Names and pronunciation
(kloz′a-peen) Clozaril, FazaClo ODT, Versacloz
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Drug reference
(kloz′a-peen) Clozaril, FazaClo ODT, Versacloz
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Func. class.: Antipsychotic
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Chem. class.: Tricyclic dibenzodiazepine derivative
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Do not confuse: Clozaril/Colazal cloZAPine/cloNIDine/clofazimine/ clonazePAM/KlonoPIN
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ACTION: Interferes with DOPamine receptor binding with lack of EPS; also acts as an adrenergic, cholinergic, hista- minergic, serotonergic antagonist
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USES: Management of psychotic symp- toms for schizophrenic patients for whom other antipsychotics have failed; recurrent suicidal behavior
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CONTRAINDICATIONS: Hyper- sensitivity, severe granulocytopenia (WBC <3500 before therapy), coma, ileus Precautions: Pregnancy, breastfeeding, children <16 yr, geriatric patients; CV, pul- C monary, cardiac, renal, hepatic disease; seizures, prostatic enlargement, closed- angle glaucoma, stroke
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Black Box Warning: Bone marrow suppres- sion, hypotension, myocarditis, orthostatic hypotension, geriatric patients with demen- tia-related psychosis, seizures, syncope Black Box Warning: Myocarditis: if sus- pected, discontinue use; myocarditis usu- ally occurs during first month of treatment; dyspnea, fever, palpitations, ECG changes Black Box Warning: Seizures: usually occur with higher doses >600 mg/day or dosage change >100 mg/day; do not use in uncontrolled seizure disorder; use cautious- ly in those with a predisposition to seizures • AIMS assessment, blood glucose, CBC differential, glycosylated hemoglobin A1c, LFTs, neurologic function, pregnancy test, serum creatinine, electrolytes, lipid pro- file, prolactin, thyroid function tests, weight Black Box Warning: Bone marrow de- pression: bilirubin, CBC, LFTs monthly; discontinue treatment if WBC <3000- 3500/mm3 or ANC <1500/mm3; test weekly; may resume when normal; if WBC <2000/mm3 or ANC <1000/mm3, discontinue; if agranulocytosis develops, never restart product • Affect, orientation, LOC, reflexes, gait, coordination, sleep pattern disturbances Black Box Warning: Hypotension, bradycardia, syncope: B/P standing and lying; take pulse, respirations q4hr during initial treatment; establish baseline prior to starting treatment; report drops of 30 mm Hg; dizziness, faintness, palpitations, tachycardia on rising • Extrapyramidal symptoms: including akathisia (inability to sit still, no pattern to movements), tardive dyskinesia (bi- zarre movements of the jaw, mouth, tongue, extremities), pseudoparkinson- ism (rigidity, tremors, pill rolling, shuf- fling gait) • Neuroleptic malignant syndrome: tachycardia, seizures, fever, dyspnea, dia- phoresis, increased/decreased B/P; notify prescriber immediately • Beers: avoid in older adults except for schizophrenia, bipolar disorder; increased risk of stroke and cognitive decline • Pregnancy/breastfeeding: no well- controlled studies; use in pregnancy only if benefits outweigh fetal risk; excreted in breast milk; discontinue breastfeeding or discontinue product; EPS may be present in neonates exposed to this product dur- ing third trimester Black Box Warning: To report sore throat, malaise, fever, bleeding, mouth sores; if these occur, CBC should be drawn and product discontinued • That heat stroke may occur in hot weather; to take extra precautions to stay cool • To avoid driving, other hazardous activities; seizures may occur • To notify prescriber if pregnant or if pregnancy is intended; not to breastfeed
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SIDE EFFECTS CNS: Neuroleptic malignant syndrome, sedation, dizziness, headache, seizures, insomnia, dystonia CV: Tachycardia, hypo/hypertension, orthostatic hypotension EENT: Blurred vision GI: Drooling or excessive salivation, constipation, nausea, abdominal dis- comfort, vomiting, anorexia, dry mouth, dyspepsia, hepatotoxicity GU: Urinary abnormalities, incontinence HEMA: Leukopenia, agranulocytosis RESP: Dyspnea, pulmonary embolism SYST: Death among geriatric patients with dementia, aggravation of diabetes mellitus
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INTERACTIONS Increase: CNS depression—CNS depres- sants, psychoactives, alcohol, antihista- mines, opioids, sedative/hypnotics Increase: cloZAPine level—caffeine, cital- opram, FLUoxetine, sertraline, ritonavir, risperiDONE, CYP1A2 inhibitors (fluvox- aMINE), CYP3A4 inhibitors (ketoconazole, erythromycin), CYP2D6 inhibitors Increase: plasma concentration—warfa- rin, digoxin, other highly protein-bound products Increase: QT prolongation—beta-blockers, class IA/III antidysrhythmias, and other drugs that increase QT Increase: hypotension, respiratory, car- diac arrest, collapse—benzodiazepines Increase: bone marrow suppression— antineoplastics, radiation therapy Increase: seizures—lithium Decrease: cloZAPine level—CYP1A2 inducers (carBAMazepine, omeprazole, rifAMPin); PHENobarbital; CYP3A4 inducers Drug/Herb Decrease: cloZAPine action—St. John's wort Drug/Lab Test Increase: cholesterol, blood glucose, triglycerides Decrease: WBC, ANC
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TREATMENT OF OVERDOSE: Lavage; provide an airway; do not induce vomiting HIGH ALERT
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DOSAGE AND ROUTES • Adult: PO 12.5 mg daily or bid; may increase by 25-50 mg/day; over 2 wk; dose >500 mg requires 3 divided doses; do not increase dose more than 2×/wk; max 900 mg/day; if dose is to be discon- tinued, taper over 1-2 wk
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Available forms: Tablets 25, 50, 100, 200 mg; orally disintegrating tablets 12.5, 25, 100, 150, 200 mg; oral suspension 50 mg/mL
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Administer: • May be taken with or without food • Patient-specific registration required before administration (cloZAPine REMS program); if WBC <3500 cells/mm3 or ANC <2000 cells/mm3, therapy should not be started; may only dispense the 7-, 14-, 28-day supply upon receipt of lab report that is appropriate • Check to confirm PO medication swal- lowed; monitor for hoarding or giving of medication to other patients, if hospital- ized; avoid giving patient >7 days’ worth of medication if outpatient • Store in tight, light-resistant container • Orally disintegrating tablet: do not push through foil; leave in foil blister until ready to take, peel back foil, place tablet in mouth; allow to dissolve, swallow; water is not needed • Oral suspension: shake before using; use oral syringe and syringe adapter
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Assess:
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Evaluate: • Therapeutic response: decrease in emotional excitement, hallucinations, delusions, paranoia, reorganization of patterns of thought, speech
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • About symptoms of agranulocytosis and need for blood tests weekly for 6 mo, then q2wk; to report flulike symptoms • That orthostatic hypotension often oc- curs; to rise gradually from sitting or lying position; to avoid hot tubs, hot showers, tub baths; hypotension may occur • To avoid abrupt withdrawal of this product because EPS may result; that product should be withdrawn over 1-2 wk • To avoid OTC preparations (cough, hay fever, cold) unless approved by prescriber because serious product interactions may occur; to avoid use with alcohol or CNS depressants, increased drowsiness may occur • About compliance with product regimen
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PHARMACOKINETICS Bioavailability 27%-47%; 97% protein bound; completely metabolized by liver enzymes involved in metabolism CYP1A2, 2D6, 3A4; excreted in urine (50%), feces (30%) (metabolites); half- life 8-12 hr
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• Adult: PO 12.5 mg daily or bid; may increase by 25-50 mg/day; over 2 wk; dose >500 mg requires 3 divided doses; do not increase dose more than 2×/wk; max 900 mg/day; if dose is to be discon- tinued, taper over 1-2 wk
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