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When Psychiatry Breaks Skin

Psych Skills Pharmacy Presentation 2012 Chelsea Markle, PharmD Dick Miyoshi, RPh

Development of Treatments for Schizophrenia

1930S 40s 50s 60s 70s 80s 90s 2003-2010 2012?

LA Aripiprazole LA Iloperidone Pimavanserine ECT Haloperidol Fluphenazine Thioridazine Loxapine Perphenazine Chlorpromazine Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole LA Risperidone (2003) Paliperidone (2006) LA Paliperidone (2009) Iloperidone & Asenapine (2009) LA Olanzapine (2010) Lurasidone (2010)

LA typicals

Highly effective in reducing relapse of schizophrenia High rates of non-adherence to oral medication non(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


Tablet or Capsule

Quick dissolving tablet

Short Acting IM injection

Long Acting IM injection

Aripiprazole Asenapine Clozapine Iloperidone Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone =formulary at HMC = nonformulary at HMC

Available Second Generation Antipsychotics

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 LongLongacting 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-copolylactide-co-glycolide polymer Gradually released as microsphere copolymer which is hydrolyzed over several weeks
Majority released during weeks 4-6 4-

LA Risperdal Consta

IM Risperdal Consta 12.5 mg 25 mg 37.5 mg 50 mg

PO Risperidone 1 mg 2 mg 3 mg 4 mg

LA Risperidal Consta

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 extendedOne pre-filled syringe containing 2 mL of diluent preOne SmartSite Needle-Free Vial Access Device NeedleOne 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 4Deltoid 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

Invega Sustenna IM 234 mg 156 mg 117 mg 78 mg 39 mg

PO Invega 12 mg 9 mg 6 mg 3 mg 1.5 mg

LA Invega Sustenna

Managing Missed Doses: Time Interval of Missed Dosing Schedule Dose From 1 month to 1.5 months 1.5 months to 6 months since last injection > 6 months since last injection Resume injections as soon as possible Dose and Injection Site Previously administered maintenance dose in the deltoid muscle

Two injections, one week Previously administered apart maintenance dose in the deltoid muscle** De novo with suggested initiation regimen 234/156 mg on days 1/8 in the deltoid muscle followed by monthly maintenance dose

**Unless the patient was stabilized on 234 mg in which case the first two injections should be 156 mg each

LA Invega Sustenna

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 shortZyprexa

LA Zyprexa Relprevv

Slow dissolution of a crystalline salt Crystals are micron-sized and suspended in micronwater 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 2concentrations similar to daily doses of oral olanzapine 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

Target Oral Zyprexa Dose

Dose of Zyprexa Maintenance Relprevv first 8 Dose of Zyprexa weeks Relvprevv after initial 8 weeks 210 mg/2 weeks or 405 mg/4 weeks 300 mg/2 weeks 150 mg/2 weeks or 300 mg/2 weeks 210 mg/2 weeks or 405 mg/4 weeks 300 mg/2 weeks

10 mg/day

15 mg/day

20 mg/day

300 mg/2 weeks

LA Zyprexa Relprevv

Kit includes:
Vial of Zyprexa Relprevv powder 3-mL of diluent One 3 mL syringe with pre-attached 19 gauge, pre1.5 inch needle Two 19 gauge, 1.5 inch needles
For obese patients, use a 2 inch, 19-gauge or 19larger 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 reresuspend should appear smooth and consistent in texture and color (yellow and opaque)

Dose 150 mg 210 mg 300 mg 405 mg

Vial Strength 210 mg 210 mg 300 mg 405 mg

Diluent to Add 1.3 mL 1.3 mL 1.8 mL 2.3 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

Dose 150 mg 210 mg 300 mg 405 mg

Final Volume to Inject 1 mL 1.4 mL 2 mL 2.7 mL

LA Zyprexa Relprevv

Black Box Warning:

PostPost-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 post0.07% Risk of syndrome occurring in a single patient for 20 years is 5%

LA Zyprexa Relprevv

LA Aripiprazole LA Iloperidone

LA Injections to Come?