An atypical antipsychotic called iloperidone (Fanapt) is used to treat schizophrenia patients.

It can also be used to treat dementia patients who are experiencing psychosis and agitation.

Iloperidone Uses:

• Schizophrenia:

  • Iloperidone is a medication used for treating schizophrenia in adults.

• Off Label Use of Iloperidone in Adults:

  • Some doctors might prescribe iloperidone to adults for problems like psychosis and agitation that are related to dementia, even though it's not officially approved for this use.

Iloperidone (Fanapt) Dose in Adults:

Iloperidone (Fanapt) Dose in the treatment of Schizophrenia:

• Start with a low dose of 1 milligram taken twice a day.

• Adjust the dose slowly, not increasing more than 2 milligrams twice a day (4 milligrams total daily) every 24 hours until you reach the recommended dose range of 6 to 12 milligrams twice a day.

• The highest dose you should take in one day is 24 milligrams. It's important to adjust the dose gradually to avoid sudden drops in blood pressure when standing up.

• If you restart the treatment after not taking it for more than three days, follow the same gradual dose adjustment schedule as before.

• Dosage adjustment in patients receiving strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine) or strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin):

  • Reduce the iloperidone dose by half if you start taking a medication that inhibits CYP2D6 or CYP3A4 enzymes. When you stop taking the inhibitor, go back to your previous iloperidone dose.

• Dosage adjustment in poor metabolizers of CYP2D6:

  • If you're a poor metabolizer of CYP2D6, cut your iloperidone dose in half.

• Discontinuation of therapy:

  • The World Federation of Societies of Biological Psychiatry (WFSBP), Canadian Psychiatric Association (CPA), and American Psychiatric Association (APA) suggest decreasing antipsychotic medications gradually to prevent withdrawal symptoms and reduce the risk of the condition coming back.

  • When antipsychotics are taken in high doses that affect anti-cholinergic or dopaminergic systems, the chance of withdrawal symptoms is higher.

  • CPA guidelines recommend a slow decrease over six months to two years when stopping antipsychotics for patients with schizophrenia.

  • APA guidelines advise reducing the dose by 10% each month.

  • Continuing anti-parkinsonism medication for a short while after stopping antipsychotics helps avoid withdrawal symptoms.

  • There are three methods suggested for switching antipsychotics:

  • Cross-titration: Gradually decreasing the first antipsychotic while slowly increasing the new one.
  • Cross over and taper: Keeping the dose of the first antipsychotic steady while gradually increasing the new one, then decreasing the first one.
  • Direct change: Stopping the first antipsychotic suddenly or increasing the new one slowly, or starting it at a full treatment dose.

  • However, there isn't much evidence supporting the best switching methods and tapering rates, and the results are inconsistent.

Use in Children:

Iloperidone is not recommended for use in children.

Pregnancy Risk Category: N

• Taking antipsychotic medication, including iloperidone, during the final trimester of pregnancy can lead to neonatal withdrawal symptoms and abnormal muscle movements in newborns.

• Babies born to mothers who took antipsychotics may show signs such as irritability, feeding difficulties, and weak muscles.

• They might also experience breathing problems, tiredness, trembling, and stiff muscles.

• These effects could go away by themselves or might require hospital care.

• Iloperidone can affect the reproductive systems of both males and females, possibly causing high levels of prolactin hormone.

• The American College of Obstetricians and Gynecologists (ACOG) suggests personalized prenatal care.

• When considering psychiatric medication during pregnancy, it's important for healthcare providers to consult with mental health professionals, primary care doctors, and pediatricians.

• There's limited safety information about using atypical antipsychotics during pregnancy, so they should be used cautiously and only when necessary.

• If a woman unintentionally takes an antipsychotic while pregnant, it might be best to continue the treatment.

• Pregnant individuals aged 18 to 45 who took iloperidone during pregnancy are encouraged to register with the Atypical Antipsychotics Pregnancy Registry.

Use while breastfeeding

• It's unclear whether iloperidone is present in breast milk.

• Due to this uncertainty, the manufacturer does not recommend breastfeeding while taking iloperidone.

Dose in Kidney Disease:

The labeling for iloperidone does not provide specific dosage adjustments for kidney disease.

However, kidney damage alone is unlikely to significantly affect how iloperidone is processed by the body (its pharmacokinetics).

Dose in Liver disease:

• For individuals with mild liver impairment, no dosage adjustment is needed when taking iloperidone.

• In cases of moderate liver impairment, the manufacturer's labeling does not offer specific dosage adjustments.

• However, caution is advised, and dosage adjustments may be necessary.

• For individuals with severe liver impairment, iloperidone use is not recommended.

Common Side Effects of Iloperidone (Fanapt):

• Cardiovascular:

  • Tachycardia

• Central nervous system:

  • Drowsiness
  • Dizziness

• Endocrine & metabolic:

  • Weight gain
  • Increased serum prolactin

Less Common Side Effects of Iloperidone (Fanapt):

• Cardiovascular:

  • Orthostatic Hypotension
  • Hypotension
  • Palpitations

• Central Nervous System:

  • Fatigue
  • Extrapyramidal Reaction
  • Lethargy
  • Aggressive Behavior
  • Delusions
  • Restlessness
  • Dystonia

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased Serum Cholesterol
  • Weight Loss
  • Increased Serum Triglycerides

• Gastrointestinal:

  • Nausea
  • Xerostomia
  • Diarrhea
  • Abdominal Distress

• Genitourinary:

  • Ejaculation Failure
  • Erectile Dysfunction
  • Urinary Incontinence
  • Priapism

• Hematologic & Oncologic:

  • Decreased Hematocrit

• Neuromuscular & Skeletal:

  • Arthralgia
  • Muscle Rigidity
  • Tremor
  • Muscle Spasm
  • Myalgia

• Ophthalmic:

  • Blurred Vision
  • Conjunctivitis

• Respiratory:

  • Nasal Congestion
  • Nasopharyngitis
  • Upper Respiratory Tract Infection
  • Dyspnea

Contraindications to Iloperidone (Fanapt):

• Some people may experience allergic reactions to iloperidone or any of the ingredients in its formulation.
• These reactions could include severe symptoms like anaphylaxis (a potentially life-threatening allergic reaction involving difficulty breathing and swelling of the throat) or angioedema (swelling under the skin).
• If you have a known allergy to iloperidone or any of its components, it's important to avoid taking it and to seek immediate medical attention if you experience any signs of an allergic reaction.

Warnings and precautions

• Modified cardiac conduction

  • Thermal regulation can be affected, and the QTc interval (a measure of heart rhythm) may be prolonged when taking iloperidone.

  • This could lead to dangerous heart rhythm problems even with normal doses of antipsychotic medication.

  • Your risk of these heart rhythm issues may increase if you have conditions or take medicines that lower potassium or magnesium levels in your body, or slow down your heart rate.

  • Only use iloperidone with other medications that also prolong the QTc interval if absolutely necessary.

  • It's not recommended for patients with untreated heart disease, a genetic condition called long QT syndrome, or a history of irregular heart rhythms.

  • Be cautious when taking iloperidone with medications that slow down its breakdown in the body.

  • If your QTc interval remains consistently longer than 500 milliseconds, stop taking iloperidone.

  • If you experience symptoms like fainting, shaking, dizziness, or irregular heartbeats, get a second evaluation of your heart health.

• Blood dyscrasias

  • Leukopenia (low white blood cell count) and neutropenia (low neutrophil count) can happen while taking iloperidone.

  • In some cases, these can be severe and life-threatening, as seen in clinical trials.

  • If there are any risk factors, like already having leukopenia or a history of drug-induced neutropenia, it's important to get regular blood tests.

  • If blood disorders are detected or if the absolute neutrophil count falls below 1,000/mm3, stop taking iloperidone immediately.

• Effects on the cerebrovascular system:

  • Research on antipsychotics not approved for treating dementia-related psychosis has shown an elevated risk of cerebrovascular events like stroke and transient ischemic attacks, as well as higher mortality rates.

• Depression in the CNS:

  • CNS depression, or central nervous system depression, can be triggered by iloperidone, potentially impairing physical or mental abilities.
  • Patients should be aware that activities requiring mental alertness, such as driving or operating machinery, may be affected while taking this medication.

• Dyslipidemia

  • Atypical antipsychotics, including iloperidone, have been associated with unwanted changes in lipid levels.
  • Patients with abnormal lipid profiles should be cautious and may need to monitor their lipid levels closely while taking this medication.

• Esophageal dysmotility/aspiration

  • Antipsychotic use has been associated with aspiration (inhaling food or liquid into the lungs) and esophageal dysmotility (problems with swallowing).
  • This risk increases as you age. Patients, especially those older than 75 years and at high risk for aspiration pneumonia (such as those with Alzheimer's disease), should be cautious when using antipsychotics.

• Extrapyramidal symptoms

  • Extrapyramidal symptoms (EPS) can happen with antipsychotics, like pseudo-parkinsonism (similar to Parkinson's disease) and severe muscle contractions (dystonia).

  • These symptoms are generally less common with newer antipsychotics than with older ones, and the reported frequency is similar to that of a placebo.

  • Risk factors for dystonia include higher doses of antipsychotics, certain antipsychotics commonly used, and being male.

  • Older individuals, especially females after menopause, are more likely to develop tardive dyskinesia, a condition involving involuntary movements.

  • If you experience symptoms of tardive dyskinesia, it might be worth considering discontinuing the treatment.

• Falls

  • Somnolence (drowsiness), orthostatic hypotension (a drop in blood pressure when standing up), and motor or sensory instability can increase the risk of falling in patients taking iloperidone.

  • It's important for patients taking this medication or those with certain medical conditions to undergo baseline and ongoing assessments to evaluate their risk of falls.

• Hyperglycemia

  • Atypical antipsychotics, including iloperidone, can lead to hyperglycemia (high blood sugar levels).

  • In severe cases, blood sugar levels can become extremely high, possibly leading to hyperosmolar or ketoacidosis, serious complications of diabetes.

  • Patients with diabetes or other glucose regulation disorders should be cautious and monitor their blood sugar levels carefully while taking iloperidone.

• Hyperprolactinemia

  • The use of iloperidone is associated with higher levels of prolactin, a hormone involved in various bodily functions, including milk production in breastfeeding individuals.

  • It's uncertain whether hyperprolactinemia (elevated prolactin levels) has clinical effects on individuals with breast cancer or other prolactin-dependent tumors.

• Hypersensitivity

  • Allergic reactions to iloperidone can manifest in various ways, including anaphylaxis (a severe allergic reaction), angioedema (swelling under the skin), throat tightening, swelling of the throat and mouth, as well as swelling of the face, lips, and mouth.
  • Other potential allergic symptoms include itching (pruritus).

• Neuroleptic malignant Syndrome (NMS).

  • There's a possible link between using iloperidone and neuroleptic malignant syndrome (NMS), a serious condition involving altered mental status, fever, and muscle rigidity.

  • Patients should be vigilant for these symptoms.

  • Those with Parkinson's disease and Lewy body dementia may be at higher risk for developing NMS.

• Orthostatic hypotension

  • • Orthostatic hypotension, a drop in blood pressure when standing up, can lead to symptoms like fainting, dizziness, and rapid heartbeat.

    • It's important to avoid giving iloperidone to individuals with confirmed heart disease (such as heart failure or a history of heart attack or ischemia), cerebrovascular disease, or conditions that increase the risk of low blood pressure (like dehydration, low blood volume, or use of blood pressure-lowering medications).

• Priapism

  • Reports of rare cases of priapism (a prolonged and painful erection) associated with iloperidone use are infrequent.

• Suicidal thoughts:

  • Psychotic illnesses can sometimes lead to suicide attempts.

  • It's crucial to be mindful of this possibility and to keep high-risk patients informed and supported at all times.

  • When prescribing iloperidone, aim for the lowest effective dose possible while providing excellent patient care.

• Temperature regulation

  • • Reduced regulation of core body temperature can occur while taking iloperidone.

    • It's important to be cautious with intense physical activity, exposure to heat, dehydration, and using other medications that have anticholinergic effects.

• Weight loss

  • Antipsychotic treatments, including iloperidone, have been linked to significant weight gain.

  • However, the extent of weight gain can vary depending on the specific medication.

  • It's important to monitor your waist circumference and body mass index (BMI) regularly while taking iloperidone to track any changes in weight and assess your overall health.

• Dementia: [US Boxed Warning]

  • Elderly patients with dementia-related psychosis who are treated with antipsychotic medication are at a higher risk of mortality.

  • The leading causes of death in these patients are heart failure and sudden death, followed by infectious disorders like pneumonia.

  • Patients with Parkinson's disease dementia or Lewy body dementia should use antipsychotics cautiously due to their increased sensitivity to side effects, including extrapyramidal symptoms.

  • There is also a greater risk of death or irreversible cognitive decline in these patients.

  • It's important to note that iloperidone is not licensed for the treatment or prevention of dementia-related psychosis.

• Hepatic impairment

  • Iloperidone should not be used by individuals with severe liver disease.
  • For patients with moderate to severe hepatic impairment, it may be necessary to reduce the dosage.

• Seizures

  • Patients who are at high risk of seizures, including those with a history of seizures, brain damage, head injury, or alcoholism, should be closely monitored while taking iloperidone.

  • Elderly patients may be at a higher risk of seizures due to various contributing factors, so extra caution should be exercised in this population.

Iloperidone: Drug Interaction

Monitoring parameters:

• Mentation should be monitored regularly for any changes.
• Vital signs should be clinically indicated and monitored regularly.
• Blood pressure should be measured at baseline, then after 3 months, and annually thereafter.
• ECG (electrocardiogram) should be performed as clinically indicated.
• Baseline measurements of weight, height, waist circumference, and BMI should be taken, then repeated at 4, 8, and 12 weeks, and every three months thereafter.
• If weight gain exceeds 5%, consider alternative medications.
• Blood counts should be taken as directed by the doctor, especially in patients with pre-existing low white blood cell counts or a history of drug-induced cytopenias.
• Electrolyte levels should be monitored annually and as clinically indicated, particularly in patients at high risk for electrolyte disorders.
• Liver function tests and other indicated tests should be performed annually.
• Family and personal history of diabetes, obesity, dyslipidemia, high cholesterol, high blood pressure, or other cardiovascular diseases should be assessed.
• Fasting plasma glucose/HbA1c levels should be measured at baseline, 3 months after treatment initiation, and annually thereafter.
• Fasting lipid profile should be assessed at baseline and three months after starting antipsychotic treatment, with subsequent monitoring intervals based on LDL levels.
• Changes in menstrual cycle, libido, development of galactorrhea, and erectile function should be monitored at each visit for the first 12 weeks after starting treatment, then annually.
• Atypical involuntary movements and parkinsonian symptoms should be observed weekly for at least two weeks following the initiation of the dose, and after any large dose increases, until the dose stabilizes.
• Tardive dyskinesia should be monitored annually (or every 6 months in high-risk patients).
• Patients over 40 years old should have annual eye examinations, while younger patients should have them every 2 years.

How to administer Iloperidone?

Iloperidone can be taken with or without food.

Mechanism of action of Iloperidone (Fanapt):

• Iloperidone is classified as a piperidinyl-benzisoxazole atypical antipsychotic, exhibiting mixed D-2/5-HT-2 antagonist activity.

• Its strong affinity is for receptors such as 5-HT-2A, NE-1, D2, and D3, with lower to moderate affinity for receptors like D-1, D-4, H-1, 5-HT-1A, 5-HT-6, and 5-HT-7.

• It does not bind to muscarinic receptors.

• This drug combines dopamine and serotonin antagonism, potentially reducing extrapyramidal side effects and alleviating psychotic symptoms.

• Its low affinity for histamine H-1 receptors may lower the risk of drowsiness and weight gain, while its affinity for NEα1/α2c receptors might improve cognitive function but increase the risk of orthostatic hypotension.

• Iloperidone is well absorbed and has a high protein-binding capacity, primarily metabolized in the liver through carbonyl reduction, hydroxylation (via CYP2D6), and O-demethylation (via CYP3A4). It forms active metabolites (P88 and P95).

• The elimination half-life varies between extensive metabolizers and poor metabolizers, with extensive metabolizers having shorter half-lives.

• Time to peak plasma concentration is around 2 to 4 hours.

• The drug is mainly excreted through urine and feces, primarily as its active metabolites (P88 and P95), with a negligible amount of unchanged iloperidone excreted.

International Brand Names of Iloperidone:

• Fanapt
• Fanapt Titration Pack
• Napoperidone
• Psychoperidone

Iloperidone Brand Names in Pakistan: