Paliperidone

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[edit] BRAND NAMES

[edit] STRUCTURE

Paliperidone.jpg

[edit] MECHANISM OF ACTION

Paliperidone, the primary active metabolite of the older antipsychotic Risperidone, is an antipsychotic drug belonging to the class of atypical antipsychotics (Second generation antipsychotics). Other atypical antipsychotic drugs include Quetiapine, Risperidone, Olanzapine, Aripiprazole, Clozapine, Ziprasidone and Amisulpride.

Atypical antipsychotics have become an increasingly popular alternative to typical antipsychotics (First generation antipsychotics) like haloperidol because they are less likely to cause extra-pyrammidal side-effects (EPS), drug induced involuntary movements, than are the older drugs.

Paliperidone interact with a broad range of neurotransmitter receptors. Its efficacy in Schizophrenia is mediated through a combination of antagonism at dopamine D2 receptors in the mesolimbic pathway and serotonin 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia.
. The dominant central antagonism at 5HT2A receptors can also reduce the tendency of paliperidone to cause extrapyramidal unwanted effects

Paliperidone acts also as an α1 and α2 adrenergic antagonist, H1 histaminergic receptors antagonist and has no affinity for cholinergic muscarinic receptors

[edit] INDICATIONS

  • Treatment of schizophrenia in adults
  • Treatment of schizophrenia in adolescents (12-17 years of age). (FDA-approved)
  • Treatment of psychotic or manic symptoms of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressant therapy in adults

Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (false beliefs).

Schizoaffective disorder is a condition in which the patient has episodes of elevated or depressed mood in addition to symptoms of schizophrenia.

[edit] DOSAGE

Tablets, Adults:

  • Schizophrenia and Schizoaffective disorder: Recommended starting dose: 6 mg/day (Initial dose titration is not required), taken in the morning, the tablet should be swallowed whole with a drink; Dose range: 3-12 mg/day.


Tablets, Adolescents (12-17 years of age)

  • Schizophrenia (FDA-approved): Recommended starting dose: 3 mg/day; Dose range: 3-6 mg/day (<50 kg) and 3-12 mg/day (≥50 kg).


Extended-release injectable suspension, Adults (Invega Sustenna): FDA Approved dosage

  • Schizophrenia: Initiate dosing with 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. Recommended monthly maintenance dose is 117 mg. Some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). Administer monthly maintenance doses in either the deltoid or gluteal muscle.

Extended-release injectable suspension, Adults (Xeplion): EMA Approved dosage

  • Schizophrenia: Initiate dosing with 150 mg on treatment day 1 and 100 mg one week later, both administered in the deltoid muscle. Recommended monthly maintenance dose is 75 mg. Some patients may benefit from lower or higher maintenance doses (25-150 mg). Administer monthly maintenance doses in either the deltoid or gluteal muscle.

[edit] CONTRAINDICATIONS

Known hypersensitivity to Paliperidone or to Risperidone

[edit] WARNINGS AND PRECAUTIONS

  • Elderly Patients with Dementia-Related Psychosis: Paliperidone is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular adverse events (e.g., stroke, transient ischemic attack).
  • Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. NMS is a rare but potentially life-threatening condition associated with antipsychotic medicinal products. Rare cases reported as NMS have also been received in association with Paliperidone. Clinical manifestations of NMS are hyperpyrexia (extreme elevation of body temperature), muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including Paliperidone must be discontinued.
  • Tardive Dyskinesia Drugs with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of the tongue and/or face. If signs and symptoms of tardive dyskinesia appear, the discontinuation of Paliperidone should be considered.
  • Hyperglycemia: Patients treated with any atypical antipsychotic, including Paliperidone, should be monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.
  • Weight gain: Significant weight gain has been reported with Paliperidone use. Weight should be monitored regularly.
  • Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, Paliperidone elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Longstanding hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with previously detected breast cancer
  • Orthostatic Hypotension: Orthostatic hypotension, based on its alpha-blocking activity, associated with dizziness, tachycardia, bradycardia and, in some patients, syncope, may occur. Use caution in patients with cardiovascular disease, cerebrovascular disease, and those conditions that could affect hemodynamic responses.
  • Use with caution in patients with a history of seizures.
  • Suicide: The possibility of a suicide attempt is inherent in schizophrenia. Close supervision of high-risk patients should accompany drug therapy

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

Pregnancy Category C (US). Paliperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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

[edit] SIDE EFFECTS

Adverse reactions include:

  • Headache
  • Insomnia/somnolence
  • Extrapyramidal symptoms: including parkinsonism (neurological symptoms including tremor and impaired muscular control), akathisia (restlessness), dystonia (involuntary muscle contractions)and tardive dyskinesia]
  • Tachycardia (increased heart rate)
  • Upper respiratory tract infection (colds)
  • Anxiety and agitation
  • Dizziness, nausea and vomiting
  • Hyperglycemia and increased weight
  • Increased triglycerides
  • Constipation
  • Fatigue (tiredness) and asthenia (weakness)
  • Depression
  • Dyspepsia (heartburn)
  • Diarrhea
  • Dry mouth
  • Toothache
  • Muscle and bone pain
  • High blood pressure
  • Back pain
  • Prolonged electrocardiogram QT (an alteration of the electrical activity of the heart)
  • Incresed prolactin that may lead (Uncommon) to sexual dysfunction and breast disorders (oligomenorrhea, erectile dysfunction, galactorrhea, sexual dysfunction, ejaculation disorder, gynecomastia, breast discomfort, menstruation irregular, menstruation delayed, menstrual disorder)
  • Cough
  • Rash

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