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Altostrata

Tips for tapering off Invega (paliperidone)

19 posts in this topic

As with other psychiatric drugs, do not taper Invega by taking a dose every other day! This causes a fluctuating level of the drug in your nervous system and can make you very sick.

To minimize the risk of withdrawal symptoms, we recommend a conservative taper of 10% from the previous dosage every few weeks. The amount of the decrease keeps getting smaller. Some people find they can go faster and some people find they have to go slower -- they can only tolerate decreases of a fraction of a milligram at a time. See Why taper by 10% of my dosage?

 

Very careful tapering is necessary when you have had psychotic symptoms. Such symptoms can appear as withdrawal symptoms; that will cause you to become diagnosed as relapsed and re-medicated. Read Psychiatrist: Some patients are better off without antipsychotics...

from Invega official FDA Information
 

INVEGA® Extended-Release Tablets are available in the following strengths and colors: 1.5 mg (orange-brown), 3 mg (white), 6 mg (beige), and 9 mg (pink).

 
Invega is also administered as an injection, Invega Sustenna http://www.drugs.com/pro/invega-sustenna.html:
 

Recommended initiation of INVEGA® SUSTENNA® is with a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. The recommended monthly maintenance dose is 117 mg; however, based on previous clinical history of tolerability and/or efficacy, some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). Following the second dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle.
 
Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the prolonged-release characteristics of INVEGA® SUSTENNA® should be considered [see Clinical Pharmacology (12.3)], as the full effect of the dose adjustment may not be evident for several months.

 
Tapering off Invega extended-release tablets
The range of dosages available in the tablets suggests one might step down using a combination of tablets. For example, to taper from 12 mg/day, one might get a prescription filled for 9mg and 1.5mg tablets, for a reduction to 10.5mg/day.
 
The extended-release characteristic is in the shell of the tablets.
According to the manufacturer http://www.invega.com/how-to-take-invega-antipsychotic-medications
 

INVEGA® releases its medicine over a 24-hour period. As the tablet passes through your body, it gives off the medicine at a constant rate.

The medicine in the INVEGA® tablet is contained in a nonabsorbable shell. This shell will leave your body in your stool. If you see the shell, do not worry. This is normal.

 
Without a shell, the half-life of the basic drug, paliperidone, in Invega appears to be 20-24 hours at a dose of 1mg http://dmd.aspetjournals.org/content/36/4/769/T1.expansion.html
 
I don't know anyone who's tapered by cutting up Invega tablets. If you've done this, please post in this topic.
 
To taper from small amounts of Invega, one might switch to risperidone liquid.
 
Taper by switching to risperidone liquid
Paliperidone is a close relative of risperidone, being it is an active metabolite of risperidone, according to http://www.drugs.com/pro/risperidone.html

Titrating a liquid is very good for very small measured decreases in dosage, allowing more precise measurements.

from Risperdal Official FDA Information
 

Risperdal® Oral Solution can be administered directly from the calibrated pipette, or can be mixed with a beverage prior to administration. Risperdal® Oral Solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea.

 
If you want to do this, be sure to read Tips for tapering off Risperdal (risperidone)

 

Injectable Invega Sustenna: Letting it wear off
Invega may be administered via injection every 4 weeks. This form is called Invega Sustenna.

 

Invega Sustenna is intended to last at "therapeutic" strength for a month, then you would get another injection to keep up the potency. Its half-life is very long -- 25 to 49 days. This means that at 25-49 days, it has worn off to half-strength in your body. It would take about 125-343 days for it to completely leave your body.

 

The blood level and side effects will be highest shortly after the injection, then wear off somewhat. Given the very long half-life, if you have gotten a single application of Invega Sustenna (often two injections close together), you must let your body gradually metabolize it to go off it.

 

Switching to tablet form to taper injectable Invega Sustenna
If you get withdrawal symptoms while letting injectable Invega Sustenna wear off, you may need to taper more slowly. Conceivably, one might switch to a lower dosage in the tablet form about a month after the injection; tablets come in a range of dosages that make tapering easier.
 
See Sec.2.6.1. Table 4 on http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554#section-2.7 for the equivalents of Invega Sustenna (injection) and Invega extended-release tablets. 

 
That page notes

If INVEGA® SUSTENNA® is discontinued, its prolonged-release characteristics must be considered....

 
If you wish to switch to the tablet form to taper (see below), the following is important http://www.drugs.com/pro/invega-sustenna.html:
 

Pharmacokinetics

Absorption and Distribution
Due to its extremely low water solubility, paliperidone palmitate dissolves slowly after intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. Following a single intramuscular dose, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentrations at a median Tmax of 13 days. The release of the drug starts as early as day 1 and lasts for as long as 126 days.
 
....The release profile and dosing regimen of INVEGA® SUSTENNA® results in sustained therapeutic concentrations....
 
Metabolism and Elimination
....The median apparent half-life of paliperidone following INVEGA® SUSTENNA® single-dose administration over the dose range of 39 mg – 234 mg ranged from 25 days – 49 days.

Long-Acting Paliperidone Palmitate Injection versus Oral Extended-Release Paliperidone
INVEGA® SUSTENNA® is designed to deliver paliperidone over a monthly period while extended-release oral paliperidone is administered on a daily basis. The initiation regimen for INVEGA® SUSTENNA® (234 mg/156 mg in the deltoid muscle on Day 1/Day 8) was designed to rapidly attain steady-state paliperidone concentrations when initiating therapy without the use of oral supplementation.
 
In general, overall initiation plasma levels with INVEGA® SUSTENNA® were within the exposure range observed with 6–12 mg extended-release oral paliperidone. The use of the INVEGA® SUSTENNA® initiation regimen allowed patients to stay in this exposure window of 6–12 mg extended-release oral paliperidone even on trough pre-dose days (Day 8 and Day 36). The intersubject variability for paliperidone pharmacokinetics following delivery from INVEGA® SUSTENNA® was lower relative to the variability determined from extended-release oral paliperidone tablets. Because of the difference in median pharmacokinetic profiles between the two products, caution should be exercised when making a direct comparison of their pharmacokinetic properties.


If you are switching from the injection to the extended-release tablets, you need to be careful about the overlap -- you could be taking a high dose if you have recently had an injection and you add tablets. Probably the safest time to make the switch would be at the end of the 4 weeks, when the injection is wearing off.

 

Gradually lowering dosage of injections

If you need to gradually lower the dosage of the injections to taper off, this can be accomplished by systematically reducing the amount of liquid injected. This requires the cooperation of a doctor.
 
This is not easy -- the manufacturer, Janssen, intends the dosage to be delivered all at once and supplies only uncalibrated syringes -- they do not have markings on them to measure the contents. Giving 2 injections of different dosages, for example 156mg and 78mg to add up to 234mg, might cause an increased blood level of Sustenna, above that of a single 234mg shot. From an e-mail from the manufacturer posted on the College of Psychiatric and Neurologic Pharmacists (CPNP) site http://cpnp.org/sites/default/files/shared/2011/pub_email.pdf 
 

ADMINISTRATION OF 234 MG PALIPERIDONE PALMITATE AS SIMULTANEOUS
156 MG AND 78 MG INJECTION
No systematically collected data is available on using paliperidone palmitate 156 mg plus
paliperidone palmitate 78 mg in place of a paliperidone palmitate 234 mg injection. However,
pharmacokinetic simulations2 show that when paliperidone palmitate 156 mg and paliperidone
palmitate 78 mg are administered as two separate injections on the same day there is an
approximate 15% increase in peak plasma paliperidone concentration and a 9% increase in
trough paliperidone concentration after the first cycle. After two and three cycles of receiving the
156 mg dose and the 78 mg dose as separate injections administered on the same day, patients
will have 11% and 11% higher peak concentrations, respectively, and 8% and 6% higher trough
concentrations, respectively. These simulated increases in plasma paliperidone concentrations
are less than the intra-subject variability seen in clinical trials.

 
If you were getting 234mg injections, it's possible you might get a 156mg plus a 39mg injection to reduce to 195mg, but I couldn't find any information about this.

Edited by Altostrata
updated

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So if this were administered tri-monthly (every third month) 

 

What would serum levels look like?

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They'd be bumped up after the injection. The graph would look like an "N", stretched out.

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Hey Altostrata, 

 

I have an inquiry. I was misdiagnosed with psychosis and was given Invega Sustenna for 5 months at 78 mg per month. I was wondering, do I need to taper the injection or will I be fine just stopping it? My psychiatrist has told me that a taper is not necessary because a depot injection has a longer half life than the pills, and therefore it tapers itself as it is excreted slowly. He just told me to stop the injections and not to get anymore as I did not need it to begin with. So should I just let the injection wear off? Or should I switch to the oral form of Invega to taper off. I really do not want to take anymore doses of Invega and I think that it is best for me to just stop the injections. What is the likelihood that I will experience withdrawal symptoms? I have read many articles online by doctors who have suggested that tapering off injections is not necessary as they are slowly excreted over a long period of time. What are your thoughts? 

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I'm not Alto but I have been digging into the pharmacokinetics of Invega Sustenna.

 

This is what your pDoc was referring to as slow excretion: In studies, the half-life of Invega Sustenna was 25-49 days. Let's use a number toward the lower end of the range, 30 days as the measure. Here's a table showing what that means [x] days after a dose:

 

+---------+---------------------+

|# days   | % drug still in     |

|         | body unmetabolized  |

+---------+---------------------+

|  30     |     50              |

+---------+---------------------+

|  60     |     25              |

+---------+---------------------+

|  90     |     12.5            |

+---------+---------------------+

| 120     |      6.25           |

+---------+---------------------+

 

As you can see the concentration of the drug drops slowly. Compare that to the worst psych drug -- Effexor with a half-life of 4 HOURS. Sixteen hours after their last dose, a person taking effexor has the same % of the drug as an Invega prescribee has at 120 days after the last Invega Sustenna injection.

 

It's not impossible, just less likely that you'll experience withdrawal symptoms. You might want to ask your pDoc whether s/he's willing to prescribe oral tablets in the event that you do start to experience withdrawal symptoms. You could then stabilize on that and taper.

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Thank you so much! I really appreciate your reply to my inquiry. I am just waiting to see what Altostrata has to say, but I really appreciate your feedback. I really do hope that I do not get any withdrawal symptoms. I have suffered enough for the past few months. Great to know that it is less likely that I will experience withdrawal symptoms.

Edited by scallywag
deleted quote of long post immediately above

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Theoretically, an Invega injection tapers itself.

 

Thank you, scallywag, for that very informative and graphically astonishing example of ASCII art.

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Theoretically, an Invega injection tapers itself.

 

Thank you, scallywag, for that very informative and graphically astonishing example of ASCII art.

 

Thanks for the confirmation Alto, I will keep you guys updated on my condition over the upcoming months as I recover from Invega Sustenna. 

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In addition, an advantage of switching to risperdone from invega (whether tablets or liquid as Alto mentioned - and especially from the depot) is that it seems the risk of akathisia and other EPS issues is less frequent .

 

Personally, since parkinsons runs in my family, even high dose old fashioned first generation anti histamines give me akathisia let alone "standard acting" atypicals like Risperdone , which for me is life threatening, personally .

 

As always, talk things over with a doctor that has your best interest at heart .

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Was just reading about this one in wikipedia:  https://en.wikipedia.org/wiki/Paliperidone

 

I was looking for receptor affinity, which seems mostly D2 and 5HT2a(serotonin) with some H1 (histamine) thrown in for fun.

 

As mentioned here, it is a descendant of risperidal, and has some of the same prolactin effects of that drug. (males growing breasts, for example, and women lactating)

 

What caught my attention was the side effect profile:

 

 

Adverse effect incidences[edit]

Sources:[10][11][12][13]

Very Common (>10% incidence)
  • Headache
  • Tachycardia
  • Somnolence (causes less sedation than most atypical antipsychotics[14])
  • Insomnia
  • Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone[14])
Common (1–10% incidence)Deaths[edit]

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.[15][16][17][18][19][20][21]

 

and those references 15-21 are here:

 

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I have successfully tapered down to 75mg of Invega Sustenna down from 150mg over the span of 8-10 months. Both these reductions were not the easiest since 150 -> 100 is a 50% decrease (didn't know about this forum and 10% rule at the time-- just felt the need to cut down on this **** and insisted on it) then there was no way to taper 10% because of set increments so I took the risk and went down to 75mg (25% decrease) which was also quiet uncomfortable.... to say the least.

 

I have been on 75 for approx 4 months and feel it maybe time to reduce again.

 

Now comes the problem.

 

Next increment is 50mg

 

I am absolutely not going from 75 to 50mg unless im under some intense medical care by a compassionate team.

 

So, the alternative is to find a way to wean off from 75 to the equivalency of 68-69mg. How on earth do i do that.

 

My psychiatrist is suggesting to (blindly) go to 50 mg and add 3mg oral pill daily.

 

I mean, what the hell? how does that even make sense.. That will lead to some unknown quantity in my body as the calculation is not that simple AND she knows that AND she doesnt want to do any work to find out more so we can make more INFORMED, CONSCIOUS decisions.

 

I am so angry.

 

How can she suggest such a thing.. also WITH NO PLAN.. i mean.. so whats next, how do i taper off from that?

 

I really hope somebody here has the/an answer.

 

I will be forever grateful.

 

Seems like the odds are just stacked against us when it comes to needing to get off these drugs.

 

Best 

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It's true, LuiB, the drugs are not designed for tapering and few physicians have given any thought to it.

 

You are fortunate in finding a doctor who will cooperate with your wish to go off the drugs. Congratulations on reducing your dosage as far as you've done.

 

The first post in this topic gives several suggestions for coming off Invega Sustenna. Please read it carefully and consider the techniques. If you have further questions, please post them in this topic.

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How long after taking Invega Sustenna does it take for dopamine to start binding to receptors again? 

 

How long does it take for your brain and body to normalize once stopping the drug?  

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Sorry, I meant to say, "How long after stopping Invega Sustenna does it take for dopamine to start binding to receptors again?" 

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There is some information about when the medication reaches its peak serum concentration.

 

You may wish to read about the pharmacokinetics of Invega Sustenna on drugs.com

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I have a friend who did not go in for her invega sustenna injection on May 9. She is not able to become a member and cannot navigate online. She wants some info on switching from Invega sustenna to the long acting tablet form. She has experienced akathisia and insomnia. Her history is: seroquel 50-100 mg early 2015 for approximately 6 mos then risperdal dose unknown for 6 mos then 256 mg Invega sustenna for a year. Then 156 mg in April then nothing but half a mg cogentin since. She seems to have a practioner who may be open to tapering. It's hard to tell. She could not bear the akathisia any longer and was not sleeping. I read the topic through. How can I help her?

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Marsha, you might print out the first post in this topic for your friend. If her symptoms arose as the Invega injection wore off, "reinstatement" with a low-dose tablet might help.

 

As your friend cannot participate, we can't do much to counsel her, we need to ask lots of questions. It's too difficult when someone is relaying the information.

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I completely understand and agree. I will try to walk her through the registration process. Thanks so much.

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