|
|
|
|
|
Clozapine
drug data and news
Clozapine drug data, resources, and news articles (when available). Onconews.org provides news on cancer research. This section, which includes profiles on medicines that may or not be cancer-related is in beta form. If things run smoothly we will be releasing a new format late in the summer of 2006.
|
| Generic name | Clozapine | ||
| Brand Names/Synonyms | Asaleptin; Clozapin; Clozapine; Clozaril; Fazaclo ODT; HF-1854; Iprox; Leponex; Lepotex; W-801 | ||
| Indication | For the management of severely ill schizophrenic patients who fail to respond adequately to standard drug treatment for schizophrenia | ||
| Sponsored links | Description | Not Available | |
| Pharmacology | Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. | ||
| Mechanism Of Action | The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism. | ||
| Clozapine News (When available) |
Adjuvant Taxotere® and Herceptin® Effective for Breast Cancer ... 06 Mar 2006 Adjuvant Docetaxel More Effective Than Vinorelbine for Early ... Feb 23, 2006 Adjuvant Docetaxel or Vinorelbine with or without Trastuzumab for ... Feb 22, 2006 Positive Findings from Clinical Studies of Quadramet in Prostate ... Feb 27, 2006 Positive Findings from Clinical Studies of QUADRAMET(R) in ... Feb 27, 2006 Breast Cancer Drugs Limit Post-Surgery Recurrence Feb 22, 2006 Optimising Herceptin-based Therapy in HER2-positive Metastatic ... Feb 22, 2006 Breast meds limit recurrence Feb 23, 2006 GPC Biotech Presents New Satraplatin Clinical Data From ... Feb 27, 2006 Options Expanding With First-line Capecitabine (Xeloda) ... Feb 22, 2006 Trails to detect effective breast cancer drugs that reduces ... Feb 23, 2006 Bioxel Signs Long-Term Paclitaxel Supply Agreement With a Second ... Feb 23, 2006 Anti-angiogenesis Therapy With Avastin (Bevacizumab): Presented at ... Feb 21, 2006 Spectrum presents new satraplatin prostate cancer data Feb 28, 2006 What Can Xeloda (capecitabine) Add to Neoadjuvant Chemotherapy? ... Feb 22, 2006 BCIRG 006 Shows Trastuzumab (Herceptin) Improves Disease-free ... Feb 20, 2006 Cell Genesys gives promising prostate cancer trial update Feb 28, 2006 ASCO Prostate: Intermittent Chemotherapy Controls Androgen ... Feb 28, 2006 Cell Genesys Reports Encouraging Follow-Up Survival Data From ... Feb 27, 2006 Taxotere® and Novantrone® Sequence Evaluated as Initial ... Feb 22, 2006 Recurrence-Free Survival Improved with Taxotere® Compared to ... Feb 23, 2006 GVAX® Vaccine Promising for Hormone-Refractory Prostate Cancer Feb 28, 2006 Neoadjuvant Herceptin® plus Taxotere® Promising in Early Breast ... Feb 24, 2006 Treatment “Holidays� Effective in Hormone-Refractory Prostate ... Mar 1, 2006 First Patient Enrolled in Point Therapeutics' Second Phase 3 ... Feb 8, 2006 Point Therapeutics Provides Clinical Update During Recent Company ... Feb 3, 2006 YM Biosciences' Cancer Drugs Are Working Feb 2, 2006 Herceptin’s wider use comes closer to EU/US approval Feb 20, 2006 Xeloda Shows Benefits as First Choice for Metastatic Breast Cancer ... Feb 22, 2006 Lung Cancer Drug Pipeline Update Lists All 243 Drugs for Lung ... Feb 16, 2006 Xeloda Expands Options in Adjuvant Treatment of Breast Cancer ... Feb 21, 2006 AUDIO SUMMARY Feb 22, 2006 Clean-up sparks lifesaving plan Feb 20, 2006 Roche Files Herceptin for Early-Stage HER2-Positive Breast Cancer ... Feb 16, 2006 Sanofi expects Acomplia launch in 06; profits up Feb 24, 2006 COMUNICADO: Roche solicita en Europa la aprobación de Herceptin ... Feb 16, 2006 YM BioSciences reports second quarter 2006 operational and ... Feb 10, 2006 Doctor questions cancer drug safety after death of his wife Feb 11, 2006 UC testing vaccine for prostate cancer Feb 14, 2006 IP Chemotherapy Encouraged for Ovarian Cancer Feb 13, 2006 Bioxel Pharma Completes a Private Placement of $4.7M Feb 16, 2006 YM Biosciences stock up as report says breast cancer drug ... Feb 4, 2006 MRI Contrast Agent Enhances Chemotherapy's Cancer Killing Feb 15, 2006 Aegera initiates third clinical trial for AEG35156 - A targeted ... Feb 15, 2006 Study Confirms Better Quality of Life with Paraplatin® than ... Feb 7, 2006 Bioxel Updates Information on Private Placement Feb 8, 2006 Cytokinetics, Incorporated Reports Fourth Quarter and Year End ... Jan 31, 2006 | ||
| Dosage Forms | TABLET | ||
| Drug_Category | Antipsychotics; Antipsychotics; ATC:N05AH02 | ||
| Absorption | rapid and almost complete | ||
| Interactions | Interactions for Clozapine: The risks of using Clozapine in combination with other drugs have not been systematically evaluated. Pharmacodynamic-related Interactions: The mechanism of Clozapine 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, Clozapine should not be used with other agents having a well-known potential to suppress bone marrow function. Given the primary CNS effects of Clozapine, caution is advised in using it concomitantly with other CNS-active drugs or alcohol. Orthostatic hypotension in patients taking clozapine can, in rare cases (approximately 1 case per 3,000 patients), be accompanied by profound collapse and respiratory and/or cardiac arrest. Some of the cases of collapse/respiratory arrest/cardiac arrest during initial treatment occurred in patients who were being administered benzodiazepines; similar events have been reported in patients taking other psychotropic drugs or even Clozapine by itself. Although it has not been established that there is an interaction between Clozapine and benzodiazepines or other psychotropics, caution is advised when clozapine is initiated in patients taking a benzodiazepine or any other psychotropic drug. Clozapine may potentiate the hypotensive effects of antihypertensive drugs and the anticholinergic effects of atropine-type drugs. The administration of epinephrine should be avoided in the treatment of drug induced hypotension because of a possible reverse epinephrine effect. Pharmacokinetic-related Interactions: Clozapine is a substrate for many CYP 450 isozymes, in particular 1A2, 2D6, and 3A4. The risk of metabolic interactions caused by an effect on an individual isoform is therefore minimized. Nevertheless, caution should be used in patients receiving concomitant treatment with other drugs that are either inhibitors or inducers of these enzymes. Concomitant administration of drugs known to induce cytochrome P450 enzymes may decrease the plasma levels of clozapine. Phenytoin, nicotine, and rifampin may decrease Clozapine plasma levels, resulting in a decrease in effectiveness of a previously effective Clozapine dose. Concomitant administration of drugs known to inhibit the activity of cytochrome P450 isozymes may increase the plasma levels of clozapine. Cimetidine, caffeine, and erythromycin may increase plasma levels of Clozapine, potentially resulting in adverse effects. Although concomitant use of Clozapine and carbamazepine is not recommended, it should be noted that discontinuation of concomitant carbamazepine administration may result in an increase in Clozapine plasma levels. In a study of schizophrenic patients who received clozapine under steady state conditions, fluvoxamine or paroxetine was added in 16 and 14 patients, respectively. After 14 days of co-administration, mean trough concentrations of clozapine and its metabolites, N-desmethylclozapine and clozapine N-oxide, were elevated with fluvoxamine by about three-fold compared to baseline concentrations. Paroxetine produced only minor changes in the levels of clozapine and its metabolites. However, other published reports describe modest elevations (less than two-fold) of clozapine and metabolite concentrations when clozapine was taken with paroxetine, fluoxetine, and sertraline. Therefore, such combined treatment should be approached with caution and patients should be monitored closely when Clozapine is combined with these drugs, particularly with fluvoxamine. A reduced Clozapine dose should be considered. A subset (3%-10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P450 isozyme P450 2D6. Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, the tricyclic antidepressants, and clozapine. These individuals may develop higher than expected plasma concentrations of clozapine when given usual doses. In addition, certain drugs that are metabolized by this isozyme, including many antidepressants (clozapine, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isozyme, and thus may make normal metabolizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interaction. Concomitant use of clozapine with other drugs metabolized by cytochrome P450 2D6 may require lower doses than usually prescribed for either clozapine or the other drug. Therefore, co-administration of clozapine with other drugs that are metabolized by this isozyme, including antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution. | ||
| Toxicity | Not Available | ||
| Organisms Affected | Humans and other mammals | ||
| Chemical IUPAC Name | Not Available | ||
| Chemical Formula | C18H19ClN4 | ||
| Molecular Weight | 326.823 g/mol | ||
| Smiles String | CN1CCN(CC1)C2=C3C=CC=CC3=NC4=C(N2)C=C(C=C4)Cl | ||
| Melting Point | 183-184 °C | ||
| Water Solubility | 11.8 mg/L | ||
| State | Solid | ||
| LogP/Hphobicity | 2.502 | ||
| Isoelectric Point | 7.5 | ||
| Biotransformation | Hepatic | ||
| Half Life | 8 hours (range 4-12 hours) | ||
| Protein Binding [%] | 97% (bound to serum proteins) | ||
| RxList Link | RXlist | ||
| Sponsored links | |||
| Drug Reference |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/clo1089.shtml http://www.drugs.com/cons/Clozapine.html http://www.rxlist.com/cgi/generic3/clozapine.htm | ||
| Drug Type | Approved Drug | ||
| Accession No | APRD00470 | ||
| CAS Registry Number | 5786-21-0 | ||
| KEGG Compound ID | C06924 | ||
| PubChem ID | SID:63934 | ||
| PharmGKB ID | PA449061 | ||
| SwissProt ID | Not Available | ||
| GenBank ID | Not Available | ||
| Drug ID Number [DIN] | 2240669 |
|
Home | About | Cancers | Treatment | Medications Copyright onconews.org 2005. All Rights Reserved. |