CLOZARIL (CLOZAPINE)
- Suicidal behavior in schizoaffective disorder
- Suicidal behavior in schizophrenia
- Treatment-resistant schizophrenia
100 mg tablet
- 1 tablet (100 mg) by oral route 3 times per day
25 mg tablet
- 1 tablet (25 mg) by oral route 3 times per day
100 mg tablet
- 1 tablet (100 mg) by oral route 3 times per day
200 mg tablet
- 1 tablet (200 mg) by oral route 2 times per day
25 mg tablet
- 1 tablet (25 mg) by oral route 3 times per day
50 mg tablet
- 2 tablets (100 mg) by oral route 2 times per day
Suicidal behavior in schizoaffective disorder
- 1 tablet (25 mg) by oral route 2 times per day
- 1 tablet (25 mg) by oral route 3 times per day
- 1 tablet (25 mg) by oral route once daily
- 2 tablets (50 mg) by oral route once daily
- 2 tablets (50 mg) by oral route 2 times per day
- 2 tablets (50 mg) by oral route 3 times per day
- 3 tablets (75 mg) by oral route 2 times per day
- 3 tablets (75 mg) by oral route once daily
- 3 tablets (75 mg) by oral route 3 times per day
- 1 tablet (100 mg) by oral route once daily
- 1 tablet (100 mg) by oral route 2 times per day
- 1 tablet (100 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 2 times per day
- 2 tablets (200 mg) by oral route once daily
- 3 tablets (300 mg) by oral route 2 times per day
- 3 tablets (300 mg) by oral route once daily
- 3 tablets (300 mg) by oral route 3 times per day
Suicidal behavior in schizophrenia
- 1 tablet (25 mg) by oral route 2 times per day
- 1 tablet (25 mg) by oral route 3 times per day
- 1 tablet (25 mg) by oral route once daily
- 2 tablets (50 mg) by oral route once daily
- 2 tablets (50 mg) by oral route 2 times per day
- 2 tablets (50 mg) by oral route 3 times per day
- 3 tablets (75 mg) by oral route 2 times per day
- 3 tablets (75 mg) by oral route once daily
- 3 tablets (75 mg) by oral route 3 times per day
- 1 tablet (100 mg) by oral route once daily
- 1 tablet (100 mg) by oral route 2 times per day
- 1 tablet (100 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 2 times per day
- 2 tablets (200 mg) by oral route once daily
- 3 tablets (300 mg) by oral route 2 times per day
- 3 tablets (300 mg) by oral route once daily
- 3 tablets (300 mg) by oral route 3 times per day
Treatment-resistant schizophrenia
- 1 tablet (100 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 3 times per day
- 2 tablets (200 mg) by oral route 2 times per day
- metoclopramide HCl
- Metozolv Odt
- Reglan
Contraindicated
- abacavir-lamivudine-zidovudine
- Abelcet
- Abraxane
- Actemra
- Actimmune
- adalimumab
- Adcetris
- ado-trastuzumab emtansine
- Adriamycin
- Adriamycin Pfs
- Adrucil
- Afinitor
- Afinitor Disperz
- Alimta
- Alkeran
- alprazolam
- Alprazolam Intensol
- altretamine
- Ambisome
- amiodarone
- amiodarone in dextrose,iso-osm
- amitriptyline-chlordiazepoxide
- amphotericin B lipid complex
- amphotericin B liposome
- anastrozole
- Ancobon
- anti-thymocyte glob (rabbit)
- aprepitant
- Arimidex
- Arranon
- arsenic trioxide
- artemether-lumefantrine
- Astagraf Xl
- Atgam
- Ativan
- Aubagio
- auranofin
- Avastin
- axitinib
- azacitidine
- Azasan
- azathioprine
- azathioprine sodium
- Azulfidine
- Azulfidine En-tabs
- belatacept
- bendamustine
- Betaseron
- bevacizumab
- bexarotene
- Bicnu
- boceprevir
- bortezomib
- Bosulif
- bosutinib
- brentuximab vedotin
- busulfan
- cabazitaxel
- Camptosar
- capecitabine
- carbamazepine
- Carbatrol
- carboplatin
- carfilzomib
- carmustine
- carmustine in polifeprosan
- Cellcept
- Cellcept Intravenous
- Cerubidine
- Chemet
- chlorambucil
- chlordiazepoxide HCl
- chlordiazepoxide-clidinium
- cidofovir
- cisplatin
- cladribine
- clobazam
- clofarabine
- Clolar
- clonazepam
- clorazepate dipotassium
- Coartem
- Combivir
- Copegus
- Cordarone
- Cosmegen
- crizotinib
- Cuprimine
- cyclophosphamide
- cytarabine
- cytarabine (PF)
- cytarabine liposome (PF)
- Cytovene
- dacarbazine
- Dacogen
- dactinomycin
- Daraprim
- dasatinib
- daunorubicin
- daunorubicin liposome
- Daunoxome
- decitabine
- deferiprone
- Depen Titratabs
- Depocyt (pf)
- Diastat
- Diastat Acudial
- diazepam
- Diazepam Intensol
- disopyramide
- Dmsa
- Docefrez
- docetaxel
- Doral
- Doxil
- doxorubicin
- doxorubicin HCl peg-liposomal
- dronedarone
- droperidol
- Droxia
- Ellence
- Eloxatin
- Emend
- epirubicin
- Epitol
- Equetro
- eribulin
- estazolam
- Etopophos
- etoposide
- etoposide phosphate
- everolimus
- Extavia
- Ferriprox
- flucytosine
- fludarabine
- fluorouracil
- flurazepam
- fluvoxamine
- Folotyn
- fosaprepitant
- foscarnet
- Foscavir
- ganciclovir sodium
- Gazyva
- gemcitabine
- Gemzar
- Geodon
- Gleevec
- Gliadel Wafer
- Halaven
- Hecoria
- Herceptin
- Hexalen
- Humira
- Humira Crohn's Dis Start Pck
- Humira Pen
- Humira Psoriasis Starter Pack
- Hycamtin
- Hydrea
- hydroxyurea
- ibrutinib
- Iclusig
- Idamycin Pfs
- idarubicin
- Ifex
- ifosfamide
- ifosfamide-mesna
- imatinib
- Imbruvica
- Imuran
- Infergen
- infliximab
- Inlyta
- interferon alfa-2b
- interferon alfacon-1
- interferon beta-1b
- interferon gamma-1b
- Intron A
- irinotecan
- Istodax
- ixabepilone
- Ixempra
- Jakafi
- Jevtana
- Kadcyla
- kit for prep Tc-99m-succimer
- kit for yttrium-90-ibritumomab
- Klonopin
- Kyprolis
- Lamisil
- lamivudine-zidovudine
- lenalidomide
- Leukeran
- Librax (with Clidinium)
- linezolid
- Lipodox
- Lipodox 50
- lomustine
- lorazepam
- Lorazepam Intensol
- Luvox Cr
- lymphocyte,anti-thymo imm glob
- Marqibo
- Matulane
- mechlorethamine
- melphalan
- meprobamate
- mercaptopurine
- methimazole
- Methotrexate (anti-rheumatic)
- methotrexate sodium
- methotrexate sodium (PF)
- midazolam
- midazolam (PF)
- mitomycin
- mitoxantrone
- Moderiba
- Moderiba Dose Pack
- Multaq
- Mustargen
- mycophenolate mofetil
- mycophenolate mofetil HCl
- mycophenolate sodium
- Myfortic
- Myleran
- Navelbine
- Nebupent
- nelarabine
- Nexavar
- Nexterone
- nilotinib
- Nipent
- Niravam
- nitisinone
- Norpace
- Norpace Cr
- Nulojix
- obinutuzumab
- omacetaxine
- Onfi
- Onxol
- Orap
- Orfadin
- oxaliplatin
- oxazepam
- Pacerone
- paclitaxel
- paclitaxel-protein bound
- pazopanib
- Pegasys
- Pegasys Convenience Pack
- Pegasys Proclick
- peginterferon alfa-2a
- pemetrexed
- penicillamine
- Pentam
- pentamidine
- pentostatin
- Perjeta
- pertuzumab
- pimozide
- pomalidomide
- Pomalyst
- ponatinib
- pralatrexate
- procarbazine
- Prograf
- Purinethol
- pyrimethamine
- Quadramet
- quazepam
- radium Ra 223 dichloride
- Rebetol
- Remicade
- Restoril
- Retrovir
- Revlimid
- Rheumatrex
- Ribapak Dose Pack
- Ribasphere
- Ribatab Dose Pack
- ribavirin
- Ridaura
- Rituxan
- rituximab
- romidepsin
- ruxolitinib
- samarium sm 153 lexidronam
- sodium oxybate
- sorafenib
- Sprycel
- succimer
- sulfasalazine
- Sulfazine
- Sulfazine Ec
- Synribo
- Tabloid
- tacrolimus
- Tapazole
- Targretin
- Tasigna
- Taxotere
- Tegretol
- Tegretol Xr
- temazepam
- Temodar
- temozolomide
- temsirolimus
- teniposide
- terbinafine
- teriflunomide
- thioguanine
- Thiola
- thioridazine
- thiotepa
- Thymoglobulin
- ticlopidine
- tiopronin
- tocilizumab
- Toposar
- topotecan
- Torisel
- Tranxene T-tab
- trastuzumab
- Treanda
- Trexall
- triazolam
- Trisenox
- Trizivir
- Valcyte
- valganciclovir
- Valium
- Velcade
- vemurafenib
- Victrelis
- Vidaza
- vinblastine
- Vincasar Pfs
- vincristine
- vincristine sulfate liposomal
- vinorelbine
- Vistide
- Votrient
- Xalkori
- Xanax
- Xanax Xr
- Xeloda
- Xofigo
- Xyrem
- Zaltrap
- Zelboraf
- Zevalin (y-90)
- zidovudine
- ziprasidone HCl
- ziprasidone mesylate
- ziv-aflibercept
- Zortress
- Zyvox
Severe
Moderate
- Ablavar
- Advair Diskus
- Advair Hfa
- alfuzosin
- amantadine HCl
- amoxicil-clarithromy-lansopraz
- Anzemet
- Aplenzin
- Apokyn
- apomorphine
- Avelox
- Avelox Abc Pack
- Avelox In Nacl (iso-osmotic)
- azithromycin
- bedaquiline
- Betapace
- Betapace Af
- Biaxin
- Biaxin Xl
- Biaxin Xl Pak
- Brisdelle
- Buproban
- bupropion HBr
- bupropion HCl
- Caprelsa
- Cardene Iv
- Cardene Iv In Dextrose
- Cardene Iv In Sodium Chloride
- Cardene Sr
- Celexa
- chloroquine phosphate
- chlorpromazine
- Cipro
- Cipro In D5W
- Cipro Xr
- ciprofloxacin
- ciprofloxacin (mixture)
- ciprofloxacin in D5W
- citalopram
- clarithromycin
- Complera
- Corvert
- Diskets
- dofetilide
- dolasetron
- Dolophine
- Edurant
- Effexor Xr
- emtricitab-rilpivirine-tenofov
- Erythrocin
- erythromycin
- erythromycin-sulfisoxazole
- escitalopram oxalate
- ezogabine
- Fareston
- felbamate
- Felbatol
- flecainide
- fluoxetine
- fluticasone-salmeterol
- Forfivo Xl
- gadofosveset trisodium
- granisetron
- granisetron (PF)
- Granisol
- Haldol
- Haldol Decanoate
- haloperidol
- haloperidol decanoate
- haloperidol lactate
- ibutilide fumarate
- indapamide
- Invega
- Invega Sustenna
- isradipine
- Kaletra
- Ketek
- lapatinib
- Levaquin
- Levaquin In 5 % Dextrose
- Levitra
- levofloxacin
- levofloxacin in D5W
- Lexapro
- lithium carbonate
- lithium citrate
- Lithobid
- lopinavir-ritonavir
- methadone
- Methadone Intensol
- Methadose
- moexipril
- moexipril-hydrochlorothiazide
- moxifloxacin
- moxifloxacin in NaCl (iso-osm)
- nicardipine
- nicardipine in dextrose,iso-os
- nicardipine in NaCl (iso-os)
- norfloxacin
- Noroxin
- Noxafil
- octreotide acetate
- ofloxacin
- olanzapine-fluoxetine
- Omeclamox-pak
- omeprazole-clarith-amoxicillin
- ondansetron
- ondansetron HCl
- ondansetron HCl (PF)
- paliperidone
- paliperidone palmitate
- paroxetine HCl
- paroxetine mesylate
- pasireotide
- Paxil
- Paxil Cr
- Pexeva
- posaconazole
- Potiga
- Prevpac
- procainamide
- propafenone
- Prozac
- Prozac Weekly
- Qualaquin
- quetiapine
- quinine sulfate
- rilpivirine
- Rythmol
- salmeterol
- Sancuso
- Sandostatin
- Sandostatin Lar Depot
- Sarafem
- Serevent Diskus
- Seroquel
- Seroquel Xr
- sertraline
- Signifor
- Sirturo
- Soltamox
- Sorine
- sotalol
- Sotalol Af
- sunitinib
- Sutent
- Symbyax
- tamoxifen
- telavancin
- telithromycin
- tetrabenazine
- Tikosyn
- tizanidine
- toremifene
- Tykerb
- Uniretic
- Univasc
- Uroxatral
- vandetanib
- vardenafil
- venlafaxine
- Vfend
- Vfend Iv
- Vibativ
- voriconazole
- Wellbutrin
- Wellbutrin Sr
- Wellbutrin Xl
- Xenazine
- Zanaflex
- Zithromax
- Zithromax Tri-pak
- Zithromax Z-pak
- Zmax
- Zofran
- Zofran Odt
- Zoloft
- Zuplenz
- Zyban
- Acute pancreatitis
- Agranulocytosis
- Congenital long QT syndrome
- Lactating mother
- Myocarditis
- Neuroleptic malignant syndrome
- Paralytic ileus
- Torsades de pointes
Contraindicated
- Angle-closure glaucoma
- Benign prostatic hyperplasia
- Bone marrow depression
- Bradycardia
- Deep venous thrombosis
- Dehydration
- Dilated cardiomyopathy
- Eosinophilia
- Fecal impaction
- Hypokalemia
- Hypomagnesemia
- Hypotension
- Lower seizure threshold
- Metabolic syndrome X
- Orthostatic hypotension
- Prolonged QT interval
- Pulmonary thromboembolism
- Seizure disorder
- Senile dementia
- Severe neutropenic disorder
- Urinary retention
Severe
Moderate
- Abnormal hepatic function tests
- Cerebrovascular accident
- Cerebrovascular disorder
- Constipation
- CYp2d6 poor metabolizer
- Diabetes mellitus
- Disease of liver
- Gastrointestinal hypomotility
- Hyperlipidemia
- Obesity
- Predisposition to aspiration
- Reduced activity of cytochrome p450 CYp1a2
- Reduced activity of cytochrome p450 CYp3a4
- Sinus tachycardia
- Tardive dyskinesia
- Tobacco smoker
- Weight gain
CLOZARIL (CLOZAPINE)
- Suicidal behavior in schizoaffective disorder
- Suicidal behavior in schizophrenia
- Treatment-resistant schizophrenia
- Hypotension
- Orthostatic hypotension
- Constipation
- Dizziness
- Drowsy
- Fever
- Headache disorder
- Hyperhidrosis
- Nausea
- Sedation
- Sialorrhea
- Tachycardia
- Tremor
- Vertigo
- Visual changes
- Vomiting
- Weight gain
- Xerostomia
More Frequent
Severe
Less Severe
- Akathisia
- Cardiac arrhythmia
- Hypertension
- Abdominal distension
- Acute abdominal pain
- Acute confusion
- Agitation
- Diarrhea
- Dyspepsia
- Eructation
- Fatigue
- Gastroenteritis
- Heartburn
- Nervousness
- Nightmares
- Parotitis
- Rectal bleeding
- Skin rash
- Syncope
- Urinary retention
Less Frequent
Severe
Less Severe
Rare / Very Rare
Severe
- Abnormal ECG
- Abnormal hepatic function tests
- Accidental fall
- Acute myocardial infarction
- Acute pancreatitis
- Acute renal failure
- Agranulocytosis
- Angioedema
- Aspiration pneumonia
- Atrial fibrillation
- Bacterial sepsis
- Blood dyscrasias
- Bradycardia
- Cardiomyopathy
- Cataplexy
- Cholestasis
- Chronic heart failure
- Colitis
- Deep venous thrombosis
- Diabetes mellitus
- Diabetic hyperosmolar coma
- Diabetic ketoacidosis
- DRESS syndrome
- Eosinophilia
- Erythema multiforme
- Extrapyramidal disease
- Fecal impaction
- Gastric ulcer
- Gastrointestinal hypomotility
- Gastrointestinal obstruction
- Granulocytopenic disorder
- Hepatic cirrhosis
- Hepatic failure
- Hepatic necrosis
- Hepatitis
- Hyperglycemia
- Hypersensitivity angiitis
- Hypokinesia
- Hyponatremia
- Ileus
- Increased hemoglobin
- Interstitial nephritis
- Jaundice
- Leukopenia
- Lower respiratory infection
- Mitral valve regurgitation
- Muscle rigidity
- Myocarditis
- Myoclonus
- Neuroleptic malignant syndrome
- Neutropenic disorder
- Paralytic ileus
- Pericardial effusion
- Pericarditis
- Pneumonia
- Polyserositis
- Priapism
- Prolonged QT interval
- Pulmonary thromboembolism
- Renal failure
- Rhabdomyolysis
- Secondary angle-closure glaucoma
- Seizure disorder
- Status epilepticus
- Steatosis of liver
- Stevens-johnson syndrome
- Systemic lupus erythematosus
- Tardive dyskinesia
- Thrombocytopenic disorder
- Thrombocytosis
- Torsades de pointes
- Vasculitis
- Ventricular fibrillation
- Ventricular tachycardia
Less Severe
- Abnormal electroencephalogram
- Acquired dystonia
- Angina
- Anorexia
- Ataxia
- Bloody vomit
- Delirium
- Depression
- Dysarthria
- Dyschromia
- Dysgeusia
- Dysmenorrhea
- Dysphagia
- Edema
- Erectile dysfunction
- Hypercholesterolemia
- Hypertriglyceridemia
- Hyperuricemia
- Insomnia
- Lethargy
- Mastalgia
- Muscle weakness
- Nocturnal enuresis
- Paresthesia
- Periorbital edema
- Polydipsia
- Retrograde ejaculation
- Skin photosensitivity
- Slurred speech
- Urinary incontinence
- Weight loss
Contraindicated
None
Severe Precaution
None
Management or Monitoring Precaution
Clozapine
Risk of severe neutropenia, seizure, cardiomyopathy, orthostatic hypotension, respiratory arrest. Safety and efficacy not established.
- 1 Day – 18 Years
- Risk of severe neutropenia, seizure, cardiomyopathy, orthostatic hypotension, respiratory arrest. Safety and efficacy not established.
Clozapine
- Severity Level:
B
- Additional Notes: Non-teratogenic complications (resp, gi,cns) with exposure during 3rd trimester
Contraindicated
Clozapine
Not recommended: possible severe hematologic adverse effects.
General | Excretion Potential | Effect on Infant | Notes |
Drug should not be given to breast feeding mothers | Excreted | Drug shown to have adverse effect | Not recommended: possible severe hematologic adverse effects. |
Precaution Exists
None
General | Excretion Potential | Effect on Infant | Notes |
None |
No Known Risk
None
General | Excretion Potential | Effect on Infant | Notes |
None |
Contraindicated
None
Precaution Exists
Clozapine
Neuro/Psych-Gen not rec'd. Inc risk of tardive dyskinesia. CNS effects; sedation, cognit impair and inc fall risk. Avoid use for behav probs of dementia or delirium unless failed nonpharm options. Inc risk of stroke, cognit decline, and death when used w/dementia. Endocrine-May exacerbate or cause SIADH or hyponatremia. Cardiovascular-Risk of orthostatic hypoten & tachycardia. Gastrointestinal-Inc constipation risk. Consider proph bowel regimen Genitourinary-Urinary retention risk
Organ / System | HEP | REN | CARD | ENDO | NEURO / PSYCH | PULM |
Increased Risk / Adverse Effects | N | Y | Y | Y | N | Y |
BEERS: Y HEDIS: Y STOPP: Y
No Known Risk
None
- While clozapine can provide great benefits, it can rarely cause serious, possibly fatal side effects. For this reason, clozapine is used when other treatments have not worked or you cannot take them. For patients to receive this medication, all doctors, pharmacists, and patients must agree to, understand, and carefully follow the requirements of the Clozapine REMS Program.<br /><br /> These requirements apply in the United States. If you live in Canada or any other country, consult your doctor and pharmacist for your country's regulations. This medication can cause a serious decrease of a certain type of white blood cells (neutropenia).<br /><br />To make sure you have enough white blood cells, your doctor will order lab tests before starting and while your are taking clozapine. Neutropenia may lower your ability to fight infections. Get medical help right away if you have any signs of severe neutropenia or infection (such as sore throat that doesn't go away, fever, swollen lymph nodes, unusual tiredness, weakness).<br /><br /> Clozapine can also cause seizures, especially in higher doses. Let your doctor or pharmacist know if you have ever had seizures. While taking this medication, avoid driving or other activities during which a sudden loss of consciousness could be dangerous (e.g., operating heavy machinery, swimming).<br /><br /> This medication may rarely cause an inflammation of the heart muscle (myocarditis) or heart failure. Get medical help right away if you develop chest pain, fast/irregular heartbeat, shortness of breath, swelling ankles/feet, unusual tiredness, or unusual/sudden weight gain. Clozapine can cause low blood pressure or a slow heartbeat, which can make you dizzy or cause you to faint when you stand up.<br /><br /> The risk is higher when you first start or increase your dose of medication. Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.<br /><br /> There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
Suicidal behavior in schizoaffective disorder | |
F25 | Schizoaffective disorders |
F25.0 | Schizoaffective disorder, bipolar type |
F25.1 | Schizoaffective disorder, depressive type |
F25.8 | Other schizoaffective disorders |
F25.9 | Schizoaffective disorder, unspecified |
Suicidal behavior in schizophrenia | |
F20 | Schizophrenia |
F20.0 | Paranoid schizophrenia |
F20.1 | Disorganized schizophrenia |
F20.2 | Catatonic schizophrenia |
F20.3 | Undifferentiated schizophrenia |
F20.5 | Residual schizophrenia |
F20.8 | Other schizophrenia |
F20.89 | Other schizophrenia |
F20.9 | Schizophrenia, unspecified |
Treatment-resistant schizophrenia | |
F20 | Schizophrenia |
F20.0 | Paranoid schizophrenia |
F20.1 | Disorganized schizophrenia |
F20.2 | Catatonic schizophrenia |
F20.3 | Undifferentiated schizophrenia |
F20.5 | Residual schizophrenia |
F20.8 | Other schizophrenia |
F20.81 | Schizophreniform disorder |
F20.89 | Other schizophrenia |
F20.9 | Schizophrenia, unspecified |
0-9 | A-Z |
---|---|
F20 | Schizophrenia |
F20 | Schizophrenia |
F20.0 | Paranoid schizophrenia |
F20.0 | Paranoid schizophrenia |
F20.1 | Disorganized schizophrenia |
F20.1 | Disorganized schizophrenia |
F20.2 | Catatonic schizophrenia |
F20.2 | Catatonic schizophrenia |
F20.3 | Undifferentiated schizophrenia |
F20.3 | Undifferentiated schizophrenia |
F20.5 | Residual schizophrenia |
F20.5 | Residual schizophrenia |
F20.8 | Other schizophrenia |
F20.8 | Other schizophrenia |
F20.81 | Schizophreniform disorder |
F20.89 | Other schizophrenia |
F20.89 | Other schizophrenia |
F20.9 | Schizophrenia, unspecified |
F20.9 | Schizophrenia, unspecified |
F25 | Schizoaffective disorders |
F25.0 | Schizoaffective disorder, bipolar type |
F25.1 | Schizoaffective disorder, depressive type |
F25.8 | Other schizoaffective disorders |
F25.9 | Schizoaffective disorder, unspecified |