INDEX TO ADVERTISERS
(clozapine) TABLETS
Ciba Pharmaceuticals
Drug Interactions The risks of using CLOZARIL in combination with other drugs have not been systematically evaluated. The mechanism of CLOZARIL-induced agranulocytosis is unknown; nonetheless, the possibility that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression warrants consideration. Therefore, CLOZARIL should not be used with other agents having a well-known potential to suppress bone marrow function. Given the primary CNS effects of CLOZARIL, caution is advised in using it concomitantly with other CNS-active drugs. Because CLOZARIL is highly bound to serum protein, the administration of CLOZARIL to a patient taking another drug which is highly bound to protein (e.g., warfarin, digoxin) may cause an increase in plasma concentrations of these drugs, potentially resulting in adverse effects. Conversely, adverse effects may resuft from displacement of protein-bound CLOZARIL by other highly bound drugs.
CLOZARIL may also potentlate the hypotensive effects of antihypertensive drugs and the anticholinergic effects ot atropine-type drugs. The administration of epinephrine should be avoided In the treatment of drug-induced hypotension because of a posible reverse epinephrine effect. Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and in view of the desirability of keeping the administration of all drugs to a minimum during pregnancy, this drug should be used only if clearly needed.
ADVERSE REACTIONS Adverse events observed in association with the use of CLOZARIL in clinical trials at an incidence of 5% or greater were: central nervous system complaints, including drowsiness/sedation, dizziness/ vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth and visual disturbances; cardiovascular findings, including tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever. Complaints of drowsiness/sedation tend to subside with continued therapy or dose reduction. Salivation may be profuse, especially during sleep, but may be diminished with dose reduction. DOSAGE AND ADMINISTRATION Initial Treatment It is recommended that treatment with CLOZARIL begin at 25 mg once or twice daily, and then be continued with daily dosage increments of 25 to 50 mg/day, if well-tolerated, to achieve a target dose of 300 to 450 mg/day by the end of two weeks. Subsequent dosage increments should be made no more than once- or twice-weekly, in increments not to exceed 100 mg. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation. Therapeutic Dose Adjustment Daily dosing should continue on a divided basis as an effective and tolerable dose level is sought. While many patients may respond adequately at doses between 300-600 mg/day, it may be necessary to raise the dose to the 600-900 mg/day range to obtain an acceptable response. [Note: In the multicenter study providing the primary support for the superiority of CLOZARIL in treatment resistant patients, the mean and median CLOZARIL doses were both approximately 600 mg/day.l Because of the possibility of increased adverse reactions at higher doses, particularly seizures, patients should ordinarily be given adequate time to respond to a given dose level before escalation to a higher dose is contemplated. Dosing should not exceed 900 mg/day. Dlscontinuatlon of Treatment In the event of planned termination of CLOZARIL therapy, gradual reduction in dose is recommended over a 1 to 2 week period. However, should a patient's medical condition require abrupt discontinuation (e.g., leukopenia), the patient should be carefully observed for the recurrence of psychotic symptoms. CLOZARIL Is avilable only through the Clozaril Patient Management System, a pregram that combines white blood cell testing, patient monitoring, pharmacy, and drug distribution services, all linked to compliance with required safety monitoring.
......
Marion Merrell Dow, Inc
..............
..............
McNeil Pharmaceutical .....................
Roerig,
A Division of Pfizer, Inc .
Sandoz Pharmaceuticals
The Upjohn Company
....
.......
156A-B
Cover 2-93, 107-108
.................
..................
108A-D, 109
95-96,
187-188
163-165, 188- Cover 4
................
99-106
While every precaution is taken to ensure accuracy, we cannot guarantee against the possibility ofan occasional change or omission in the preparation of this index.
To prescribe CLOZARIL call 1-800-237-CPMS (2767) or mall in a completed CPMS Enrollment Form.
What will you tell her about
screening mammography? Many of your patients will hear about screening mam-
mography through a program launched by the American Cancer Society and the American College of Radiology, and they may come to you with questions. What will you tell them? We hope you'll encourage them to have a screening mammogram, because that, along with your regular breast examinations and their monthly self examinations, offers the best chance of early detection of breast cancer, a disease which
will strike one woman in 10. If you have questions about breast cancer detection for asymptomatic women, please contact us.
/ SANDOZPHARMACEUTICALS E. Hanover, NJ 07936 (201) 503-7500
1/89
1 1/89
Corporon,
CLO-6002
AAAER,j Protessional Eduation Dept CANCER Nationat Headquarters S SOaCEw- 90 Park Avenue Ne York. NewYork 10016 oryour 1oal soiely
American 1891 Preston White Dr X ylColiege of Reston, Virginia 22091 (703) 648 8900
adiology
165
Downloaded From: http://archpsyc.jamanetwork.com/ by a Monash University Library User on 06/21/2015
(clozapine) TABLETS
Ciba Pharmaceuticals
Drug Interactions The risks of using CLOZARIL in combination with other drugs have not been systematically evaluated. The mechanism of CLOZARIL-induced agranulocytosis is unknown; nonetheless, the possibility that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression warrants consideration. Therefore, CLOZARIL should not be used with other agents having a well-known potential to suppress bone marrow function. Given the primary CNS effects of CLOZARIL, caution is advised in using it concomitantly with other CNS-active drugs. Because CLOZARIL is highly bound to serum protein, the administration of CLOZARIL to a patient taking another drug which is highly bound to protein (e.g., warfarin, digoxin) may cause an increase in plasma concentrations of these drugs, potentially resulting in adverse effects. Conversely, adverse effects may resuft from displacement of protein-bound CLOZARIL by other highly bound drugs.
CLOZARIL may also potentlate the hypotensive effects of antihypertensive drugs and the anticholinergic effects ot atropine-type drugs. The administration of epinephrine should be avoided In the treatment of drug-induced hypotension because of a posible reverse epinephrine effect. Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and in view of the desirability of keeping the administration of all drugs to a minimum during pregnancy, this drug should be used only if clearly needed.
ADVERSE REACTIONS Adverse events observed in association with the use of CLOZARIL in clinical trials at an incidence of 5% or greater were: central nervous system complaints, including drowsiness/sedation, dizziness/ vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth and visual disturbances; cardiovascular findings, including tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever. Complaints of drowsiness/sedation tend to subside with continued therapy or dose reduction. Salivation may be profuse, especially during sleep, but may be diminished with dose reduction. DOSAGE AND ADMINISTRATION Initial Treatment It is recommended that treatment with CLOZARIL begin at 25 mg once or twice daily, and then be continued with daily dosage increments of 25 to 50 mg/day, if well-tolerated, to achieve a target dose of 300 to 450 mg/day by the end of two weeks. Subsequent dosage increments should be made no more than once- or twice-weekly, in increments not to exceed 100 mg. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure, and sedation. Therapeutic Dose Adjustment Daily dosing should continue on a divided basis as an effective and tolerable dose level is sought. While many patients may respond adequately at doses between 300-600 mg/day, it may be necessary to raise the dose to the 600-900 mg/day range to obtain an acceptable response. [Note: In the multicenter study providing the primary support for the superiority of CLOZARIL in treatment resistant patients, the mean and median CLOZARIL doses were both approximately 600 mg/day.l Because of the possibility of increased adverse reactions at higher doses, particularly seizures, patients should ordinarily be given adequate time to respond to a given dose level before escalation to a higher dose is contemplated. Dosing should not exceed 900 mg/day. Dlscontinuatlon of Treatment In the event of planned termination of CLOZARIL therapy, gradual reduction in dose is recommended over a 1 to 2 week period. However, should a patient's medical condition require abrupt discontinuation (e.g., leukopenia), the patient should be carefully observed for the recurrence of psychotic symptoms. CLOZARIL Is avilable only through the Clozaril Patient Management System, a pregram that combines white blood cell testing, patient monitoring, pharmacy, and drug distribution services, all linked to compliance with required safety monitoring.
......
Marion Merrell Dow, Inc
..............
..............
McNeil Pharmaceutical .....................
Roerig,
A Division of Pfizer, Inc .
Sandoz Pharmaceuticals
The Upjohn Company
....
.......
156A-B
Cover 2-93, 107-108
.................
..................
108A-D, 109
95-96,
187-188
163-165, 188- Cover 4
................
99-106
While every precaution is taken to ensure accuracy, we cannot guarantee against the possibility ofan occasional change or omission in the preparation of this index.
To prescribe CLOZARIL call 1-800-237-CPMS (2767) or mall in a completed CPMS Enrollment Form.
What will you tell her about
screening mammography? Many of your patients will hear about screening mam-
mography through a program launched by the American Cancer Society and the American College of Radiology, and they may come to you with questions. What will you tell them? We hope you'll encourage them to have a screening mammogram, because that, along with your regular breast examinations and their monthly self examinations, offers the best chance of early detection of breast cancer, a disease which
will strike one woman in 10. If you have questions about breast cancer detection for asymptomatic women, please contact us.
/ SANDOZPHARMACEUTICALS E. Hanover, NJ 07936 (201) 503-7500
1/89
1 1/89
Corporon,
CLO-6002
AAAER,j Protessional Eduation Dept CANCER Nationat Headquarters S SOaCEw- 90 Park Avenue Ne York. NewYork 10016 oryour 1oal soiely
American 1891 Preston White Dr X ylColiege of Reston, Virginia 22091 (703) 648 8900
adiology
165
Downloaded From: http://archpsyc.jamanetwork.com/ by a Monash University Library User on 06/21/2015
