Names and pronunciation
(kloe-na′zi-pam) KlonoPIN, Rivotril
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Drug reference
(kloe-na′zi-pam) KlonoPIN, Rivotril
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Func. class.: Anticonvulsant
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Chem. class.: Benzodiazepine derivative Controlled Substance Schedule IV
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Do not confuse: clonazePAM/LORazepam/cloNIDine KlonoPIN/cloNIDine
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ACTION: Inhibits spike, wave forma- tion during absence seizures (petit mal); decreases amplitude, frequency, dura- tion, spread of discharge during minor motor seizures
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USES: Absence, atypical absence, aki- netic, myoclonic seizures; Lennox-Gastaut syndrome, panic disorder
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity to benzodiazepines, acute closed-angle glaucoma, psychosis, severe hepatic disease Precautions: Breastfeeding, geriatric patients, open-angle glaucoma, chronic respiratory disease, renal/hepatic disease
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Black Box Warning: Coadministration with other CNS depressants, especially opiates Black Box Warning: Increase: CNS depression—alcohol, barbiturates, opiates, antidepressants, other anticonvulsants, general anesthetics, hypnotics, sedatives Decrease: clonazePAM effect—CYP3A4 inducers (carBAMazepine, PHENobarbi- tal, phenytoin); monitor effect Drug/Herb Black Box Warning: Increase: CNS de- pression—kava, chamomile, valerian Increase: clonazePAM effect—ginkgo, melatonin Decrease: clonazePAM effect—ginseng, St. John’s wort Drug/Lab Test Increase: AST, alkaline phosphatase, bilirubin Decrease: platelets, WBC Black Box Warning: Coadministration with other CNS depressants, espe- cially opioids: increased risk of sedation causing death with benzodiazepines and opioids • Beers: may be appropriate in older adults for seizure disorders, rapid eye movement sleep disorder, benzodiaze- pine/ethanol withdrawal; avoid in those with delirium or at high risk of delirium Black Box Warning: Coadministration with other CNS depressants, especial- ly opioids: to avoid driving, other activi- ties that require alertness • To take as prescribed, not to skip or take double doses, provide “Medication Guide” • To avoid driving and other hazardous activities until response is known • ODT: open when ready to use, peel foil back with dry hands, place on tongue to dissolve • To avoid alcohol, other CNS depres- sants; increased sedation may occur • Not to discontinue medication quickly after long-term use; to taper off over several weeks • To notify prescriber of yellowing of skin/eyes, clay-colored stools, bleeding, fever, extreme fatigue, sore throat, sui- cidal thoughts/behaviors • Pregnancy/breastfeeding: to notify prescriber if pregnancy is planned or suspected or if breastfeeding, to register with North American Antiepileptic Drug Pregnancy Registry (888-233-2334) if pregnant, not to use during pregnancy/ breastfeeding
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SIDE EFFECTS CNS: Drowsiness, dizziness, confusion, behavioral changes, tremors, insomnia, headache, suicidal tendencies, slurred speech, fatigue CV: Palpitations, bradycardia EENT: Nystagmus, diplopia GI: Nausea, constipation, anorexia, diarrhea GU: Dysuria, enuresis, nocturia, reten- tion, libido changes HEMA: Anemia, thrombocytopenia, leukopenia INTEG: Rash RESP: Congestion, respiratory depres- sion
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INTERACTIONS Increase: clonazePAM effects—CYP3A4 inhibitors (azoles, cimetidine, clarithro- mycin, diltiazem, erythromycin, FLUox- etine), oral contraceptives; adjust dosage
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TREATMENT OF OVERDOSE: Lavage, flumazenil, monitor electrolytes, VS, administer vasopressors, sodium bicarbonate
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DOSAGE AND ROUTES Lennox-Gastaut syndrome/atypical absence seizures/akinetic and myclonic seizures • Adult: PO up to 1.5 mg/day in 3 divided doses; may be increased 0.5-1 mg q3days until desired response, max 20 mg/day • Geriatric: PO 0.25 daily-bid initially, increase by 0.25/day q7-14days as needed • Child ≤10 yr or ≤30 kg: PO initial 0.01-0.03 mg/kg/day in divided doses q8hr, max 0.05 mg/kg/day; may be in- creased 0.25-0.5 mg q3days until desired response, max 0.1-0.2 mg/kg/day Panic disorder • Adult: PO 0.25 mg bid, increase to 1 mg daily after 3 days, max 4 mg/day
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Available forms: Tablets 0.5, 1, 2 mg; orally disintegrating tablets 0.125, 0.25, 0.5, 1, 2 mg
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Administer: PO route • With food, milk for GI symptoms • Orally disintegrating tablets: open pouch by peeling back foil on blister pack (do not push tablet through foil), place on tongue, allow to dissolve; may be swal- lowed with/without water • Store at room temperature
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Assess: • Seizures: monitor duration, type, in- tensity, with/without aura • Blood studies: RBC, Hct, HB, reticulo- cyte counts periodically • Hepatic studies: ALT, AST, bilirubin, creatinine • Abrupt discontinuation: do not dis- continue abruptly; seizures may increase • Signs of physical withdrawal if medi- cation suddenly discontinued • Mental status: mood, sensorium, af- fect, oversedation, behavioral changes, suicidal thoughts/behaviors; if mental status changes, notify prescriber • Allergic reaction: red, raised rash; product should be discontinued • Blood dyscrasias: fever, sore throat, bruising, rash, jaundice • Toxicity: bone marrow depression, nausea, vomiting, ataxia, diplopia, CV col- lapse; drug levels during initial treatment (therapeutic 20-80 ng/mL)
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Evaluate: • Therapeutic response: decreased sei- zure activity
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To carry emergency ID bracelet stating name, products taken, condition, pre- scriber’s name, phone number • About potential drug tolerance, with- drawal symptoms • To continue with follow-up exams, lab work
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PHARMACOKINETICS PO: Peak 1-2 hr, metabolized by liver, C excreted in urine, half-life 18-50 hr, duration 6-12 hr, protein binding 85%
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• Child ≤10 yr or ≤30 kg: PO initial 0.01-0.03 mg/kg/day in divided doses q8hr, max 0.05 mg/kg/day; may be in- creased 0.25-0.5 mg q3days until desired response, max 0.1-0.2 mg/kg/day Panic disorder
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