쐽 Iloperidone ꔴ SPECIAL CONCERNS

Transcription

쐽 Iloperidone ꔴ SPECIAL CONCERNS
Iloperidone
쐽 SPECIAL CONCERNS
( EYE -loh- PER -i-done)
Classification(s): Antipsychotic.
RX: Fanapt.
INDICATIONS/USES
Acute treatment of schizophrenia in adults.
NOTE: When deciding whether to prescribe iloperidone, consider the drug is associated with prolongation of the QTc interval.
ACTION/KINETICS
Action
Mechanism is unknown. High affinity for dopamine D2, D3 and serotonin 5-HT2A receptors;
moderate affinity for dopamine D4, serotonin 5HT6 and 7, and norepinephrine NEalpha 1 receptors;
and, low affinity for serotonin 5-HT1A, dopamine
D1, and histamine H1 receptors. Manifests moderate incidence of sedation and orthostatic hypotension and a low incidence of extrapyramidal symptoms, anticholinergic effects, and weight gain.
Pharmacokinetics
Well absorbed; relative bioavailability: 96%. Peak
plasma levels: 2–4 hr. Can be given without regard to meals. Metabolized primarily by three
pathways: carbonyl reduction, hydroxylation (mediated by CYP2D6), and O-demethylation (mediated by CYP3A4); there are both extensive and
poor metabolizers. One of the metabolites (P88)
is active. Excreted in both the urine (about 50%)
and feces (about 20%). t1/2, elimination: 18, 26,
and 23 hr, respectively, for iloperidone, P88, and
P95 (another metabolite) in extensive metabolizers and 33, 37, and 31 hr, respectively, for poor
metabolizers. Plasma protein binding: About
95%.
CONTRAINDICATIONS
Hypersensitivity to iloperidone or any component
of the product. Use with other drugs known to
prolong QTc. Use in those with hepatic impairment, in those with dementia-related psychosis, in
those with congenital long QT syndrome, in
those with a history of cardiac arrhythmias, in
those with a history of significant CV illness (e.g.,
QT prolongation, recent acute MI, uncompensated heart failure). Lactation.
ꔴ (1) Increased mortality in elderly clients
with dementia-related psychosis. Elderly
clients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analysis of 17 placebocontrolled trials (modal duration, 10 weeks),
largely in clients taking atypical antipsychotic
drugs, revealed a risk of death in the drugtreated clients of between 1.6 and 1.7 times
the risk of death in placebo-treated clients.
Over the course of a typical 10-week controlled trial, the rate of death in drug-treated
clients was about 4.5%, compared with a rate
of about 2.6% in the placebo group. Although
the causes of death were varied, most of the
deaths appeared to be either CV (e.g., heart
failure, sudden death) or infectious (e.g.,
pneumonia) in nature. (2) Observational
studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional
antipsychotic drugs may increase mortality.
The extent to which the findings of increased
mortality in observational studies may be attributed to antipsychotic drug as opposed to
some characteristic(s) of the clients is not
clear. (3) Iloperidone is not approved for the
treatment of clients with dementia-related
psychosis. ꔴ
● Use with caution with known CV disease (e.g.,
heart failure, history of MI ischemia, conduction
abnormalities), CV disease, or conditions that
predispose to hypotension (e.g., dehydration, hypovolemia, antihypertensive drugs).
● Use with caution in those at risk for aspiration
pneumonia (e.g., elderly especially those with
advanced Alzheimer’s dementia).
● Those with Parkinson’s disease or dementia have
an increased sensitivity to antipsychotic drugs.
● Use with caution when used with other CNS
drugs and alcohol.
● Safety and efficacy not known in children and
adolescents.
SIDE EFFECTS
Most Common
Dizziness, dry mouth, fatigue, nasal congestion,
somnolence, tachycardia, orthostatic hypotension,
increased weight.
CNS: Dizziness, somnolence, extrapyramidal disorder, tremor, lethargy, tardive dyskinesia, extra-
pyramidal symptoms (akathisia, bradykinesia, dyskinesia, Parkinsonism, tremor), dystonia, pseudoparkinsonism, vertigo, depression (may be significant), seizures, suicide attempt, paresthesia,
psychomotor hyperactivity, restlessness, amnesia,
aggression, delusion, hostility, paranoia, confusional state, mania, catatonia, mood swings, panic
attack, OCD, bulimia nervosa, delirium, psychogenic polydipsia, impulse-control disorder. Impaired judgment, thinking, or motor skills. GI:
Nausea, dry mouth, diarrhea, abdominal discomfort, dysphagia, gastritis, salivary hypersecretion,
fecal incontinence, mouth ulceration, aphthous
stomatitis, duodenal ulcer, esophageal ulcer, esophagitis, hiatal hernia, hyperchlorhydria, lip ulceration, GERD, reflux esophagitis, stomatitis, cholelithiasis. CV: Tachycardia, bradycardia, orthostatic hypotension, hypotension, syncope, palpitations, arrhythmia, first-degree AV block, CHF,
acute cardiac failure. Prolongation of QT interval leading to arrhythmia (including torsades de
pointes and sudden death). NOTE: Elderly
clients with dementia-related psychosis are at an
increased risk of death and CV-related side effects,
including stroke. Respiratory: Nasopharyngitis,
URTI, bronchopneumonia, nasal congestion,
dyspnea, epistaxis, asthma, rhinorrhea, sinus congestion, nasal dryness, dry throat, sleep apnea syndrome, exertional dyspnea. Musculoskeletal: Arthralgia, joint pain, musculoskeletal stiffness, difficulty walking, myalgia, muscle spasms, torticollis,
restless legs syndrome. Dermatologic: Rash, skin
pigmentation (especially in women on long-term
therapy). GU: Ejaculation failure, priapism, decreased/loss of libido, anorgasmia, urinary incontinence, dysuria, pollakiuria, enuresis, nephrolithiasis, urinary retention, acute renal failure, erectile dysfunction, testicular pain, amenorrhea,
breast pain, irregular menses, gynecomastia, menorrhagia, metrorrhagia, menstrual irregularities,
urinary retention, postmenopausal hemorrhage,
prostatitis. Metabolic/Endocrine: Hyperglycemia, diabetes mellitus, hypothyroidism. Hematologic: Leukopenia, neutropenia, anemia, iron deficiency anemia, thrombocytopenia, agranulocytosis. Ophthalmic: Blurred vision, conjunctivitis
(including allergic), dry eyes, blepharitis, eyelid
edema, eye swelling, lenticular/corneal opacities,
cataract, hyperemia, nystagmus. Otic: Tinnitus.
Body as a whole: Fatigue, weight gain/loss, edema, thirst, hyperthermia, dehydration, fluid reten-
tion. Miscellaneous: Neuromalignant syndrome
(including symptoms of hyperpyrexia, muscle rigidity, altered mental status, catatonic signs, irregular pulse or BP, tachycardia, diaphoresis, cardiac
dysrhythmia, rhabdomyolysis, acute renal failure).
Disruption of control of body temperature, increased appetite.
LABORATORY TEST CONSIDERATIONS
e Neutrophils. a H&H. Hyperprolactinemia, hypokalemia.
DRUG INTERACTIONS
Amiodarone / Prolongation of QTc interval c cardiac arrhythmias, including torsades de pointes;
use together contraindicated
Chlorpromazine / Prolongation of QTc interval c
cardiac arrhythmias, including torsades de
pointes; use together contraindicated
Fluoxetine / e Iloperidone blood levels R/T inhibition of CYP2D6
Gatifloxacin / Prolongation of QTc interval c cardiac arrhythmias, including torsades de pointes;
use together contraindicated
Ketoconazole / e Iloperidone blood levels R/T inhibition of CYP3A4
Methadone / Prolongation of QTc interval c cardiac arrhythmias, including torsades de pointes;
use together contraindicated
Moxifloxacin / Prolongation of QTc interval c
cardiac arrhythmias, including torsades de
pointes; use together contraindicated
Paroxetine / e Iloperidone blood levels R/T inhibition of CYP2D6
Pentamidine / Prolongation of QTc interval c
cardiac arrhythmias, including torsades de
pointes; use together contraindicated
Procainamide / Prolongation of QTc interval c
cardiac arrhythmias, including torsades de
pointes; use together contraindicated
Quinidine / Prolongation of QTc interval c cardiac arrhythmias, including torsades de pointes; use
together contraindicated
Sotalol / Prolongation of QTc interval c cardiac
arrhythmias, including torsades de pointes; use together contraindicated
Thioridazine / Prolongation of QTc interval c
cardiac arrhythmias, including torsades de
pointes; use together contraindicated
HOW SUPPLIED
Tablets: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg,
12 mg.
DOSAGE
TABLETS
Schizophrenia in adults.
Adults, initial: 1 mg twice a day on
day 1; then, 2, 4, 6, 8, 10, and 12 mg
twice a day on days, 2, 3, 4, 5, 6, and 7
respectively. Maintenance: 6–12 mg
twice a day. Maximum dose: 12 mg
twice a day (i.e., 24 mg/day). No data
are available to determine the length of
treatment; however, those responding
should be continued beyond the acute
response. Periodically reassess to determine the need for continued treatment.
NURSING IMPLICATIONS
IMPLEMENTATION/ADMINISTRATION/STORAGE
1. Dosage adjustment is not routinely indicated
on the basis of age, gender, race, or renal impairment.
2. Can be given without regard to meals.
3. Titrate slowly from a starting dose to avoid orthostatic hypotension (iloperidone is an alpha-adrenergic blocker).
4. Clients must be titrated to an effective dose.
Thus, control of symptoms may be delayed
during the first 1–2 weeks of therapy compared with some other antipsychotic drugs
that do not require similar titration.
5. Reduce the dose of iloperidone by one-half if
coadministered with strong CYP2D6 inhibitors
(e.g., fluoxetine, paroxetine). When the
CYP2D6 inhibitor is withdrawn, increase the iloperidone dose to where it was before.
6. Reduce the dose of iloperidone by one-half if
coadministered with strong CYP3A4 inhibitors
(e.g., clarithromycin, ketoconazole). When the
CYP3A4 inhibitor is withdrawn, increase the iloperidone dose to where it was before.
7. Poor metabolizers of CYP2D6 have a higher
exposure to iloperidone compared with extensive metabolizers. Laboratory tests can determine CYP2D6 poor metabolizers.
8. Whenever a client has had an interval of more
than 3 days off iloperidone, reinitiate using a
titration schedule.
9. When switching from other antipsychotics,
immediate discontinuation may be appropri-
ate for some clients but not others. In all
cases, the period of overlapping medications
should be minimized.
10. Store from 15–30°C (59–86°F). Protect from
light and moisture.
ASSESSMENT
1. Note reasons for therapy, clinical, and behavioral manifestations, other agents trialed and
outcome.
2. Assess for any history of CVD, QT prolongation, arrhythmias, or dementia related psychosis.
3. Monitor VS, ECG, weight, CBC, K+, Mg++, BS,
renal and LFTs.
CLIENT/FAMILY TEACHING
1. Review dosing guidelines and take as prescribed with or without food. Drug is started at
a low dose and titrated up slowly to prevent
sudden drop in BP.
2. Avoid activities that require mental alertness
until drug effects realized; may impair judgment, thinking, or motor skills.
3. Change positions slowly to prevent a sudden
drop in BP. Hot tubs, hot showers, or baths
may aggravate dizziness.
4. Practice reliable contraception, report if pregnancy suspected.
5. May alter temperature regulation. Avoid alcohol, CNS depressants, OTC agents, strenuous
exercise, overheating, or dehydration.
6. Report any suicide ideations, change in ability
to interact or increased psychosis.
7. Any S&S of NMS (neuroleptic malignant syndrome): increased temperature, muscle rigidity, irregular heart rate/BP, arrhythmias, or severe diaphoresis require immediate attention.
8. Report any movements that become involuntary, slow, repetitive, rhythmical (tardive dyskinesia) in select or groups of muscles; may
become irreversible.
9. Keep all F/U to assess response and for adverse SE.
OUTCOMES/EVALUATE
● Improvement in PANSS and DSM III/IV-TR
schizophrenia criteria
● Improved behavioral and emotional presentation
● a Delusions/suspiciousness and hostility