long acting injections
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When Psychiatry Breaks Skin
Psych Skills Pharmacy Presentation 2012Chelsea Markle, PharmDDick Miyoshi, RPh
Chlorpromazine
1930’S
’40s ‘50s 60’s ‘70s ‘80s ‘90s 2003-2010
2012?
ECT
HaloperidolFluphenazineThioridazineLoxapinePerphenazine
LA typicals
Clozapine
RisperidoneOlanzapineQuetiapineZiprasidoneAripiprazole
LA Risperidone (2003)Paliperidone (2006)LA Paliperidone (2009)Iloperidone & Asenapine (2009)LA Olanzapine (2010)Lurasidone (2010)
LA AripiprazoleLA IloperidonePimavanserine
Development of Treatments for Schizophrenia
Highly effective in reducing relapse of schizophrenia
High rates of non-adherence to oral medication (up to 42%)
Maintenance treatment with antipsychotics
Second generation antipsychotics generated hope to increase medication adherence
Many epidemiological analyses show not much difference between second generation and conventional antipsychotics
Maintenance treatment of antipsychotics
Drug Tablet or Capsule
Quick dissolving tablet
Short Acting IM injection
Long Acting IM injection
Aripiprazole ✔ ✔ ✗
Asenapine ✗
Clozapine ✔
Iloperidone ✗
Lurasidone ✗
Olanzapine ✔ ✔ ✔ ✗
Paliperidone ✗ ✔
Quetiapine ✔
Risperidone ✔ ✔ ✔
Ziprasidone ✔ ✔
Available Second Generation Antipsychotics
✔=formulary at HMC ✗= nonformulary at HMC
Knowing the appropriate injection site Using the correct needle length Rotating sites when appropriate
Good Practice in Administering Injections
Nodules and indurations Muscle granulomas Fibrosis Abscess formation Observed in up to a quarter of patients
Risks when administering LAIs
Risperdal Consta Invega Sustenna Zyprexa Relprevv
Second Generation Long-acting antipsychotics
Indicated for the treatment of schizophrenia or as monotherapy or adjunct therapy in maintenance treatment of bipolar
First second generation long acting IM antipsychotic
Administered every two weeks Requires oral overlap for at least three
weeks Complicated kinetics
LA Risperdal Consta
Aqueous suspension Active drug is encapsulated in a
microsphere of polylactide-co-glycolide polymer
Gradually released as microsphere copolymer which is hydrolyzed over several weeks
Majority released during weeks 4-6
LA Risperdal Consta
LA Risperidal Consta
IM Risperdal Consta
PO Risperidone
12.5 mg 1 mg
25 mg 2 mg
37.5 mg 3 mg
50 mg 4 mg
First establish tolerability with oral risperidone
Requires refrigeration but can be kept at room temperature for 7 days
Allow dose pack to come to room temperature prior to reconstitution
Must be administered within 6 hours after reconstitution
Resuspension by shaking necessary if not given within 2 minutes of reconstitution
LA Risperidal Consta
Kit includes: Risperidone extended-release
microspheres One pre-filled syringe containing 2 mL of
diluent One SmartSite Needle-Free Vial Access
Device One 21 gauge 1 inch needle for deltoid
injection One 20 gauge 2 inch needle for gluteal
injection
LA Risperdal Consta
Steady state plasma concentrations achieved after 4 injections
Maintained 4-6 weeks after last injection Deltoid and gluteal injections are
interchangeable and bioequivalent
LA Risperidal Consta
Indicated for the treatment of schizophrenia
Once monthly injection Aqueous based formulation Manufacturer claims no overlap required
with oral therapy No refrigeration
LA Invega Sustenna
Prefilled syringes Needle size into deltoid muscle
determined by patients weight For those >90 kg or 200 lbs use 1.5 inch,
22 gauge needle For those <90kg or 200 lbs use 1 inch, 23
gauge needle Injection in the gluteal muscle requires
the 1.5 inch, 22 gauge needle Shake syringe vigorously for a minimum of
10 seconds prior to attaching the needle
LA Invega Sustenna
First establish tolerabilty with po risperidone or paliperidone
Begin with initial loading dose of 234 mg Give second shot of 156 mg 7 days later
(+/- 2 days) First two injections must be administered
in deltoid muscle Start maintenance dose 36 days after
first shot (+/- 7 days)
LA Invega Sustenna
LA Invega Sustenna
Invega Sustenna IM PO Invega
234 mg 12 mg
156 mg 9 mg
117 mg 6 mg
78 mg 3 mg
39 mg 1.5 mg
Time Interval of Missed Dose
Dosing Schedule Dose and Injection Site
From 1 month to 1.5 months
Resume injections as soon as possible
Previously administered maintenance dose in the deltoid muscle
1.5 months to 6 months since last injection
Two injections, one week apart
Previously administered maintenance dose in the deltoid muscle**
> 6 months since last injection
De novo with suggested initiation regimen
234/156 mg on days 1/8 in the deltoid muscle followed by monthly maintenance dose
LA Invega Sustenna
**Unless the patient was stabilized on 234 mg in which case the first two injections should be 156 mg each
Managing Missed Doses:
Indicated for the treatment of schizophrenia
Intended for deep intramuscular gluteal injection only
Must establish tolerability with po olanzapine prior to use
Not to be confused with short-acting IM Zyprexa
LA Zyprexa Relprevv
Slow dissolution of a crystalline salt Crystals are micron-sized and suspended
in water When injected into muscle, the salt
slowly dissolves and dissociates into separate molecular entities of olanzapine and pamoic acid
LA Zyprexa Relprevv
Injections every 2-4 weeks provides olanzapine concentrations similar to daily doses of oral olanzapine
½ life of Zyprexa Relprevv is 30 days Plasma concentrations peak within a
week of injecting and are at trough level immediately prior to next injection
LA Zyprexa Relprevv
LA Zyprexa Relprevv
Target Oral Zyprexa Dose
Dose of Zyprexa Relprevv – first 8 weeks
Maintenance Dose of Zyprexa Relvprevv – after initial 8 weeks
10 mg/day 210 mg/2 weeks or 405 mg/4 weeks
150 mg/2 weeks or 300 mg/2 weeks
15 mg/day 300 mg/2 weeks
210 mg/2 weeks or 405 mg/4 weeks
20 mg/day 300 mg/2 weeks
300 mg/2 weeks
Kit includes: Vial of Zyprexa Relprevv powder 3-mL of diluent One 3 mL syringe with pre-attached 19
gauge, 1.5 inch needle Two 19 gauge, 1.5 inch needles
For obese patients, use a 2 inch, 19-gauge or larger needle (Not included in kit)
LA Zyprexa Relprevv
Must be suspended using only the diluent supplied in kit
Reconstitution is complicated and specific to dose If foam forms, let vial stand to allow foam to dissipate If product not used right away, shake vigorously to re-
suspend – should appear smooth and consistent in texture and color (yellow and opaque)
LA Zyprexa Relprevv
Dose Vial Strength Diluent to Add
150 mg 210 mg 1.3 mL
210 mg 210 mg 1.3 mL
300 mg 300 mg 1.8 mL
405 mg 405 mg 2.3 mL
Dose Final Volume to Inject
150 mg 1 mL
210 mg 1.4 mL
300 mg 2 mL
405 mg 2.7 mL
LA Zyprexa Relprevv
Before administering, confirm there will be someone to accompany the patient after the 3 hour observation period
If this cannot be confirmed, do not give the injection
Remains stable up to 24 hours in the vial
Black Box Warning: Post-injection Delirium/Sedation
Syndrome Consistent with olanzapine overdose Sedation Coma Delirium
Must be administered in a registered healthcare facility with ready access to emergency response services
LA Zyprexa Relprevv
Post Injection Syndrome Observe patient for 3 hours at the
healthcare facility by a health care professional for at least 3 hours
Zyprexa Relprevv only available through a restricted distribution program called Zyprexa Relprevv patient care program
Requires enrollment by prescriber, healthcare facility, patient, and pharmacy
LA Zyprexa Relprevv
Documented risk of post-injection syndrome is 0.07%
Risk of syndrome occurring in a single patient for 20 years is 5%
LA Zyprexa Relprevv
LA Aripiprazole LA Iloperidone
LA Injections to Come?
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