Paliperidone - Indications, Contraindications, Dosage, Side Effects, and Precautions

Overview

Paliperidone extended-release tablet is a second-generation antipsychotropic drug that got its first approval by the United States Food and Drug Administration (FDA) in 2006 for the treatment of schizophrenia in elderly people. However, the drug is often potentially used off-label to treat conditions such as bipolar disorder, schizoaffective disorder, and other psychotic conditions.

Indications

Paliperidone is used to treat mental disorders such as schizophrenia (a mental disorder that affects the ability of a person to behave, think, and feel) and schizoaffective (a mental disorder causing a combination of mood disorder symptoms, such as mania or depression, and schizophrenia symptoms, such as delusions or hallucinations) or delusional disorders (a psychotic disorder with the presence of one or more delusion symptoms ).

For Patients:

What Is Schizophrenia?

Schizophrenia is a mental disorder that affects the ability of a person to behave, think, and feel. People suffering from this condition often seem to be losing touch with reality. This makes them and their friends and family members stressed.

What Is Paliperidone Prescribed For?

Paliperidone belongs to an atypical antipsychotic class of drugs prescribed for the treatment of schizophrenia. The drug works by changing the brain’s activity with the natural substance.

How Should One Use Paliperidone?

The medication is available as an extended-release tablet to be taken orally. It is recommended to be taken once a day, with or without food. A person should take the drug as prescribed by the doctor or at the same time daily. The person should alter the drug dosage and take it as directed by the pharmacist or doctor.

The drug should be taken along with water or fluid as a whole. One should not crush, spit, or chew the tablet. If a person cannot swallow this drug, they must consult a doctor to prescribe them some other medication to treat the condition.

The doctor can adjust the drug dosage based on the person’s response to the treatment, and the doctor can also increase the drug dosage after more than five days.

One should remember that Paliperidone cannot cure schizophrenia but can only control the symptoms of the condition. Therefore, one must not stop taking the medication if they feel well without consulting the doctor.

What Precautions Should Be Followed While Taking Paliperidone?

• A person should inform the doctor if they are allergic to Paliperidone, its ingredients, or any other drug.

• The doctor should also be informed about all prescription and non-prescription drugs, such as herbal products, vitamins, and nutritional supplements, that a person might be taking or is planning to take.

• One should also inform the doctor if the person is pregnant or planning to get pregnant, breastfeeding, or getting pregnant while taking this drug. Paliperidone can affect the newborn and the delivery if taken in the last few months of the pregnancy.

• The drug can make a person dizzy and thus affect their movement and thinking. Therefore, one must not operate heavy machinery or drive a car while taking this medication.

• If a person is planning to undergo surgery, including any dental procedure, they must inform the doctor that they are taking Paliperidone.

• The doctor must also be informed about any past or present medical condition, such as prolonged QT interval, heart attack, seizures, low levels of magnesium and potassium in the blood, brain tumor, stroke, head injury, diabetes, Parkinson’s disease, breast cancer, inflammatory bowel disease, or any liver, kidney, or heart disease.

• A person should avoid taking alcohol, as it adds to the drowsiness caused by Paliperidone.

• The drug also delays the cooling down of the body when it becomes too hot; therefore, a person should inform the doctor if they are planning to exercise or get exposed to extreme heat while taking this drug.

• Paliperidone can also cause lightheadedness, fainting, and dizziness when a person gets up from a lying position. This usually happens when the medication is just started or the dosage is increased. Therefore, one must get out of bed slowly and rest on the floor for some time before standing up.

• Also, a person may experience hyperglycemia while taking this drug, even if they are not suffering from diabetes. Therefore, a person suffering from schizophrenia is more likely to develop diabetes than a person without schizophrenia.

What Are the Side Effects of Paliperidone?

Common Side Effects:

• Weakness.

• Headache.

• Weight gain.

• Dry mouth.

• Increased saliva.

• Extreme tiredness.

• Unsteady feeling, dizziness, and body imbalance.

• Stomach pain.

Serious Side Effects:

• Sweating.

• Fever.

• Confusion.

• Stiffness or muscle pain.

• Restlessness.

• Stiff movements.

• Irregular, fast, or pounding heartbeats.

• Painful erection, lasting for hours.

• Falling.

Dosage and Administration:

For Adults

The recommended drug dosage for adults is 6 milligrams (mg) administered once a day. The initial dose titration is not needed; however, it has been established that a higher drug dosage can offer additional benefits. This must be achieved by analyzing the dose-related adverse effects caused by the drug. In some cases, the drug dosage can be increased up to 12 mg per day, while in others, 3 mg per day is sufficient.

It is recommended to increase the drug dosage beyond 6 mg per day only after proper clinical re-evaluation. The dose should be increased only after a five days interval. The maximum recommended dosage of Paliperidone is 12 milligrams per day, given in a 3 milligrams per day increment.

For Adolescents

The recommended dosage of the drug for schizophrenia adolescents (12 to 17 years old) is 3 mg once a day. An increase in dose is not required initially; however, it can be considered after clinical reassessment. The adolescents can be given an increment of 3 mg per day after more than a five days interval.

Missed Dose:

If a person misses out on the drug dose, it should be taken as soon as one remembers it. However, if it is already time for the next scheduled dose, one should skip the missed dose and take the scheduled dose. Do not take the double drug doses to compensate for the missed one.

Overdose:

If a person overdoses with this medication, the poison control department should be contacted. In case the person collapses, has trouble breathing, or has seizures, emergency medical help should be available immediately.

Symptoms of Drug Overdose

• Drowsiness.

• Restlessness.

• Stiff or slow movements.

• Fast heartbeat.

• Unusual and uncontrollable movements of body or face.

• Unsteadiness.

Drug Storage and Disposal:

The drug should be kept away from the children in an air-tight container. Store the drug at room temperature, away from excessive moisture and heat.

Unneeded or expired medications should be discarded safely so that pets, children, and others cannot accidentally consume them. The drug can be disposed of safely and thus should not be flushed down toilets. The drug can be discarded through a take-back program by contacting the nearest pharmacist, recycling department, or local garbage disposal department. However, if one cannot access the take-back program, one should check the Food and Drug Administration's (FDA) guidelines for safe drug disposal.

For Doctors:

Clinical Pharmacology

Mechanism of Action:

Paliperidone is an active metabolite of Risperidone. The mechanism of action of these drugs, along with other drugs that have efficacy for schizophrenia, is still not known. However, the therapeutic activity of Paliperidone for schizophrenia is thought to be mediated through a combination of serotonin type 2 (5HT2A) receptor antagonists and central dopamine type 2 (D2) receptor antagonists.

Pharmacodynamics

Paliperidone is a centrally active serotonin type 2 (5HT2A) receptor antagonist and central dopamine Type 2 (D2) receptor antagonist. The drug is also active as an antagonist at H1 histaminergic receptors and α1 and α2 adrenergic receptors. Paliperidone has no affinity for r β1- and β2-adrenergic receptors or cholinergic muscarinic.

Pharmacokinetics

Absorption:

The oral bioavailability of the drug following administration is 28 percent, with 74 percent of plasma protein binding of racemic paliperidone.

Distribution:

The volume of distribution of Paliperidone is 487 liters.

Metabolism:

The drug does not undergo an extensive metabolism. A significant portion of Paliperidone metabolism occurs in the kidneys.

Excretion:

Following the administration of oral dose (1-milligram immediate-release), 59 percent of the drug gets excreted unchanged into the urine, about 32 percent of the drug is recovered as a metabolite, and six to 12 percent is not recovered.

The terminal half-life of the drug is approximately 23 hours.

Ingredients

Active Ingredients: Paliperidone

Passive Ingredients: Cellulose acetate, carnauba wax, Polyethylene oxides, hydroxyethyl cellulose, povidone, sodium chloride, propylene glycol, polyethylene glycol, hypromellose, stearic acid, butylated hydroxytoluene, iron oxides, and titanium dioxide

Drug Form and Strength

Paliperidone is available in available in extended-release tablets having the following strengths:

• 1.5 mg Tablets (orange-brown).

• 3 mg Tablets (white).

• 6 mg Tablets (Beige).

• 9 mg Tablets (Pink).

What Are the Contraindications for Paliperidone?

Paliperidone is contraindicated in people with a known history of hypersensitivity to Paliperidone, any of its ingredients, or any other drug.

What Are Drug Warning and Precautions for Paliperidone?

• The drug is known to cause increased mortality in elderly people suffering from dementia-related psychosis.

• Antipsychotic drugs, such as Paliperidone, can also cause neuroleptic malignant syndrome (NMS), which causes altered mental status, hyperpyrexia, muscle rigidity, and autonomic instability, such as tachycardia, irregular pulse, and cardiac dysrhythmia. Therefore, if neuroleptic malignant syndrome is suspected, Paliperidone should be stopped immediately, and the patient should be carefully monitored.

• Antipsychotic drugs have been reported to cause hyperglycemia associated with ketoacidosis, hyperosmolar coma, or death. Therefore, diabetic patients receiving antipsychotic drugs should be monitored for symptoms.

• Tardive dyskinesia (movement disorder) is also reported, especially during a brief treatment with Paliperidone or when the medication is stopped. The condition usually appears in elderly people, especially elderly women. The risk of developing this condition and becoming irreversible usually depends on the duration and total dosage of the antipsychotic drug. Abnormal movements of the tongue and face and muscle twitching characterize the condition

Use in Specific Population

Renal Impairment:

The drug dosage of Paliperidone is based on an individual's renal function status. The recommended dosage for a person with creatinine clearance of more than or equal to 50 mL/min to less than 80 mL/min (mild renal impairment) is a single tablet of 3 mg daily. Based on the patient’s clinical response and tolerability, the dose titration can be done to a maximum of a single tablet of 6 mg per day. For a person with creatinine clearance of more than or equal to 10 mL/min to less than 50 mL/min (moderate to severe renal impairment), the recommended dosage is 1.5 mg per day. It can be increased to a single tablet of 3 mg daily after clinical assessment. The dose adjustment for patients with creatinine below 10 mL per minute is not established yet.

Hepatic Impairment

Dose adjustment is not established in patients with mild to moderate hepatic impairment. In severe cases, the study has yet to be performed.

Geriatric Use

Dose adjustment is strictly based on the renal function status of this population.

Smoking. Dose adjustment in this group is similar to that of the young patients with normal renal function. For those with moderate to severe renal impairment, the recommended dosage is a single tablet of 3 mg per day.

Drug interactions

• Alcohol.

• Aldesleukin.

• Aliskiren.

• Alpha-agonists (Clonidine, Methyldopa).

• Alpha-blockers (Alfuzosin, Doxazosin, Silodosin, Tamsulosin).

• Amantadine.

• Amiodarone.

• Amphetamines (Dextroamphetamine, Lisdexamfetamine).

• Angiotensin-converting enzyme inhibitors (Captopril, Ramipril).

• Angiotensin receptor blockers (Candesartan, Irbesartan, Losartan).

• Antihistamines (Cetirizine, Doxylamine, Diphenhydramine, Hydroxyzine, Loratadine).

• Apalutamide.

• Azelastine.

• Antifungals (Itraconazole, Ketoconazole, Voriconazole).

• Barbiturates (Butalbital, Phenobarbital).

• Benzodiazepines (Alprazolam, Diazepam, Lorazepam).

• Beta-adrenergic blockers (Atenolol, Propranolol, Sotalol).

• Brimonidine.

• Buprenorphine.

• Bupropion.

• Buspirone.

• Calcium channel blockers (Amlodipine, Diltiazem, Nifedipine, Verapamil).

• Cannabis.

• Chloral hydrate.

• Cyclosporine.

• Diabetes medications (Chlorpropamide, Glyburide, Insulin, Metformin, Rosiglitazone).

• Disopyramide.

• Diuretics (Furosemide, Hydrochlorothiazide, Indapamide, Triamterene).

• Dofetilide.

• Donepezil.

• Dopamine agonists (Parkinson's disease medications, such as Apomorphine, Bromocriptine, Levodopa, Pramipexole, Ropinirole, and Rotigotine).

• Dronedarone.

• Efavirenz.

• Eliglustat.

• Galantamine.

• General anesthetics (medications to put you to sleep for surgery).

• Grapefruit juice.

• Hepatitis C antivirals (Glecaprevir, Ledipasvir, Ombitasvir, Paritaprevir, Velpatasvir).

• Hydralazine.

• Hydroxychloroquine.

• Lapatinib.

• Lithium.

• Loperamide.

• Lumacaftor and Ivacaftor.

• Macrolide antibiotics (Azithromycin, Clarithromycin, Erythromycin).

• Methadone.

• Methylphenidate.

• Metoclopramide.

• Monoamine oxidase inhibitors (Moclobemide, Phenelzine, Rasagiline, Selegiline, tranylcypromine).

• Muscle relaxants (Baclofen, Cyclobenzaprine, Methocarbamol, Orphenadrine).

• Nabilone.

• Narcotic pain relievers (Codeine, Fentanyl, Morphine, Oxycodone).

• Obinutuzumab.

• Other antipsychotics (Chlorpromazine, Clozapine, Haloperidol, Olanzapine, Pimozide, Quetiapine, Risperidone).

• Procainamide.

• Propafenone.

• Quinidine.

• Quinine.

• Quinolone antibiotics (Ciprofloxacin, Moxifloxacin).

• Rifampin.

• Ritonavir.

• Rivastigmine.

• St. John's Wort.

• Seizure Medications (Carbamazepine, Gabapentin, Levetiracetam, Perampanel, Phenytoin, Topiramate).

• Selective serotonin reuptake inhibitors (Citalopram, Fluoxetine, Paroxetine, and Sertraline).

• Serotonin-norepinephrine reuptake inhibitors (Desvenlafaxine, Duloxetine, and Venlafaxine).

• Sodium oxybate.

• Suvorexant.

• Tapentadol.

• Tetrabenazine.

• Thalidomide.

• Tolcapone.

• Tramadol.

• Trazodone.

• Tricyclic antidepressants (Amitriptyline, Clomipramine, Desipramine, and Trimipramine).

• Tryptophan.

• Zolpidem.

• Zopiclone.