Functional class
Func. class.: Antipsychotic
PDF page 581
Loading InternPractice…
Drug reference
Func. class.: Antipsychotic
PDF page 581
Chem. class.: Phenothiazine, piperazine
PDF page 581
ACTION: Depresses cerebral cortex, hypothalamus, limbic system, which con- trol activity and aggression; blocks neu- rotransmission produced by DOPamine at synapse; exhibits strong α-adrenergic and anticholinergic blocking action; mechanism for antipsychotic effects is unclear
PDF page 581
USES: Schizophrenia
PDF page 581
CONTRAINDICATIONS: Hyper- sensitivity, blood dyscrasias, coma, bone marrow depression Precautions: Pregnancy, breastfeeding, children <12 yr, geriatric patients, seizure disorders, hypertension, cardiac/hepatic disease, abrupt discontinuation, acciden- tal exposure, agranulocytosis, ambient temperature increase, angina, hypersensi- tivity to benzyl alcohol/parabens/sesame oil/tartrazine dye, QT prolongation, sui- cidal ideation, renal failure, Parkinson’s disease, hypocalcemia, head trauma, prostatic hypertrophy, pulmonary disease, F infection, ileus, chemotherapy, breast cancer
PDF page 581
Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis Black Box Warning: Beers: avoid in old- er adults except for schizophrenia, bipo- lar disorder, or short-term use as an an- tiemetic during chemotherapy; increased risk of stroke, cognitive decline, mortality • Pregnancy/breastfeeding: no well- controlled studies; use only if benefits outweigh fetal risk; may cause EPS in in- fant if used during 3rd trimester; ex- creted in breast milk
PDF pages 581, 583
SIDE EFFECTS CNS: EPS: pseudoparkinsonism, aka thisia, dystonia, tardive dyskinesia, drowsiness, headache, seizures, neuro- leptic malignant syndrome CV: Orthostatic hypotension, hyperten- sion, cardiac arrest, ECG changes, tachycardia EENT: Blurred vision, glaucoma, dry eyes, nasal congestion GI: Dry mouth, nausea, vomiting, anorexia, constipation, diarrhea, jaundice, weight gain, paralytic ileus, hepatitis, cholecystic jaundice GU: Urinary retention, urinary frequency, enuresis, impotence, amenorrhea, gynecomastia HEMA: Anemia, leukopenia, leukocytosis, agranulocytosis, aplastic anemia, throm bocytopenia INTEG: Rash, photosensitivity, dermatitis, hyperpigmentation (long-term use) RESP: Laryngospasm, dyspnea, respira- tory depression
PDF page 582
INTERACTIONS Increase: QT prolongation, torsades de pointes (at higher doses)—amiodarone, arsenic trioxide, astemizole, dasatinib, disopyramide, dofetilide, droperidol, erythromycin, flecainide, gatifloxacin, ibutilide, levomethadyl, ondansetron, paliperidone, palonosetron, some anti- depressants, vorinostat, ziprasidone, haloperidol, phenothiazines, ARIPipra- zole, lurasidone Increase: sedation—other CNS depres- sants, alcohol, barbiturate anesthetics, haloperidol, metyrosine, risperiDONE Increase: toxicity—EPINEPHrine Increase: anticholinergic effects— anticholinergics Decrease: effects of levodopa, lithium Decrease: fluPHENAZine effects—smok- ing, barbiturates Drug/Lab Test Increase: LFTs, cardiac enzymes, choles- terol, blood glucose, prolactin, bilirubin, cholinesterase Decrease: hormones (blood and urine) False positive: pregnancy tests, PKU uri- nary steroids, 17-OHCS
PDF page 582
TREATMENT OF OVERDOSE: Lavage; if orally ingested, provide an air- way; do not induce vomiting See Appendix B See Appendix B
PDF page 583
DOSAGE AND ROUTES Decanoate • Adult and child >12 yr: IM/SUBCUT 12.5-25 mg q1-3wk, may increase slowly, max 100 mg/dose HCl • Adult: PO 2.5-10 mg in divided doses q6-8hr, max 40 mg/day; IM initially 1.25 mg, then 2.5-10 mg in divided doses q6-8hr
PDF page 581
Available forms: Decanoate: inj 25, 100 mg/mL; HCl: tabs 1, 2.5, 5, 10 mg; inj 2.5 mg/mL; elixir 2.5 mg/5 mL; oral solution 5 mg/mL
PDF page 581
Administer: PO route • Give with food, milk, or a full glass of water to minimize gastric irritation • Oral concentrate: Give using a cali- brated measuring device; dilute just before use with 120-240 mL of water, saline, milk, 7-Up, carbonated orange beverage, or apricot, orange, pineapple, prune, tomato, or V-8 juice; do not mix with beverages containing caffeine (coffee, cola), tannics (tea), or pectinates (apple juice) or with other liquid medications; avoid spilling the solution on the skin and clothing • Oral elixir: Give using a calibrated measuring device; avoid spilling the solu- tion on the skin and clothing Injectable routes • Visually inspect for particulate matter and discoloration before use, slight yel- low to amber color does not alter po- tency, markedly discolored solutions should be discarded, protect from light IM route (fluPHENAZine HCl only) • No dilution necessary; if irritation oc- curs, subsequent IM doses may be diluted with NS for injection or 2% procaine • Inject slowly and deeply into the upper outer quadrant of the gluteal muscle us- ing a dry syringe and needle, aspirate before injection • Keep patient in a recumbent position ≥30 min following injection to minimize hypotensive effects • Rotate the site of injection to avoid irritation or sterile abscess formation with repeat use IM injection (fluPHENAZine decanoate) • Use syringe and needle of at least 21-G, do not dilute • Inject slowly and deeply into the upper outer quadrant of the gluteal muscle, aspirate • Keep patient in a recumbent position for at least 30 min following the initial injection to minimize hypotensive effects; rotate the site of injection to avoid irrita- tion or sterile abscess formation with repeat administration Subcut injection route (fluPHENAZine decanoate) • Use a dry syringe and a needle of at least 21-G, do not dilute • Inject subcut, taking care not to inject intradermally • Keep patient in a recumbent position for at least 30 min following the initial injection to minimize hypotensive effects; rotate the injection sites
PDF pages 581, 582
Assess: • QT prolongation, torsades de pointes: ECG for changes • Bilirubin, CBC, LFTs monthly; ophthal- mic exams periodically • Urinalysis recommended before and during prolonged therapy • Affect, orientation, LOC, reflexes, gait, coordination, sleep pattern distur- bances • B/P standing and lying; pulse and res- pirations q4hr during initial treatment; establish baseline before starting treat- ment; report drops of 30 mm Hg • Dizziness, faintness, palpitations, tachycardia on rising • EPS including akathisia (inability to sit still, no pattern to movements), tardive dyskinesia (bizarre movements of jaw, mouth, tongue, extremities), pseudopar- kinsonism (rigidity, tremors, pill rolling, shuffling gait) • Anticholinergic effects: constipation, urinary retention daily; if these occur, increase bulk, water in diet • Supervised ambulation until stabilized on medication; do not involve patient in strenuous exercise; fainting possible; pa- tient should not stand still for long periods
PDF page 583
Evaluate: • Therapeutic response: decrease in emotional excitement, hallucinations, delusions, paranoia, reorganization of patterns of thought, speech
PDF page 583
CLINICAL CONSIDERATIONS
PDF page 583
Patient and caregiver information: • That orthostatic hypotension occurs often; to rise from sitting or lying position gradually; to avoid hazardous activities until stabilized on medication • To avoid hot tubs, hot showers, tub baths because hypotension may occur; that in hot weather, heat stroke may occur; to take extra precautions to stay cool • To avoid abrupt withdrawal of this prod- uct or EPS may result; that product should be withdrawn slowly • To avoid OTC preparations (cough, hay F fever, cold) unless approved by pre- scriber; that serious product interactions may occur; to avoid use with alcohol, CNS depressants; that increased drowsi- ness may occur • To use a sunscreen to prevent burns • About the importance of compliance with product regimen, follow-up, lab, ophthalmic exams • About EPS; about the need for meticu- lous oral hygiene because oral candidia- sis may occur • To report sore throat, malaise, fever, bleeding, mouth sores; if these occur, CBC should be drawn, product discon- tinued • That urine may turn pink to reddish brown
PDF page 583
PHARMACOKINETICS Metabolized by liver, excreted in urine (metabolites), crosses placenta, enters breast milk, protein binding >90%, not dialyzable PO/IM (HCl): Onset 1 hr, peak 90-120 min, duration 6-8 hr, half-life 15 hr IM/SUBCUT (decanoate): Onset 1-3 days; peak 1-2 days, duration over 4 wk, single-dose half-life 7-10 days, multiple dose 14.3 days
PDF page 582
• Adult and child >12 yr: IM/SUBCUT 12.5-25 mg q1-3wk, may increase slowly, max 100 mg/dose HCl
PDF page 581
• Adult: PO 2.5-10 mg in divided doses q6-8hr, max 40 mg/day; IM initially 1.25 mg, then 2.5-10 mg in divided doses q6-8hr
PDF page 581