Dosage and Administration for Naltrexone®

Starting Treatment
Patient education comes first

Patients must be taught how naltrexone works and what to expect while taking it. Treatment providers should tell patients that the medication is not a "magic bullet"; instead, naltrexone is likely to reduce the urge to drink and the risk of returning to heavy drinking. Providers should negotiate a treatment plan with the patient at each stage of therapy.

Initial medical workup
The pretreatment medical workup should include:

  • A complete physical examination, including the liver
  • Various laboratory tests, including LFTs (e.g., serum aminotransferases, total bilirubin)
  • A pregnancy test
  • A urine toxicology screen
  • A complete/updated medical history to rule out possible contraindications
  • A substance abuse history that focuses on the use of other substances, especially opiates, as well as the patient's history of use, misuse, or abuse of prescribed medications
  • A mental health/psychiatric status screening
Positive mental health/psychiatric screens may necessitate more formal mental status examinations to determine the severity of the illness and the appropriate course of treatment. The Consensus Panel recommends focusing the psychiatric interview on anxiety symptoms, depression, psychosis, and cognitive functioning because these elements may complicate therapy. (1)
Pretreatment abstinence
Naltrexone should be initiated after signs and symptoms of acute alcohol withdrawal have subsided. The Consensus Panel recommends that patients be abstinent for 3 to 7 days before initiating naltrexone treatment. (2)
Starting doses
The FDA has established guidelines for the dosage and administration of naltrexone. Within general parameters, treatment with naltrexone must be individualized according to these factors as well as to the particular needs of each patient. The FDA guidelines recommend an initiation and maintenance dose of 50 mg/day of naltrexone for most patients, usually supplied in a single tablet. Because adverse events may make the patient reluctant to continue the medication, the starting dose can be reduced for several days or divided in two. (2) For example, treatment can begin with either one-quarter of a tablet (12.5 mg/day) or one-half of a tablet (25 mg/day) daily, with food, and eventually move to a full tablet daily (50 mg/day) within 1 to 2 weeks if tolerated.
Management of common adverse effects
Common adverse effects, which may include nausea, headache, dizziness, fatigue, nervousness, insomnia, vomiting, and anxiety, occur at the initiation of treatment in approximately 10 percent of patients. The Consensus Panel recommends the following strategies:
  • Patient education. If patients are going to experience common adverse effects, these tend to occur early in treatment, and the symptoms generally resolve within 1 to 2 weeks. Support and reassurance can help patients better tolerate these transient adverse effects.
  • Timing of doses. The Consensus Panel recommends morning dosing for most patients to establish a routine and ensure better compliance. (1) Naltrexone should ideally be taken after the "regular" morning routine, preferably with food. Individual patient needs can also guide the timing of doses.
  • Split dosage. If there is a need to split the dose, then the patient should take half in the morning and half in the evening, preferably with dinner.
  • Management of nausea. Nausea is a problem for approximately 10 percent of patients and may reduce compliance. To minimize nausea, patients can take naltrexone with complex carbohydrates such as bagels or toast and not take the medication on an empty stomach. (2) The use of simethicone (e.g., Maalox) or bismuth subsalicylate (e.g., Pepto-Bismol) before taking naltrexone may help. Strategies for controlling persistent nausea or other adverse events include dose reduction, slow titration, and cessation of the medication for 3 or 4 days and then reinitiating it at a lower dose. (2)
  • Withdrawal. Patients may not be able to discriminate between the common effects of withdrawal from alcohol and the common adverse effects caused by naltrexone. Patients should be reassured that their symptoms will get better with time. Alcohol withdrawal can be managed with support or benzodiazepines if indicated.

Ongoing Treatment With Naltrexone
Maintenance doses

Low doses
Maintenance doses of less than the standard 50 mg/day regimen may be considered in patients who do not tolerate the standard maintenance dose but who are otherwise good candidates for naltrexone. It is preferable to decrease the maintenance dose to 25 mg/day to avoid noncompliance and relapse due to common adverse effects rather than to rule out naltrexone as a treatment option for these patients. Some patients may ask to take naltrexone twice daily in order to experience subjective relief from craving. In these cases, the daily dose may be divided in two and given at those times of the day when craving is strongest.

Higher doses
Under certain circumstances, providers may increase the daily naltrexone dose to greater than 50 mg. Patients who may be considered for an increase include those who report persistent feelings of craving, discomfort, and even brief relapses, despite compliance with their treatment plan. In such cases, dosages of 100 mg/day are sometimes used, with appropriate medical monitoring. There is evidence that naltrexone is well tolerated, safe, and efficacious at these higher doses.
Before adjusting dosage, providers should first consider intensification of other treatment interventions, particularly psychosocial components. The reason the medication is not working should be explored. Providers should view a patient's request for increased dose as a sign of engagement and motivation in treatment, not as drug-seeking behavior. In some outpatient treatment, higher doses of naltrexone have been given under observation either 2 days a week or 3 days a week. If this is necessary and the patient tolerates a higher dose, possible protocols are 100 mg on Monday and Wednesday, with 150 mg on Friday; 150 mg on Monday and 200 mg on Thursday; or 150 mg every third day.

Duration of treatment
Although FDA guidelines indicate that naltrexone should be used for up to 3 months to treat alcoholism, the Consensus Panel recommends that treatment providers individualize the length of naltrexone treatment according to each patient's needs. (2) Initially, the patient can be treated with naltrexone for 3 to 6 months, after which the patient and the therapist can reevaluate the patient's progress. At this time, the decision to extend treatment must be based on clinical judgment. The Consensus Panel concurs that certain patients may be appropriate candidates for long-term (e.g., up to 1 year) naltrexone treatment if they demonstrate evidence of compliance with medication and psychosocial treatment regimens. (2) Factors to be weighed in the clinical decision to extend treatment beyond 3 to 6 months include patient interest, recent dose adjustment, partial treatment response, and prophylaxis in high-risk situations.

Other Clinical Considerations During Treatment

Followup liver function tests
After the initial screening, followup LFTs should be completed after 1 month of naltrexone treatment. If the results are acceptable, followup LFTs may then be conducted at 3 and 6 months after the initiation of treatment, depending on the severity of liver dysfunction at the start of treatment. More frequent monitoring is indicated for cases in which dose adjustments are being made, baseline LFTs are high, there is a history of hepatic disease, disulfiram or other potential hepatic-toxic medication is added to the treatment, or symptomatology indicates the need for monitoring.

Pain management
Because naltrexone blocks the effects of usual doses of therapeutic opioids, providers should use nonnarcotic methods of analgesia as first line of treatment for pain conditions. If narcotic pain relief is indicated, patients must discontinue naltrexone use for the period during which analgesics are required. If a painful event such as surgery is anticipated, then naltrexone should be discontinued 72 hours prior to the procedure. (1) If a patient is taken off naltrexone and put on an opioid analgesic, he or she should be abstinent from the narcotic for at least 3 to 5 days before resuming naltrexone treatment. (1)
In emergencies such as cases of acute severe pain, higher doses of opioid analgesics may be used with extreme caution to override the blockade produced by naltrexone. The narcotic dose needs to be carefully titrated to achieve adequate pain relief without oversedation or respiratory suppression. Both the dose and the patient's vital signs (including respiratory rate, level of awareness, and level of analgesia) must be closely monitored. Respiratory assistance and support must be available, should this be necessary. The Consensus Panel recommends that patients on naltrexone always carry safety identification cards providing information that the patient is receiving naltrexone and instructions for treating patients in the event of an emergency.

Continued drinking
The continued or periodic drinking of alcohol may not be a sufficient reason to discontinue naltrexone: Some patients respond to naltrexone treatment at first by reducing rather than stopping their drinking. When a patient drinks during treatment, the treatment provider should evaluate whether the patient is taking his or her medication regularly and actively participating in treatment. The intensity of care along with the expectations placed on the patient may be increased. Dose adjustments may also be indicated.
Abstinence should be a desired goal for the patient; however, reductions in drinking may be an acceptable intermediate outcome. Failure to maintain complete abstinence is not necessarily a failure of treatment because there are many other areas of a patient's life that can improve, such as job performance, social relationships, and general physical health.

Use of naltrexone in conjunction with disulfiram
The concomitant use of two potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks. If naltrexone is used with disulfiram, then treatment providers should perform LFTs shortly after the initiation of combined use. Providers should retest patients every 2 weeks for 1 to 2 months and thereafter at regular intervals, such as monthly. (2) Combination therapy with disulfiram and naltrexone should not be used for very long periods, and generally, the two drugs should not be started simultaneously.

Ending Naltrexone Therapy

Successful termination of naltrexone

Because naltrexone is not addicting, patients who stop taking the medication do not suffer from withdrawal symptoms, so naltrexone therapy can be discontinued without tapering the dose. Nonetheless, dose reductions may be psychologically useful to the patient. The treatment team should work with the patient in developing structured plans in the event of threatened or actual relapse. Scheduled followup visits ("booster visits") may also be helpful in providing support for the patient and opportunities for intervention based on identifying early signs of potential relapse. Naltrexone may be restarted if the patient and the treating clinicians feel that it may be helpful in preventing relapse.

Monitoring the outcome of treatment
In evaluating the outcome of naltrexone therapy, providers should expect to see evidence of positive improvement over time as evaluated by the treatment program's indicators of progress. Some of the possible criteria that can be used and selected to fit each program's needs and policies include
  • Compliance with treatment plan
  • Stable abstinence or significant reduction in the frequency and amount of drinking, as indicated by patient self-reports, collateral reports, and biological markers
  • Markedly diminished craving
  • Improvement in quality of life, including physical and mental health status, family and social relationships, work and/or vocational status, and legal status
  • Abstinence from other substances of abuse

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