Invega: Full Drug Profile

Invega - General Information

Invega 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 the same, pathways. It has been proposed that the drug's therapeutic activity in schizophrenia ismediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism. Invega is also active as an antagonist at alpha 1 and alpha 2 adrenergic receptors and H1 histaminergic receptors, which may explain some of the other effects of the drug. Invega was approved by the FDA for treatment of schizophrenia on December 20, 2006.

Pharmacology of Invega

Invega is an atypical antipsychotic developed by Janssen Pharmaceutica. Chemically, paliperidone is primary active metabolite of the older antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone, i.e. risperidone with an extra hydroxyl group). While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not the same, pathways.

Invega for patients

Physicians are advised to discuss the following issues with patients for whom they prescribe INVEGA™.

Patients should be advised that there is risk of orthostatic hypotension, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose.

As INVEGA™ has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that INVEGA™ therapy does not affect them adversely.

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with INVEGA™.

Patients should be advised not to breast-feed an infant if they are taking INVEGA™.

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, as there is a potential for interactions.

Patients should be advised to avoid alcohol while taking INVEGA™.

Patients should be advised regarding appropriate care in avoiding overheating and dehydration.

Patients should be informed that INVEGA™ should be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice something that looks like a tablet in their stool.

Invega Interactions

Potential for INVEGA™ to Affect Other Drugs

Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes. In vitro studies in human liver microsomes showed that paliperidone does not substantially inhibit the metabolism of drugs metabolized by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. Therefore, paliperidone is not expected to inhibit clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner. Paliperidone is also not expected to have enzyme inducing properties.

At therapeutic concentrations, paliperidone did not inhibit P-glycoprotein. Paliperidone is therefore not expected to inhibit P-glycoprotein-mediated transport of other drugs in a clinically relevant manner.

Given the primary CNS effects of paliperidone, INVEGA™ should be used with caution in combination with other centrally acting drugs and alcohol. Paliperidone may antagonize the effect of levodopa and other dopamine agonists.

Because of its potential for inducing orthostatic hypotension, an additive effect may be observed when INVEGA™ is administered with other therapeutic agents that have this potential.

Potential for Other Drugs to Affect INVEGA™

Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19, so that an interaction with inhibitors or inducers of these isozymes is unlikely. While in vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by these isozymes and they contribute to only a small fraction of total body clearance.

Invega Contraindications

INVEGA™ (paliperidone) is contraindicated in patients with a known hypersensitivity to paliperidone, risperidone, or to any components in the INVEGA™ formulation.

Additional information about Invega

Invega Indication: For the treatment of schizophrenia. Mechanism Of Action: Invega is the major active metabolite of risperidone. The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown, but it has been proposed that the drug's therapeutic activity in schizophrenia ismediated through a combination of central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonism. Drug Interactions: Not Available Food Interactions: Not Available Generic Name: Paliperidone Synonyms: 9-Hydroxyrisperidone Drug Category: Antipsychotic Agents Drug Type: Small Molecule; Approved Other Brand Names containing Paliperidone: Invega; Absorption: The absolute oral bioavailability of paliperidone following paliperidone administration is 28%. Toxicity (Overdose): The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Protein Binding: The plasma protein binding of racemic paliperidone is 74%. Biotransformation: Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, in vivo results indicate that these isozymes play a limited role in the overall elimination of paliperidone. Four primary metabolic pathways have been identified in vivo, none of which could be shown to account for more than 10% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Half Life: The terminal elimination half-life of paliperidone is approximately 23 hours. Dosage Forms of Invega: Tablet, extended release OralTablet, extended release OralTablet, extended release Oral Chemical IUPAC Name: 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[2,1-b]pyrimidin-4-one Chemical Formula: C23H27FN4O3 Paliperidone on Wikipedia: https://en.wikipedia.org/wiki/Paliperidone Organisms Affected: Humans and other mammals