How to Load Haloperidol Decanoate

Jonathan Meyer, MD

Clinical Professor of Psychiatry
University of California, San Diego

Last updated: January 17, 2019

 

  • Haloperidol decanoate provides more D2 blockade than atypical long-acting injectables and can be loaded.
  • Patients may need oral coverage for the first week due to the low initial levels.
  • Use plasma levels to look for inadequate response.

 


As you know, for drugs with long half-lives like long-acting injectables, loading is the best method to get people to steady state quickly. As you can see, the terminal half-life for haloperidol decanoate with multiple dosing is around 21 days and the Tmax is somewhere between three and nine days. And here is actually the curve from a single dose kinetics study of haloperidol decanoate 100 mg. So you give 100 mg and it peaks somewhere between days five and seven and the peak level was around 5.73 ng/mL. So this is what you get for giving a dose of 100.


So the question is how do I convert somebody from oral? And what we’ve seen is that the maintenance dose for people is approximately 20 times the oral daily dose. So let’s say you had somebody who was in the hospital and they were stabilized on 10 mg a day of haloperidol and they were taking it. Their maintenance haloperidol decanoate dose will be 20 times oral dose which will be 200 mg.


But what’s the best way to do this? And there are a number of loading strategies covered in the literature but the best one is from this 100 mg loading study. What they found in this study is that if you loaded people weekly for four weeks and then converted them over to their maintenance dose, you got them to steady state levels very, very quickly with minimal need for oral supplementation.


So I’m going to walk you through this slide very carefully. Down below, we have the plasma levels for the people who were on oral medication first and everybody was on 10 mg a day of oral. And as you recall from what I talked about before, if you’re on 10 mg a day of oral haloperidol, your plasma level should be around 7.8. And look at this, if you look at the days just before and the day of their injection, you can see the levels were 8.06, 7.54 and 7.9. So you average those all out. It’s almost exactly 7.8. So that’s perfect. That’s exactly what you would expect from somebody on 10 mg a day of oral haloperidol. In this study, they actually abruptly stopped the oral drug when they gave them their first weekly injection of 100 mg. So what you can see in the next week is the plasma level was 3.59. So it’s dropped quite a bit and then it slowly climbs back up over the next couple of weeks. Now, these people again had been stabilized on 10 mg a day of oral haloperidol. So we know from the prior discussion that the maintenance dose should be 20 time that or 200. But for some reason in this study, they chose to give them as a monthly maintenance dose only 100. And what you can see there is exactly what might be expected. It’s that the plasma levels dropped below what was necessary to keep these patients at a plasma level of around 7.8.


So this study illustrates a couple of points. Number one, for somebody on oral haloperidol, you can load them with weekly injections over a month with no oral coverage and except for the first week, their plasma levels will be exactly like what the oral is. And the conversion formula for the loading portion is that 10 mg a day would translate to weekly injections of 100 mg. So for example, your patient was stabilized on 5 mg qhs of haloperidol. You would load them with four weekly injections of 50 mg. And then the maintenance dose for them would be 20 times oral dose which would be 100. And we usually start the maintenance dose two weeks after the last loading injection. So again, this is the way to get people to steady state very quickly especially if their oral adherence is iffy.


Now, some people say that first week the plasma levels do look kind of low and I do agree. And so if you have somebody who’s willing to take some oral medication in the first week, I think it’s not unreasonable simply because maybe you don’t want their plasma levels to be too low for a week. But after that first week, their levels are going to be very close to what you would expect, that steady state for their oral. And this will get you to steady state very quickly and then obviate the need for long periods of oral coverage.


And let’s give you a case example. I have a patient who refuses oral medication and is violent. This is very common in a state hospital where I work. He was given haloperidol decanoate 200 mg weekly over three weeks with excellent response and no adverse effects. So the question is what is the maintenance dose for the patient?


So as I mentioned before in the loading study previously, 10 mg of oral corresponded to the loading doses of 100 weekly. So in this case, if we gave him 200 weekly and he responded, that would correspond if he were actually taking it to an oral dose of around 20 mg per day. Since his oral dose would be 20 mg per day, that means his maintenance dose would be 20 times that or 400 mg. Now, we can’t give persons one haloperidol decanoate a 400 mg injection because the volume is too large. And so his maintenance dose will be 200 mg every 2 weeks which is 400 a month. And that would start two weeks after the last loading injection.


And let’s give you another case here. So we have a 29-year-old Latino who is admitted with involuntary medication order and he was on supposedly olanzapine 40 mg at bedtime and Depakote 1000 b.i.d. His olanzapine level is exactly what you’d expect. He’s a nonsmoker and his level is almost exactly two times the oral dose, 79 ng/mL. And his valproate level is also acceptable. He’s clearly taking his medications but he is still assaulting people. He is still requiring seclusion and restraints. So the feeling was this person needs more D2 antagonism.


He previously had tolerated 20 mg a day of oral haloperidol and we want to get this gentleman to a steady state very soon. So given his tolerance in the past of 20 mg a day, the doctor said, you know, I think he could probably even use 30 given how ill he is. And so if you know somebody who could tolerate 30, their loading injection would be actually 300. And this is exactly what he was given. So he was given 300 mg IM weekly times three. Now, in theory, this would correspond to plasma levels that will be the same as 30 mg at bedtime of oral haloperidol. So we would expect his plasma level somewhere to be around 23.85 ng/mL . You know, three times is somewhere around 7.8. But sadly, when we obtained this gentleman’s plasma level, it was 6.4.


So what did we learn from this? Assuming the nurses were actually giving the injection to the right patient, what we learned is that this gentleman is an ultrarapid metabolizer of cytochrome P450 2D6. And so we had to find solutions to treat his psychosis for medications that were not dependent on 2D6. And more likely than not, we probably would have to go to higher doses of olanzapine to push his plasma level way up into the hundreds and maybe even as high as 200 ng/mL. But medications that go through 2D6 were not going to solve this gentleman’s problem because he was just going to chew them up as an ultrarapid metabolizer.


So once again, haloperidol decanoate is very useful. It provides a lot more D2 blockade than we can get with other long-acting injectables and it can be loaded. So once again, 100 mg weekly, I put times three or even times four will be the equivalent to 10 mg a day of oral haloperidol. You may need some oral coverage for the first week just due to the low levels. But once again, use plasma levels to look for inadequate response to avoid futility. And knowing what the oral dose relationships are, you can have a sense of what levels you might expect. When you get the levels in cases like the one just presented where you have an ultrarapid metabolizer, you’ll know exactly why his plasma level is so low despite the fact you were giving him injections of the medication.

References

  1. Davis JM, et al. Drugs 1994; 47(5): 741-773
  2. Chang W-H, et al. Human Psychopharmacol 1995; 10(1): 47 – 51
  3. Jann et al. Clin Pharmacokinetics1985; 10: 315-333
  4. Jann MW et al. Prog Neuropsychopharmacol Biol Psychiatry. 1996;20:73-86.
  5. Meyer JM. CNS Spectrums 2014; 19(5): 432-438

 

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