ILOPERIDONE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Atypical antipsychotic (serotonin– dopamine antagonist; second-generation antipsychotic; also a mood stabilizer)

ILOPERIDONE commonly prescribed for

(Bold for FDA approved)

How ILOPERIDONE works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms

• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms

• Blockade of central alpha 1 adrenergic receptors may contribute to low potential for drug-induced parkinsonism

How long until ILOPERIDONE works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition

• Slow titration may delay antipsychotic effects during the first 1 to 2 weeks compared to some other antipsychotic drugs that do not require similar titration

• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients may require up to 16–20 weeks to show a good response, especially on negative or cognitive symptoms

Notable Side Effects

• Orthostatic hypotension

• Sedation, dose-dependent dizziness, fatigue

• Dry mouth, nasal congestion

• Dose-dependent weight gain

• May increase risk for diabetes and dyslipidemia

• Dose-dependent tachycardia

• Tardive dyskinesia (reduced risk compared to conventional antipsychotics)

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

Life Threatening Side Effects

• Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking atypical antipsychotics

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

• Rare seizures

weight gain

common

sedation

common

What to do about ILOPERIDONE side effects

• Wait

• Wait

• Wait

• Anticholinergics may reduce drug-induced parkinsonism when present

• Beta blockers, benzodiazepines, or serotonin 2A antagonists may reduce akathisia

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

• Switch to another atypical antipsychotic

usual dosage range

• 12–24 mg/day in 2 divided doses

Dosage Forms

• Tablet 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg

long term use

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Dose adjustment not generally necessary

Hepatic Impairment

• Not recommended for patients with hepatic impairment

Cardiac Impairment

• Use in patients with cardiac impairment has not been studied, so use with caution because of risk of orthostatic hypotension

• Use with caution if patient is taking concomitant antihypertensive or alpha 1 antagonist

• Not recommended for patients with significant cardiovascular illness

Elderly

• Some patients may tolerate lower doses better

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

• Consider pimavanserin for dementiarelated psychosis or Parkinson’s disease psychosis instead of an atypical antipsychotic

Children and Adolescents

Safety and efficacy have not been established

• Children and adolescents using iloperidone may need to be monitored more often than adults and may tolerate lower doses better

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• When administered to pregnant rats during organogenesis, iloperidone was not teratogenic at doses up to 26 times the maximum recommended human dose (MRHD); however, at the highest dose it prolonged the duration of pregnancy and parturition; increased stillbirths, early intrauterine deaths, and incidence of developmental delays; and decreased postpartum pup survival

• When administered to pregnant rabbits during organogenesis, iloperidone was not teratogenic at doses up to 20 times the MRHD; however, at the highest dose, which was also a maternally toxic dose, it increased early intrauterine deaths and decreased fetal viability at term

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Iloperidone may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

• Unknown if iloperidone is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed

• Infants of women who choose to breast feed while on iloperidone should be monitored for possible adverse effects