Invega Sustenna

Indication(s)

Schizophrenia; Schizoaffective Disorder

Dosing available as prefilled syringes

39 (injection volume of 0.25 ml) corresponds to a daily oral dose of paliperidone 3 mg
78 mg (injection volume of 0.5 ml) corresponds to a daily oral dose of paliperidone 3 mg
117 mg (injection volume of 0.75 ml) corresponds to a daily oral dose of paliperidone 6 mg
156 mg (injection volume of 1 ml) corresponds to a daily oral dose of paliperidone 9 mg
234 mg (injection volume of 1.5 ml) corresponds to a daily oral dose of paliperidone 12 mg

Recommended starting and maintenance dose

Recommended maintenance dose for treatment of schizophrenia is 117 mg.

Drug Metabolizing Enzyme

CYP3A4

Dosing exclusions

CrCL dosing:
For patients with mild renal impairment (CrCl >/= 50 mL/min to < 80 mL/min: Initiate Sustenna with a dose of 156 mg on treatment day 1, 117 mg one week later. Monthly maintenance dose of 78 mg ; adjust monthly maintenance dose based on tolerability and/or efficacy
Not recommended in patients with moderate or severe renal impairment (CrCl < 50 mL/min

Loading dose

Loading dose strategy is recommended after tolerability has been established with oral risperidone or paliperidone (for patients naïve to Invega Sustenna):On day 1 administer Invega Sustenna 234 mg in the deltoid.
One week later administer Invega Sustenna 156 mg in the deltoid per medication label, while using clinical judgment. (Published data suggests Invega Sustenna 234 mg for both initiation doses and maintenance is safe.)
Seven days is recommended for the second loading dose, but a window of 4-10 days is acceptable.
The first maintenance dose should be administered 5 weeks following the first (of 2) loading doses.Maintenance dose should be selected to correspond with appropriate oral dose equivalent (as detailed above).
The loading dose strategy should NOT be used for patients switching from one LAI to another, i.e., Aristada to Invega Sustenna. Detailed protocols for switching between LAIs have not been established, but it is recommended that there is overlap of 1-3 weeks when switching to oral paliperidone. Therefore, prescribers should stop the previous LAI and initiate the new LAI at targeted maintenance dose when possible.

Oral overlap

No oral supplementation is necessary.

Establishing tolerability

Prior to initiating Invega Sustenna, establish tolerability with oral paliperidone or risperidone.

Storage

Room temperature

Reconstitution or mixing

N/A

Injection site

Choose between the deltoid or gluteal muscle (for maintenance doses) based on the patient preference and body habitus. Both loading doses should be administered in the deltoid muscle.Rotate injection sites to avoid muscle hypertrophy, abscesses, and tissue damage by repeated, frequent injections at the same site.
For deltoid injections: For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended.
For patients weighing 90 kg or more, the 1 ½-inch, 22 gauge needle is recommended.
For gluteal injections:The recommended needle size for administration of Invega Sustenna into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.
Deltoid is specifically recommended for faster distribution during the initiation phase.

Injection interval

Every 4 weeks

Preparation

Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous suspension. Priming the syringe is recommended.

Administration considerations

Administer the injection within 5 minutes of shaking. Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal muscle of the patient.

Timing variations

For initiation dosing: the second initiation dose can be given within a 4 to 10 day window after the first injection.

To avoid a missed maintenance injection, patients may be given the injection up to 7 days before or after the monthly time point.

When a dose is missed

See this tip on how to manage missed doses of Invega Sustenna.
Monthly doses can be flexibly administered one week before or after the scheduled dose to avoid missed doses.

REMS

No

Invega Trinza

Indication(s)

Schizophrenia

Dosing available as prefilled syringes

273 mg (injection volume of 0.875 ml) 
410 mg (injection volume of 1.315 ml)
546 mg (injection volume of 1.75 ml)
819 mg (injection volume of 2.625 ml)

Recommended starting and maintenance dose

Used only after establishment of four months of Invega Sustenna once monthly injection (last 2 months with the same dose); dose based on Invega Sustenna IM once monthly dose

CYP3A4

Dosing exclusions

Invega Trinza is not recommended in patients with moderate or severe renal impairment

Loading dose

Dose equivalence to Sustenna:
39 mg Invega Sustenna to N/A for Trinza
78 mg of Invega Sustenna to 273 mg for Trinza
117 mg Invega Sustenna to 410 mg Trinza
156 mg Sustenna to 546 mg Trinza
234 mg Sustenna to 819 Trinza

Oral overlap

None required.

Establishing tolerability

Prior to initiating Invega Trinza, treat the patient with Invega Sustenna (1 month formulation of paliperidone palmitate) for at least 4 months to ensure optimal dosing. In order to establish a consistent maintenance dose, it is recommended that the last two doses of Invega Sustenna be the same dosage strength before starting Invega Trinza.

Storage

Room temperature

Reconstitution or mixing

No reconstitution required
See Invega Sustenna for any changes

Injection site

Choose between the deltoid or gluteal muscle based on the patient preference and body habitus. Rotate injection sites to avoid muscle hypertrophy, abscesses, and tissue damage by repeated, frequent injections at the same site.

Injection interval

Every 12 weeks

Preparation

With the syringe tip pointing up, shake vigorously with a loose wrist for at least 15 seconds to ensure a homogeneous suspension. If more than 5 minutes pass before injection, shake vigorously, with the syringe tip pointing up, again for at least 15 second to re-suspend the medication. Priming the syringe is recommended.

Administration considerations

Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal muscle of the patient.
The thin-walled needles included in the Invega Trinza kit must be used for the injection.

Timing variations

To avoid a missing dose: patients may be given the injection up to 2 weeks before or after the 3-month time point.

When a dose is missed

If a patient has missed a dose and it is 3.5 months to 4 months since last injection: the previously administered Trinza dose should be administered as soon as possible, then continue with the 3-month injections following the dose.

If 4 months to 9 months since last injection: This requires re-initiation via table 2 in the package insert.

REMS

No

Dose Conversion of Oral Paliperidone to Paliperidone Palmitate 12-week LAI

PO Dose 

LAI/Invega Sustenna Dose **Stabilization with Invega Sustenna required prior to initiation of Invega Trinza

LAI/Invega Trinza Dose

< 3 mg paliperidone

39 mg Invega Sustenna every 4 weeks

3 mg paliperidone

78 mg Invega Sustenna every 4 weeks

273 mg Invega Trinza every 12 weeks

6 mg paliperidone

117 mg Invega Sustenna every 4 weeks

410 mg Invega Trinza every 12 weeks

9 mg paliperidone

156 mg Invega Sustenna every 4 weeks

546 mg Invega Trinza every 12 weeks

12 mg paliperidone

234 mg Invega Sustenna every 4 weeks

819 mg Invega Trinza every 12 weeks

Perseris

Indication(s)

Schizophrenia

Dosing available as prefilled syringes

Available in 90 mg or 120 mg kits:
4 mg oral risperidone corresponds to 120 mg (injection volume of 0.8 ml) Perseris
3 mg oral risperidone corresponds to 90 mg (injection volume of 0.6 ml) Perseris 

Recommended starting and maintenance dose

Based on the oral dose of risperidone 

Drug Metabolizing Enzyme

Dosing exclusions

In patients with renal or hepatic impairment, titrate with oral risperidone up to at least 3 mg daily. 

Loading dose

No loading dose recommended

Oral overlap

No oral supplementation recommended

Establishing tolerability

Prior to initiating Perseris, establish tolerability with oral risperidone in risperidone-naïve patients.

Storage

Must remain refrigerated, but can remain at room temperature for up to 7 days.
Should be brought to room temperature for at least 15 minutes prior to mixing.

Reconstitution or mixing

Should be brought to room temperature for at least 15 minutes prior to mixing. Mixing requires at least 60 cycles between liquid and powder syringes.

Injection site

Subcutaneous abdominal or back of upper arm injection

Injection interval

Every 4 weeks

Preparation

Hold the powder syringe upright and tap the barrel of the syringe to dislodge the packed powder. Remove the cap from the liquid syringe, then remove the cap from the powder syringe.  Place the liquid syringe on top of the powder syringe and connect the syringes by twisting approximately ¾ turn.  Keep your fingers off the plungers during this step to avoid spillage of the medication.  Transfer the contents of the liquid syringe into the powder syringe. Gently push the powder syringe plunger until you feel resistance.  Repeat this gently back and forth process for 5 cycles.  Continue mixing the syringes for an additional 55 cycles.  Transfer all contents into the liquid syringe.  Simultaneously maintain slight pressure on the powder syringe plunger and pull back gently on the liquid syringe plunger while twisting the syringes apart.  Attach needle and inject as directed per the package insert. Priming of the syringe is recommended.

Administration considerations

Select the injection site: subcutaneously in the abdomen or back of the upper arm.  See package insert for full details.  Pinch the skin around the injection area.  Lift the adipose tissue from the underlying muscle to prevent accidental intramuscular injection.  Insert needle fully into the subcutaneous tissue.  Inject the medication slow and steady.  Withdraw the needle at the same angle used for insertion and release pinched skin.

When a dose is missed

Refer to this tip on how to address missed doses.

REMS

No

Additional information

Use of this LAI formulation of risperidone (Perseris) decreases necessary frequency of injections over original risperidone LAI (Risperdal Consta).  
Provides initial peak plasma concentration in 4 to 6 hours of both risperidone and its metabolite, yielding steady plasma levels following initial injection.
Patients who are stable on oral risperidone doses lower than 3 mg/day or higher than 4 mg/day may not be candidates for Perseris.

Dose Conversion of Oral Risperidone to Risperidone Subcutaneous LAI

PO Dose

LAI/SC Dose

3 mg daily

90 mg every 4 weeks

4 mg daily

120 mg every 4 weeks

Recommended available dose formulations include 90 mg and 120 mg pre-filled vial kits.

Dose reduction may be necessary for CYP450 interactions of side effect intolerance.

References:
1. Indivior. (2018). Perseris dosing and administration.
2. American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. American Psychiatric Association Publishing. https://doi.org/10.1176/appi.books.9780890424841

Risperdal Consta 

Indication(s)

Schizophrenia

Dosing available as prefilled syringes

12.5 mg (2 mL)
25 mg (2 mL)
37.5 mg (2 mL)
50 mg (2 mL)

Recommended starting and maintenance dose

The recommended dose is 25 mg IM every 2 weeks.
Consta is initiated with the 25 mg dose unless clinical factors suggest to start with 12.5 mg.

Drug Metabolizing Enzyme

Dosing exclusions

Patients with renal or hepatic impairment should be treated with titrated doses of oral Risperdal prior to initiating treatment with Risperdal Consta.

Loading dose

No established loading-dose strategy.

Oral overlap

Initiating Consta requires overlap with oral risperidone (at a therapeutic dose) for 3 weeks.
Risperdal Consta 12.5 mg IM every two weeks corresponds to 1 mg oral risperidone per day. This means that the highest available Consta dose of 50 mg IM every two weeks corresponds to 4 mg oral per day. For many chronic patients with schizophrenia, this is at the low end of the dose range. Since Consta injections should not be combined, clinicians sometimes supplement Consta with oral risperidone if a higher dose is desired.

Establishing tolerability

Prior to initiating Risperdal Consta, establish tolerability with oral risperidone in risperidone-naïve patients. 

Storage

Requires refrigeration

Reconstitution or mixing

Use only components of the pre-packed dose packages containing the drug and syringe prefilled with diluent. Follow instructions from package insert regarding reconstitution.

Injection site

Deltoid or gluteal injections are bioequivalent; the site can be chosen based on patient preference. Alternate sites and use 1-inch needle for deltoid, 2-inch needle for gluteal injection.

Injection interval

Every 2 weeks

Preparation

Allow product to come to room temperature for at least 30 minutes before reconstituting.  Flip the cap from the vial.  Attach the vial adapter to the vial.  Swab the syringe connection point with an alcohol pad.  Snap the white cap off the prefilled syringe.  Attach the syringe to the vial adapter.  Inject the entire contents of the syringe containing the diluent into the vial. Shake the vial vigorously while holding the plunger rod down with the thumb for a minimum of 10 seconds to ensure a homogeneous suspension.  If 2 minutes pass before injection, re-suspend by shaking vigorously.  Invert the vial completely and slowly withdraw the suspension from the vial into the syringe.  Unscrew the syringe from the vial adapter and inject per package insert instructions.  Priming of the syringe is recommended.

Administration considerations

The injection is water-based which is less painful than decanoates. You don’t need to push hard.
Always give the full vial that you selected (the microspheres are not evenly distributed in the syringe). You should also not combine different doses of Consta.

Timing variations

N/A

When a dose is missed

Refer to this tip on how to address missed doses.

REMS

No

Additional information

Adjustment in dose should not be made more frequently than every 4 weeks.
This product is now available generically. 

Dose Conversion of Oral Risperidone to Risperidone Microspheres LAI

PO Dose 

LAI/IM Dose

1 mg daily

12.5 mg (injection volume of 2 ml) every 2 weeks

2 mg daily

25 mg (injection volume 2 ml) every 2 weeks

3-5 mg daily

37.5 mg (injection volume 2 ml) every 2 weeks

4-5 mg daily

50 mg (injection volume 2 ml) every 2 weeks

Recommended available dose formulations include 12.5 mg, 25 mg, 37.5 mg, and 50 mg pre-filled vial kits.

Dose reduction may be necessary for CYP450 interactions, in patients with hepatic or renal impairment, or in patients who have a history of poor tolerability to psychotropic medications. 

References:
1. Bai, Y.M., Chen, T.T., Chen, J-Y., Chang, W-H., Wu, B., Hung, C.H., & Lin, W.K. (2007). Equivalent switching dose from oral risperidone to risperidone long-acting injection: A 48-week randomized, prospective, single-blind pharmacokinetic study. Journal of Clinical Psychiatry, 68(8), 1218-1225. doi: 10.4088/jcp.v68n0808.
2. Stahl, S. M. (2017). The prescriber’s guide: Stahl’s essential psychopharmacology (6th ed.). New York: Cambridge University Press.
3. American Psychiatric Association. (2020). The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. American Psychiatric Association Publishing. https://doi.org/10.1176/appi.books.9780890424841
4. RISPERDAL CONSTA USPI Section 2.1: Schizophrenia; Section 2.2: Bipolar Disorder; Section 2.3: General Dosing Information; Section 2.8: Instructions for Use

5. Taylor, D.M., Barnes, T.R.E, & Young, A.H. (2021). The Maudsley prescribing guidelines in psychiatry (14th ed.). Wiley Blackwell. 

Uzedy 

Indication(s)

Schizophrenia

Dosing available as prefilled syringes

50 mg/0.14 mL
75 mg/0.21 mL
100 mg/0.28 mL
125 mg/0.35 mL
150 mg/0.42 mL
200 mg/0.56 mL
250 mg/0.7 mL 

Recommended starting and maintenance dose

To start: Switch from oral daily risperidone. Initiate as either once monthly injection or a once every 2 month injection, the day after the last dose of oral therapy. See table 1 in package insert to determine oral dose.

Drug Metabolizing Enzyme

CYP2D6, CYP3A4

Dosing exclusions

In patients with renal or hepatic impairment, titrate with oral risperidone (up to at least 2 mg daily) before initiating Uzedy.

Loading dose

No loading dose recommended

Oral overlap

No oral supplementation recommended

Establishing tolerability

Prior to initiating Uzedy, establish tolerability with oral risperidone in risperidone-naïve patients.

Storage

Requires refrigeration. May store for up to 90 days in its unopened original packaging at room temperature.

Reconstitution or mixing

Doesn't require reconstitution; but mixing in terms of shaking is required

Injection site

Subcutaneously in the abdomen or back of the upper arm

Injection interval

Every 4 or 8 weeks

Preparation

Allow product to come to room temperature for at least 30 minutes.  Uzedy is a solid at refrigerated temperatures and must reach room temperature prior to administration. Flick syringe forcefully three times to move the bubble to the cap. Standing while you do this may help achieve required force.  Holding the syringe up to a light or against a dark backdrop may improve visibility. If the bubble is not at the cap, repeat the flicking until it is.  Bend and snap off the cap and attach the needle.  Do not prime the syringe.   Inject per the package insert instructions.

Administration considerations

Select the injection site: subcutaneously in the abdomen or back of the upper arm.  See package insert for full details.  Pinch at least 1 inch of the selected area.  Insert the needle into subcutaneous tissue.  Release the pinched skin once the needle is in the subcutaneous tissue.  Inject the medication- using a slow, firm, and steady push until the entire dose is delivered.  Inject the entire dose at one time, without interruption.  Resistance will be experienced during dose delivery.  Do not use excessive force in an attempt to deliver Uzedy faster.  Wait 2-3 seconds after the entire dose is delivered before removing the needle.  Slowly pull the needle out from the injection site at the same angle as insertion.

Timing variations

N/A

When a dose is missed

When a dose of Uzedy is missed, administer the next Uzedy injection as soon as possible. See this tip for more information.

REMS

No

Additional information

Patients who are stable on oral risperidone doses lower than 2 mg/day or higher than 5 mg/day may not be candidates for Uzedy.
The medication provides a quick initial release.

Zyprexa Relprevv

Indication(s)

Schizophrenia

Dosing available as prefilled syringes

150 mg (1 mL)
210 mg (1.4 mL)
300 mg (2 mL)
405 mg (2.7 mL)

Recommended starting and maintenance dose

Recommended dosing for Zyprexa Relprevv is based on correspondence to oral Zyprexa doses (see table below).

Drug Metabolizing Enzyme

CYP1A2, CYP2D6 

Dosing exclusions

Requires a REMS

Loading dose

Not required

Oral overlap

Not required

Establishing tolerability

Prior to initiating Zyprexa Relprevv, establish tolerability with oral olanzapine.

Storage

Room temperature not to exceed 30°C (86°F). When the drug product is suspended in the solution for Zyprexa Relprevv, it may be held at room temperature for 24 hours.

Reconstitution or mixing

Reconstitution required

Injection site

Deep intramuscular gluteal injection using a 19-gauge, 1.5-inch needle

Injection interval

Every 2 to 4 weeks 

Preparation

Lightly tap the vial to loosen powder. Withdraw the pre-determined diluent volume into the provided syringe. Inject diluent into the powder vial. Tap the vial firmly and repeatedly on a surface until no powder is visible. Shake the vial vigorously until the suspension appears smooth. If foam forms, let vial stand to allow foam to dissipate.

Administration considerations

After insertion of the needle into the muscle, aspirate for several seconds to ensure that no blood appears. If any blood is drawn into the syringe, discard the syringe and the dose and being with a new convenience kit. The injection should be performed with steady, continuous pressure. Post injection monitoring must occur for three hours and the patient must be accompanied by someone to their destination when leaving.

Timing variations

None noted

When a dose is missed

No information provided

REMS

Yes

Additional information

Zyprexa®Relprevv™ can cause serious reactions following injection called post-injection delirium sedation syndrome. Post-Injection Delirium/Sedation Syndrome signs and symptoms are consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium. The risk of post-inection delirium sedation syndrome is present with every injection, although it is a small risk. Zyprexa® Relprevv™ must be administered in a registered healthcare facility with ready access to emergency response services. After each injection, patients must be observed at the healthcare facility by a healthcare professional for at least 3 hours. Because of this risk, Zyprexa® Relprevv™ is available only through a restricted distribution program called Zyprexa® Relprevv™ Patient Care Program and requires prescriber, healthcare facility, patient, and pharmacy enrollment. Community pharmacies are eligible for administration per the REMS criteria.