Clozapine: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Automated text replacement (-{{SIB}} + & -{{EH}} + & -{{EJ}} + & -{{Editor Help}} + & -{{Editor Join}} +))
No edit summary
Line 1: Line 1:
{{Drugbox|
{{DrugProjectFormSinglePage
| IUPAC_name = 8-chloro-11-(4-methyl-1-piperazinyl)-<br />5''H''-dibenzo(b,e)(1,4)diazepine
|genericName=generic name
| CAS_number = 5786-21-0
|aOrAn=a
| ATC_prefix = N05
|drugClass=Adrenergic receptor agonist
| ATC_suffix = AH02
|indication=a list of indications, separated by commas.
| PubChem = 2818
|hasBlackBoxWarning=Yes
| DrugBank = APRD00470
|adverseReactions=a list of adverse reactions, separated by commas.
| C=18 | H=19 | Cl=1 | N=4
|blackBoxWarningTitle=Warning Title
| molecular_weight = 326.823 g/mol
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
| melting_point = 183
|fdaLIADAdult======Condition 1=====
| solubility = 0
 
| bioavailability = 60 to 70%
* Dosing Information
| metabolism = [[Liver|Hepatic]], by several [[Cytochrome P450|CYP]] [[isozyme]]s
 
| elimination_half-life = 6 to 26 hours (mean value 14.2 hours in steady state conditions)
:* (Dosage)
| excretion = 80% in metabolized state: 30% biliary and 50% [[kidney|renal]]
 
| pregnancy_category = B
=====Condition 2=====
| legal_status = [[Prescription drug|Prescription only]], special restrictions imposed in many countries
 
| routes_of_administration = Oral
* Dosing Information
}}
 
:* (Dosage)
|offLabelAdultGuideSupport======Condition 1=====
 
* Developed by: (Organisation)
 
* Class of Recommendation: (Class) (Link)
 
* Strength of Evidence: (Category A/B/C) (Link)
 
* Dosing Information/Recommendation
 
:* (Dosage)
 
=====Condition 2=====
 
* Developed by: (Organisation)
 
* Class of Recommendation: (Class) (Link)
 
* Strength of Evidence: (Category A/B/C) (Link)
 
* Dosing Information/Recommendation
 
:* (Dosage)
|offLabelAdultNoGuideSupport======Condition 1=====
 
* Dosing Information
 
:* (Dosage)
 
=====Condition 2=====
 
* Dosing Information
 
:* (Dosage)
 
=====Condition 3=====
 
* Dosing Information
 
:* (Dosage)
|fdaLIADPed======Condition 1=====
 
* Dosing Information
 
:* (Dosage)
 
=====Condition 2=====
 
* Dosing Information
 
:* (Dosage)
|offLabelPedGuideSupport======Condition 1=====
 
* Developed by: (Organisation)
 
* Class of Recommendation: (Class) (Link)
 
* Strength of Evidence: (Category A/B/C) (Link)
 
* Dosing Information/Recommendation
 
:* (Dosage)
 
=====Condition 2=====
 
* Developed by: (Organisation)
 
* Class of Recommendation: (Class) (Link)
 
* Strength of Evidence: (Category A/B/C) (Link)
 
* Dosing Information/Recommendation
 
:* (Dosage)
|offLabelPedNoGuideSupport======Condition 1=====
 
* Dosing Information
 
:* (Dosage)
 
=====Condition 2=====
 
* Dosing Information
 
:* (Dosage)
 
=====Condition 3=====
 
* Dosing Information
 
:* (Dosage)
|contraindications=* Condition 1
* Condition 2
* Condition 3
* Condition 4
* Condition 5
|warnings======Conidition 1=====
 
(Description)
 
|clinicalTrials=======Central Nervous System======
 
: (list/description of adverse reactions)
 
======Cardiovascular======
 
: (list/description of adverse reactions)
 
======Respiratory======
 
: (list/description of adverse reactions)
 
======Gastrointestinal======
 
: (list/description of adverse reactions)
 
======Hypersensitive Reactions======
 
: (list/description of adverse reactions)
 
======Miscellaneous======
 
: (list/description of adverse reactions)
 
=====Condition 2=====
 
======Central Nervous System======
 
: (list/description of adverse reactions)
 
======Cardiovascular======
 
: (list/description of adverse reactions)
 
======Respiratory======
 
: (list/description of adverse reactions)
 
======Gastrointestinal======
 
: (list/description of adverse reactions)
 
======Hypersensitive Reactions======
 
: (list/description of adverse reactions)
 
======Miscellaneous======
 
: (list/description of adverse reactions)
|postmarketing=(Description)
|drugInteractions=* Drug 1
* Drug 2
* Drug 3
* Drug 4
* Drug 5
 
=====Drug 1=====
 
(Description)
 
=====Drug 2=====
 
(Description)
 
=====Drug 3=====
 
(Description)
 
=====Drug 4=====
 
(Description)
 
=====Drug 5=====
 
(Description)
|useInPregnancyFDA=(Description)
|useInPregnancyAUS=(Description)
|useInLaborDelivery=(Description)
|useInNursing=(Description)
|useInPed=(Description)
|useInGeri=(Description)
|useInGender=(Description)
|useInRace=(Description)
|useInRenalImpair=(Description)
|useInHepaticImpair=(Description)
|useInReproPotential=(Description)
|useInImmunocomp=(Description)
|othersTitle=Others
|useInOthers=(Description)
 
|administration=(Oral/Intravenous/etc)
|monitoring======Condition 1=====
 
(Description regarding monitoring, from ''Warnings'' section)
 
=====Condition 2=====
 
(Description regarding monitoring, from ''Warnings'' section)
 
=====Condition 3=====
 
(Description regarding monitoring, from ''Warnings'' section)
|IVCompat====Solution===
 
====Compatible====
 
* Solution 1
* Solution 2
* Solution 3
 
====Not Tested====
 
* Solution 1
* Solution 2
* Solution 3
 
====Variable====
 
* Solution 1
* Solution 2
* Solution 3
 
====Incompatible====
 
* Solution 1
* Solution 2
* Solution 3
 
===Y-Site===
 
====Compatible====
 
* Solution 1
* Solution 2
* Solution 3
 
====Not Tested====
 
* Solution 1
* Solution 2
* Solution 3


{{SI}}
====Variable====


* Solution 1
* Solution 2
* Solution 3


==Overview==
====Incompatible====
'''Clozapine''' (sold as '''Clozaril''', '''Leponex''', '''Fazaclo''';  '''Gen-Clozapine''' in Canada) was the first of the [[atypical antipsychotic]]s to be developed. It was approved by the United States [[Food and Drug Administration]] (FDA) in 1989 and is the only FDA-approved medication indicated for treatment-resistant [[schizophrenia]] and for reducing the risk of suicidal behaviour in patients with schizophrenia.


Clozapine has been shown to be superior in efficacy in treating schizophrenia. Were it not for its [[adverse drug reaction|side effect]]s it would be first line treatment; however the rare but potentially lethal side effects of [[agranulocytosis]] and [[myocarditis]] relegate it to third-line use. Furthermore it may rarely lower seizure threshold, cause hepatic dysfunction, weight gain and be associated with [[Diabetes mellitus type 2|type II]] [[Diabetes mellitus|diabetes]]. More common side effects are predominantly [[anticholinergic]] in nature, with dry mouth, sedation and constipation. It is also a strong antagonist at different subtypes of [[adrenergic receptor|adrenergic]], [[muscarinic acetylcholine receptor|cholinergic]], [[histamine receptor|histaminergic]] and [[serotonin receptor|serotonergic]] receptors.
* Solution 1
* Solution 2
* Solution 3


Safer use of clozapine requires weekly [[full blood count|blood monitoring]] for around five months followed by four weekly testing thereafter. [[Echocardiogram]]s are recommended every 6 months to exclude cardiac damage.
===Admixture===


==History==
====Compatible====
Clozapine was developed by Sandoz in 1961, and introduced in Europe ten years later.  In 1975, after reports of [[agranulocytosis]] leading to death in some clozapine-treated patients, clozapine was voluntarily withdrawn by the manufacturer.  Clozapine fell out of favor for more than a decade.  However, when studies demonstrated that clozapine was more effective against treatment-resistant [[schizophrenia]] than other [[antipsychotics]], the [[FDA]] and health authorities in most other countries approved its use only for treatment-resistant schizophrenia, and required regular [[hematological]] monitoring to detect [[granulocytopenia]], before [[agranulocytosis]] develops. In December of 2002, clozapine was also approved for reducing the risk of suicide in schizophrenic or schizoaffective patients judged to be at chronic risk for suicidal behavior.


==Indications==
* Solution 1
Clozapine is used principally in treating treatment-resistant schizophrenia,<ref name ="Wahlbecko7">{{cite journal | author = Wahlbeck K, Cheine MV, Essali A | title = Clozapine versus typical neuroleptic medication for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = | issue = 2 | pages = | publisher = John Wiley and Sons, Ltd. | date = 2007 | url = http://www.cochrane.org/reviews/en/ab000059.html (abstract) | doi = 10.1002/14651858.CD000059 | id = ISSN 1464-780X}}</ref> a term generally used for the failure of symptoms to respond satisfactorily to at least two different antipsychotics;<ref>{{cite journal | author = Meltzer HY | title = Treatment-resistant schizophrenia--the role of clozapine. | journal = Current Medical Research and Opinion | volume = 14 | issue = 1 | pages = 1-20  | date = 1997 | url = http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9524789&dopt=Abstract (Abstract) | doi = }}</ref> It clearly has been shown to be more effective in reducing symptoms of schizophrenia than the older [[typical antipsychotics]], with maximal effects in those who have responded poorly to other medication; though the relapse rate is lower and patient acceptability better, this has not translated to significant observed benefits in global functioning.<ref name ="Wahlbecko7"/>
* Solution 2
* Solution 3


It is also used for reducing the risk of suicide in patients judged to belong to a high risk group with chronic risk for suicidal behavior. Clozapine was shown to prolong the time to suicidal attempt significantly greater than [[olanzapine]].
====Not Tested====


Clozapine works well against positive (e.g. delusions, hallucinations) and negative (e.g. emotional and social withdrawal) symptoms of schizophrenia. It has no dyscognitive effect often seen with other psychoactive drugs and is even able to increase the capabilities of the patient to react to this environment and thereby fosters social rehabilitation.
* Solution 1
* Solution 2
* Solution 3


===Off-label and investigational drug use===
====Variable====
* Treatment of psychosis in L-Dopa treated patients (25 to 50 mg at bedtime is often sufficient); this indication is currently approved in Switzerland
* Treatment of psychotic symptoms occurring in patients with [[dementia]] of the Lewy-body-type
* Treatment of otherwise resistant acute episodes of [[mania]]
* Treatment of intractable chronic [[insomnia]], if all other measures have failed
* Treatment of [[schizoid personality disorder]]


Though much research has been done evaluating the benefit of clozapine in treating the aforementioned conditions, it is too early to come to a conclusive result. If you contemplate clozapine as drug for these conditions, weigh carefully benefits and risks and inform the patients fully, if possible, about the advantages and risks of clozapine treatment, before a joint decision is made. If the patient is not able to make own decisions, parents or guardians or the competent court must give their consent...
* Solution 1
* Solution 2
* Solution 3


==Contraindications==    
====Incompatible====
Clozapine is [[contraindicated]] in individuals with uncontrolled [[epilepsy]], [[myeloproliferative disease]], or [[agranulocytosis]] with prior clozapine treatment.


Many other (relative) contraindications (e.g. preexisting cardiovascular or liver damage, epilepsy) also exist.
* Solution 1
* Solution 2
* Solution 3


==Adverse effects==
===Syringe===
The use of clozapine is associated with a fair number of side effects, many minor though some serious and potentially fatal: the more common include [[constipation]], [[drooling]], [[muscle]] stiffness, [[sedation]], [[tremor]]s, [[orthostasis]], [[hyperglycemia]], and [[weight gain]].  The risks of [[extrapyramidal symptom]]s such as [[tardive dyskinesia]] are much less with clozapine when compared to the [[typical antipsychotics]]; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine.


Clozapine may have a synergistic effect with the sedating action of other drugs such as [[benzodiazepines]], and thus respiratory depression may result with concomitant use. Care should be taken, especially if the latter drugs are given parenterally.
====Compatible====


Many [[male]] patients have experienced ceasure of [[ejaculation]] during [[orgasm]] as a side effect of Clozapine though this is not documented in official drug guides.
* Solution 1
* Solution 2
* Solution 3


===Agranulocytosis===
====Not Tested====
Clozapine carries a [[black box warning]] for drug-induced [[agranulocytosis]].  Without monitoring, agranulocytosis occurs in about 1% of patients who take clozapine during the first few months of treatment;<ref name="GoodmanGilman">{{cite book |last=Baldessarini |first=Ross J. |coauthors=Frank I. Tarazi |editor=Laurence Brunton, John Lazo, Keith Parker (eds.) |title=[[Goodman & Gilman's The Pharmacological Basis of Therapeutics]] |edition=11<sup>th</sup> ed. |year=2006 |publisher=McGraw-Hill|location=New York |isbn=978-0071422802|pages= |chapter=Pharmacotherapy of Psychosis and Mania}}</ref> the risk of developing it is highest about three months into treatment, and decreases substantially thereafter, to less than 0.01% after one year.<ref name="Alvir1993">{{cite journal |author=Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA |title=Clozapine-induced agranulocytosis. Incidence and risk factors in the United States |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=329 |issue=3 |pages=162–7 |year=1993 |pmid=8515788 |doi=}} [http://content.nejm.org/cgi/content/full/329/3/162 Free full text with registration]</ref> Patients who have experienced agranulocytosis with prior treatment of clozapine should not receive it again.  Clozapine also carries black box warnings for [[seizures]], [[myocarditis]], and "other adverse [[cardiovascular]] and [[Respiration (physiology)|respiratory]] effects."  Lowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures.  Slow titration of dosing may also decrease the risk for [[orthostatic hypotension]] and other adverse cardiovascular side effects.


===Cardiac toxicity===
* Solution 1
A more recently identified and sometimes fatal side effect is that of [[myocarditis]] which usually develops within the first month of commencement and presents with signs of [[cardiac failure]] and cardiac arrhythmias.<ref>{{cite journal | author = Haas SJ, Hill R, Krum H  | title = Clozapine-associated myocarditis | journal = Drug Safety | volume = 30 | pages = 47–57 | date = 2007 | doi = }}</ref>  [[Cardiomyopathy]] is another potentially fatal cardiac condition which may arise less acutely.
* Solution 2
* Solution 3


===Weight gain and diabetes===
====Variable====
The FDA requires the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and [[diabetes]] with these medications. Indeed, there are case reports of clozapine-induced hyperglycemia and diabetes; additionally, there are case reports of clozapine-induced diabetic [[ketoacidosis]]. There is data showing that clozapine can decrease insulin sensitivity. Clozapine should be used with caution in patients who are diagnosed with diabetes or in patients at risk for developing diabetes.  All patients receiving clozapine should have their fasting blood glucose monitored.


In addition to [[hyperglycemia]], weight gain may be experienced by patients treated with clozapine. Impaired glucose metabolism and obesity have been shown to be constituents of the metabolic syndrome and may increase the risk of cardiovascular disease. The data suggests that clozapine may be more likely to cause adverse metabolic effects than some of the other atypical antipsychotics. Research has indicated that clozapine may cause a deficiency of [[selenium]].<ref>{{cite journal |author=Vaddadi KS, Soosai E, Vaddadi G |title=Low blood selenium concentrations in schizophrenic patients on clozapine |journal=British journal of clinical pharmacology |volume=55 |issue=3 |pages=307-9 |year=2003 |pmid=12630982 |doi=}}</ref>
* Solution 1
* Solution 2
* Solution 3


In 2007, a pharmacogenetic test was introduced to measure the probability of developing agranulocytosis.<!--
====Incompatible====


--><ref name="Pgxhealth_2007_site">[http://www.pgxhealth.com/genetictests/clozapine/ PGxPredict:CLOZAPINE] - a page about the agranulocytosis risk test.</ref><ref name="Forbes_pr_2007_test"> [http://www.forbes.com/businesswire/feeds/businesswire/2007/01/23/businesswire20070123005298r1.html Clinical Data Launches Pharmacogenetic Test for Clozapine-Induced Agranulocytosis on Schedule] - press release at the Forbes site.</ref><!--
* Solution 1
* Solution 2
* Solution 3


--><!--
===TPN/TNA===


--> The test has two gradations - Higher and Lower risk, with a relative agranulocytosis risk of 2.5 and 0.5 compared to general level. The company states that the test is based on two [[Single nucleotide polymorphism|SNP]]s of the [[Human leukocyte antigen|HLA]]-DQB1 gene.
====Compatible====


==Chemistry==
* Solution 1
It is insoluble in water, soluble in [[acetone]], very well soluble in [[chloroform]].
* Solution 2
* Solution 3


Its solubility in water is 11.8 mg/L (25 C)
====Not Tested====


The manufacturer Novartis claim a solubility of <0.01% in water
* Solution 1
<ref>
* Solution 2
{{Citation
* Solution 3
  | last = Novartis Pharmaceuticals
  | author-link = Novartis
  | title = Prescribing Information
  | url=http://www.novartis.ca/downloads/en/products/clozaril_scrip_e.pdf
  | accessdate = 2007-06-29
  | date = April 2006
  | year = 2006
  | publisher = Novartis Pharmaceuticals
  | pages = p36    }}
</ref>
==Pharmacology==
Clozapine is classified as an [[atypical antipsychotic]] drug because its profile of binding to [[serotonin receptor|serotonergic]] as well as [[dopamine]] receptors;<ref name ="Nahgre01">{{cite journal |author=Naheed M, Green B. |year=2001|title=Focus on clozapine|journal= |volume=17 |issue=3 |pages=223-9 |pmid=11900316 |url=http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11900316 (abstract) |accessdate= 2007-07-02}}</ref> its effects on various dopamine mediated behaviors also differ from those exhibited by more typical antipsychotics. In particular, clozapine interferes to a lower extent with the binding of dopamine at D<sub>1</sub>, D<sub>2</sub>, D<sub>3</sub> and D<sub>5</sub> receptors, and has a high affinity for the D<sub>4</sub> receptor, but it does not induce [[catalepsy]] nor inhibit [[apomorphine]]-induced [[Stereotypy (psychiatry)|stereotypy]] in animal models as is seen with [[typical antipsychotic|'conventional' neuroleptics]]. This evidence suggests clozapine is preferentially more active at limbic than at striatal dopamine receptors and may explain the relative freedom of clozapine from [[extrapyramidal]] side effects together with strong [[anticholinergic]] activity.


Clozapine is also partial agonists at the 5-HT1A receptor, putatively improving depression, anxiety, and negative/cognitive symptoms.
====Variable====


Clozapine also is a strong antagonist at different subtypes of [[adrenergic receptor|adrenergic]], [[muscarinic acetylcholine receptor|cholinergic]] and  [[histamine receptor|histaminergic]] receptors, the last two being predominantly responsible for its side effect profile.
* Solution 1
* Solution 2
* Solution 3


It has approximately the same potency as [[chlorpromazine]].
====Incompatible====


===Pharmacokinetics===
* Solution 1
The absorption of clozapine is almost complete, but the oral [[bioavailability]] is only 60 to 70% due to [[first-pass metabolism]]. The time to peak concentration after oral dosing is about 2.5 hours, and food does not appear to effect the bioavailability of clozapine.
* Solution 2
The [[elimination half-life]] of clozapine is about 14 hours at steady state conditions (varying with daily dose).
* Solution 3
|overdose====Acute Overdose===


Clozapine is extensively metabolized in the liver, via the [[cytochrome P450]] system, to [[Chemical polarity|polar]] metabolites suitable for elimination in the urine and faeces. The major metabolite, ''norclozapine'' ([[demethylation|desmethyl]]-clozapine), is pharmacologically active. The cytochrome P450 [[isoenzyme]] [[CYP1A2|1A2]] is primarily responsible for clozapine metabolism, but 2C, [[CYP2D6|2D6]], [[CYP2E1|2E1]] and [[CYP3A4|3A3/4]] appear to play roles as well.  Agents which [[enzyme induction and inhibition|induce]] (e.g. cigarette smoke) or [[enzyme inhibitor|inhibit]] (e.g. [[theophylline]], [[ciprofloxacin]], [[fluvoxamine]]) CYP1A2 may increase or decrease, respectively, the metabolism of clozapine.
====Signs and Symptoms====


==Monitoring==
(Description)
In the USA, patients who take clozapine are required to have a [[blood cell count]] every week, for the first six months of therapy.  After this, they are required to have a blood cell count every other week for the second six months after therapy. After twelve months, blood cell counts need be performed every four weeks.


If the number of white blood-cells drops notably, one should consult with a [[hematology|hematologist]].  If you are using clozapine and have a [[sore throat]], or [[fever]], then you should inform your [[physician|doctor]]. 
====Management====


Clozapine and norclozapine plasma levels may also be monitored, though they show a significant degree of variation and are higher in women and increase with age.<ref>{{cite journal |author= Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW.  |year=1999 |month=January |title=Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics |journal=J Clin Psychiatry |volume=60 |issue=1 |pages=36-40 |pmid=10074876 |url=http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10074876&dopt=Abstract (abstract) |accessdate=2007-06-24}}</ref>
(Description)


More recently, a regular six-monthly [[echocardiogram]] is also recommended to detect [[myocarditis]].
===Chronic Overdose===


The manufacturers of both the brand and generic clozapine are required by the FDA to track white blood cells counts for patients receiving clozapine, and pharmacies are required to obtain a copy of the [[Full blood count|CBC]] prior to dispensing the medication to the patient.  The purpose of the monitoring system is to prevent rechallenge with clozapine in patients with a history of clozapine-induced agranulocytosis and to detect [[leukopenia|leukopenic]] events among patients taking clozapine. In other countries (e.g. in Europe), restrictions have been eased.
====Signs and Symptoms====


==Dosage==
(Description)
Due to risk of serious side effects, clozapine treatment is commenced at a very low dose  (25&nbsp;mg daily) and increased slowly until a therapeutic dose (300–600&nbsp;mg daily) is reached.<ref>{{cite web | author = Novartis Pharmaceuticals | authorlink = | title = Clozaril Dosing Guide  | publisher = Novartis Pharmaceuticals | date = | url = http://www.clozaril.com/hcp/tools/dosing_guide.jsp | accessdate = 2007-06-29}}</ref> In severely ill and/or younger patients up to 900 mg may be needed. In the elderly, much lower doses may be sufficient (25 to 100 mg). Once the patient is stabilized and the maintenance dose has been determined, the greater part or all of the daily dose may be given at bedtime. This will ameliorate daytime sedation and orthostatic problems; most people benefit from the sedation to get to sleep anyway. Furthermore, compliance on medication taken more frequently than once daily drops off dramatically.


==Undocumented side-effects==
====Management====
Known to cause inability to [[ejaculate]] while [[orgasm]]ing in some [[male]] patients.


==See also==
(Description)
*[[DHA-clozapine]]
|drugBox={{Drugbox2
| verifiedrevid =  
| IUPAC_name =  
| image =  
| drug_name =


== References ==
<!--Clinical data-->
=== Notes ===
| tradename =  
{{Reflist}}
| MedlinePlus =  
| licence_US =  
| pregnancy_AU =  
| pregnancy_US =  
| legal_status =  
| routes_of_administration =


=== Sources ===
<!--Pharmacokinetic data-->
* Benkert, Hippius: Kompendium der Psychiatrischen Pharmakotherapie (German), 4th. ed., Springer Verlag
| bioavailability =  
* B. Bandelow, S. Bleich, and S. Kropp: Handbuch Psychopharmaka (German), 2nd. ed. Hogrefe
| metabolism =  
* Crilly JF (2007)  ''The history of clozapine and its emergence in the US Market:  A review and Analysis.''  History of Psychiatry,  18(1):  39-60. {{doi|10.1177/0957154X07070335}}
| elimination_half-life =  
| excretion =


==External links==
<!--Identifiers-->
* [http://www.clozaril.com Clozaril] - [[Novartis]]
| CAS_number_Ref =
* [http://www.mentalhealth.com/drug/p30-c02.html Clozapine]
| CAS_number =
* [http://www.pharma.us.novartis.com/product/pi/pdf/Clozaril.pdf US Clozaril Package Insert] (PDF)
| ATC_prefix =
* [https://www.clozarilregistry.com/care/Splash.jsp Clozaril Registry Website]
| ATC_suffix =
| PubChem =
| IUPHAR_ligand =
| DrugBank_Ref =  
| DrugBank =  
| ChemSpiderID_Ref =  
| ChemSpiderID =  
| UNII_Ref =
| UNII =
| KEGG_Ref =
| KEGG =
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref =
| ChEMBL =


<!--Chemical data-->
| C= | H= | N= | O=
| molecular_weight =
| smiles =
| InChI =
| InChIKey =
| StdInChI_Ref =
| StdInChI =
| StdInChIKey_Ref =
| StdInChIKey =
| melting_point =
}}
|mechAction=(Description)
|structure=(Description with picture)
|PD=(Description)
|PK=(Description)
|nonClinToxic=(Description)
|clinicalStudies======Condition 1=====


{{Antipsychotics}}
(Description)


=====Condition 2=====


[[Category:Atypical antipsychotics]]
(Description)


[[es:Clozapina]]
=====Condition 3=====
[[fr:Clozapine]]
[[ru:Клозапин]]


{{WH}}
(Description)
{{WS}}
|howSupplied=(Description)
|fdaPatientInfo=(Patient Counseling Information)
|nlmPatientInfo=(Link to patient information page)
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)
* (Paired Confused Name 2a) — (Paired Confused Name 2b)
* (Paired Confused Name 3a) — (Paired Confused Name 3b)
|drugShortage=Drug Shortage
}}

Revision as of 01:15, 12 December 2014

Clozapine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

Disclaimer

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.

Black Box Warning

Warning Title
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)

Overview

Clozapine is a Adrenergic receptor agonist that is FDA approved for the {{{indicationType}}} of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Condition 1
  • Dosing Information
  • (Dosage)
Condition 2
  • Dosing Information
  • (Dosage)

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition 1
  • Developed by: (Organisation)
  • Class of Recommendation: (Class) (Link)
  • Strength of Evidence: (Category A/B/C) (Link)
  • Dosing Information/Recommendation
  • (Dosage)
Condition 2
  • Developed by: (Organisation)
  • Class of Recommendation: (Class) (Link)
  • Strength of Evidence: (Category A/B/C) (Link)
  • Dosing Information/Recommendation
  • (Dosage)

Non–Guideline-Supported Use

Condition 1
  • Dosing Information
  • (Dosage)
Condition 2
  • Dosing Information
  • (Dosage)
Condition 3
  • Dosing Information
  • (Dosage)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition 1
  • Dosing Information
  • (Dosage)
Condition 2
  • Dosing Information
  • (Dosage)

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition 1
  • Developed by: (Organisation)
  • Class of Recommendation: (Class) (Link)
  • Strength of Evidence: (Category A/B/C) (Link)
  • Dosing Information/Recommendation
  • (Dosage)
Condition 2
  • Developed by: (Organisation)
  • Class of Recommendation: (Class) (Link)
  • Strength of Evidence: (Category A/B/C) (Link)
  • Dosing Information/Recommendation
  • (Dosage)

Non–Guideline-Supported Use

Condition 1
  • Dosing Information
  • (Dosage)
Condition 2
  • Dosing Information
  • (Dosage)
Condition 3
  • Dosing Information
  • (Dosage)

Contraindications

  • Condition 1
  • Condition 2
  • Condition 3
  • Condition 4
  • Condition 5

Warnings

Warning Title
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)
Conidition 1

(Description)

Adverse Reactions

Clinical Trials Experience

Central Nervous System
(list/description of adverse reactions)
Cardiovascular
(list/description of adverse reactions)
Respiratory
(list/description of adverse reactions)
Gastrointestinal
(list/description of adverse reactions)
Hypersensitive Reactions
(list/description of adverse reactions)
Miscellaneous
(list/description of adverse reactions)
Condition 2
Central Nervous System
(list/description of adverse reactions)
Cardiovascular
(list/description of adverse reactions)
Respiratory
(list/description of adverse reactions)
Gastrointestinal
(list/description of adverse reactions)
Hypersensitive Reactions
(list/description of adverse reactions)
Miscellaneous
(list/description of adverse reactions)

Postmarketing Experience

(Description)

Drug Interactions

  • Drug 1
  • Drug 2
  • Drug 3
  • Drug 4
  • Drug 5
Drug 1

(Description)

Drug 2

(Description)

Drug 3

(Description)

Drug 4

(Description)

Drug 5

(Description)

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): (Description)
Pregnancy Category (AUS): (Description)

Labor and Delivery

(Description)

Nursing Mothers

(Description)

Pediatric Use

(Description)

Geriatic Use

(Description)

Gender

(Description)

Race

(Description)

Renal Impairment

(Description)

Hepatic Impairment

(Description)

Females of Reproductive Potential and Males

(Description)

Immunocompromised Patients

(Description)

Others

(Description)

Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

Solution

Compatible

  • Solution 1
  • Solution 2
  • Solution 3

Not Tested

  • Solution 1
  • Solution 2
  • Solution 3

Variable

  • Solution 1
  • Solution 2
  • Solution 3

Incompatible

  • Solution 1
  • Solution 2
  • Solution 3

Y-Site

Compatible

  • Solution 1
  • Solution 2
  • Solution 3

Not Tested

  • Solution 1
  • Solution 2
  • Solution 3

Variable

  • Solution 1
  • Solution 2
  • Solution 3

Incompatible

  • Solution 1
  • Solution 2
  • Solution 3

Admixture

Compatible

  • Solution 1
  • Solution 2
  • Solution 3

Not Tested

  • Solution 1
  • Solution 2
  • Solution 3

Variable

  • Solution 1
  • Solution 2
  • Solution 3

Incompatible

  • Solution 1
  • Solution 2
  • Solution 3

Syringe

Compatible

  • Solution 1
  • Solution 2
  • Solution 3

Not Tested

  • Solution 1
  • Solution 2
  • Solution 3

Variable

  • Solution 1
  • Solution 2
  • Solution 3

Incompatible

  • Solution 1
  • Solution 2
  • Solution 3

TPN/TNA

Compatible

  • Solution 1
  • Solution 2
  • Solution 3

Not Tested

  • Solution 1
  • Solution 2
  • Solution 3

Variable

  • Solution 1
  • Solution 2
  • Solution 3

Incompatible

  • Solution 1
  • Solution 2
  • Solution 3

Overdosage

Acute Overdose

Signs and Symptoms

(Description)

Management

(Description)

Chronic Overdose

Signs and Symptoms

(Description)

Management

(Description)

Pharmacology

Clozapine
Systematic (IUPAC) name
?
Identifiers
CAS number ?
ATC code ?
PubChem ?
Chemical data
Formula ?
Mol. mass ?
Pharmacokinetic data
Bioavailability ?
Metabolism ?
Half life ?
Excretion ?
Therapeutic considerations
Pregnancy cat.

?

Legal status
Routes ?

Mechanism of Action

(Description)

Structure

(Description with picture)

Pharmacodynamics

(Description)

Pharmacokinetics

(Description)

Nonclinical Toxicology

(Description)

Clinical Studies

Condition 1

(Description)

Condition 2

(Description)

Condition 3

(Description)

How Supplied

(Description)

Storage

There is limited information regarding Clozapine Storage in the drug label.

Images

Drug Images

{{#ask: Page Name::Clozapine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}

Package and Label Display Panel

{{#ask: Label Page::Clozapine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

(Patient Counseling Information)

Precautions with Alcohol

Alcohol-Clozapine interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Clozapine Brand Names in the drug label.

Look-Alike Drug Names

  • (Paired Confused Name 1a) — (Paired Confused Name 1b)
  • (Paired Confused Name 2a) — (Paired Confused Name 2b)
  • (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Retrieved from "https://www.wikidoc.org/index.php?title=Clozapine&oldid=1047410"