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UP Health System – Marquette
Pharmacy and Therapeutics Committee
Medication Guideline
Drug Classification: 28:16.08.04 Atypical Antipsychotics
Agent:
Formulary
X
Aripiprazole (Abilify®)
Asenapine (Saphris®)
X
Clozapine (Clozaril®)
Iloperidone (Fanapt®)
X
Lurasidone (Latuda®)
X
Olanzapine (Zyprexa®)
Olanzapine pamoate (Zyprexa® Relprevv®)
X
Paliperidone (Invega®)
Paliperidone palmitate (Invega® Sustenna®)
X
Quetiapine (Seroquel®)
X
Risperidone (Risperdal®)
X
Risperidone injection (Risperdal® Consta®)
X
Ziprasidone (Geodon®)
Nonformulary
Restricted
X
X
Nonstock
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacy and Therapeutics Committee-approved Indications for Inpatient Use:
 Each of the atypical antipsychotics have unique pharmacological properties that may be considered in certain
situations as follows: aripiprazole, ziprasidone, or lurasidone may be preferred in patients who are over-weight or
obese; quetiapine may be preferred in patients who experience intolerable extrapyramidal symptoms on
risperidone. Lower initial dosages should be considered for elderly patients.
 Atypical antipsychotic agents should be reserved for patients unable to tolerate or who have failed traditional
antipsychotic agents (i.e., haloperidol, perphenazine). Additionally, generic versions of the atypical antipsychotic
agents should be considered whenever possible.
 Intramuscular therapy:
 Olanzapine/ziprasidone (short-acting only):
o
o

Treatment of acute agitation in patients with schizophrenia or bipolar mania unable to receive oral therapy.
These atypical antipsychotic injections will be made available in the Emergency Department and Psychiatric
care areas only, use outside of these areas must be approved by Psychiatry.
Risperidone injection:
o
o
Risperidone long-acting injection is available for continuation of chronic, stable outpatient therapy.
Therapy initiated in hospitalized patients requires the following criteria to be met:

A history of non-adherence to oral medications has been documented and behavioral and other
adherence interventions have been aggressively attempted and failed.

Risperidone long-acting injection will be continued as an outpatient.

Patient has a documented history of tolerability to oral risperidone.

Carbamazepine is discontinued prior to initiating risperidone long-acting injection.

Patient is 18 years of age or older.

Formulary depot first-generation antipsychotics have been attempted at a clinically significant dosage and
duration without response, with the development of intolerable side effects, or are documented to be
clinically inappropriate.
 Oral therapy:
 Continuation of chronic, stable outpatient therapy.
 Clozapine: see special procedures for clozapine utilization starting on page 4.
 Low-dose therapy (i.e., quetiapine <100 mg daily) for the treatment of symptoms associated with dementia
(psychosis, agitation) must be approved by Psychiatry.
 Unless used for conditions stated above, requests for all oral atypical antipsychotic agents must be
approved by Psychiatry.
 Note: Atypical antipsychotics should not be used as sleep aids.
Document created: 04/12.
Revised: 03/16.
Cross Reference: None
UP Health System – Marquette
A Duke LifePoint Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
UP Health System – Marquette
Pharmacy and Therapeutics Committee
Medication Guideline
Usual Dosage: See table below for dosing information.
Monitoring / Outcomes:
Therapeutic Response:
Reduction in symptoms including positive symptoms (i.e., hallucinations, irritability, delusions, incoherent speech,
suspiciousness) and negative symptoms (i.e., blunted affect, emotional or social withdrawal, poverty of speech
content, lack of initiative).
Adverse Effects:
Extrapyramidal symptoms (i.e., continuous pacing, restlessness, fine tremor, abnormal posturing, spasticity,
hypertonus), tardive dyskinesia, neuroleptic malignant syndrome, prolongation of the QT interval, orthostatic
hypotension, somnolence, impaired judgment or motor skills, weight gain, hyperlipidemia, hyperglycemia.
Special Handling Procedures:
 Atypical antipsychotics are not considered hazardous drugs.
 Atypical antipsychotics are not considered high-alert drugs.
Document created: 04/12.
Revised: 03/16.
Cross Reference: None
UP Health System – Marquette
A Duke LifePoint Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
UP Health System – Marquette
Pharmacy and Therapeutics Committee
Medication Guideline
Table: Available Atypical Antipsychotic Agents Dosage Comparison.
Agent
Maximum Daily
Dose
Dose Adjustment in Renal/Hepatic Impairment?
10-30 mg
(once daily)
30 mg
No dosage adjustment required for renal or hepatic impairment
12.5 mg once or twice daily (titration is required, see
detailed information below for clozapine)
300-450 mg (divided twice daily)
900 mg
No dosage adjustment required for renal or hepatic impairment
40 mg once daily
Give with food.
40-80 mg (once daily)
80 mg
5-10 mg daily (titrate by 5 mg/day at intervals of at least
several days)
5-20 mg
(once daily)
20 mg
5-10 mg IM as required (may repeat 10 mg every 2 hours)
N/A
30 mg
3 mg once or twice daily
(titrate by 3 mg/day at intervals of at least 5 days)
6-12 mg
(divided 2 times daily)
12 mg
Starting Dose
Maintenance Dosage
10-15 mg once daily
(titrate at intervals of least two weeks)
Clozapine
Lurasidone
Aripiprazole
Olanzapine
Paliperidone
Quetiapine
Risperidone
Ziprasidone
25-50 mg twice daily (titrate by 50 mg at intervals of at least
2 days)
Renal
Do not exceed 40 mg/day for moderate to
severe impairment
Hepatic
Do not exceed 40 mg/day for moderate to
severe impairment
No dosage adjustment required for renal or hepatic impairment
200-800 mg
(divided 1-2 times daily)
800 mg
Renal
50-80 ml/min: 6 mg/day max
10-50 ml/min: 3 mg/day max
Hepatic
Limited data available at this time;
however, paliperidone undergoes limited
hepatic metabolism
Renal
No dosage adjustment required
Hepatic
Initiate therapy at 25 mg/day
300 mg once daily (titrate at intervals of at least 1 day)
300-800 mg
(once daily)
1 mg twice daily (titrate by 1 mg twice daily on days 2 and
3, as tolerated)
2-8 mg
(divided 1-2 times daily)
8 mg
Recommended initial dose in severe renal or hepatic impairment is 0.5 mg twice daily
(titrate by 0.5 mg twice daily to max of 3 mg/day)
25-50 mg every 2 weeks
50 mg every 2 weeks
25 mg every 2 weeks (max)
120-160 mg
(divided 2 times daily)
160 mg
12.5-25 mg every 2 weeks (titrate at intervals of at least 4
weeks)*
20 mg twice daily (titrate at intervals of at least 2 days)
Give with food.
No dosage adjustment required for renal or hepatic impairment
10 to 20 mg IM as required (may repeat 10 mg every two
N/A
40 mg
hours or 20 mg every four hours) †
* Oral risperidone or another antipsychotic medication should be given with the initial injection and should be continued for 3 weeks and then discontinued.
† Intramuscular administration of ziprasidone for more than three consecutive days has not been studied.
Document created: 04/12.
Revised: 03/16.
Cross Reference: None
UP Health System – Marquette
A Duke LifePoint Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
UP Health System – Marquette
Pharmacy and Therapeutics Committee
Medication Guideline
Pharmacy and Therapeutics Committee-approved Indications for Inpatient Use of Clozapine:
 Management of treatment-resistant schizophrenia in severely ill patients who fail to respond adequately to
other antipsychotic therapy and/or in whom such therapy produces intolerable adverse effects.
 Reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder
who are judged to be at chronic risk for re-experiencing suicidal behavior.
NOTE: Due to the significant risk of agranulocytosis, clozapine is only available to MGH through a restricted distribution
system and may only be dispensed following confirmation of patient and physician registration with the Clozapine REMS
(Risk Evaluation and Mitigation Strategy) Program. This registry ensures appropriate monitoring of absolute neutrophil
counts (ANC) throughout the course of therapy. Patients may not receive the medication at MGH without verification of
registration. In addition, physicians ordering clozapine must be registered via the Clozapine REMS Program and this
information confirmed by pharmacy prior to order verification. Failure to comply with these registration requirements
will jeopardize the ability of MGH to maintain and dispense clozapine. Prescribers or their designees can enroll
patients at the Clozapine REMS Program website located at www.clozapinerems.com. The pharmacist can then verify
prescriber certification and patient eligibility at the Clozapine REMS website.
Dosage & Administration:
Treatment Initiation & Maintenance: Begin with 12.5 mg (one-half of a 25 mg tablet) twice daily. If well
tolerated, increase dose according to the CLOZARIL (CLOZAPINE) TITRATION order. In general, doses
should be increased by 25 to 50 mg daily over a 2-week period until a target dose of 300 to 450 mg daily is
achieved. Subsequent dosage increments should not exceed 100 mg and should be made no more than once
or twice-weekly. Dosing should not exceed 900 mg/day and should be administered in divided doses (i.e., 2 to
3 times daily) to minimize the risk of certain adverse effects. Patients should be maintained on the lowest
effective dose of clozapine. Prior to initiation of clozapine, it should be confirmed that the patient is not taking
any medications that have the potential to cause agranulocytosis or otherwise suppress bone marrow function
(e.g., carbamazepine).
Discontinuation of treatment: Gradually reducing the dose over a 1- to 2-week period is recommended;
however, abrupt discontinuation may be warranted if the patient develops leukopenia, granulocytopenia, or
agranulocytosis.
Re-Initiation of treatment: If treatment is interrupted for ≥48 hours, dosing must be reinitiated at 12.5 to 25
mg/day. Therapy can NOT be reinitiated in patients in whom therapy was discontinued due to an absolute
neutrophil count (ANC) <1,000/µL in the general population.
Pharmacy Dispensing Procedures
Dispensing of clozapine is contingent upon confirmation of patient and physician registration and ANC results.
Dose
How available
12.5 mg
dose will be dispensed as half of a 25 mg tablet
37.5 mg
dose will be dispensed as a one 12.5 mg (half of 25 mg tab) + one 25 mg tablet
50 mg
dose will be dispensed as a one 50 mg tablet
Doses >50 mg
variable with 25 mg, 50 mg, and 100 mg tablets
I.
New/Continuing Therapy
1. Providers and/or their designees registered in the Clozapine REMS Program must initially enroll
patients on the Clozapine REMS Program website The pharmacist should then collect the following
Document created: 04/12.
Revised: 03/16.
Cross Reference: None
UP Health System – Marquette
A Duke LifePoint Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
UP Health System – Marquette
Pharmacy and Therapeutics Committee
Medication Guideline
2.
3.
4.
5.
patient demographic information and most recent (≤7 days) ANC for entry into the Clozapine REMS
Program Website in order to verify patient eligibility: 1) patient first and last name, 2) date of birth, and 3)
prescribing physician name and DEA number. The pharmacist will then verify that the patient ANC
result is current and acceptable as well as verify prescriber certification and patient enrollment in the
registry.
For patient and physician registration verification in the Clozapine REMS program, the pharmacist may
sign into the website at www.clozapinerems.com or by calling the Clozapine REMS Program contact
center at 1-844-267-8678. The patient’s status in the registry will state “The below patient is eligible to
receive clozapine” once the above information is entered into the website.
Once approval is noted during the patient eligibility check from the Clozapine REMS Program, the
pharmacist may verify the order in the electronic medical record (EMR).
The pharmacist should communicate with the prescribing physician that an “ANC” needs to be ordered
weekly while the patient is receiving treatment.
Pharmacist will record the ANC data throughout hospitalization as required in the
Monitoring/Outcomes section of these guidelines. This information must be entered in the patients file
on the Clozapine REMS program website.
Monitoring / Outcomes:
Laboratory: WBC and ANC*, fasting blood glucose, liver function tests.
*ANC = Total WBC count x total percentage of neutrophils obtained from the differential
Example (WBC = 4.3 & Neutrophils = 50%): ANC=4300 x 0.5 = 2,150 (2.15)





First 6 months: ANC must be obtained at baseline and weekly.
Month 6-12: If counts remained acceptable (ANC ≥1500/µL) during the first 6 weeks, monitoring may be
decreased to every 2 weeks for the next 6 months.
Month 13-18: If ANC continues to remain within these acceptable limits after the second 6 months of
therapy, monitoring can be decreased to every 4 weeks..
After discontinuation of clozapine for neutropenia: If therapy is interrupted due to moderate neutropenia
(ANC of 500-999/µL) or severe neutropenia (ANC < 500/µL) in the general population ,the ANC must be
reported daily until the ANC is ≥ 1000/µL and then three times weekly until the ANC is ≥ 1500/µL.
Patients diagnosed with Benign Ethnic Neutropenia (BEN) have different overall recommendations for
monitoring recommendations when neutropenia is noted (ANC < 1000/µL) and specific recommendations for
monitoring can be found at the Clozapine REMS website. Specifically, clozapine therapy should be
interrupted in the BEN population only in severe neutropenia (ANC < 500/µL) and then must reported daily
until the ANC is ≥ 500/µL and then three times weekly until the ANC is ≥ patient’s established baseline ANC
values.
Therapeutic Response: Improvement of psychotic symptomatology (e.g., improved communication, decreased
hallucinations and delusions, improved socialization, decreased paranoia)
Adverse Effects: Leukopenia, granulocytopenia, agranulocytosis, tachycardia, hypotension, ECG changes,
sedation/drowsiness, dizziness/vertigo, sialorrhea, seizures, fever, constipation.
Document created: 04/12.
Revised: 03/16.
Cross Reference: None
UP Health System – Marquette
A Duke LifePoint Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.