Paliperidone

Paliperidone

File:(±)-Paliperidone Enantiomers Structural Formulae.png
Systematic (IUPAC) name
(RS)-3-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-1-piperidyl]ethyl]-7-hydroxy-4-methyl-1,5-diazabicyclo[4.4.0]deca-3,5-dien-2-one
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]	EU EMA: Invega US FDA: Paliperidone
Pregnancy category	C
Routes of administration	oral- extended release, long-acting, once-monthly IM injection
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Bioavailability	28% (oral)
Biological half-life	23 hours (oral)
Identifiers
CAS Number	144598-75-4
ATC code	N05AX13 (WHO)
PubChem	CID 115237
DrugBank	DB01267
Chemical data
Formula	C23H27FN4O3
Molar mass	426.484 g/mol[[]]

Paliperidone (sold as INVEGA, INVEGA Sustenna), also known as 9-hydroxyrisperidone, is an atypical antipsychotic 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. Invega Sustenna (paliperidone palmitate) is a long-acting injectable formulation of paliperidone indicated for once-monthly injection after an initial titration period. Chemically, paliperidone is the primary active metabolite of the older atypical antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone, i.e. risperidone with an extra hydroxyl group). It is indicated for the acute and maintenance treatment of schizophrenia.

Pharmacology

While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways; therapeutic effect may be due to a combination of D₂ and 5-HT2_A receptor antagonism. Paliperidone also has antagonist effect at α₁ and α₂ adrenergic receptors and at H₁ histamine receptors. It does not bind to muscarinic acetylcholine receptors.

Paliperidone (as Invega) was approved by the FDA for the treatment of schizophrenia on December 20, 2006. This agent will initially be marketed for the treatment of schizophrenia and then for bipolar mania. Clinical trials of paliperidone for the treatment of schizoaffective disorder are also planned. It may also be used off-label for other conditions. Like risperidone, its possible use in people with autism and Asperger syndrome may be studied. Recently, the long-acting injectable form of paliperidone, marketed as INVEGA Sustenna, was approved by the FDA on July 31, 2009. [1]

Side effects and Adverse reactions

According to the Invega website, the most common side effects of paliperidone are reported to be restlessness and extrapyramidal disorder, including involuntary movements, tremors and muscle stiffness. Some users reported experiencing sexual dysfunction while administering this drug in combination with SSRIs such as Zoloft. Invega website's Important Safety Information page includes this warning in bold type:

IMPORTANT SAFETY INFORMATION FOR INVEGA: Elderly Patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. INVEGA (paliperidone) is not approved for the treatment of patients with dementia-related psychosis.

The web page goes on to mention Neuroleptic Malignant Syndrome as a rare, but potentially lethal reaction to the medication. Heart rhythm changes—potentially serious—may make paliperidone risky for people with some heart conditions.

Other risks include:

• Tardive Dyskinesia, a serious, sometimes permanent side effect reported with INVEGA and other neuroleptics. The risk of tardive dyskinesia increases with total dose and thus becomes more likely the longer a person takes Invega.
• High blood sugar and diabetes
• Hyperprolactinemia, or elevated levels of the hormone prolactin, potentially leading to the absence of a menstrual period; breasts producing milk; the development of breasts by males; and erectile dysfunction.
• Complications associated with pre-existing narrowing or blockage of the gastrointestinal tract (esophagus, stomach or small or large intestine)
• Fainting or lightheadedness when standing up or sitting up too quickly.
• Impairment of alertness and driving ability
• Risk in people with a seizure disorder or a history or health conditions that make seizures more likely
• Extrapyramidal effects -- persistent movement disorders or muscle disturbances, such as restlessness, tremors, and muscle stiffness.
• Caution should be exercised before prescribing Invega to pregnant or nursing women.
• Increased sensitivity to heat, difficulty cooling off, and increased likelihood of dehydration.

See also

• Risperidone
• OROS

External links

• INVEGA Web site
• INVEGGA Sustenna (paliperidone palmitate Extended Release Injectable Suspension) Web site

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