Paliperidone

Paliperidone

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
Trade names	Invega
AHFS/Drugs.com	monograph
MedlinePlus	a607005
Licence data	EMA:Link, US FDA:link
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	oral- extended release, long-acting, once-monthly IM injection
Pharmacokinetic data
Bioavailability	28% (oral)
Half-life	23 hours (oral)
Identifiers
CAS number	144598-75-4 Y
ATC code	N05AX13
PubChem	CID 9802545
DrugBank	DB01267
ChemSpider	7978307 Y
UNII	838F01T721 Y
KEGG	D05339 Y
ChEMBL	CHEMBL1621 N
Chemical data
Formula	C23H27FN4O3
Mol. mass	426.484 g/mol
SMILES O=C/1N5/C(=N\C(=C\1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)[C@H](O)CCC5
InChI InChI=1S/C23H27FN4O3/c1-14-17(23(30)28-9-2-3-19(29)22(28)25-14)8-12-27-10-6-15(7-11-27)21-18-5-4-16(24)13-20(18)31-26-21/h4-5,13,15,19,29H,2-3,6-12H2,1H3/t19-/m1/s1 Y Key:PMXMIIMHBWHSKN-LJQANCHMSA-N Y
N (what is this?)  (verify)

Paliperidone (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine 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) 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 (as Invega) was approved by the FDA for the treatment of schizophrenia in 2006. It is marketed for the treatment of schizophrenia and 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.^{[citation needed]} 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 50 mg, 75 mg, 100 mg, and 150 mg of paliperidone without the 25 mg injection that is available in the U.S. A dose of 75 mg for a month in an injection is the equivalent of 6 mg per day of paliperidone oral. 6 mg of paliperidone oral (Invega) is equivalent to 2 to 3 mg of risperidone.

Side effects and adverse reactions

Adverse effects differ depending on the amount of the dose. The higher the dose the more adverse effects there are and the greater the level of the side effects and vice versa. Also some adverse effects only occur after long-term use of paliperidone. The aim is to use the lowest dose possible of oral or injectable paliperidone. Also if it is used concurrently with another psychiatric medicine it will become very complicated telling which drug is responsible for the side effect. Also people react differently and adverse effects vary between individual users. Furthermore, some adverse effects occur with every user of paliperidone while some adverse effects occur with only a tiny percentage of the users. Usually adverse effects go away after either discontinuation or reducing of the drug but some will stay with the user for their lifetime. The aim is to use psychiatric medications at the lowest level possible to prevent symptoms of the psychiatric disorder. Often many medications at a high level are used during hospitalization to shorten the time and cost of a patient being in the psychiatric hospital and much lower doses are needed for maintenance once the patient is stabilized. Also, sometimes a few side effects may diminish once the body adapts to the medicine.

The most common side effects of paliperidone are restlessness and extrapyramidal disorder, including involuntary movements, tremors and muscle stiffness. Some users reported experiencing sexual dysfunction while administering this drug in combination with serotonin reuptake inhibitors such as sertraline. Invega website's Important Safety Information page includes this warning: 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.

Neuroleptic malignant syndrome is a rare, but potentially lethal reaction to any antipsychotic medication.

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.
• Hyperprolactinemia, or elevated levels of the hormone prolactin, potentially leading to the absence of a menstrual period; breasts producing milk; the enlargement of breasts in males; and erectile dysfunction.
• 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.

Rare side effects include:

• Impairment of alertness and driving ability
• Risk in people with a seizure disorder or a history or health conditions that make seizures more likely

Dosing

1 mg to 12 mg. Injection 25 mg to 150 mg monthly. Many people have success at the lowest dose for maintenance purposes. To get out of a manic episode for bipolar disorder a high dose should be used for about 4 to 6 weeks and then reduduced to a low dose. Staying at a high dose is not necessary to prevent another manic episode. If adverse changes occur to the body then you should taper off the drug and use another drug.

External links

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