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When and How to Use Long-Acting Injectable Antipsychotics

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When and How to Use Long-Acting Injectable Antipsychotics Savvy Psychopharmacology When and how to use long-acting injectable antipsychotics William Klugh Kennedy, PharmD, BCPP, FASHP ong-acting injectable antipsychotics Understanding the similarities and dif- (LAIs) are a pharmacotherapeutic op- ferences among LAIs7 and potential inter- L tion to help clinicians individualize patient variability of each LAI allows pre- schizophrenia treatment. LAIs have been scribers to tailor the dosing regimen to the available since the 1960s, starting with flu- patient more safely and efficiently (Table, phenazine and later haloperidol; however, page 42).1,8-11 All LAI antipsychotic formu- second-generation antipsychotics were not lations rely on absorption pharmacokinet- Vicki L. Ellingrod, available in the United States until 20071,2 ics (PK) rather than elimination PK, which PharmD, BCPP, FCCP and more are in development (Box).3,4 generally is true for sustained-release oral Series Editor Up to one-half of patients with schizo- formulations as well. Absorption half-life phrenia do not adhere to their medica- duration and absorption half-life variabil- tions.5 LAI use may mitigate relapse in ity are key concepts in LAI dosing. acute schizophrenia that is caused by poor adherence to oral medications. LAIs may Clinical pearls have a lower risk of dose-related adverse Before prescribing an LAI, check that your effects because of lower peak antipsychotic patient has no known contraindications plasma levels and less variation between to the active drug or delivery method. peak and trough plasma levels. LAIs may Peak-related adverse effects typically are decrease the financial burden of schizo- not contraindications, although they may phrenia and increase individual quality prompt you to start at a lower dose. of life because patients spend fewer days Ensure that your patient will have long- hospitalized due to acute exacerbations.6 term outpatient access to the LAI and the Some widely used schizophrenia treat- entire treatment team—inpatient and out- ment algorithms, such as the Harvard patient—is committed to LAI treatment. Schizophrenia Algorithm, neglect LAIs. Also, LAIs have not been well studied for Practice Points maintenance treatment of bipolar disorder • Long-acting injectable antipsychotics (BD) even though nonadherence is a sub- (LAIs) are an important therapeutic option stantial problem in these patients. Patients, for patients with schizophrenia that allows families, and legal guardians may choose clinicians to tailor pharmacotherapy to LAI antipsychotics over oral formulations each patient’s needs. to decrease the frequency and severity of • When selecting a specific LAI, consider psychotic relapse or for convenience be- class similarities and individual cause patients who receive LAIs do not antipsychotic differences. need to take a medication every day. • Although some LAIs are expensive, they Dr. Kennedy is Clinical Associate Professor of Pharmacy potentially reduce the financial burden of Current Psychiatry Practice and Psychiatry, Mercer University, Memorial schizophrenia and improve quality of life. 40 August 2012 University Medical Center, Savannah, GA. Savvy Psychopharmacology Do not rule out first-generation LAIs Box such as haloperidol and fluphenazine. The Clinical Antipsychotic Trials of Long-acting injectable Intervention Effectiveness study, Cost antipsychotics in development Utility of the Latest Antipsychotic Drugs in ripiprazole microsphere long- Schizophrenia Study, and other published Aacting injectable (LAI) is a phase III data suggest older antipsychotics are not investigational drug that at press time was 12,13 being reviewed by the FDA. This formulation inferior to newer medications. appears to be similar to risperidone LAI. The Verify that your patient has had an oral active antipsychotic differs in side effect trial of the active drug—ideally in the last profile and pharmacokinetics. Because the pharmaceutical science of microsphere 12 months—that resulted in at least partial construction allows many variations, it is positive response and no serious adverse not possible to determine the strengths and drug effects (ADEs). Oral medications’ weaknesses of aripiprazole LAI compared with Clinical Point shorter duration of action may help iden- risperidone LAI microspheres at this time. The dosing intervals currently under investigation Do not rule out 1 tify ADEs before administering an LAI. 3 are 14 and 28 days. first-generation LAIs; Discontinue the oral medication as Iloperidone crystalline LAI is a phase quickly as evidence, guidance, and good II-III investigational drug. FDA registration data suggest older documents and early publication and clinical judgment allow. Develop a plan to presentation data report that iloperidone antipsychotics, such transition from oral to LAI that you will LAI will be a crystalline salt structure as haloperidol and follow unless the patient develops intol- pharmaceutically similar to paliperidone and olanzapine LAI formulations.4 The dosing fluphenazine, are not erable ADEs or other problems. There is interval under investigation is 28 days. no evidence to suggest that patients who inferior to newer drugs receive partial LAI therapy decompensate less frequently or less severely than those who take oral medication. level to assess drug metabolism and oth- If antipsychotic polypharmacy is neces- er PK factors and characteristics may be sary, document your rationale. useful. In patients who are naïve to a specific LAI dosage form, ensure that the first LAI options dose does not exceed FDA and evidence- Fluphenazine decanoate is an older, inex- based guidelines for the initial dose (eg, pensive LAI with considerable interpatient 100 mg intramuscular [IM] for haloperidol variability in absorption rate and peak ef- decanoate).1 fects, and a relatively short duration of Consider a loading dose strategy to action. Dosing every 7 days may be neces- minimize the time a patient has to take an sary to avoid peak plasma level adverse ef- oral and LAI antipsychotic combination.14 fects or symptom recurrence. Variable PK Ensure that the total volume injected make it difficult to accurately calculate an intramuscularly is not >3 ml per injection empiric conversion dose from oral to LAI; site per dose. therefore, start at the low end (eg, 1.2 to 1.6 Use the recommended injection tech- times the total daily oral dose) or 12.5 or 25 nique for the particular LAI (eg, Z-tract).1,15 mg for the initial IM fluphenazine decano- Individualize the dose and dosing in- ate dose. A short overlap period—usually Discuss this article at terval based on patient response, peak- 1 to 2 weeks—may be necessary. Successful www.facebook.com/ CurrentPsychiatry related adverse effects (time to peak is ap- subcutaneous administration is possible.2 proximately 5 half-lives for most drugs), and possible reduced symptom control at Haloperidol decanoate. A 28-day dosing the end of the dosing interval.8 interval is effective for most patients. It is If your patient does not respond as ex- possible to administer a loading dose so Current Psychiatry pected, taking an antipsychotic plasma that no overlapping taper is required. My Vol. 11, No. 8 41 Savvy Psychopharmacology Table Characteristics of long-acting injectable antipsychotics Clinically Oral Oral Time relevant overlapping Loading elimination Absorption between PK/PD taper dose Antipsychotic half-life Formulation half-life injections variabilitya necessary? possible? Fluphenazine 1 day Decanoate 14 days 7 to 21 +++ Yes No in organic oil days Haloperidol 1 day Decanoate 21 days 28 days +/- No Yes in organic oil Olanzapine 1.5 days Pamoate 30 days 14 to 28 ++ Maybe No crystalline days Clinical Point Risperidone 1 day Microspheres 5 days 14 days ++ Yes No Paliperidone 1 day Palmitate 45 days 28 days + No Yes Administering crystalline olanzapine pamoate aMore + indicates greater variability among patients requires enrollment PD: pharmacodynamics; PK: pharmacokinetics Source: References 1,8-11 in a national registry that documents the incidence of rare but team has had good results using an initial ing difficulties and the expense may have in- serious ADEs loading dose 15 to 20 times the effective hibited olanzapine LAI use, even in patients oral dose and a second dose 28 days lat- who are likely to benefit. er of 10 times the oral daily maintenance dose, with the same dose every month Risperidone microspheres. This agent thereafter. If a patient is receiving his or has been evolutionary, if not revolutionary, her first haloperidol decanoate injection, in schizophrenia treatment and data on its the initial dose should not exceed 100 mg. efficacy for BD will be available soon. Its The remainder of the loading dose may be 2-week dosing interval, necessity of oral administered 3 to 7 days later if no adverse overlap, and anecdotal reports of “dose effects occur. Similar to fluphenazine dec- dumping” possibly because of fragility of anoate, haloperidol decanoate is relatively the microsphere formulation suggest the inexpensive. When considering giving a need for an improved version, which was haloperidol decanoate loading dose >400 addressed by the introduction of paliperi- mg or a maintenance dose >200 mg every done palmitate.10,17,18 28 days, carefully document the rationale (eg, rapid metabolism).16 Paliperidone palmitate has a 28-day dos- ing interval. No overlapping oral taper is Olanzapine pamoate. Clinicians who ad- necessary. Details of a week-long, 2-dose minister olanzapine pamoate must enroll in loading dose strategy
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