10.562 x 10.062

Epic Naltrexone HCl Tabs Iss: 09/11 Size: 12.125 x 11.125 Fold Size: 1-1/8 x 1-1/8 Type: 6 pt. Side A Proof 5 10/25/11 DC Naltrexone Hydrochloride Tablets USP, film coated
Elimination
reported in the literature have employed the following dosing regimen: 100 receptor blockade. As a consequence, the patient may be in immediate danger The renal clearance for naltrexone ranges from 30 to 127 mL/min and mg on Monday, 100 mg on Wednesday, and 150 mg on Friday. This dosing of suffering life endangering opioid intoxication (e.g., respiratory arrest, suggests that renal elimination is primarily by glomerular filtration. In schedule appeared to be acceptable to many naltrexone patients successfully circulatory collapse). Patients should be told of the serious consequences of comparison, the renal clearance for 6-b-naltrexol ranges from 230 to 369 maintaining their opioid-free state.
trying to overcome the opiate blockade (see PRECAUTIONS, Information for
mL/min, suggesting an additional renal tubular secretory mechanism. The Patients).
DESCRIPTION
urinary excretion of unchanged naltrexone accounts for less than 2% of an Experience with the supervised administration of a number of potentially There is also the possibility that a patient who has been treated with Naltrexone hydrochloride, an opioid antagonist, is a synthetic congener of oral dose; urinary excretion of unchanged and conjugated 6-b-naltrexol hepatotoxic agents suggests that supervised administration and single doses naltrexone will respond to lower doses of opioids than previously used, oxymorphone with no opioid agonist properties. Naltrexone hydrochloride accounts for 43% of an oral dose. The pharmacokinetic profile of naltrexone of naltrexone hydrochloride higher than 50 mg may have an associated particularly if taken in such a manner that high plasma concentrations remain differs in structure from oxymorphone in that the methyl group on the suggests that naltrexone and its metabolites may undergo enterohepatic increased risk of hepatocellular injury, even though three-times a week dosing in the body beyond the time that naltrexone exerts its therapeutic effects. This nitrogen atom is replaced by a cyclopropylmethyl group. Naltrexone has been well-tolerated in the addict population and in initial clinical trials in could result in potentially life-threatening opioid intoxication (respiratory hydrochloride is also related to the potent opioid antagonist, naloxone, or alcoholism. Clinics using this approach should balance the possible risks compromise or arrest, circulatory collapse, etc.). Patients should be aware n-allylnoroxymorphone. The chemical name for naltrexone hydrochloride is Hepatic and Renal Impairment
against the probable benefits and may wish to maintain a higher index of that they may be more sensitive to lower doses of opioids after naltrexone Morphinan-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-, Naltrexone appears to have extra-hepatic sites of drug metabolism and its suspicion for drug-associated hepatitis and ensure patients are advised of the hydrochloride, (5a)-. The structural formula is as follows: major metabolite undergoes active tubular secretion (see Metabolism above).
need to report non-specific abdominal complaints (see PRECAUTIONS,
Adequate studies of naltrexone in patients with severe hepatic or renal Information for Patients).
Ultra Rapid Opioid Withdrawal
impairment have not been conducted (see PRECAUTIONS, Special Risk
Safe use of naltrexone in ultra rapid opiate detoxification programs has not Patients).
INDICATIONS AND USAGE
been established (see ADVERSE REACTIONS).
Naltrexone hydrochloride tablets are indicated in the treatment of alcohol Clinical Trials
dependence and for the blockade of the effects of exogenously administered PRECAUTIONS
Naltrexone has not been shown to provide any therapeutic benefit except as When Reversal of Naltrexone Blockade is Required: The efficacy of naltrexone as an aid to the treatment of alcoholism was tested in placebo-controlled, outpatient, double blind trials. These studies used a part of an appropriate plan of management for the addictions.
In an emergency situation in patients receiving fully blocking doses of dose of naltrexone hydrochloride 50 mg once daily for 12 weeks as an adjunct naltrexone, a suggested plan of management is regional analgesia, conscious to social and psychotherapeutic methods when given under conditions that CONTRAINDICATIONS
sedation with a benzodiazepine, use of non-opioid analgesics or general enhanced patient compliance. Patients with psychosis, dementia, and secondary psychiatric diagnoses were excluded from these studies.
1. Patients receiving opioid analgesics.
In a situation requiring opioid analgesia, the amount of opioid required may Naltrexone hydrochloride is a white, crystalline compound. The hydrochloride In one of these studies, 104 alcohol-dependent patients were randomized to 2. Patients currently dependent on opioids, including those currently be greater than usual, and the resulting respiratory depression may be deeper salt is soluble in water to the extent of about 100 mg/mL. Each film-coated receive either naltrexone hydrochloride 50 mg once daily or placebo. In this maintained on opiate agonists [e.g., methadone or LAAM (levo- alpha- tablet, for oral administration, contains 50 mg of naltrexone hydrochloride. In study, naltrexone proved superior to placebo in measures of drinking addition each film-coated tablet contains the following inactive ingredients: including abstention rates (51% vs. 23%), number of drinking days, and A rapidly acting opioid analgesic which minimizes the duration of respiratory carnauba wax powder, colloidal silicon dioxide, croscarmellose sodium, relapse (31% vs. 60%). In a second study with 82 alcohol-dependent 3. Patients in acute opioid withdrawal (see WARNINGS).
depression is preferred. The amount of analgesic administered should be hypromellose, hydroxypropyl cellulose, lactose anhydrous, magnesium patients, the group of patients receiving naltrexone were shown to have lower titrated to the needs of the patient. Non-receptor mediated actions may occur stearate, microcrystalline cellulose, polyethylene glycol, titanium dioxide and relapse rates (21% vs. 41%), less alcohol craving, and fewer drinking days 4. Any individual who has failed the naloxone challenge test or who has a and should be expected (e.g., facial swelling, itching, generalized erythema, compared with patients who received placebo, but these results depended on or bronchoconstriction) presumably due to histamine release.
CLINICAL PHARMACOLOGY
5. Any individual with a history of sensitivity to naltrexone or any other Irrespective of the drug chosen to reverse naltrexone blockade, the patient Pharmacodynamic Actions
The clinical use of naltrexone as adjunctive pharmacotherapy for the components of this product. It is not known if there is any cross-sensitivity should be monitored closely by appropriately trained personnel in a setting Naltrexone hydrochloride is a pure opioid antagonist. It markedly attenuates treatment of alcoholism was also evaluated in a multicenter safety study. This with naloxone or the phenanthrene containing opioids.
equipped and staffed for cardiopulmonary resuscitation.
or completely blocks, reversibly, the subjective effects of intravenously study of 865 individuals with alcoholism included patients with comorbid psychiatric conditions, concomitant medications, polysubstance abuse and 6. Any individual with acute hepatitis or liver failure.
When co-administered with morphine, on a chronic basis, naltrexone blocks HIV disease. Results of this study demonstrated that the side effect profile of Severe opioid withdrawal syndromes precipitated by the accidental ingestion the physical dependence to morphine, heroin and other opioids.
naltrexone appears to be similar in both alcoholic and opioid dependent WARNINGS
of naltrexone have been reported in opioid-dependent individuals. Symptoms Naltrexone has few, if any, intrinsic actions besides its opioid blocking populations, and that serious side effects are uncommon.
Hepatotoxicity
of withdrawal have usually appeared within five minutes of ingestion of properties. However, it does produce some pupillary constriction, by an naltrexone and have lasted for up to 48 hours. Mental status changes In the clinical studies, treatment with naltrexone supported abstinence, Naltrexone has the capacity to cause hepatocellular injury when given in
including confusion, somnolence and visual hallucinations have occurred.
The administration of naltrexone is not associated with the development of prevented relapse and decreased alcohol consumption. In the uncontrolled excessive doses.
Significant fluid losses from vomiting and diarrhea have required intravenous tolerance or dependence. In subjects physically dependent on opioids, study, the patterns of abstinence and relapse were similar to those observed Naltrexone is contraindicated in acute hepatitis or liver failure, and its
fluid administration. In all cases patients were closely monitored and therapy naltrexone will precipitate withdrawal symptomatology.
in the controlled studies. Naltrexone was not uniformly helpful to all patients, use in patients with active liver disease must be carefully considered in
with non-opioid medications was tailored to meet individual requirements.
Clinical studies indicate that 50 mg of naltrexone hydrochloride will block the and the expected effect of the drug is a modest improvement in the outcome light of its hepatotoxic effects.
pharmacologic effects of 25 mg of intravenously administered heroin for The margin of separation between the apparently safe dose of
Use of naltrexone does not eliminate or diminish withdrawal symptoms. If periods as long as 24 hours. Other data suggest that doubling the dose of naltrexone and the dose causing hepatic injury appears to be only
naltrexone is initiated early in the abstinence process, it will not preclude the naltrexone hydrochloride provides blockade for 48 hours, and tripling the five-fold or less. Naltrexone does not appear to be a hepatotoxin at the
patient’s experience of the full range of signs and symptoms that would be dose of naltrexone hydrochloride provides blockade for about 72 hours.
Naltrexone has been shown to produce complete blockade of the euphoric recommended doses.
experienced if naltrexone had not been started. Numerous adverse events are Naltrexone blocks the effects of opioids by competitive binding (i.e., effects of opioids in both volunteer and addict populations. When Patients should be warned of the risk of hepatic injury and advised to
known to be associated with withdrawal.
analogous to competitive inhibition of enzymes) at opioid receptors. This administered by means that enforce compliance, it will produce an effective stop the use of naltrexone and seek medical attention if they experience
makes the blockade produced potentially surmountable, but overcoming full opioid blockade, but has not been shown to affect the use of cocaine or symptoms of acute hepatitis.
Special Risk Patients
naltrexone blockade by administration of very high doses of opiates has resulted in excessive symptoms of histamine release in experimental subjects.
Naltrexone and its primary metabolite are excreted primarily in the urine, and The mechanism of action of naltrexone in alcoholism is not understood; There are no data that demonstrate an unequivocally beneficial effect of Evidence of the hepatotoxic potential of naltrexone is derived primarily from caution is recommended in administering the drug to patients with renal however, involvement of the endogenous opioid system is suggested by naltrexone on rates of recidivism among detoxified, formerly opioid- a placebo controlled study in which naltrexone hydrochloride was preclinical data. Naltrexone, an opioid receptor antagonist, competitively dependent individuals who self- administer the drug. The failure of the drug administered to obese subjects at a dose approximately five-fold that binds to such receptors and may block the effects of endogenous opioids.
in this setting appears to be due to poor medication compliance.
recommended for the blockade of opiate receptors (300 mg per day). In that Opioid antagonists have been shown to reduce alcohol consumption by study, 5 of 26 naltrexone recipients developed elevations of serum Caution should be exercised when naltrexone hydrochloride is administered animals, and naltrexone has been shown to reduce alcohol consumption in The drug is reported to be of greatest use in good prognosis opioid addicts transaminases (i.e., peak ALT values ranging from a low of 121 to a high of to patients with liver disease. An increase in naltrexone AUC of approximately who take the drug as part of a comprehensive occupational rehabilitative 532; or 3 to 19 times their baseline values) after three to eight weeks of 5- and 10-fold in patients with compensated and decompensated liver Naltrexone is not aversive therapy and does not cause a disulfiram-like program, behavioral contract, or other compliance-enhancing protocol.
treatment. Although the patients involved were generally clinically cirrhosis, respectively, compared with subjects with normal liver function has reaction either as a result of opiate use or ethanol ingestion.
Naltrexone, unlike methadone or LAAM (levo- alpha-acetyl-methadol), does asymptomatic and the transaminase levels of all patients on whom follow-up been reported. These data also suggest that alterations in naltrexone not reinforce medication compliance and is expected to have a therapeutic was obtained returned to (or toward) baseline values in a matter of weeks, the bioavailability are related to liver disease severity.
Pharmacokinetics
effect only when given under external conditions that support continued use lack of any transaminase elevations of similar magnitude in any of the 24 Naltrexone is a pure opioid receptor antagonist. Although well absorbed placebo patients in the same study is persuasive evidence that naltrexone is orally, naltrexone is subject to significant first pass metabolism with oral a direct (i.e., not idiosyncratic) hepatotoxin.
The risk of suicide is known to be increased in patients with substance abuse bioavailability estimates ranging from 5 to 40%. The activity of naltrexone is This conclusion is also supported by evidence from other placebo controlled with or without concomitant depression. This risk is not abated by treatment believed to be due to both parent and the 6-b-naltrexol metabolite. Both DO NOT ATTEMPT TREATMENT WITH NALTREXONE UNLESS, IN THE studies in which exposure to naltrexone hydrochloride at doses above the with naltrexone (see ADVERSE REACTIONS).
parent drug and metabolites are excreted primarily by the kidney (53% to MEDICAL JUDGEMENT OF THE PRESCRIBING PHYSICIAN, THERE IS NO amount recommended for the treatment of alcoholism or opiate blockade (50 79% of the dose), however, urinary excretion of unchanged naltrexone REASONABLE POSSIBILITY OF OPIOID USE WITHIN THE PAST 7 TO 10 mg/day) consistently produced more numerous and more significant Information for Patients
accounts for less than 2% of an oral dose and fecal excretion is a minor DAYS. IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, elevations of serum transaminases than did placebo. Transaminase elevations It is recommended that the prescribing physician relate the following elimination pathway. The mean elimination half-life (T-1/2) values for in 3 of 9 patients with Alzheimer's Disease who received naltrexone information to patients being treated with naltrexone: naltrexone and 6-b-naltrexol are 4 hours and 13 hours, respectively.
hydrochloride (at doses up to 300 mg/day) for 5 to 8 weeks in an open clinical You have been prescribed naltrexone hydrochloride tablets as part of the Naltrexone and 6-ß-naltrexol are dose proportional in terms of AUC and Cmax comprehensive treatment for your alcoholism or drug dependence. You over the range of 50 to 200 mg and do not accumulate after 100 mg daily The placebo-controlled studies that demonstrated the efficacy of naltrexone Although no cases of hepatic failure due to naltrexone administration have should carry identification to alert medical personnel to the fact that you are as an adjunctive treatment of alcoholism used a dose regimen of naltrexone ever been reported, physicians are advised to consider this as a possible risk taking naltrexone hydrochloride. A naltrexone medication card may be hydrochloride 50 mg once daily for up to 12 weeks. Other dose regimens or of treatment and to use the same care in prescribing naltrexone as they would obtained from your physician and can be used for this purpose. Carrying the Absorption
durations of therapy were not studied in these trials.
other drugs with the potential for causing hepatic injury.
identification card should help to ensure that you can obtain adequate Following oral administration, naltrexone undergoes rapid and nearly treatment in an emergency. If you require medical treatment, be sure to tell complete absorption with approximately 96% of the dose absorbed from the Physicians are advised that 5 to 15% of patients taking naltrexone for Unintended Precipitation of Abstinence
the treating physician that you are receiving naltrexone therapy.
gastrointestinal tract. Peak plasma levels of both naltrexone and 6-b-naltrexol alcoholism will complain of non-specific side effects, chiefly gastrointestinal To prevent occurrence of an acute abstinence syndrome, or exacerbation
You should take naltrexone as directed by your physician. If you attempt to upset. Prescribing physicians have tried using an initial 25 mg dose, splitting of a pre-existing subclinical abstinence syndrome, patients must be
self-administer heroin or any other opiate drug, in small doses while on the daily dose, and adjusting the time of dosing with limited success. No dose opioid-free for a minimum of 7-10 days before starting naltrexone. Since
naltrexone, you will not perceive any effect. Most important, however, if you Distribution
or pattern of dosing has been shown to be more effective than any other in the absence of an opioid drug in the urine is often not sufficient proof that
attempt to self-administer large doses of heroin or any other opioid (including The volume of distribution for naltrexone following intravenous reducing these complaints for all patients.
a patient is opioid-free, a naloxone challenge should be employed if the
methadone or LAAM) while on naltrexone, you may die or sustain serious administration is estimated to be 1350 liters. In vitro tests with human prescribing physician feels there is a risk of precipitating a withdrawal
plasma show naltrexone to be 21% bound to plasma proteins over the reaction following administration of naltrexone. The naloxone challenge
Naltrexone is well-tolerated in the recommended doses, but may cause liver Once the patient has been started on naltrexone hydrochloride, 50 mg once a test is described in the DOSAGE AND ADMINISTRATION section.
injury when taken in excess or in people who develop liver disease from other day will produce adequate clinical blockade of the actions of parenterally causes. If you develop abdominal pain lasting more than a few days, white Metabolism
administered opioids. As with many non-agonist treatments for addiction, Attempt to Overcome Blockade
bowel movements, dark urine, or yellowing of your eyes, you should stop The systemic clearance (after intravenous administration) of naltrexone is naltrexone is of proven value only when given as part of a comprehensive While naltrexone is a potent antagonist with a prolonged pharmacologic taking naltrexone immediately and see your doctor as soon as possible.
~3.5 L/min, which exceeds liver blood flow (~1.2 L/min). This suggests both plan of management that includes some measure to ensure the patient takes effect (24 to 72 hours), the blockade produced by naltrexone is that naltrexone is a highly extracted drug (>98% metabolized) and that extra surmountable. This is useful in patients who may require analgesia, but poses Laboratory Tests
hepatic sites of drug metabolism exist. The major metabolite of naltrexone is a potential risk to individuals who attempt, on their own, to overcome the A high index of suspicion for drug-related hepatic injury is critical if the 6-b-naltrexol. Two other minor metabolites are 2-hydroxy-3-methoxy-6-ß- A flexible approach to a dosing regimen may be employed to enhance blockade by administering large amounts of exogenous opioids. Indeed, any occurrence of liver damage induced by naltrexone is to be detected at the naltrexol and 2-hydroxy-3-methyl-naltrexone. Naltrexone and its metabolites compliance. Thus, patients may receive 50 mg of naltrexone hydrochloride attempt by a patient to overcome the antagonism by taking opioids is very earliest possible time. Evaluations, using appropriate batteries of tests to are also conjugated to form additional metabolic products.
every weekday with a 100 mg dose on Saturday or patients may receive 100 mg dangerous and may lead to a fatal overdose. Injury may arise because the detect liver injury are recommended at a frequency appropriate to the clinical every other day, or 150 mg every third day. Several of the clinical studies plasma concentration of exogenous opioids attained immediately following situation and the dose of naltrexone.
their acute administration may be sufficient to overcome the competitive Epic Naltrexone HCl Tabs Iss: 09/11 Size: 12.125 x 11.125 Fold Size: 1-1/8 x 1-1/8 Type: 6 pt. Side B Proof 5 10/25/11 DC Naltrexone does not interfere with thin-layer, gas-liquid, and high pressure cause of any other serious adverse reaction for the patient who is in liver enzymes or bilirubin, hepatic function abnormalities or hepatitis, Naloxone Challenge Test:
liquid chromatographic methods which may be used for the separation and "opioid-free." It is critical to recognize that naltrexone hydrochloride can palpitations, myalgia, anxiety, confusion, euphoria, hallucinations, insomnia, The naloxone challenge test should not be performed in a patient showing detection of morphine, methadone or quinine in the urine. Naltrexone may or precipitate or exacerbate abstinence signs and symptoms in any individual nervousness, somnolence, abnormal thinking, dyspnea, rash, increased clinical signs or symptoms of opioid withdrawal, or in a patient whose urine may not interfere with enzymatic methods for the detection of opioids who is not completely free of exogenous opioids.
contains opioids. The naloxone challenge test may be administered by either depending on the specificity of the test. Please consult the test manufacturer Patients with addictive disorders, especially opioid addiction, are at risk for the intravenous or subcutaneous routes.
multiple numerous adverse events and abnormal laboratory findings, including Depression, suicide, attempted suicide and suicidal ideation have been liver function abnormalities. Data from both controlled and observational reported in the post-marketing experience with naltrexone used in the Intravenous
Drug Interactions
studies suggest that these abnormalities, other than the dose- related treatment of opioid dependence. No causal relationship has been Studies to evaluate possible interactions between naltrexone and drugs other hepatotoxicity described above, are not related to the use of naltrexone.
demonstrated. In the literature, endogenous opioids have been theorized to than opiates have not been performed. Consequently, caution is advised if the Among opioid-free individuals, naltrexone administration at the recommended contribute to a variety of conditions. In some individuals the use of opioid Observe for 30 seconds for signs or symptoms of withdrawal.
concomitant administration of naltrexone and other drugs is required.
dose has not been associated with a predictable profile of serious adverse or antagonists has been associated with a change in baseline levels of some If no evidence of withdrawal, inject 0.6 mg of naloxone.
The safety and efficacy of concomitant use of naltrexone and disulfiram is untoward events. However, as mentioned above, among individuals using hypothalamic, pituitary, adrenal, or gonadal hormones. The clinical unknown, and the concomitant use of two potentially hepatotoxic opioids, naltrexone may cause serious withdrawal reactions (see significance of such changes is not fully understood.
Observe for an additional 20 minutes.
medications is not ordinarily recommended unless the probable benefits CONTRAINDICATIONS, WARNINGS, DOSAGE AND ADMINISTRATION).
Adverse events, including withdrawal symptoms and death, have been Subcutaneous
Lethargy and somnolence have been reported following doses of naltrexone Reported Adverse Events
reported with the use of naltrexone hydrochloride in ultra rapid opiate Naltrexone has not been shown to cause significant increases in complaints detoxification programs. The cause of death in these cases is not known (see Patients taking naltrexone may not benefit from opioid containing medicines, in placebo-controlled trials in patients known to be free of opioids for more WARNINGS).
Observe for 20 minutes for signs or symptoms of withdrawal.
such as cough and cold preparations, antidiarrheal preparations, and opioid than 7 to 10 days. Studies in alcoholic populations and in volunteers in analgesics. In an emergency situation when opioid analgesia must be clinical pharmacology studies have suggested that a small fraction of patients Note: Individual patients, especially those with opioid dependence, may administered to a patient receiving naltrexone, the amount of opioid required may experience an opioid withdrawal-like symptom complex consisting of With the exception of liver test abnormalities (see WARNINGS and
respond to lower doses of naloxone. In some cases, 0.1 mg IV naloxone has may be greater than usual, and the resulting respiratory depression may be tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, PRECAUTIONS), results of laboratory tests, like adverse reaction reports,
deeper and more prolonged (see PRECAUTIONS).
myalgia, and nasal symptoms. This may represent the unmasking of occult have not shown consistent patterns of abnormalities that can be attributed to opioid use, or it may represent symptoms attributable to naltrexone. A number Interpretation of the Challenge:
Carcinogenesis, Mutagenesis and Impairment of Fertility
of alternative dosing patterns have been recommended to try to reduce the Monitor vital signs and observe the patient for signs and symptoms of opioid The following statements are based on the results of experiments in mice and frequency of these complaints (see CLINICAL PHARMACOLOGY, Clinical
Idiopathic thrombocytopenic purpura was reported in one patient who may withdrawal. These may include, but are not limited to: nausea, vomiting, rats. The potential carcinogenic, mutagenic and fertility effects of the Trials, Individualization of Dosage).
have been sensitized to naltrexone in a previous course of treatment with dysphoria, yawning, sweating, tearing, rhinorrhea, stuffy nose, craving for metabolite 6-b-naltrexol are unknown.
naltrexone. The condition cleared without sequelae after discontinuation of opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, In a two-year carcinogenicity study in rats, there were small increases in the Alcoholism
naltrexone and corticosteroid treatment.
disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental numbers of testicular mesotheliomas in males and tumors of vascular origin In an open label safety study with approximately 570 individuals with lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, in males and females. The incidence of mesothelioma in males given alcoholism receiving naltrexone, the following new-onset adverse reactions DRUG ABUSE AND DEPENDENCE
changes in blood pressure, pulse or temperature, anxiety, depression, naltrexone at a dietary dose of 100 mg/kg/ day (600 mg/m2/day; 16 times the occurred in 2% or more of the patients: nausea (10%), headache (7%), Naltrexone is a pure opioid antagonist. It does not lead to physical or irritability, backache, bone or joint pains, tremors, sensations of skin crawling recommended therapeutic dose, based on body surface area) was 6%, dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting psychological dependence. Tolerance to the opioid antagonist effect is not or fasciculations. If signs or symptoms of withdrawal appear, the test is compared with a maximum historical incidence of 4%. The incidence of (3%), anxiety (2%) and somnolence (2%).
positive and no additional naloxone should be administered.
vascular tumors in males and females given dietary doses of 100 mg/kg/day (600 mg/m2/day) was 4% but only the incidence in females was increased Depression, suicidal ideation, and suicidal attempts have been reported in all OVERDOSAGE
Warning: If the test is positive, do NOT initiate naltrexone therapy. Repeat the compared with a maximum historical control incidence of 2%. There was no groups when comparing naltrexone, placebo, or controls undergoing There is limited clinical experience with naltrexone overdosage in humans. In challenge in 24 hours. If the test is negative, naltrexone therapy may be evidence of carcinogenicity in a two-year dietary study with naltrexone in one study, subjects who received 800 mg daily of naltrexone hydrochloride started if no other contraindications are present. If there is any doubt about for up to one week showed no evidence of toxicity.
the result of the test, hold naltrexone and repeat the challenge in 24 hours.
There was limited evidence of a weak genotoxic effect of naltrexone in one RATE RANGES OF NEW ONSET EVENTS
In the mouse, rat and guinea pig, the oral LD50s were 1,100 to 1,550 mg/kg; gene mutation assay in a mammalian cell line, in the Drosophila recessive 1,450 mg/kg; and 1,490 mg/kg; respectively. High doses of naltrexone Alternative Dosing Schedules
lethal assay, and in non-specific DNA repair tests with E. coli. However, no (generally ≥1,000 mg/kg) produced salivation, depression/reduced activity, Once the patient has been started on naltrexone hydrochloride, 50 mg every evidence of genotoxic potential was observed in a range of other in vitro tremors, and convulsions. Mortalities in animals due to high-dose naltrexone 24 hours will produce adequate clinical blockade of the actions of parenterally tests, including assays for gene mutation in bacteria, yeast, or in a second administration usually were due to clonic-tonic convulsions and/or administered opioids (i.e., this dose will block the effects of a 25 mg mammalian cell line, a chromosomal aberration assay, and an assay for DNA Although no causal relationship with naltrexone is suspected, physicians intravenous heroin challenge). A flexible approach to a dosing regimen may damage in human cells. Naltrexone did not exhibit clastogenicity in an in vivo should be aware that treatment with naltrexone does not reduce the risk of need to be employed in cases of supervised administration. Thus, patients suicide in these patients (see PRECAUTIONS).
Treatment of Overdosage
may receive 50 mg of naltrexone hydrochloride every weekday with a 100 mg Naltrexone (100 mg/kg/day [600 mg/m2/day] PO; 16 times the recommended In view of the lack of actual experience in the treatment of naltrexone dose on Saturday, 100 mg every other day, or 150 mg every third day. The therapeutic dose, based on body surface area) caused a significant increase in Opioid Addiction
overdose, patients should be treated symptomatically in a closely supervised degree of blockade produced by naltrexone may be reduced by these pseudopregnancy in the rat. A decrease in the pregnancy rate of mated female The following adverse reactions have been reported both at baseline and environment. Physicians should contact a poison control center for the most rats also occurred. There was no effect on male fertility at this dose level. The during the naltrexone clinical trials in opioid addiction at an incidence rate of There may be a higher risk of hepatocellular injury with single doses above relevance of these observations to human fertility is not known.
50 mg, and use of higher doses and extended dosing intervals should balance Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea DOSAGE AND ADMINISTRATION
the possible risks against the probable benefits (see WARNINGS and
Pregnancy
and/or vomiting, low energy, joint and muscle pain, and headache.
IF THERE IS ANY QUESTION OF OCCULT OPIOID DEPENDENCE, PERFORM CLINICAL PHARMACOLOGY, Clinical Trials, Individualization of Dosage).
Teratogenic Effects:
A NALOXONE CHALLENGE TEST AND DO NOT INITIATE NALTREXONE THERAPY UNTIL THE NALOXONE CHALLENGE IS NEGATIVE.
Patient Compliance
Naltrexone has been shown to increase the incidence of early fetal loss when Loss of appetite, diarrhea, constipation, increased thirst, increased energy, Naltrexone should be considered as only one of many factors determining the given to rats at doses ≥30 mg/kg/day (180 mg/m2/day; 5 times the feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased Treatment of Alcoholism
success of treatment. To achieve the best possible treatment outcome, recommended therapeutic dose, based on body surface area) and to rabbits at A dose of 50 mg once daily is recommended for most patients (see CLINICAL
appropriate compliance-enhancing techniques should be implemented for all oral doses ≥60 mg/kg/day (720 mg/m2/day; 18 times the recommended PHARMACOLOGY, Clinical Trials, Individualization of Dosage). The
components of the treatment program, including medication compliance.
therapeutic dose, based on body surface area). There was no evidence of The following events occurred in less than 1% of subjects: placebo-controlled studies that demonstrated the efficacy of naltrexone as an teratogenicity when naltrexone was administered orally to rats and rabbits adjunctive treatment of alcoholism used a dose regimen of naltrexone 50 mg HOW SUPPLIED
during the period of major organogenesis at doses up to 200 mg/kg/day (32 once daily for up to 12 weeks. Other dose regimens or durations of therapy Naltrexone Hydrochloride Tablets, USP 50 mg are yellow, round film-coated and 65 times the recommended therapeutic dose, respectively, based on nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or tablets, bisected on one side, debossed with “EL” on one side of the bisect phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of A patient is a candidate for treatment with naltrexone if: and “15” on the other side of the bisect. They are available in bottles of: Rats do not form appreciable quantities of the major human metabolite, 6-b-naltrexol; therefore, the potential reproductive toxicity of the metabolites in • the patient is willing to take a medicine to help with alcohol dependence There are no adequate and well-controlled studies in pregnant women.
nose bleeds, phlebitis, edema, increased blood pressure, non-specific ECG • the patient is opioid-free for 7 to 10 days Naltrexone should be used during pregnancy only if the potential benefit Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
justifies the potential risk to the fetus.
• the patient does not have severe or active liver or kidney problems (Typical Dispense in a tight, light-resistant container as defined in the USP, with a Gastrointestinal: excessive gas, hemorrhoids, diarrhea, ulcer.
guidelines suggest liver function tests no greater than 3 times the upper child-resistant closure (as required). Protect from light.
Labor and Delivery
Whether or not naltrexone affects the duration of labor and delivery is painful shoulders, legs or knees; tremors, twitching.
• the patient is not allergic to naltrexone, and no other contraindications are Nursing Mothers
In animal studies, naltrexone and 6-b-naltrexol were excreted in the milk of increased frequency of, or discomfort during, urination; increased or Refer to CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections
lactating rats dosed orally with naltrexone. Whether or not naltrexone is excreted in human milk is unknown. Because many drugs are excreted in Naltrexone should be considered as only one of many factors determining the human milk, caution should be exercised when naltrexone is administered to success of treatment of alcoholism. Factors associated with a good outcome oily skin, pruritus, acne, athlete's foot, cold sores, alopecia.
in the clinical trials with naltrexone were the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of Pediatric Use
community-based support groups; and good medication compliance. To The safe use of naltrexone in pediatric patients younger than 18 years old has depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams.
compliance-enhancing techniques should be implemented for all components of the treatment program, especially medication compliance.
ADVERSE REACTIONS
During two randomized, double-blind placebo-controlled 12-week trials to eyes–blurred, burning, light sensitive, swollen, aching, strained; Treatment of Opioid Dependence
evaluate the efficacy of naltrexone as an adjunctive treatment of alcohol ears–"clogged," aching, tinnitus.
Initiate treatment with Naltrexone using the following guidelines
dependence, most patients tolerated naltrexone well. In these studies, a total 1. Treatment should not be attempted unless the patient has remained of 93 patients received naltrexone hydrochloride at a dose of 50 mg once opioid-free for at least 7 to10 days. Self-reporting of abstinence from daily. Five of these patients discontinued naltrexone because of nausea. No increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry opioids in opioid addicts should be verified by analysis of the patient's serious adverse events were reported during these two trials.
mouth, head "pounding," inguinal pain, swollen glands, "side" pains, cold feet, urine for absence of opioids. The patient should not be manifesting While extensive clinical studies evaluating the use of naltrexone in detoxified, withdrawal signs or reporting withdrawal symptoms.
formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone use, placebo-controlled studies employing up to 2. If there is any question of occult opioid dependence, perform a naloxone fivefold higher doses of naltrexone hydrochloride (up to 300 mg per day) than Data collected from post-marketing use of naltrexone show that most events challenge test. If signs of opioid withdrawal are still observed following that recommended for use in opiate receptor blockade have shown that usually occur early in the course of drug therapy and are transient. It is not naloxone challenge, treatment with naltrexone should not be attempted.
naltrexone causes hepatocellular injury in a substantial proportion of patients always possible to distinguish these occurrences from those signs and The naloxone challenge can be repeated in 24 hours.
exposed at higher doses (see WARNINGS and PRECAUTIONS, Laboratory
symptoms that may result from a withdrawal syndrome. Events that have been reported include anorexia, asthenia, chest pain, fatigue, headache, hot 3. Treatment should be initiated carefully, with an initial dose of 25 mg of Aside from this finding, and the risk of precipitated opioid withdrawal, flushes, malaise, changes in blood pressure, agitation, dizziness, naltrexone hydrochloride. If no withdrawal signs occur, the patient may be available evidence does not incriminate naltrexone, used at any dose, as a hyperkinesia, nausea, vomiting, tremor, abdominal pain, diarrhea, elevations

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