Paliperidone (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications. It is developed by Janssen Pharmaceutica. Invega is an extended release formulation of paliperidone that uses the OROS extended release system to allow for once-daily dosing.
Paliperidone palmitate (trade name Invega Sustenna, named Xeplion in Europe and other countries) is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-monthly injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also used for schizophrenia and schizoaffective disorder.
Pharmacology
Paliperidone is the primary active metabolite of the older antipsychotic risperidone. While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.
Paliperidone has antagonist effect at α1 and α2 adrenergic receptors and at H1 histamine receptors. It does not bind to muscarinic acetylcholine receptors. In addition, it binds with dopamine and serotonin receptors.
Paliperidone has less affinity for D4 receptors than risperidone.
Paliperidone (as Invega) was approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in 2006. It is marketed for the treatment of schizophrenia and schizoaffective disorder. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. It may also be used off-label for other conditions. Recently, the long-acting injectable form of paliperidone, marketed as INVEGA Sustenna in U.S. and Xeplion in Europe, was approved by the FDA on July 31, 2009. It was approved in Europe in 2011 for schizophrenia. In Europe the monthly (every 28 days) injection comes in 50Â mg, 75Â mg, 100Â mg, and 150Â mg of paliperidone without the 25Â mg injection that is available in the U.S. A dose of 75Â mg for a month in an injection is the equivalent of 6Â mg per day of paliperidone oral. 6Â mg of paliperidone oral (Invega) is equivalent to 2 to 3Â mg of risperidone.
Effects
Adverse effects
Adverse effect incidences
Sources:
- Very Common (>10% incidence)
- Headache
- Tachycardia
- Somnolence (causes less sedation than most atypical antipsychotics)
- Insomnia
- Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)
- Common (1-10% incidence)
- Cough
- Extrapyramidal side effects (EPSE; e.g. dystonia, akathisia, muscle rigidity, parkinsonism. It appears to produce similar EPSE to risperidone, asenapine and ziprasidone and more EPSE than olanzapine, clozapine, aripiprazole, quetiapine, amisulpride and sertindole)
- Orthostatic hypotension
- Weight gain (tends to produce a moderate degree of weight gain, possibly related to its potent blockade of the 5-HT2C receptor)
- QT interval prolongation (tends to produce less QT interval prolongation than most other atypical antipsychotics and approximately as much QT interval prolongation as aripiprazole and lurasidone)
- Nasopharyngitis
- Anxiety
- Indigestion
- Constipation
- Rare/Uncommon (<1% incidence)
- Sialorrhoea
- Priapism
- Neuroleptic malignant syndrome, a potentially life-threatening condition characterized by:
- - Hyperthermia
- - Muscle rigidity
- - Autonomic dysregulation
- - Mental status changes (e.g. confusion, agitation, etc.)
- - Dysphagia
- - Tremor
- - Dyspnoea
- - Elevated creatine kinase
- Tardive dyskinesia, an often irreversible neurologic condition characterised by, frequently distressing, movement disorders.
- Dysphagia
- Agranulocytosis, a potentially fatal drop in white blood cell count. More common in patients on clozapine than in those on paliperidone.
- Leukopenia
- Thrombocytopaenia
- Pancreatitis
- Atrial fibrilation
- Dysgeusia
- Mania
- Diabetes mellitus
- Diabetic ketoacidosis
- Hypoglycaemia
- Ileus
- Jaundice
- Angiooedema
- Alopecia
- Urinary retention
- Hypothermia
Controversy
In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.
References
External links
- Invega Official website
- Invega Sustenna Official website