Am/ Psychiatry. 1987; 144:1148-53.
`23 . Cummings JL, Wirshing WC. Recognition and differential
`diagnosis of tardive dyskinesia. Inf ) Psyclriatry Med. 1989;
`19(2): 133-44.
`24. Rodnitsky RL, Keyser DL. Neurologic complications of drugs:
`tardive dyskinesias, neuroleptic malignant syndrome, and co(cid:173)
`caine-related syndromes Psychiatric Clin North Am . 1992;
`
`15:491-510.
`25. Bostram AC, Walker MK. Validation of tardive dyskinesia as
`measured on the dyskinesia identification system-coldwater.
`Nurs Res. 1990; 39:274-9
`26. Mills MJ, Norquist GS, Shelton RC et al. Consent and liability
`with neuroleptics: the problem of tardive dyskinesia. Int) Law
`Psychiatry. 1986; 8:243-52.
`
`Movement disorders Reports
`
`Pharmacists' role in clozapine therapy
`at a Veterans Affairs medical center
`
`BENJAMIN R. DISHMAN, GARY L. ELLENOR, JONATHAN P. LACRO, AND )AMES B. LOHR
`
`Abstract: A program in
`which pharmacists have an
`active role in prescribing and
`dispensing psychoactive
`drugs is described.
`The Department of Veter(cid:173)
`ans Affairs (VA) has estab(cid:173)
`lished a National Clozapine
`Coordinating Center (NCCC)
`that must approve all cloza(cid:173)
`pine therapy in VA medical
`centers. Clinical and demo(cid:173)
`graphic information is re(cid:173)
`quired for all new patients,
`and weekly status reports are
`required throughout cloza-
`
`pine therapy. To comply with
`NCCC requirements, phar(cid:173)
`macists with specialized
`training in psychopharmacol(cid:173)
`ogy organized a clozapine
`clinic at one VA medical cen(cid:173)
`ter, in conjunction with the
`psychiatry service. The phar(cid:173)
`macists screen potential can(cid:173)
`didates for clozapine therapy
`and forward the required in(cid:173)
`formation to the NCCC for
`approval. During treatment,
`they ensure that necessary
`laboratory tests and clinical
`evaluations are performed for
`
`inpatients and recommend
`dosage adjustments to the
`psychiatry residents. The
`pharmacists see outpatients
`receiving clozapine weekly to
`monitor and record vital
`signs, laboratory results, and
`response to therapy and
`make dosage adjustments ac(cid:173)
`cordingly. For both inpatients
`and outpatients, the pharma(cid:173)
`cists send weekly patient
`evaluations to the NCCC.
`Pharmacists at a VA medi(cid:173)
`cal center provide direct care
`to patients receiving cloza-
`
`pine and help their institu(cid:173)
`tion comply with the strin(cid:173)
`gent therapy-monitoring
`requirements of the NCCC.
`
`Index terms: ' Administra(cid:173)
`tion; Ambulatory care; Cloza(cid:173)
`pine; Department of Veterans
`Affairs; Dosage; Pharmacists,
`hospital; Pharmacy, institu(cid:173)
`tional, hospital; Tests, labora(cid:173)
`tory; Toxicity; Tranquilizers
`Am J Hosp Pharm. 1994;
`51 :899-901
`
`C lozapine is considered a breakthrough in the
`
`treatment of schizophrenia. 1 It was released in
`Europe in 1972, but a high frequency of agranu(cid:173)
`locytosis associated with the drug (2%) delayed approv(cid:173)
`al for marketing in the United States until September
`1989. 2 This approval came with prescribing and dis(cid:173)
`pensing restrictions never before imposed by a manu(cid:173)
`facturer. The manufacturer, Sandoz, requires all pre(cid:173)
`scribers and patients to be registered with the Clozaril
`National Registry, which requires weekly monitoring
`of each patient's white blood cell (WBC) count and
`limits medication dispensing to a one-week supply. 3
`The registry permits community and hospital pharma-
`
`cies to dispense clozapine only upon the pharmacist's
`verification that the WBC count is within acceptable
`limits. The Department of Veterans Affairs (VA) re(cid:173)
`quires that patients receiving clozapine through its
`facilities have weekly monitoring of the WBC count
`and differential, vital signs, and adverse effects. 4 This
`complicated process requires the cooperation and co(cid:173)
`ordinated efforts of the patient, physician, laboratory,
`and pharmacy. Some pharmacists in our institution
`have specialized training in psychiatry and have ac(cid:173)
`quired clinical privileges that allow them to prescribe
`psychotropic medications and order laboratory tests. 5
`We describe how these pharmacists provide the clinical
`
`BENJAlAIN R. DISHMAN, PHARM.D., BCNSS, is Psychiatry Clinical
`Pharmacy Specialist, San Diego Veterans Affairs Medical Center
`(SDVAMC), and Adjunct Assistant Professor of Pharmacy, Univer(cid:173)
`sity of Southern California (USC), Los Angeles. GARY L. El LENOR,
`PHARM.D., is Psychiatry Clinical Pharmacy Specialist, SDVAMC,
`and Assistant Clinical Professor of Pharmacy, USC and University
`of the Pacific, Stockton, CA. )ONAfHAN P. LACRO, PHARM.D., is
`Psychiatry Clinical Pharmacy Specialist, SDVAMC. and Assistant
`
`Clinical Professor of Psychiatry, University of California, San Di(cid:173)
`ego. JAMES B. LOHR, M.D., is Chief of Psychiatry, SDVAMC, and
`Associate Professor of Psychiatry, University of California, San
`Diego.
`Address reprint requests to Dr. Dishman, Veterans Affairs Med(cid:173)
`ical Center ( 119), 3350 Lajolla Village Drive, San Diego, CA
`92161.
`
`Vol SI Apr 11994 AmJ HospPharm 899
`
`CFAD VI 1007-0001
`
`

`

`Reports Clozapine therapy
`
`care necessary to meet all the requirements of clozapine
`therapy.
`
`Practice site
`The VA medical center in San Diego is a 450-bed
`teaching hospital associated with the University of
`California Medical School at San Diego. The pharmacy
`department employs 21 inpatient and 11 outpatient
`and ambulatory-clinic pharmacists.
`The psychiatry service comprises 101 total beds: 15
`intensive care, 44 acute care, 28 alcohol or drug treat(cid:173)
`ment, and 14 research beds. The mental health ambula(cid:173)
`tory-care clinic handles approximately 35,000 visits per
`year. There are two full-time pharmacists and one half(cid:173)
`time pharmacist designated as psychiatry clinical phar(cid:173)
`macy specialists. The primary function of these specialists
`is to provide comprehensive care to the psychiatric
`inpatient and ambulatory-care areas. The specialists
`also help educate psychiatry residents; medical, phar(cid:173)
`macy, and nursing students; and permanent members
`of the psychiatry staff. All three specialists have the
`doctor of pharmacy degree and have completed a one(cid:173)
`year general hospital pharmacy residency program (two
`completed an ASHP-accredited program). Although
`none has completed a specialized psychiatry residency,
`all three pharmacists have clinical experience in psychi(cid:173)
`atry (2, 6, and 20 years).
`
`VA program for clozapine monitoring
`In 1991 the VA developed its own clozapine monitor(cid:173)
`ing program and received approval from Sandoz to dis(cid:173)
`pense clozapine. The VA Central Office established a
`National Clozapine Coordinating Center (NCCC). Physi(cid:173)
`cians at the NCCC review each clozapine candidate's file
`before granting approval for use and review weekly track(cid:173)
`ing sheets that report patient status. Each VA medical
`center is required to establish a clozapine treatment
`team, headed by the chief of the psychiatry service and
`including representatives from the psychiatry, pharma(cid:173)
`cy, laboratory, medicine, and nursing services. The cloza(cid:173)
`pine treatment team reviews new applications for
`clozapine use and provides clinical and demographic
`information for all new patients to the NCCC.
`The NCCC requires that each hospital have a comput(cid:173)
`erized clozapine prescription lockout system. The lock(cid:173)
`out system ties the hospital's laboratory database to the
`outpatient pharmacy dispensing software. The program
`will allow clozapine prescriptions to be processed only
`when WBC counts are within the defined limits. At our
`institution, the lockout system prevents the filling of any
`clozapine prescription if the computer notices three
`consecutive drops in the WBC count. Only the psychia(cid:173)
`try clinical pharmacy specialists and the chief of psychi(cid:173)
`atry are authorized to override the lockout.
`The NCCC guidelines require extensive patient eval(cid:173)
`uation and documentation. To receive clozapine, a
`patient must have undergone trials with two different
`
`900 Am J Hosp Ph arm Vol 51 Apr 15 1994
`
`neuroleptics and either failed to derive therapeutic
`benefit or experienced a significant adverse reaction. A
`complete physical examination, including laboratory
`testing and electrocardiographic analysis, is required.
`According to the NCCC, contraindications to clozapine
`therapy include a seizure history, cardiac disease, preg(cid:173)
`nancy, pre-existing leukopenia, a history of hematolog(cid:173)
`ic reactions to drugs, or a lymphoproliferative disorder.
`The NCCC also recommends that clozapine not be used
`in patients who, because of social situation, substance
`abuse, or other factors, cannot be relied upon to keep
`follow-up appointments.
`
`Pharmacists' duties
`Psychiatry residents at our facility rotate to other
`hospitals monthly; this creates concerns about continu(cid:173)
`ity of patient care and follow-up. The psychiatry clinical
`pharmacy specialists coordinate the education of resi(cid:173)
`dents on the screening and physical-examination re(cid:173)
`quirements for clozapine evaluation. As a member of the
`clozapine treatment team, the pharmacist screens poten(cid:173)
`tial candidates before they undergo extensive evaluation.
`The screening involves reviewing the patient's case with
`the requesting practitioner, reviewing the patient's file,
`and interviewing the patient to ensure 'that the patient
`and family members are committed to weekly blood tests
`and follow-up. This screening ensures that the physician
`does not waste time evaluating patients who are ineligi(cid:173)
`ble for clozapine therapy. After the physician completes
`the evaluation, the pharmacist reviews the documenta(cid:173)
`tion with the rest of the clozapine treatment team. After
`a patient has been determined eligible for clozapine
`therapy, the pharmacist forwards all pertinent informa(cid:173)
`tion to the NCCC. After NCCC approval, the pharmacist
`enrolls the patient into the hospital's clozapine tracking
`system, and clozapine therapy is begun.
`Role in inpatient care. Because of the severity of
`their illness, most patients are hospitalized when their
`current neuroleptic is withdrawn and clozapine is add(cid:173)
`ed. During the patient's hospitalization, the pharmacist
`ensures that the psychiatry resident orders the neces(cid:173)
`sary laboratory tests, performs the required clinical
`evaluation, and documents the results in a weekly
`tracking sheet, which the pharmacist forwards to the
`NCCC. The pharmacist meets with the patient many
`times during the hospitalization to assess adverse ef(cid:173)
`fects and monitor target symptoms to gauge response.
`In addition, the pharmacist acts as a consultant to the
`psychiatry resident by suggesting dosage adjustments
`and treatment of any adverse effects.
`Role in outpatient clinic. At our facility, the care
`of outpatients receiving clozapine therapy is provided
`directly by pharmacists, under the supervision of a phy(cid:173)
`sician. All outpatients in the clozapine prescription pro(cid:173)
`gram are seen by a psychiatry clinical pharmacy specialist
`weekly, as required by the NCCC. Patients are monitored
`for agranulocytosis, sedation, hypotension, tachycardia,
`
`CFAD VI 1007-0002
`
`

`

`sialorrhea, seizures, constipation, hyperthermia, weight
`gain, and other adverse effects. In addition, the pharma(cid:173)
`cist monitors and records vital signs, psychiatric target
`symptoms, laboratory results, and response to therapy.
`The pharmacist adjusts the clozapine dosage as necessary
`and treats serious adverse effects after consulting with a
`psychiatrist. Once the pharmacist and psychiatrist have
`selected a drug regimen for treating the adverse effects,
`the pharmacist makes routine dosage adjustments. After
`each weekly follow-up appointment, the pharmacist
`faxes a tracking sheet containing an evaluation of the
`patient to the NCCC and places the original document in
`the patient's medical record.
`
`Conclusion
`Pharmacists working with patients receiving cloza-
`
`Clozapine therapy Reports
`
`pine at a VA medical center provide direct patient care
`and help the institution comply with the stringent ther(cid:173)
`apy-monitoring requirements of the NCCC.
`
`References
`1. Ere:;hefsky L, Watanahe MD, Tran-Johnson Tl<. Clozapine: an
`atypical antipsychotic agent. Clin Pharm. 1989; 8:691-709.
`2. Rascati l<L, Rascati EJ. Use of clozapine in Texas state mental
`health facilities. Am J Hosp Pharm. 1993; 50:1663-6.
`3. Sandoz Pharmaceuticals Clozaril prescribing information
`(CLO-Z7). East Hanover, NJ; 1992Jun 1.
`4. Department of Veterans Affairs. Circular 10-91-099. Washing(cid:173)
`ton, DC: Department of Veterans Affairs Central Office. 1991
`Sep 9.
`S. Ellenor G, Dishman B. Pharmacist role in a mental health
`clinic as a primary provider. Paper presented at 27th Annual
`ASHP Midyear Clinical Meeting. Orlando, FL: 1992 Dec 8.
`
`Stability of aztreonam and ampicillin sodium(cid:173)
`sulbactam sodium in 0.9°;6 sodium chloride injection
`
`PAUL P. BELLIVEAU, CHARLES H. NIGHTINGALE, AND RICHARD QUJKTJLIANI
`
`Abstract: The stability of
`aztreonam, ampicillin sodi(cid:173)
`um, and sulbactam sodium
`admixed in 0.9% sodium
`chloride injection and stored
`at room temperature and un(cid:173)
`der refrigeration was studied.
`Each of the following ad(cid:173)
`mixtures was prepared in
`0.9% sodium chloride injec(cid:173)
`tion: (1) aztreonam 10 mg/
`ml; (2) ampicillin 20 mg/ml
`(as the sodium salt) and sul(cid:173)
`bactam 10 mg/ml (as the so(cid:173)
`dium salt); and (3) aztreonam
`10 mg/ml, ampicillin 20 mg/
`
`ml, and sulbactam IO mg/
`ml. Three minibags of each
`admixture were stored at
`room temperature and three
`were refrigerated. Every 12
`hours, up to 96 hours, the ad(cid:173)
`mixtures were visually in(cid:173)
`spected and 5-ml samples
`were withdrawn for high-per(cid:173)
`formance liquid chromatog(cid:173)
`raphy and pH testing.
`No color change or precipi(cid:173)
`tation was observed in any
`sample. In admixtures con(cid:173)
`taining ampicillin, ampicillin
`was the first or only drug to
`
`lose more than 10% of initial
`concentration. ln the ampi(cid:173)
`cillin-sulbactam admixture,
`ampicillin was stable for 32
`hours at room temperature
`and 68 hours refrigerated. ln
`the aztreonam-ampicillin(cid:173)
`sulbactam admixture, ampi(cid:173)
`cillin was stable for 30 hours
`at room temperature and 94
`hours refrigerated.
`Aztreonam IO mg/ml, am
`picillin 20 mg/ml (as the so(cid:173)
`dium salt), and sulbactam 10
`mg/ml (as the sodium salt)
`in 0.9% sodium chloride in-
`
`jection were stable in combi(cid:173)
`nation for up to 30 hours at
`room temperature and 94
`hours under refrigeration.
`
`Index terms: Additives;
`Ampicillin sodium; Antibiot(cid:173)
`ics; Aztreonam; Dosage
`forms; lncompatibilities; Pen(cid:173)
`icillins; Sodium chloride; Sta(cid:173)
`bility; Storage; Sulbactam
`sodium; Temperature;
`Vehicles
`Am J Hosp Pharm. 1994;
`51:901-4
`
`A ztreonam, a monocyclic ~-lactam antibiotic, is
`
`active against aerobic gram-negative organisms
`but inactive against anaerobic and gram-positive
`organisms. 1 It is not appropriate monotherapy for intra(cid:173)
`abdominal infections, because both aztreonam-sensitive
`
`(enteric gram-negative rods) and aztreonam-resistant
`(Bacteroides fragilis) organisms are encountered. 2 In such
`situations, an antimicrobial (such as ampicillin-sulbac(cid:173)
`tam) must be added to provide coverage against anaero(cid:173)
`bic organisms. 3
`
`PAUL P. BELLIVEAU, PHARM.D., is Clinical Specialist, Antimicrobial
`Therapy, Department of Pharmacy and Clinical Pharmacy, Uni(cid:173)
`versity of Massachusetts Medical Center, Worcester, MA; at the
`time of this study, he was Clinical Pharmacy Fellow in Antibiotic
`Management, Department of Pharmacy Services, Hartford Hospi(cid:173)
`tal, Hartford, CT. CHARLf-~ H. NIGHTINGALE, PH.D., is Vice President
`for Research, Office for Research, Hartford Hospital. RICHAHU
`QUINTILIAN!, M.D., is Director, Division of Infectious Diseases and
`Allergy-Immunology, Hartford Hospital.
`Address reprint requests to Dr. Belliveau at the Department of
`
`Pharmacy and Clinical Pharmacy, University of Massachusetts
`Medical Center, SS Lake Avenue North, Worcester, MA 01655.
`Supported by a grant from f.. R. Squibb & Sons, Inc., Princeton,
`
`NJ.
`
`The technical assistance of Qiang Fu is acknowledged.
`Presented at the 28th Annual Midyear Clinical Meeting, Atlan(cid:173)
`ta, GA, December 9, 1993.
`
`Copyright© 1994, American Society of Hospital Pharmacists,
`Inc. All rights reserved. 0002-9289/94/0401-0901SOl.OO.
`
`Vol 51 Apr 1 1994 Am J Hosp Pharm 901
`
`CFAD VI 1007-0003
`
`