2-hydroxy-3-methoxy-6-beta-naltrexol and 2-hydroxy-3-methyl-naltrexone. The cytochrome P450 isoenzyme system is not involved in the metabolism of naltrexone. There appears to be little accumulation of naltrexone and 6-beta-naltrexol after chronic administration. Naltrexone is a highly extracted drug (more than 98% metabolized), and extra-hepatic sites of metabolism may exist. Following hepatic metabolism, both naltrexone and its metabolites conjugate with glucuronic acid. The maximum serum concentration and systemic exposure for both naltrexone and 6-beta-naltrexol are dose-proportional. Total naltrexone exposure is 3 to 4-fold higher after a single, 380 mg IM injection as compared with oral doses of 50 mg/day for 28 days.
Both naltrexone and its metabolite are excreted primarily by the kidney (53% to 79% of the dose) and the major metabolite undergoes active tubular secretion. Only about 2% of naltrexone is excreted in the urine unchanged within 24 hours. 6-beta-naltrexol appears to undergo renal tubular secretion. Although naltrexone and its metabolites may undergo enterohepatic recycling, fecal elimination is a minor elimination pathway. The mean elimination half-life of naltrexone after oral administration is 4 hours, and the elimination half-life of 6-beta-naltrexol is roughly 14 hours. The mean elimination half-life of both naltrexone and 6-beta-naltrexol after intramuscular administration is 5 to 10 days; elimination of naltrexone is dependent on erosion of the polymer.
Affected Cytochrome P450 isoenzymes and drug transporters: None
-Route-Specific Pharmacokinetics
Oral Route
Oral absorption of naltrexone is rapid and almost complete (roughly 96%). Due to extensive first-pass metabolism in the liver, however, only 5% to 40% of the drug reaches the systemic circulation unchanged. Studies indicate that oral naltrexone 50 mg will block the pharmacologic effects of 25 mg IV heroin for as long as 24 hours. Additional data suggest that doubling the dose of naltrexone provides blockade for 48 hours and tripling the dose provides blockade for up to 72 hours.
Intramuscular Route
After administration of naltrexone extended-release intramuscular injection suspension, an initial drug peak occurs around 2 hours. A second peak occurs 2 to 3 days later; measurable concentrations are available for more than 1 month. Steady-state is achieved at the end of the dosing interval after the first injection. First pass metabolism is reduced with intramuscular administration.
-Special Populations
Hepatic Impairment
Pharmacokinetic parameters of naltrexone extended-release intramuscular injection are essentially unchanged in patients with mild or moderate (Child-Pugh class A or B) hepatic impairment; the disposition of this dosage form in patients with severe hepatic impairment has not been evaluated. In patients with compensated and decompensated liver cirrhosis, the AUC of oral naltrexone increased 5- and 10-fold, respectively, as compared to patients with normal liver function. Oral dosage adjustments may be necessary in patients with hepatic dysfunction.
Renal Impairment
Pharmacokinetic parameters of naltrexone extended-release intramuscular injection are essentially unchanged in patients with mild renal impairment (CrCl of 50 to 80 mL/minute) and no dosage adjustments are necessary; the disposition of this dosage form in patients with moderate to severe renal impairment has not been evaluated. Naltrexone appears to have extra-hepatic sites of drug metabolism and its major metabolite undergoes active tubular secretion. Adequate studies of oral naltrexone in patients with severe renal impairment have not been conducted.