{"id":11699,"date":"2018-07-14T17:41:29","date_gmt":"2018-07-14T14:41:29","guid":{"rendered":"http:\/\/seragpsych.com\/wordpress\/?p=11699"},"modified":"2018-07-14T17:41:29","modified_gmt":"2018-07-14T14:41:29","slug":"clozapine","status":"publish","type":"post","link":"https:\/\/seragpsych.com\/wordpress\/clozapine\/","title":{"rendered":"CLOZAPINE"},"content":{"rendered":"<p><span style=\"font-weight: 400;\">Clozapine<\/span><br style=\"font-weight: 400;\" \/><br style=\"font-weight: 400;\" \/><\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">What&#8217;s of Interest:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Clozapine REMS and ANC monitoring update<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Brands<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Clozaril, Leponex, Versacloz (oral suspension), Fazaclo ODT (oral disintegrating tablet)<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter wp-image-11700 size-full\" src=\"http:\/\/seragpsych.com\/wordpress\/wp-content\/uploads\/2018\/07\/klozapin.jpg\" alt=\"\" width=\"299\" height=\"299\" srcset=\"https:\/\/seragpsych.com\/wordpress\/wp-content\/uploads\/2018\/07\/klozapin.jpg 299w, https:\/\/seragpsych.com\/wordpress\/wp-content\/uploads\/2018\/07\/klozapin-150x150.jpg 150w\" sizes=\"auto, (max-width: 299px) 100vw, 299px\" \/><\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Class<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Atypical antipsychotic (serotonin-dopamine antagonist; second-generation antipsychotic; also a mood stabilizer)<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Approved For:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Treatment-resistant schizophrenia<\/li>\n<li style=\"font-weight: 400;\">\u00a0 Reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Formulation:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Tablet 12.5 mg, 25 mg scored, 50 mg, 100 mg scored<\/li>\n<li style=\"font-weight: 400;\">Orally disintegrating tablet 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg<\/li>\n<li style=\"font-weight: 400;\">Oral suspension 50 mg\/mL<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Dosing Tips:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Initial 25 mg at night; increase by 25\u201350 mg\/day every 48\u201372 hours as tolerated; obtain trough plasma level on 200 mg at bedtime<\/li>\n<li style=\"font-weight: 400;\">The threshold for response is 350 ng\/mL<\/li>\n<li style=\"font-weight: 400;\">Median time to response after achieving therapeutic plasma levels of (350 ng\/mL) is approximately 3 weeks; if there is no response after 3 weeks of therapeutic plasma levels, recheck plasma levels and continue titration<\/li>\n<li style=\"font-weight: 400;\">Levels greater than 700 ng\/mL are often not well tolerated<\/li>\n<li style=\"font-weight: 400;\">No evidence to support dosing that results in plasma levels greater than 1,000 ng\/mL<\/li>\n<li style=\"font-weight: 400;\">Plasma half-life suggests twice daily administration, but in practice, it may be given once a day at night<\/li>\n<li style=\"font-weight: 400;\">Doses greater than 500 mg per day may require a split dose<\/li>\n<li style=\"font-weight: 400;\">Because of the monitoring schedule, prescriptions are generally given 1 week at a time for the first 6 months, then every 2 weeks for months 6\u201312, and then monthly after 12 months<\/li>\n<li style=\"font-weight: 400;\">Lower ANC threshold for starting clozapine:<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>General population: \u22651,500\/\u00b5L<\/li>\n<li>Benign ethnic neutropenia (BEN): \u22651,000\/\u00b5L<\/li>\n<li><\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">If treatment is discontinued for more than 2 days, reinitiate with 12.5 mg once or twice daily; if that dose is tolerated, the dose may be increased to the previously therapeutic dose more quickly than recommended for initial treatment<\/li>\n<li style=\"font-weight: 400;\">If abrupt discontinuation of clozapine is necessary, the patient must be covered for cholinergic rebound; those with higher clozapine plasma levels may need extremely high doses of anticholinergic medications to prevent delirium and other rebound symptoms<\/li>\n<li style=\"font-weight: 400;\">Slow off-titration is preferred if possible to avoid cholinergic rebound and rebound psychosis<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Contraindications:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">In patients with a myeloproliferative disorder<\/li>\n<li style=\"font-weight: 400;\">In patients with uncontrolled epilepsy<\/li>\n<li style=\"font-weight: 400;\">In patients with paralytic ileus<\/li>\n<li style=\"font-weight: 400;\">In patients with CNS depression<\/li>\n<li style=\"font-weight: 400;\">If there is a proven allergy to clozapine<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>NOTE THAT<\/p>\n<p>&nbsp;<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 Clozapine is the gold standard treatment for refractory schizophrenia<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 Clozapine is not used the first line due to side effects and monitoring burden<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 In strictly-defined refractory schizophrenia, 50-60% of patients will respond to clozapine<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 The response rate to another atypical antipsychotic in the refractory patient population ranges from 0\u20139%<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 May reduce violence and aggression in difficult cases, including forensic cases<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 Reduces suicide in schizophrenia<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 May reduce substance abuse<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 Little or no prolactin elevation, motor side effects, or tardive dyskinesia<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 Cigarette smoke can decrease clozapine levels and patients may be at risk for relapse if they begin or increase smoking<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 The US FDA has changed the requirements for monitoring, prescribing, dispensing, and receiving clozapine in order to address concerns related to neutropenia; in addition to updating the prescribing information for clozapine, the FDA has approved a new, shared risk evaluation and mitigation strategy (REMS)<\/p>\n<p class=\"BodyText1\">\u2022\u00a0 The Clozapine REMS program replaces the six existing clozapine registries, which are maintained by individual clozapine manufacturers. Prescribers, pharmacies, and patients will now be required to enroll in a single centralized program; patients already treated with clozapine will be automatically transferred. In order to prescribe and dispense clozapine, prescribers and pharmacies will be required to be certified in the Clozapine REMS Program.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\"><span style=\"font-style: inherit; font-weight: inherit;\">Side Effects<\/span><\/strong><\/b><\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Weight Gain:<\/strong><\/b><\/p>\n<p style=\"font-weight: 400;\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-thumbnail wp-image-11702\" src=\"http:\/\/seragpsych.com\/wordpress\/wp-content\/uploads\/2018\/07\/weight_scale_800x600-150x150.jpg\" alt=\"\" width=\"150\" height=\"150\" \/><\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Sedation:<\/strong><\/b><\/p>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">\u00a0Other Notable or Dangerous Side Effects:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Orthostasis<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Slow titration<\/li>\n<li>Minimize use of other alpha 1 antagonists<\/li>\n<li>If orthostasis remains a problem, Florines 0.1\u20130.3 mg qd for volume expansion (contraindicated in congestive heart failure)<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Sialorrhea<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Atropine 1% drops, 1\u20133 drops sublingually at bedtime; can use up to 3 times per day if needed<\/li>\n<li>Ipratropium bromide 0.06% spray, 1\u20133 sprays intra-orally at bedtime; can use up to 3 times per day if needed<\/li>\n<li>Avoid use of systemic anticholinergic agents, which increase risk of ileus (benztropine, glycopyrrolate, etc.)<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Constipation, paralytic ileus<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Avoid psyllium as it may worsen symptoms<\/li>\n<li>All patients should receive docusate 250 mg when starting clozapine<\/li>\n<li>If needed, add Miralax 17 g<\/li>\n<li>If docusate + Miralax are ineffective, add either bisacodyl or sennosides<\/li>\n<li>If constipation still remains a problem, prescribe lubiprostone 8\u201324 mcg twice per day<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Sedation<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Slow titration<\/li>\n<li>Take at bedtime<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Tachycardia<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Atenolol 12.5 mg QD, increase to keep resting HR&lt;100 bpm<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Weight gain and metabolic effects<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Consider prophylactic metformin; start at 500 mg for 1 week, then increase dose<\/li>\n<li>All patient should be referred for lifestyle management and exercise<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Myocarditis (rare; occurs only in the first 6 weeks of treatment)<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Baseline: check troponin I\/T, CRP<\/li>\n<li>Obtain workup if patient reports chest pain<\/li>\n<li>Weekly troponin I\/T and CRP for the first month<\/li>\n<li>Clozapine should be stopped if troponin \u2265 2x ULN or CRP &gt; 100 mg\/L<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Benign fever (~20%)<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>In the absence of elevated troponin and myocarditis symptoms, fever is usually self-limited and there is no need to stop clozapine<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Seizures<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Valproate for myoclonic or generalized seizures<\/li>\n<li>Avoid phenytoin and carbamazepine because of kinetic interactions<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Pulmonary embolism (may include deep vein thrombosis or respiratory symptoms)<\/li>\n<li style=\"font-weight: 400;\">Dilated cardiomyopathy<\/li>\n<\/ul>\n<ul style=\"font-weight: 400;\">\n<li>Late complication; consider annual echocardiogram<\/li>\n<\/ul>\n<ul>\n<li style=\"font-weight: 400;\">Increased risk of death and cerebrovascular events in elderly patients with dementia-related psychosis<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">Drug Interactions:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Use clozapine plasma levels to guide treatment due to a propensity for drug interactions<\/li>\n<li style=\"font-weight: 400;\">In presence of a strong CYP450 1A2 inhibitor (e.g., fluvoxamine, ciprofloxacin): use 1\/3 the dose of clozapine<\/li>\n<li style=\"font-weight: 400;\">In the presence of a strong CYP450 1A2 inducer (e.g., cigarette smoke), clozapine plasma levels are decreased<\/li>\n<li style=\"font-weight: 400;\">May need to decrease clozapine dose by up to 50% during periods of extended smoking cessation (&gt;1 week)<\/li>\n<li style=\"font-weight: 400;\">Strong CYP450 2D6 inhibitors (e.g., bupropion, duloxetine, paroxetine, fluoxetine) can raise clozapine levels; dose adjustment may be necessary<\/li>\n<li style=\"font-weight: 400;\">Strong CYP450 3A4 inhibitors (e.g., ketoconazole) can raise clozapine levels; dose adjustment may be necessary<\/li>\n<li style=\"font-weight: 400;\">Clozapine may enhance the effects of antihypertensive drugs<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">\u00a0Cardiac Impairment:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Should be used with caution, particularly if the patient is taking concomitant antihypertensive or alpha 1 antagonist<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">\u00a0Renal Impairment:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Should be used with caution<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n<p style=\"font-weight: 400;\"><b><strong style=\"font-style: inherit;\">\u00a0Hepatic Impairment:<\/strong><\/b><\/p>\n<ul>\n<li style=\"font-weight: 400;\">Should be used with caution<\/li>\n<\/ul>\n<p style=\"font-weight: 400;\">\n","protected":false},"excerpt":{"rendered":"<p>Clozapine What&#8217;s of Interest: Clozapine REMS and ANC monitoring update Brands Clozaril, Leponex, Versacloz (oral suspension), Fazaclo ODT (oral disintegrating tablet) Class Atypical antipsychotic (serotonin-dopamine antagonist; second-generation antipsychotic; also a mood stabilizer) Approved For: Treatment-resistant schizophrenia \u00a0 Reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder &nbsp; &nbsp; Formulation: Tablet [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":11701,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,1572,152],"tags":[],"class_list":["post-11699","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-6","category-explain-medication","category-152","entry"],"_links":{"self":[{"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/posts\/11699","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/comments?post=11699"}],"version-history":[{"count":1,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/posts\/11699\/revisions"}],"predecessor-version":[{"id":11703,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/posts\/11699\/revisions\/11703"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/media\/11701"}],"wp:attachment":[{"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/media?parent=11699"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/categories?post=11699"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/seragpsych.com\/wordpress\/wp-json\/wp\/v2\/tags?post=11699"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}