Clozapine
Systematic (IUPAC) name
8-chloro-11-(4-methyl-1-piperazinyl)- 5H-dibenzo(b,e)(1,4)diazepine
Identifiers
CAS number	5786-21-0
ATC code	N05AH02
PubChem	2818
DrugBank	APRD00470
Chemical data
Formula	C18H19ClN4
Mol. mass	326. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Chlorine (ˈklɔriːn from the Greek word 'χλωρóς' ( khlôros, meaning 'pale green' is the Chemical element with Atomic number 17 and Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 823 g/mol
Physical data
Melt. point	183 °C (361 °F)
Solubility in water	0 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability	60 to 70%
Metabolism	Hepatic, by several CYP isozymes
Half life	6 to 26 hours (mean value 14. The melting point of a solid is the temperature range at which it changes state from solid to Liquid. Solubility is the characteristic Physical property referring to the ability of a given substance the Solute, to dissolve in a Solvent. Water ( H2[[oxygen O]] H OH) is the most abundant Molecule on Earth 's surface composing of about 70% of the Earth's surface as In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 2 hours in steady state conditions)
Excretion	80% in metabolized state: 30% biliary and 50% renal
Therapeutic considerations
Pregnancy cat.	B
Legal status	Prescription only, special restrictions imposed in many countries
Routes	Oral

Clozapine (sold as Clozaril, Leponex, Fazaclo, Froidir; Gen-Clozapine in Canada; Clozaril, Denzapine, Zaponex in the UK; Klozapol in Poland) was the first of the atypical antipsychotics to be developed. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained In Pharmacology and Toxicology, a route The atypical antipsychotics (also known as second generation antipsychotics) are a group of Antipsychotic drugs used to treat psychiatric conditions Clozapine was first introduced in Europe in 1971, but was voluntarily withdrawn by the manufacturer in 1975 after it was shown to cause agranulocytosis that lead to death in some clozapine-treated patients. Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood In 1989, after studies demonstrated that it was more effective than any other antipsychotic for treating schizophrenia, the FDA approved clozapine's use but only for treatment-resistant schizophrenia. The FDA requires weekly blood testing for patients taking clozapine. [1] The FDA also requires clozapine to carry five black box warnings for agranulocytosis, seizures, myocarditis, for "other adverse cardiovascular and respiratory effects", and for "increased mortality in elderly patients with dementia-related psychosis. Black box is a technical term for a device or system or object when it is viewed primarily in terms of its input and output characteristics Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood " [2] In 2002 the FDA approved clozapine for reducing the risk of suicidal behavior but only for patients with schizophrenia.

Clozapine has been shown to be the most effective drug in treating schizophrenia but due to its potential to cause many severe side effects, it is relegated to third-line use. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Clozapine is only used in patients after other anti-psychotics have failed. Safer use of clozapine requires weekly blood monitoring for around five months followed by four weekly testing thereafter. A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is

Contents 1 History 2 Indications 2.1 Off-label and investigational drug use 3 Contraindications 4 Adverse effects 4.1 Agranulocytosis 4.2 Cardiac toxicity 4.3 Central nervous system 4.4 Weight gain and diabetes 5 Chemistry 6 Pharmacology 6.1 Pharmacokinetics 7 Monitoring 8 Dosage 9 See also 10 Notes 11 References 12 External links

History

Clozapine was developed by Sandoz in 1961, and introduced in Europe ten years later. Sandoz is the generics subsidiary of Novartis, a multinational Pharmaceutical company. Year 1961 ( MCMLXI) was a Common year starting on Sunday (link will display full calendar of the Gregorian calendar. In 1975, after reports of agranulocytosis leading to death in some clozapine-treated patients, clozapine was voluntarily withdrawn by the manufacturer. Year 1975 ( MCMLXXV) was a Common year starting on Wednesday (link will display full calendar of the Gregorian calendar. Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood 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. Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn Antipsychotics are a group of Psychoactive drugs commonly but not exclusively used to treat Psychosis, which is typified by Schizophrenia. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Granulocytes are a category of White blood cells characterised by Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood 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. Schizoaffective disorder is a Psychiatric Diagnosis of neurobiological illness.

Indications

Clozapine is used principally in treating treatment-resistant schizophrenia,^[1] a term generally used for the failure of symptoms to respond satisfactorily to at least two different antipsychotics;^[2] 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. Typical antipsychotics (sometimes referred to as first generation antipsychotics, conventional antipsychotics, classical neuroleptics, or major tranquilizers ^[1]

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. Olanzapine ( Zyprexa, Zyprexa Zydis, Zalasta, Zolafren, Olzapin, or in combination with Fluoxetine Symbyax) is

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.

Off-label and investigational drug use

• 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, results have been inconclusive regarding its actual efficacy in treating those conditions. Dementia (from Latin de- "apart away" + Mens ( genitive mentis) "mind" is the progressive decline Mania (from Greek μανία and that from μαίνομαι - mainomai, "to rage to be furious" is a severe medical condition Insomnia is a symptom of a sleeping disorder characterized by persistent difficulty falling asleep or staying asleep despite the opportunity

Contraindications

Clozapine is contraindicated in individuals with uncontrolled epilepsy, myeloproliferative disease, or agranulocytosis with prior clozapine treatment. In Medicine, a contraindication (pronounced as contra-indication is a condition or factor that increases the Risks involved in using a particular drug, Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. The myeloproliferative diseases ("MPD"s are a group of diseases of the Bone marrow in which excess cells are produced Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood

Many other (relative) contraindications (e. g. preexisting cardiovascular or liver damage, epilepsy) also exist.

Adverse effects

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, tremors, orthostasis, hyperglycemia, and weight gain. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that Drooling (also known as ptyalism or sialorrhea) is when Saliva flows outside the Mouth. Muscle (from Latin musculus, diminutive of mus "mouse" is contractile tissue of the body and is derived from the Sedation is a Medical procedure involving the administration of Sedative drugs generally to facilitate a medical procedure with Local anaesthesia. Tremor is an unintentional somewhat rhythmic muscle movement involving to-and-from movements (oscillations of one or more parts of the body Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma Weight gain is an increase in Body weight. This can be either an increase in Muscle mass, fat deposits or excess fluids such as Water. The risks of extrapyramidal symptoms such as tardive dyskinesia are much less with clozapine when compared to the typical antipsychotics; this may be due to clozapine's anticholinergic effects. In Human anatomy, the extrapyramidal system is a Neural network located in the brain that is part of the Motor system involved in the coordination Tardive dyskinesia is a variety of dyskinesia (involuntary repetitive movements manifesting as a side effect of long-term or high-dose use of Dopamine antagonists Typical antipsychotics (sometimes referred to as first generation antipsychotics, conventional antipsychotics, classical neuroleptics, or major tranquilizers 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. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic Care should be taken, especially if the latter drugs are given parenterally.

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. Male (♂ refers to the sex of an organism or part of an organism which produces small mobile Gametes called spermatozoa. Ejaculation is the ejecting of Semen from the Penis, and is usually accompanied by Orgasm. An orgasm (sexual climax is the conclusion of the plateau phase of the sexual response cycle, and may be experienced by both males and females

Agranulocytosis

Clozapine carries a black box warning for drug-induced agranulocytosis. In the United States, a black box warning (also sometimes called a black label warning or boxed warning) is a type of warning that appears on the Package Agranulocytosis is an acute condition involving a severe and dangerous Leukopenia particularly of neutrophils causing a Neutropenia in the circulating blood Without monitoring, agranulocytosis occurs in about 1% of patients who take clozapine during the first few months of treatment;^[3] the risk of developing it is highest about three months into treatment, and decreases substantially thereafter, to less than 0. 01% after one year. ^[4] 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 respiratory effects. An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting In Medicine ( Cardiology) myocarditis is Inflammation of the Myocardium, the muscular part of the Heart. This is an article about the rock music band "Circulatory System" In Animal physiology, respiration is the transport of Oxygen from the outside air to the cells within tissues and the transport of Carbon dioxide " Lowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures. A seizure threshold is the balance between excitatory and inhibitory forces in the brain which affects how susceptible one is to Seizures Drugs such as Bupropion can Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. Orthostatic hypotension (also known as postural hypotension, and colloquially as head rush or a dizzy spell) is a form of Hypotension in which

In 2007, a pharmacogenetic test was introduced to measure the probability of developing agranulocytosis. ^[5][6] 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 SNPs of the HLA-DQB1 gene. A single nucleotide polymorphism ( SNP, pronounced snip) is a DNA sequence variation occurring when a single Nucleotide - A, T The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans

Cardiac toxicity

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. In Medicine ( Cardiology) myocarditis is Inflammation of the Myocardium, the muscular part of the Heart. Heart failure is a Cardiac condition that occurs when a problem with the structure or function of the Heart impairs its ability to supply ^[7] Cardiomyopathy is another potentially fatal cardiac condition which may arise less acutely. Cardiomyopathy, which literally means "heart muscle disease" is the deterioration of the function of the Myocardium (i

Central nervous system

Psychotic symptoms can worsen while under influence and following the discontinuation especially after long-term use. ^[8]

Weight gain and diabetes

The FDA requires the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes with these medications. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Indeed, there are case reports of clozapine-induced hyperglycemia and diabetes; additionally, there are case reports of clozapine-induced diabetic ketoacidosis. Ketoacidosis is a type of metabolic Acidosis which is caused by high concentrations of Ketone bodies, formed by the Deamination of Amino acids 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, significant weight gain is frequently experienced by patients treated with clozapine. Hyperglycemia, hyperglycaemia, or high blood sugar is a condition in which an excessive amount of Glucose circulates in the Blood plasma ^[9] 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. Selenium (səˈliniəm is a Chemical element with the Atomic number 34 represented by the chemical symbol Se, an atomic mass of 78 ^[10]

Chemistry

It is insoluble in water, soluble in acetone, and very soluble in chloroform. Acetone (also known as propanone, dimethyl ketone, 2-propanone, propan-2-one and β-ketopropane) is a colorless mobile flammable Chloroform, also known as trichloromethane and methyl trichloride, is a Chemical compound with formula C[[Hydrogen H]] Cl

Its solubility in water is 11. 8 mg/L (25 C)

The manufacturer Novartis claim a solubility of <0. 01% in water ^[11]

Pharmacology

Clozapine is classified as an atypical antipsychotic drug because its profile of binding to serotonergic as well as dopamine receptors;^[12] its effects on various dopamine mediated behaviors also differ from those exhibited by more typical antipsychotics. The atypical antipsychotics (also known as second generation antipsychotics) are a group of Antipsychotic drugs used to treat psychiatric conditions In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also Dopamine is a Hormone and Neurotransmitter occurring in a wide variety of animals including both vertebrates and invertebrates In particular, clozapine interferes to a lower extent with the binding of dopamine at D₁, D₂, D₃ and D₅ receptors, and has a high affinity for the D₄ receptor, but it does not induce catalepsy nor inhibit apomorphine-induced stereotypy in animal models as is seen with 'conventional' neuroleptics. This page is about the medical condition for the deathcore band see Catalepsy (band Catalepsy is a nervous condition characterized by muscular A stereotypy (ˈstɛriəˌtаɪpi (plural stereotypies) is a repetitive or ritualistic movement posture or utterance found in patients with Mental retardation, Typical antipsychotics (sometimes referred to as first generation antipsychotics, conventional antipsychotics, classical neuroleptics, or major tranquilizers 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. In Human anatomy, the extrapyramidal system is a Neural network located in the brain that is part of the Motor system involved in the coordination An anticholinergic agent is a substance that blocks the Neurotransmitter acetylcholine in the central and the Peripheral nervous system.

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

Clozapine also is a strong antagonist at different subtypes of adrenergic, cholinergic and histaminergic receptors, the last two being predominantly responsible for its side effect profile. The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the Catecholamines Adrenergic receptors Muscarinic receptors, or mAChRs, are Acetylcholine receptors that form Metabotropic Ion channels in the Plasma membranes of certain The histamine receptors are a class of G-protein coupled receptors with Histamine as their Endogenous Ligand.

It has approximately the same potency as chlorpromazine. Chlorpromazine (as chlorpromazine Hydrochloride, abbreviated CPZ, marketed in the US as Thorazine) is a Phenothiazine Antipsychotic

Pharmacokinetics

The absorption of clozapine is almost complete, but the oral bioavailability is only 60 to 70% due to first-pass metabolism. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of Drug metabolism whereby the Concentration The time to peak concentration after oral dosing is about 2. 5 hours, and food does not appear to affect the bioavailability of clozapine. The elimination half-life of clozapine is about 14 hours at steady state conditions (varying with daily dose). The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Steady state is a more general situation than Dynamic equilibrium.

Clozapine is extensively metabolized in the liver, via the cytochrome P450 system, to polar metabolites suitable for elimination in the urine and faeces. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains "Polar molecule" and "Non-polar" redirect here The major metabolite, norclozapine (desmethyl-clozapine), is pharmacologically active. Demethylation is the chemical process resulting in the removal a Methyl group (CH3 from a molecule The cytochrome P450 isoenzyme 1A2 is primarily responsible for clozapine metabolism, but 2C, 2D6, 2E1 and 3A3/4 appear to play roles as well. Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction Cytochrome P450 1A2 (abbreviated CYP1A2) a member of the Cytochrome P450 mixed-function oxidase system is involved in the metabolism of Xenobiotics Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics Cytochrome P450 2E1 (abbreviated CYP2E1,) a member of the Cytochrome P450 mixed-function oxidase system is involved in the metabolism of Xenobiotics in Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Agents which induce (e. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. g. cigarette smoke) or inhibit (e. Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. g. theophylline, ciprofloxacin, fluvoxamine) CYP1A2 may increase or decrease, respectively, the metabolism of clozapine. Theophylline, also known as dimethylxanthine, is a Methylxanthine drug used in therapy for Respiratory diseases such as COPD or Asthma Fluvoxamine ( Luvox) is an Antidepressant which functions as a Selective serotonin reuptake inhibitor. Smoking increases the metabolism of Clozapine to the extent that approximately double the dose is required in heavy smokers compared to non-smokers.

Monitoring

In the USA, patients who take clozapine are required to have a blood cell count every week, for the first six months of therapy. A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is 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.

Patients are advised to inform their doctor if they develop a sore throat, or fever. A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health See also Strep throat. Pharyngitis (ˌfarɪnˈdʒʌɪtɪs is in most cases a Painful inflammation of the Pharynx, and is Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris If the number of white blood-cells drops notably then referral to a hematologist is undertaken. Hematology ( American English) or haematology ( British English) is the branch of biology (physiology Pathology, Clinical laboratory

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. ^[13]

More recently, a regular six-monthly echocardiogram is also recommended to detect myocarditis. An echocardiogram is a Sonography of the Heart. Also known as a cardiac ultrasound it uses standard ultrasound techniques to image two-dimensional slices of In Medicine ( Cardiology) myocarditis is Inflammation of the Myocardium, the muscular part of the Heart.

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 CBC prior to dispensing the medication to the patient. A complete blood count ( CBC) also known as full blood count ( FBC) or full blood exam ( FBE) or blood panel, is The purpose of the monitoring system is to prevent rechallenge with clozapine in patients with a history of clozapine-induced agranulocytosis and to detect leukopenic events among patients taking clozapine. Challenge-dechallenge-rechallenge ( CDR) is a medical testing protocol in which a Medicine or Drug is administered withdrawn then re-administered Leukopenia (or leukocytopenia, or leucopenia, from Greek λευκό -white and πενία -deficiency is a decrease in the number of In other countries (e. g. in Europe), restrictions have been eased.

Dosage

Due to risk of serious side effects, clozapine treatment is commenced at a very low dose and increased slowly until a therapeutic dose is reached. ^[14][15] In severely ill and/or younger patients higher doses may be needed, while in the elderly much lower doses may be sufficient. 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. ^[15] 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.

See also

• DHA-clozapine

Notes

References

• Benkert, Hippius: Kompendium der Psychiatrischen Pharmakotherapie (German), 4th. ed. , Springer Verlag
• B. Bandelow, S. Bleich, and S. Kropp: Handbuch Psychopharmaka (German), 2nd. ed. Hogrefe
• 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

External links

• Clozaril - Novartis
• Clozapine
• US Clozaril Package Insert (PDF)
• Clozaril Registry Website
• Fazaclo

A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. Novartis International AG is a multinational Pharmaceutical company based in Basel Switzerland that manufactures drugs such as Clozapine

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