Package insert for injectable naltrexone does not specify that you need to have a trial of oral naltrexone before the injection. If the patient has a sufficient duration of abstinence from opioids (of 7-10 days) the injection can be safely given. You should carry out urine toxicology test (for morphine, oxycodone, methadone, and buprenorphine) on site right before the injection to confirm that patients did not use any opioids. Please remember that not all opioids would be detected with the rapid test so patients need to be asked about any medications taken in the previous week, to make sure they did not take opioids, and warned of the risk of precipitated withdrawal if naltrexone is given to a person taking opioids. A naloxone test can be conducted by giving 0.8-1.2 mg im and monitoring response over the next 30-45 min. If the test is negative (no change how patient feels- no withdrawal signs/symptoms on COWS scale) then it is very unlikely that withdrawal will be precipitated with injection naltrexone. However if you cannot guarantee the abstinence, and naloxone is not available then you should introduce oral naltrexone at low dose, like 12.5 mg (1/4 of the tablet) or less, at first and if no withdrawal emerges then injection can be safely given (same day few hours later or the next day. 25 mg of oral naltrexone (1/2 of the tablet) is probably too much and may precipitate severe withdrawal as the blood level is comparable to the level after the injection. It is very important to minimize the risk of withdrawal/side-effects with oral formulation since patients that have an adverse experience at the first contact with the medication might be dissuaded from continuing with it as an injection.
Giving small doses of oral naltrexone at first is necessary, but it is a barrier since naltrexone is not commercially available in smaller doses. You can always order low dose oral from a compounding pharmacy in order to get the dose to use for oral induction.
The injectable naltrexone is usually better tolerated than comparable oral doses. There’s less GI distress and nausea, possibly because much lower doses are needed as parenteral formulation bypasses the first-pass metabolism. Bioavailability of injection naltrexone is approximately 4 times greater than bioavailability of oral formulation.
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Naltrexone is an excellent option for patients who would like to discontinue treatment buprenorphine, but would like to be protected against relapse, which is seen with high frequency during the first few months after stopping buprenorphine.
Buprenorphine is best tapered down to low dose before stopping it, to reduce the level of physiological dependence and to decrease time required for elimination. Usually taper to 2 mg is sufficient, most patients find it difficult to stabilize on lower doses. Alternatively one can use adjunctive medications to minimize symptoms of withdrawal. Adjunctive medications targeting emerging symptoms are also very useful during the washout period and during initiation of treatment with oral naltrexone. Washout period of 4-6 days is usually sufficient after which naltrexone can be started, first at the low oral dose (6-12mg) followed by an injection of XR-naltrexone. With the longer washout there is less risk of withdrawal following injection but higher risk of relapse. Adjunctive medications can be continued during the first 1-2 weeks following injections (see Sigmon, Bisaga et al., 2012 for the list of medications and doses). During this transition patients need to be supported, as it is an outpatient detoxification, preferably with daily medical checkup (in person or on the phone) and psychosocial support if available.
