How Much Does Naltrexone Cost in Mexico vs the USA?

INDICATIONS AND USAGE Naltrexone hydrochloride tablets USP 50 mg is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Naltrexone hydrochloride tablets USP 50 mg has not been shown to provide any therapeutic benefit except as part of an appropriate plan of management for the addictions.

DOSAGE AND ADMINISTRATION To reduce the risk of precipitated withdrawal in patients dependent on opioids, or exacerbation of a preexisting subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids. Switching from Buprenorphine, Buprenorphine/Naloxone, or Methadone There are no systematically collected data that specifically address the switch from buprenorphine or methadone to naltrexone hydrochloride; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy (see WARNINGS ).Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications. Treatment of Alcoholism A dose of 50 mg once daily is recommended for most patients The placebo-controlled studies that demonstrated the efficacy of naltrexone hydrochloride as an adjunctive treatment of alcoholism used a dose regimen of naltrexone hydrochloride 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials. Naltrexone hydrochloride should be considered as only one of many factors determining the success of treatment of alcoholism. Factors associated with a good outcome in the clinical trials with naltrexone hydrochloride were the type, intensity, and duration of treatment; appropriate management of comorbid conditions; use of community-based support groups; and good medication compliance. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, especially medication compliance. Treatment of Opioid Dependence Treatment should be initiated with an initial dose of 25 mg of naltrexone hydrochloride. If no withdrawal signs occur, the patient may be started on 50 mg a day thereafter. A dose of 50 mg once a day will produce adequate clinical blockade of the actions of parenterally administered opioids. As with many non-agonist treatments for addiction, naltrexone hydrochloride is of proven value only when given as part of a comprehensive plan of management that includes some measure to ensure the patient takes the medication. Naloxone Challenge Test Clinicians are reminded that there is no completely reliable method for determining whether a patient has had an adequate opioid-free period. A naloxone challenge test may be helpful if there is any question of occult opioid dependence,If signs of opioid withdrawal are still observed following naloxone challenge, treatment with, naltrexone hydrochloride should not be attempted. The naloxone challenge can be repeated in 24 hours. The naloxone challenge test should not be performed in a patient showing clinical signs or symptoms of opioid withdrawal, or in a patient whose urine contains opioids. The naloxone challenge test may be administered by either the intravenous or subcutaneous routes. Intravenous Inject 0.2 mg naloxone. Observe for 30 seconds for signs or symptoms of withdrawal. If no evidence of withdrawal, inject 0.6 mg of naloxone. Observe for an additional 20 minutes. Subcutaneous Administer 0.8 mg naloxone. Observe for 20 minutes for signs or symptoms of withdrawal. Note: Individual patients, especially those with opioid dependence, may respond to lower doses of naloxone. In some cases, 0.1 mg IV naloxone has produced a diagnostic response. Interpretation of the Challenge Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorrhea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, backache, bone or joint pains, tremors, sensations of skin crawling, or fasciculations. If signs or symptoms of withdrawal appear, the test is positive and no additional naloxone should be administered. Warning: If the test is positive, do NOT initiate naltrexone hydrochloride therapy. Repeat the challenge in 24 hours. If the test is negative, naltrexone hydrochloride therapy may be started if no other contraindications are present. If there is any doubt about the result of the test, hold naltrexone hydrochloride and repeat the challenge in 24 hours. Alternative Dosing Schedules A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Thus, patients may receive naltrexone hydrochloride tablets 50 mg every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by naltrexone hydrochloride may be reduced by these extended dosing intervals. 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 (see WARNINGS .) Patient Compliance Naltrexone hydrochloride should be considered as only one of many factors determining the success of treatment. To achieve the best possible treatment outcome, appropriate compliance-enhancing techniques should be implemented for all components of the treatment program, including medication compliance.

CONTRAINDICATIONS Naltrexone hydrochloride is contraindicated in Patients receiving opioid analgesics. Patients currently dependent on opioids, including those currently maintained on opiate agonists (e.g., methadone ) or partial agonists (e.g., buprenorphine) Patients in acute opioid withdrawal (see WARNINGS ). Any individual who has failed the naloxone challenge test or who has a positive urine screen for opioids. Any individual with a history of sensitivity to naltrexone hydrochloride or any other components of this product.It is not known if there is any cross-sensitivity with naloxone or the phenanthrene containing opioids.

WARNINGS Vulnerability to Opioid Overdose After opioid detoxification, patients are likely to have reduced tolerance to opioids. As the blockade of exogenous opioids provided by naltrexone hydrochloride wanes and eventually dissipates completely, patients who have been treated with naltrexone hydrochloride may respond to lower doses of opioids than previously used, just as they would shortly after completing detoxification. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.) if the patient uses previously tolerated doses of opioids. Cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing treatment. Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after naltrexone hydrochloride treatment is discontinued. It is important that patients inform family members, and the people closest to the patient of this increased sensitivity to opioids and the risk of overdose. (see PRECAUTIONS, Information for Patients ). There is also the possibility that a patient who is treated with naltrexone hydrochloride could overcome the opioid blockade effect of naltrexone hydrochloride. Although naltrexone hydrochloride is a potent antagonist , the blockade produced by naltrexone hydrochloride is surmountable. The plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. This poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids.Any attempt by a patient to overcome the antagonism by taking opioids is especially dangerous and may lead to life-threatening opioid intoxication or fatal overdose. Patients should be told of the serious consequences of trying to overcome the opioid blockade (see PRECAUTIONS, Information for Patients ). Precipitated Opioid Withdrawal The symptoms of spontaneous opioid withdrawal (which are associated with the discontinuation of opioid in a dependent individual) are uncomfortable, but they are not generally believed to be severe or necessitate hospitalization. However, when withdrawal is precipitated abruptly by the administration of an opioid antagonist to an opioid-dependent patient, the resulting withdrawal syndrome can be severe enough to require hospitalization. Symptoms of withdrawal have usually appeared within five minutes of ingestion of naltrexone hydrochloride and have lasted for up to 48 hours. Mental status changes including confusion, somnolence and visual hallucinations have occurred. Significant fluid losses from vomiting and diarrhea have required intravenous fluid administration. Review of postmarketing cases of precipitated opioid withdrawal in association with naltrexone treatment has identified cases with symptoms of withdrawal severe enough to require hospital admission, and in some cases, management in the intensive care unit. To prevent occurrence of precipitated withdrawal in patients dependent on opioids, or exacerbation of a pre-existing subclinical withdrawal syndrome, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free (including tramadol) before starting naltrexone hydrochloride treatment. An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks. If a more rapid transition from agonist to antagonist therapy is deemed necessary and appropriate by the healthcare provider, monitor the patient closely in an appropriate medical setting where precipitated withdrawal can be managed. In every case, healthcare providers should always 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. 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). Patients should be made aware of the risks associated with precipitated withdrawal and encouraged to give an accurate account of last opioid use. Patients treated for alcohol dependence with naltrexone hydrochloride should also be assessed for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with naltrexone hydrochloride. 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. Hepatotoxicity Cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone hydrochloride exposure during the clinical development program and in the postmarketing period. Transient, asymptomatic hepatic transaminase elevations were also observed in the clinical trials and postmarketing period. When 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. Although clinically significant liver dysfunction is not typically recognized as a manifestation of opioid withdrawal, opioid withdrawal that is precipitated abruptly may lead to systemic sequelae, including acute liver injury. Patients should be warned of the risk of hepatic injury and advised to seek medical attention if they experience symptoms of acute hepatitis. Use of naltrexone hydrochloride should be discontinued in the event of symptoms and/or signs of acute hepatitis. Depression and Suicidality Depression, suicide, attempted suicide and suicidal ideation have been reported in the postmarketing experience with naltrexone hydrochloride used in 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. Alcohol-and opioid-dependent patients, including those taking naltrexone hydrochloride, should be monitored for the development of depression or suicidal thinking. Families and caregivers of patients being treated with naltrexone hydrochloride should be alerted to the need to monitor patients for the emergence of symptoms of depression or suicidality, and to report such symptoms to the patient’s healthcare provider.

Drug Interactions Studies to evaluate possible interactions between naltrexone hydrochloride and drugs other than opiates have not been performed. Consequently, caution is advised if the concomitant administration of naltrexone hydrochloride and other drugs is required. The safety and efficacy of concomitant use of naltrexone hydrochloride and disulfiram is unknown, and the concomitant use of two potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks. Lethargy and somnolence have been reported following doses of naltrexone hydrochloride and thioridazine. Patients taking naltrexone hydrochloride may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrheal preparations, and opioid analgesics. In an emergency situation when opioid analgesia must be administered to a patient receiving naltrexone hydrochloride, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged (see PRECAUTIONS )

ADVERSE REACTIONS During two randomized, double-blind placebo-controlled 12 week trials to evaluate the efficacy of naltrexone hydrochloride as an adjunctive treatment of alcohol dependence, most patients tolerated naltrexone hydrochloride well. In these studies, a total of 93 patients received naltrexone hydrochloride at a dose of 50 mg once daily. Five of these patients discontinued naltrexone hydrochloride because of nausea. No serious adverse events were reported during these two trials. While extensive clinical studies evaluating the use of naltrexone hydrochloride in detoxified, formerly opioid-dependent individuals failed to identify any single, serious untoward risk of naltrexone hydrochloride use, placebo-controlled studies employing up to five-fold higher doses of naltrexone hydrochloride (up to 300 mg per day) than that recommended for use in opiate receptor blockade have shown that naltrexone hydrochloride causes hepatocellular injury in a substantial proportion of patients exposed at higher doses (see WARNINGS and PRECAUTIONS: Laboratory Tests ). Aside from this finding, and the risk of precipitated opioid withdrawal, available evidence does not incriminate naltrexone hydrochloride, used at any dose, as a cause of any other serious adverse reaction for the patient who is“opioid free.” It is critical to recognize that naltrexone hydrochloride can precipitate or exacerbate abstinence signs and symptoms in any individual who is not completely free of exogenous opioids. Patients with addictive disorders, especially opioid addiction, are at risk for multiple numerous adverse events and abnormal laboratory findings, including liver function abnormalities. Data from both controlled and observational studies suggest that these abnormalities, other than the dose-related hepatotoxicity described above, are not related to the use of naltrexone hydrochloride. Among opioid free individuals, naltrexone hydrochloride administration at the recommended dose has not been associated with a predictable profile of serious adverse or untoward events. However, as mentioned above, among individuals using opioids, naltrexone hydrochloride may cause serious withdrawal reactions (see CONTRAINDICATIONS , WARNINGS , DOSAGE AND ADMINISTRATION ). Reported Adverse Events Naltrexone hydrochloride has not been shown to cause significant increases in complaints in placebo-controlled trials in patients known to be free of opioids for more than 7 to 10 days. Studies in alcoholic populations and in volunteers in clinical pharmacology studies have suggested that a small fraction of patients may experience an opioid withdrawal-like symptom complex consisting of tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, myalgia, and nasal symptoms. This may represent the unmasking of occult opioid use, or it may represent symptoms attributable to naltrexone. A number of alternative dosing patterns have been recommended to try to reduce the frequency of these complaints. Alcoholism In an open label safety study with approximately 570 individuals with alcoholism receiving naltrexone hydrochloride, the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%). Depression, suicidal ideation, and suicidal attempts have been reported in all groups when comparing naltrexone, placebo, or controls undergoing treatment for alcoholism. RATE RANGES OF NEW ONSET EVENTS Naltrexone Placebo Depression 0 to 15% 0 to 17% Suicide Attempt/Ideation 0 to 1% 0 to 3% Although no causal relationship with naltrexone hydrochloride is suspected, physicians should be aware that treatment with naltrexone hydrochloride does not reduce the risk of suicide in these patients (see PRECAUTIONS ). Opioid Addiction The following adverse reactions have been reported both at baseline and during the naltrexone hydrochloride clinical trials in opioid addiction at an incidence rate of more than 10%: Difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache. The incidence was less than 10% for: Loss of appetite, diarrhea, constipation, increased thirst, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased potency, and chills. The following events occurred in less than 1% of subjects: Respiratory: Nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath. Cardiovascular: Nose bleeds, phlebitis, edema, increased blood pressure, non-specific ECG changes, palpitations, tachycardia. Gastrointestinal: Excessive gas, hemorrhoids, diarrhea, ulcer. Musculoskeletal: Painful shoulders, legs or knees; tremors, twitching. Genitourinary: Increased frequency of, or discomfort during, urination; increased or decreased sexual interest. Dermatologic: Oily skin, pruritus, acne, athlete's foot, cold sores, alopecia. Psychiatric: Depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams. Special senses: Eyes-blurred, burning, light sensitive, swollen, aching, strained; ears-“clogged”, aching, tinnitus. General: Increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head“pounding”, inguinal pain, swollen glands,“side” pains, cold feet,“hot spells.” Postmarketing Experience Data collected from postmarketing use of naltrexone hydrochloride show that most events usually occur early in the course of drug therapy and are transient. It is not always possible to distinguish these occurrences from those signs and symptoms that may result from a withdrawal syndrome. Events that have been reported include anorexia, asthenia, chest pain, fatigue, headache, hot flushes, malaise, changes in blood pressure, agitation, dizziness, hyperkinesia, nausea, vomiting, tremor, abdominal pain, diarrhea, palpitations, myalgia, anxiety, confusion, euphoria, hallucinations, insomnia, nervousness, somnolence, abnormal thinking, dyspnea, rash, increased sweating, vision abnormalities, and idiopathic thrombocytopenic purpura. In some individuals the use of opioid antagonists has been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal, or gonadal hormones. The clinical significance of such changes is not fully understood. Adverse events, including withdrawal symptoms and death, have been reported with the use of naltrexone hydrochloride in ultra rapid opiate detoxification programs. The cause of death in these cases is not known (see WARNINGS ). Laboratory Tests In a placebo controlled study in which naltrexone hydrochloride was administered to obese subjects at a dose approximately five-fold that recommended for the blockade of opiate receptors (300 mg per day), 19% (5/26) of naltrexone hydrochloride recipients and 0% (0/24) of placebo-treated patients developed elevations of serum transaminases (i.e., peak ALT values ranging from 121 to 532; or 3 to 19 times their baseline values) after three to eight weeks of treatment. The patients involved were generally clinically asymptomatic, and the transaminase levels of all patients on whom follow-up was obtained returned to (or toward) baseline values in a matter of weeks. Transaminase elevations were also observed in other placebo controlled studies in which exposure to naltrexone hydrochloride at doses above the amount recommended for the treatment of alcoholism or opioid blockade consistently produced more numerous and more significant elevations of serum transaminases than did placebo. Transaminase elevations occurred in 3 of 9 patients with Alzheimer's Disease who received naltrexone hydrochloride (at doses up to 300 mg/day) for 5 to 8 weeks in an open clinical trial.

Pregnancy:Teratogenic Effects Pregnancy Category C:- Naltrexone has been shown to increase the incidence of early fetal loss when given to rats at doses ≥ 30 mg/kg/day (180 mg/m 2 /day; 5 times the recommended therapeutic dose, based on body surface area) and to rabbits at oral doses ≥ 60 mg/kg/day (720 mg/m 2 /day; 18 times the recommended therapeutic dose, based on body surface area). There was no evidence of teratogenicity when naltrexone was administered orally to rats and rabbits during the period of major organogenesis at doses up to 200 mg/kg/day (32 and 65 times the recommended therapeutic dose, respectively, based on body surface area). Rats do not form appreciable quantities of the major human metabolite, 6-β-naltrexol; therefore, the potential reproductive toxicity of the metabolite in rats is not known. There are no adequate and well-controlled studies in pregnant women. Naltrexone hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.