Paliperidone Palmitate

May alter cardiac conduction and prolong the QTc interval; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics (Ray 2009). Risk may be increased by conditions or concomitant medications which cause bradycardia, hypokalemia, and/or hypomagnesemia. Avoid use in combination with QTc-prolonging drugs. Avoid use in patients with congenital long QT syndrome and in patients with history of cardiac arrhythmia.

May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye's syndrome, brain tumor) due to antiemetic effects.

Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or ANC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Monitor patients with clinically significant neutropenia for a fever or other signs of infection, and discontinue therapy if absolute neutrophil count 3.

An increased incidence of cerebrovascular adverse effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of risperidone (paliperidone is the primary active metabolite of risperidone) for the unapproved use in elderly patients with dementia-related psychosis.

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Increased cholesterol and triglycerides and decreased HDL have been noted. Use with caution in patients with a pre-existing abnormal lipid profile.

Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of aspiration pneumonia (eg, Alzheimer disease). Do not use in patients unable to swallow the tablet whole.

May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. All patients should be monitored for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness). Use with caution in patients with diabetes (or risk factors) or other disorders of glucose regulation; monitor for worsening of glucose control. Patients with risk factors for diabetes (eg, obesity or family history) should have a baseline fasting blood sugar (FBS) and periodically during treatment.

Use is associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.

Few case reports describe IFIS in patients receiving risperidone and undergoing cataract surgery (Ford, 2011). IFIS has not been reported with paliperidone but caution is advised since it is the active metabolite of risperidone. Prior to cataract surgery, evaluate for prior or current paliperidone or risperidone use. The benefits or risks of interrupting paliperidone or risperidone prior to surgery have not been established; clinicians are advised to proceed with surgery cautiously.

Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson disease or Lewy body dementia).

May cause orthostatic hypotension and syncope; use with caution in patients with known cardiovascular disease (heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications).

Rare cases of priapism have been reported.

The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.

Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI. Disease-related concerns:

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. (APA [Reus 2016]). Paliperidone is not approved for the treatment of dementia-related psychosis.

Use with caution in patients with Parkinson disease; may be more sensitive to CNS-related and extrapyramidal effects. Antipsychotics may aggravate motor disturbances in patients with Parkinson disease (APA [Lehman 2004]; APA [Reus 2016]).

Use with caution in patients with mild renal disease; dosage reduction is recommended. Not recommended in patients with moderate to severe impairment.

Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Use is not recommended in patients with preexisting severe gastrointestinal narrowing disorders (nondeformable controlled release formulation). Patients with upper GI tract alterations in transit time may have increased or decreased bioavailability of paliperidone. Formulation consists of drug within a nonabsorbable shell; following drug release/absorption, the shell is expelled in the stool. Other warnings/precautions:

When discontinuing antipsychotic therapy, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).