Paliperidone

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking paliperidone it is important that your doctor knows:

• If you are pregnant or breast-feeding.
• If you have a heart condition or blood vessel disease.
• If you have liver, kidney, or prostate problems.
• If you have any problems with your breathing.
• If you have any of the following: epilepsy, depression, Parkinson's disease, raised pressure in your eye (glaucoma) or a condition which causes muscle weakness, called myasthenia gravis.
• If you have ever had yellowing of your skin or the whites of your eyes (jaundice) or a blood disorder.
• If you have any difficulties swallowing, or if you have a disorder which could cause a blockage in your intestines.
• If you are scheduled to have cataract eye surgery.
• If you have a tumour on your adrenal gland (a condition called phaeochromocytoma), or if you have been told you have 'a prolactin-dependent tumour'.
• If you have had an allergic reaction to a medicine.
• If you are taking or using any other medicines. This includes any medicines you are taking which are available to buy without a prescription, such as herbal and complementary medicines.

Paliperidone is not for use in psychotic conditions related to dementia. Paliperidone may cause heart failure, sudden death, or pneumonia in older adults with dementia-related conditions.

You should not use this medication if you are allergic to paliperidone or a similar drug called risperidone (Risperdal).

To make sure you can safely take paliperidone, tell your doctor if you have any of these other conditions:

• a history of low white blood cell (WBC) counts;
• a personal or family history of Long QT syndrome;
• heart disease, heart rhythm problems, or a history of heart attack or stroke;
• high or low blood pressure;
• an electrolyte imbalance, such as low potassium or magnesium levels in your blood;
• a history of breast cancer;
• seizures or epilepsy;
• kidney or liver disease;
• diabetes (paliperidone may raise your blood sugar);
• high cholesterol or triglycerides (a type of fat in the blood);
• a stomach or intestinal disorder;
• a history of suicidal thoughts;
• Parkinson's disease; or
• trouble swallowing.

FDA pregnancy category C. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Taking antipsychotic medication during the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant while taking paliperidone, do not stop taking it without your doctor's advice.

Paliperidone can pass into breast milk and may harm a nursing baby. You should not breast-feed while taking paliperidone.

Older adults may be more likely to have side effects from this medicine.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Your pharmacist can provide more information about paliperidone.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Paliperidone may be found in some form under the following brand names:

• Invega

Some medicines may interact with paliperidone which may increase side effects, and increase or decrease the action of either drug. Your doctor may need to change the doses of your medicines or carefully monitor for side effects if you are taking medicines that interact with paliperidone.

Tell your doctor about the medicines you take including prescription and nonprescription medications, vitamins, nutritional supplements, and herbal supplements. Especially tell your doctor if you take:

• antidepressants
• certain antibiotics such as erythromycin (E.E.S., E-Mycin, Erythrocin), and moxifloxacin (Avelox)
• certain antipsychotics such as chlorpromazine (Thorazine), pimozide (Orap), risperidone (Risperdal) and thioridazine
• levodopa (in Sinemet, in Stalevo)
• medications for anxiety
• high blood pressure medicines 
• medications for seizures
• medications for irregular heartbeat such as amiodarone (Cordarone), disopyramide (Norpace), dofetilide (Tikosyn), procainamide (Procanbid, Pronestyl), quinidine (Quinidex), and sotalol (Betapace, Betapace AF)
• sedatives
• sleeping pills
• tranquilizers

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of paliperidone there are no specific foods that you must exclude from your diet when receiving paliperidone.

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if palidperidone is excreted in human breast milk or if it will harm your nursing baby.

While you are taking paliperidone, you may be more sensitive to temperature extremes such as very hot or cold conditions. Avoid getting too cold, or becoming overheated or dehydrated. Drink plenty of fluids, especially in hot weather and during exercise. It is easier to become dangerously overheated and dehydrated while you are taking paliperidone.

Avoid drinking alcohol. Dangerous side effects could occur.

This medicine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Dizziness or severe drowsiness can cause falls, fractures, or other injuries.

Usual Adult Dose for Schizophrenia:

EXTENDED-RELEASE TABLETS:
-Recommended dose: 6 mg orally once a day
-Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 5 days.
-Maximum dose: 12 mg/day

Comments:
-Initial dose titration is not required.
-Greater effects may be seen with higher doses, however this must be weighed against dose-related increases in adverse events.
-Doses above 6 mg per day have not been systematically studied for additional benefit.
-Efficacy was established with 3 trials using patients with schizophrenia for 6-weeks; efficacy in maintenance therapy was established with one adult trial.

1-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:
-For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with paliperidone extended-release injectable suspension.
-Dosing in the US and Canada is the same; however, paliperidone extended-release injectable suspension is dosed as the salt (paliperidone palmitate) in the US and as the base (paliperidone) in Canada:

Paliperidone palmitate:
-Initial dose: 234 mg IM on day 1 followed by 156 mg IM one week later; administer IM into deltoid muscle
-Maintenance dose: 117 mg IM monthly; administer into deltoid or gluteal muscle
-Dose range: 39 to 234 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months

Paliperidone (base):
-Initial dose: 150 mg IM on day 1 followed by 100 mg IM one week later; administer IM into deltoid muscle
-Maintenance dose: 75 mg IM monthly; administer into deltoid or gluteal muscle
-Dose range: 25 to 150 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months

Comments:
-The dosing window for maintenance doses is 7 days before or after monthly time point.
-If a dose is missed during initial titration or maintenance dosing, see dosage adjustment section for guidance.

3-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:
-Patients should be adequately treated for at least 4 months with the 1-month extended-release suspension prior to starting on the 3-month extended-release formulation.
-In order to establish a consistent maintenance dose, it is recommended that the last 2 doses of the 1-month extended-release suspension be of the same dosage strength.
-Initiate with the 3-month extended release injection when the next 1-month extended-release suspension dose is scheduled (up to 7-days before or after the monthly dose is scheduled).

Initial dose (based on the 1-month extended-release suspension dose):
-Initiate with 273 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 78 mg
-Initiate with 410 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 117 mg
-Initiate with 546 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 156 mg
-Initiate with 819 mg IM every 3 months if the last dose of the 1-month extended-release suspension was 234 mg
Dose adjustments may be made every 3 months in increments within the range of 273 mg to 819 mg based on efficacy and tolerability; due to long-acting nature of the formulation, it may take several months for the patient's response to be apparent.

Comments:
-The initial dose will be 3.5-fold higher than monthly dose.
-The dosing window is 2 weeks before or after the 3-month time point.
-Missed doses should be avoided. If a dose is missed, see dosage adjustment section for guidance.
-Conversion from 39 mg IM once-monthly was not studied.
-If the needle becomes clogged during administration, the remaining dose should not be re-injected. Instead, the patient should be monitored and treated with oral supplementation until the next scheduled 3-month injection.

Use: For the treatment of schizophrenia

Usual Adult Dose for Schizoaffective Disorder:

EXTENDED RELEASE TABLETS:
-Recommended dose: 6 mg orally once a day
-Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 4 days.
-Maximum dose: 12 mg/day

Comments:
-Initial dose titration is not required.
-Greater effects may be seen with higher doses; however, this must be weighed against dose-related increases in adverse events.
-Doses above 6 mg per day have not been systematically studied for additional benefit.
-Efficacy was established with 2 trials using patients with schizoaffective disorder for 6 weeks.

1-MONTH EXTENDED-RELEASE INJECTABLE SUSPENSION:
-For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with paliperidone extended-release injectable suspension.
-Dosing in the US and Canada is the same; however, paliperidone extended-release injectable suspension is dosed as the salt (paliperidone palmitate) in the US and as the base (paliperidone) in Canada:

Paliperidone palmitate:
-Initial dose: 234 mg IM on day 1 followed by 156 mg IM one week later; administer IM into deltoid muscle
-Dose range: 78 to 234 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months
-Maximum dose: 234 mg/month

Paliperidone (base):
-Initial dose: 150 mg IM on day 1 followed by 100 mg IM one week later; administer IM into deltoid muscle
-Dose range: 50 to 150 mg based on patient tolerability and efficacy; dose adjustments may be made monthly, although full effect may not be evident for several months

Comments:
-The dosing window for maintenance doses is 7 days before or after monthly time point.
-If a dose is missed during initial titration or maintenance dosing, see dosage adjustment section for guidance.

Use: Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants

Usual Pediatric Dose for Schizophrenia:

EXTENDED-RELEASE TABLETS:
12 to 17 years old:
-Initial dose: 3 mg orally once a day
-Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 5 days.
-Maximum dose: 12 mg per day

Comments:
-Initial dose titration is not required.
-In the adolescent schizophrenia trials, higher doses (6 mg per day in patients weighing less than 51 kg; 12 mg per day in patients weighing 51 kg or more) did not demonstrate greater efficacy, while adverse events were dose-related.
-Efficacy was established with a 6-week trial in adolescent patients with schizophrenia.

Use: Treatment of schizophrenia

Atypical or second-generation antipsychotic agent.1 2 3 4 5 6 7 8 12 39 41

It is very important that your doctor check the progress of you or your child at regular visits to make sure that paliperidone is working properly. Blood and urine tests may be needed to check for any unwanted effects.

Check with your doctor right away if you have any of the following symptoms while using paliperidone: convulsions (seizures), difficulty with breathing, a fast heartbeat, a high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

paliperidone may cause tardive dyskinesia (a movement disorder). Check with your doctor right away if you have any of the following symptoms while taking paliperidone: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

paliperidone may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or urination. If you have diabetes, you may notice a change in the results of your urine or blood sugar tests. If you have any questions, check with your doctor.

Dizziness, lightheadedness, or fainting may occur, especially when you suddenly get up from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

paliperidone can cause changes in heart rhythm, such as a condition called QT prolongation. It may change the way your heart beats and cause fainting or serious side effects in some patients. Call your doctor right away if you have any symptoms of heart rhythm problems, such as dizziness, feeling faint, or a fast, pounding, or irregular heartbeat.

Paliperidone can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

paliperidone may cause drowsiness, trouble with thinking, or trouble with controlling body movements, which may lead to falls, fractures, or other injuries. Make sure you know how you react to paliperidone before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.

Paliperidone may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your doctor right away.

Check with your doctor before using paliperidone with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with risperidone may worsen the side effects of paliperidone, including dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicines, medicine for depression, medicine for anxiety, prescription pain medicine or narcotics, medicine for attention deficit and hyperactivity disorder, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics.

paliperidone may make it more difficult for your body to cool itself down.Use care not to become overheated during exercise or hot weather since overheating may result in heat stroke. Also, use extra care not to become too cold while you are taking risperidone. If you become too cold, you may feel drowsy, confused, or clumsy.

paliperidone may increase your weight. Your doctor may need to check your weight on a regular basis while you are using paliperidone.

paliperidone may increase prolactin blood levels if used for a long time. Check with your doctor if you have breast swelling or soreness, unusual breast milk production, absent, missed, or irregular menstrual periods, stopping of menstrual bleeding, loss in sexual ability, desire, drive, or performance, decreased interest in sexual intercourse, or an inability to have or keep an erection.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Pregnancy

Pregnancy Category C.

There are no adequate and well controlled studies of Paliperidone Extended-Release Tablets in pregnant women.

Use of first generation antipsychotic drugs during the last trimester of pregnancy has been associated with extrapyramidal symptoms in the neonate. These symptoms are usually self-limited. It is not known whether Paliperidone, when taken near the end of pregnancy, will lead to similar neonatal signs and symptoms.

In animal reproduction studies, there were no increases in fetal abnormalities when pregnant rats and rabbits were treated during the period of organogenesis with up to 8 times the maximum recommended human dose of Paliperidone (on a mg/m2 basis).

In rat reproduction studies with risperidone, which is extensively converted to Paliperidone in rats and humans, there were increases in pup deaths seen at oral doses which are less than the maximum recommended human dose of risperidone on a mg/m2 basis (see risperidone package insert).

Non-teratogenic Effects

Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Paliperidone Extended-Release Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Paliperidone is excreted in human breast milk. The known benefits of breastfeeding should be weighed against the unknown risks of infant exposure to Paliperidone.

Pediatric Use

Safety and effectiveness of Paliperidone Extended-Release Tablets in the treatment of schizophrenia were evaluated in 150 adolescent subjects 12–17 years of age with schizophrenia who received Paliperidone Extended-Release Tablets in the dose range of 1.5 mg to 12 mg/day in a 6-week, double-blind, placebo-controlled trial.

Safety and effectiveness of Paliperidone Extended-Release Tablets for the treatment of schizophrenia in patients < 12 years of age have not been established. Safety and effectiveness of Paliperidone Extended-Release Tablets for the treatment of schizoaffective disorder in patients < 18 years of age have not been studied.

In a study in which juvenile rats were treated with oral Paliperidone from days 24 to 73 of age, a reversible impairment of performance in a test of learning and memory was seen, in females only, with a no-effect dose of 0.63 mg/kg/day, which produced plasma levels (AUC) of Paliperidone similar to those in adolescents. No other consistent effects on neurobehavioral or reproductive development were seen up to the highest dose tested (2.5 mg/kg/day), which produced plasma levels of Paliperidone 2–3 times those in adolescents.

Juvenile dogs were treated for 40 weeks with oral risperidone, which is extensively metabolized to Paliperidone in animals and humans, at doses of 0.31, 1.25, or 5 mg/kg/day. Decreased bone length and density were seen with a no-effect dose of 0.31 mg/kg/day, which produced plasma levels (AUC) of risperidone plus Paliperidone which were similar to those in children and adolescents receiving the maximum recommended human dose of risperidone. In addition, a delay in sexual maturation was seen at all doses in both males and females. The above effects showed little or no reversibility in females after a 12-week drug-free recovery period.

The long-term effects of Paliperidone Extended-Release Tablets on growth and sexual maturation have not been fully evaluated in children and adolescents.

Geriatric Use

The safety, tolerability, and efficacy of Paliperidone Extended-Release Tablets were evaluated in a 6-week placebo-controlled study of 114 elderly subjects with schizophrenia (65 years of age and older, of whom 21 were 75 years of age and older). In this study, subjects received flexible doses of Paliperidone Extended-Release Tablets (3 mg to 12 mg once daily). In addition, a small number of subjects 65 years of age and older were included in the 6-week placebo-controlled studies in which adult schizophrenic subjects received fixed doses of Paliperidone Extended-Release Tablets (3 mg to 15 mg once daily) [see Clinical Studies (14)]. There were no subjects ≥ 65 years of age in the schizoaffective disorder studies.

Overall, of the total number of subjects in schizophrenia clinical studies of Paliperidone Extended-Release Tablets (n=1796), including those who received Paliperidone Extended-Release Tablets or placebo, 125 (7.0%) were 65 years of age and older and 22 (1.2%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney and clearance is decreased in patients with moderate to severe renal impairment [see Clinical Pharmacology (12.3)], who should be given reduced doses. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.5)].

Renal Impairment

Dosing must be individualized according to the patient's renal function status [see Dosage and Administration (2.5)].

Hepatic Impairment

No dosage adjustment is required in patients with mild to moderate hepatic impairment. Paliperidone Extended-Release Tablets have not been studied in patients with severe hepatic impairment.

NDC 10147-0954-3

Paliperidone
Extended-Release Tablets

9mg

Tablets should be swallowed whole.
Do not divide, crush, or chew.
Paliperidone should be taken once daily.

Rx only
30 Tablets

PATRIOT
PHARMACEUTICALS LLC

Slower monthly IM absorption observed in women.

Refer to adult dosing. Additional monitoring of renal function and orthostatic blood pressure may be warranted.

Psychosis/agitation associated with dementia (off-label use): Oral: Initial: One-third to one-half the usual dose to treat psychosis in younger adults or the smallest available dosage. In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]).

Schizophrenia: Adolescents 12 to 17 years: Oral: Initial: 3 mg once daily; titration not required (no known benefit to efficacy from higher doses [ie, 6 mg daily for patients <51 kg and 12 mg daily for patients ≥51 kg]). If exceeding 3 mg daily, increases of 3 mg daily are recommended no more frequently than every 5 days.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Paliperidone is not approved for the treatment of patients with dementia-related psychosis.

12 to 17 years old:
Recommended dose: 3 mg orally once a day
Dose range: 3 to 12 mg per day; dose increases may be made in increments of 3 mg per day and should occur at intervals of more than 5 days.
Maximum dose: 12 mg per day

Comments: Initial dose titration is not required; in the adolescent schizophrenia trials, higher doses (6 mg per day in patients weighing less than 51 kg; 12 mg per day in patients weighing 51 kg or more) did not demonstrate greater efficacy, while adverse events were dose-related.

Use: Treatment of schizophrenia

US BOXED WARNING:
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
-Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
-Paliperidone is not approved for the treatment of patients with dementia-related psychosis.

Safety and efficacy of the long-acting injection in patients younger than 18 years have not been established.

Safety and efficacy of paliperidone in patients younger than 12 years in the treatment of schizophrenia have not been established.

Safety and efficacy of paliperidone in patients younger than 18 years in the treatment of schizoaffective disorder have not been established

Consult WARNINGS section for additional precautions.