Clozapine: safe prescribing. Diseases & Conditions Clozapine is a highly effective drug for treatment-resistant schizophrenia, however careful monitoring for, and accurate diagnosis of, clozapine-related adverse effects is essential. Controlled studies in pregnant women show no evidence of fetal risk.Demonstrates weak D2-receptor and D1-receptor blocking activity, but noradrenolytic, anticholinergic, antihistaminic, and arousal reaction inhibiting effects are significant; also possesses antiserotoninergic (5-HT1C, 5-HT2, 5-HT3) propertiesAffinity for mesolimbic dopamine D4 receptor accounts for striking effects in control of behavioral and psychiatric symptoms with low incidence of EPS; histamine receptor blockade accounts for increased incidence of sleep disturbancesMetabolized by hepatic P450 enzyme CYP1A2, N-demethylation, N-oxidation, 3'-carbon oxidation, epoxidation of chlorine-containing aromatic ring, substitution of chlorine by hydroxyl or thiomethyl groups, and sulfur oxidation; also CYP2D6 and CYP3A4Minimize risk of orthostatic hypotension, bradycardia, and syncope by using low starting dose, gradual titration schedule, and divided dosagesAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Individual plans may vary Clozaril (clozapine). Delayed-onset distinguishes clozapine-associated hypogammaglobulinaemia from agranulocytosis or neutropenia that occur at lesser frequency. Common side effects include However, many side-effects can be managed and may not warrant discontinuation.Clozapine carries a black box warning for drug-induced agranulocytosis. News The relapse rate is lower and patient acceptability is better.It may be better than other antipsychotics in people with both Clozapine may cause side effects, some of which are serious and potentially fatal. Clozapine … Biomarker searches in treatment-resistant schizophrenia highlight an immune signature associated with long-term clozapine use. It is also used to help reduce the risk of suicidal behavior in people with schizophrenia or similar disorders. Clozapine is often effective for patients with treatment-resistant schizophrenia, however, proactive and co-ordinated … 2010 All generic drug interactions for … This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Your list will be saved and can be edited at any time.The above information is provided for general https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9yZWZlcmVuY2UubWVkc2NhcGUuY29tL2RydWcvY2xvemFyaWwtdmVyc2FjbG96LWNsb3phcGluZS0zNDI5NzI= Therapeutic interventions to treat adverse effects are underused yet may significantly improve the quality of life of patients. Indicated for reducing risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder in patients who are judged to be at chronic risk to re-experience suicidal behaviorAlso indicated for treatment-resistant schizophrenia in patients who fail to respond adequately to standard antipsychotic treatment12.5 mg PO once daily or q12hr initially; increase in increments of 25-50 mg/day, if well tolerated, to achieve target dosage of 300-450 mg/day (administered in divided doses) by end of 2 weeksSubsequently, may increase dose once or twice weekly in increments of up to 100 mg; not to exceed 900 mg/dayMaintenance: Generally, patients who respond should continue maintenance treatment on their effective dose beyond the acute episodeLower initial dosage of 12.5-25 mg/day indicated; may be titrated more slowly than in younger adultsElderly patients, particularly those with compromised cardiovascular functioning, may be more susceptible to orthostatic hypotension and tachycardia; anticholinergic effects are also common (constipation, confusion, urinary retention)Skin: Hypersensitivity reactions: photosensitivity, vasculitis, erythema multiforme, and Stevens-Johnson Syndrome, skin pigmentation disorderMusculoskeletal system: Myasthenic syndrome, rhabdomyolysis, systemic lupus erythematosusRespiratory system: Aspiration, pleural effusion, pneumonia and lower respiratory tract infection (LRTI), which may be fatal, sleep apneaCentral nervous system: Delirium, EEG abnormal, myoclonus, paresthesia, possible cataplexy, status epilepticus, obsessive compulsive symptoms, and post-discontinuation cholinergic rebound adverse reactions, tardive dyskinesia, neuroleptic malignant syndromeCardiovascular: Atrial or ventricular tachycardia or fibrillation, periorbital edema, myocardial infarction, cardiac arrest, QT prolongation, Torsades de pointes, hypertension, mitral valve incompetence, bradycardia, cardiomyopathyGastrointestinal system: Acute pancreatitis, dysphagia, salivary gland swelling, colitis, hypersalivation, dry mouthHepatobiliary: Hepatotoxicity, hepatic steatosis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, liver injury (hepatic, cholestatic, and mixed), and liver failureImmune system disorders: Angioedema, leukocytoclastic vasculitisUrogenital: Renal failure, nocturnal enuresis, acute interstitial nephritis, priapism, retrograde ejaculationHemic and lymphatic system: DVT; elevated hemoglobin/hematocrit, ESR; sepsis, pulmonary embolism, thrombocytosis, thrombocytopenia, angioedema, leukocytoclastic vasculitis, eosinophiliaMiscellaneous: CPK elevation, hyperuricemia, hyponatremia, weight lossHypersensitivity (eg, photosensitivity, vasculitis, erythema multiforme, Stevens-Johnson syndrome)Increased risk of cerebrovascular adverse events reported with some atypical antipsychotics (mechanism unknown)FDA warning regarding off-label use for dementia-related psychosis in elderly patients; increased risk of deathAntipsychotic drugs can cause the potentially fatal symptom complex referred to as neuroleptic malignant syndrome (NMS); if NMS occurs, immediately discontinue antipsychotic drug, and other drugs not essential to therapy; implement intensive symptomatic treatment and medical monitoringPossible QT prolongation; use with caution in patients with history of long QT syndrome or other conditions that may increase risk (eg, hypokalemia, hypomagnesemia)Severe, life threatening, and in some cases fatal hepatotoxicity including hepatic failure, hepatic necrosis, and hepatitis reported in post marketing studies; monitor for appearance of signs and symptoms of hepatotoxicity such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, coagulopathy, and hepatic encephalopathy; perform serum tests for liver injury and consider permanently discontinuing treatment if hepatitis or transaminase elevations combined with other systemic symptoms are due to clozapineTransient fever reported; peak incidence is within first 3 weeks of treatment; although this fever is generally benign and self-limited, it may necessitate discontinuing treatment since fever can be associated with an increase or decrease in WBC count; evaluate patients with fever to rule out severe neutropenia or infection; consider possibility of NMSPulmonary embolism (PE) and DVT reported; unclear whether PE and DVT can be attributed to clozapineThere is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including clozapine, during pregnancy; health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmental health.org/clinical-and-research-programs/pregnancyregistry/Neonates exposed to antipsychotic drugs during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery; overall, available data from published epidemiologic studies of pregnant women exposed to clozapine have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks to the mother associated with untreated schizophrenia and with exposure to antipsychotics, during pregnancyClozapine is present in human milk; there are reports of sedation and a report of agranulocytosis in an infant exposed to clozapine through human milk; there is no information on effects of clozapine on milk production; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on breastfed-child from drug or from underlying maternal conditionInfants exposed to drug should be monitored for excess sedationA: Generally acceptable.