Invega Sustenna

Invega Sustenna

paliperidone

Manufacturer:

Johnson & Johnson

Distributor:

Zuellig
Full Prescribing Info
Contents
Paliperidone palmitate.
Action
Pharmacology: Mechanism of Action: The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown. However, it has been proposed that paliperidone's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2A) receptor antagonism.
Pharmacodynamics: Paliperidone palmitate is hydrolyzed to paliperidone. It is a centrally active dopamine D2 antagonist with predominant serotonergic 5-HT2A antagonistic activity. Paliperidone is also active as an antagonist at α1- and α2-adrenergic receptors and H1-histaminergic receptors. Paliperidone has no affinity for cholinergic muscarinic or β1- and β2-adrenergic receptors. The pharmacological activity of the (+)- and (-)-paliperidone enantiomers is qualitatively and quantitatively similar.
Pharmacokinetics: Due to its extremely low water solubility, paliperidone palmitate dissolves slowly after IM injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. Following a single IM dose, the plasma concentrations of paliperidone gradually rise to reach maximum plasma concentration (Cmax) at a median tmax of 13 days. The release of the drug starts as early as day 1 and lasts for as long as 126 days.
One week following administration of a single oral dose of immediate-release 14C-paliperidone 1 mg, 59% of the dose was excreted unchanged into urine, indicating that paliperidone is not extensively metabolized in the liver. Approximately 80% of the administered radioactivity was recovered in urine and 11% in the feces.
Indications/Uses
Acute and maintenance treatment of schizophrenia in adults.
Dosage/Direction for Use
For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with Invega Sustenna.
Adults: Initially 150 mg on day 1 and 100 mg 1 week later, both administered in the deltoid muscle. The recommended subsequent monthly dose is 75 mg; this can be increased or decreased in the range of 25-150 mg based on individual patient tolerability and/or efficacy. Following the 2nd dose, monthly doses can be administered in either the deltoid or gluteal muscle.
There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to Invega Sustenna, or concerning concomitant administration with other antipsychotics. Previous oral antipsychotics can be discontinued at the time of initiation of treatment with Invega Sustenna.
When switching patients from previous long-acting injectable antipsychotics, initiate Invega Sustenna therapy in place of the next scheduled injection. Invega Sustenna therapy should then be continued at monthy intervals. The 1-week initiation dosing regimen as described is not required.
If Invega Sustenna is discontinued, its prolonged-release characteristics must be considered. As recommended with other antipsychotic medications, the need to continuing existing extrapyramidal symptoms (EPS) medication should be re-evaluated periodically.
Elderly >60 years: In general, recommended dosing of Invega Sustenna for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. However, dose adjustment may be required due to age-related decreases in creatinine clearance.
Contraindications
Known hypersensitivity to paliperidone or to any of the components of Invega Sustenna. Since paliperidone is an active metabolite of risperidone, Invega Sustenna is contraindicated in patients with a known hypersensitivity to risperidone.
Use in lactation: In animal studies with paliperidone and in human studies with risperidone, paliperidone was excreted in the milk. Therefore, women receiving Invega Sustenna should not breastfeed infants.
Special Precautions
Avoid use in patients with congenital long QT syndrome or history of cardiac arrhythmia. Increased risk of tardive dyskinesia in the elderly, especially in women. Monitor glucose control in patients with or with risk factors for diabetes or other disorders of glucose regulation. Monitor for mental status changes, fever, muscle rigidity and/or autonomic instability. May cause orthostatic hypotension, impaired core body temperature, significant weight gain and/or sedation. Monitor for behavior changes or suicidal ideation. Patients with breast cancer or other prolactin-dependent tumors, renal impairment or at risk of seizures. May mask toxicity of other drugs or conditions eg, intestinal obstruction, Reye's syndrome and brain tumor. Care must be taken to avoid inadvertent injection of Invega Sustenna into blood vessel.
Use in pregnancy: The safety of IM injected paliperidone palmitate for use during human pregnancy has not been established. No teratogenic effect was noted in any animal study.
Use in children: Safety and efficacy of Invega Sustenna have not been established in children <18 years.
Use in the elderly: Not to be used in elderly patients with dementia-related psychosis due to increased risk of mortality.
Use In Pregnancy & Lactation
Use in pregnancy: The safety of IM injected paliperidone palmitate for use during human pregnancy has not been established. No teratogenic effect was noted in any animal study.
Use in lactation: In animal studies with paliperidone and in human studies with risperidone, paliperidone was excreted in the milk. Therefore, women receiving Invega Sustenna should not breastfeed infants.
Adverse Reactions
The following are commonly observed adverse events in double-blind, placebo-controlled clinical trials: Abdominal discomfort/upper abdominal pain, constipation, diarrhea, dry mouth, nausea, toothache, vomiting, asthenia, fatigue, injection site pain, upper respiratory tract infection, increased weight, pain in extremity, akathisia, dizziness, extrapyramidal disorder, headache, somnolence/sedation, agitation, insomnia, nightmare and hypertension.
The following are additional uncommon adverse reactions that occurred in Invega Sustenna-treated subjects in the trials mentioned previously, or in Invega Sustenna-treated subjects with schizophrenia who participated in other clinical trials: Bradycardia, bundle-branch block, QT prolongation, palpitations, postural orthostatic tachycardia syndrome, vertigo, hyperprolactinemia, eye rolling, oculogyric crisis, blurred vision, salivary hypersecretion, increased blood cholesterol level, decreased appetite, hyperglycemia, increased appetite.
Drug Interactions
Caution is advised when prescribing Invega Sustenna with drugs known to prolong the QT interval. Since paliperidone palmitate is hydrolyzed to paliperidone, results from studies with oral paliperidone should be taken into consideration when assessing drug-drug interaction potential. Given the primary CNS effects of paliperidone, Invega Sustenna 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 Sustenna is administered with other therapeutic agents that have this potential. Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P-450 isozymes.
Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, CYP2C19 and CYP3A5. This suggests that an interaction with inhibitors or inducers of these isozymes is unlikely. Paliperidone is metabolized to a limited extent by CYP2D6. In an interaction study in healthy subjects in which oral paliperidone was administered concomitantly with paroxetine, a potent CYP2D6 inhibitor, no clinically relevant effects on the pharmacokinetics of paliperidone were observed.
Co-administration of oral paliperidone extended-release once daily with carbamazepine 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state Cmax and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone likely as a result of induction of renal P-gp by carbamazepine.
Paliperidone, a cation under physiological pH, is primarily excreted unchanged by the kidneys, approximately half via filtration and half via active secretion. Concomitant administration of trimethoprim, a drug known to inhibit active renal cation drug transport, did not influence the pharmacokinetics of paliperidone.
Concomitant use of Invega Sustenna with risperidone has not been studied. Since paliperidone is an active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is co-administered with Invega Sustenna.
Storage
Store at temperatures not exceeding 30°C.
Shelf-Life: 24 months.
MIMS Class
ATC Classification
N05AX13 - paliperidone ; Belongs to the class of other antipsychotics.
Presentation/Packing
Susp for inj (pre-filled syringe, prolonged-release) 50 mg/0.5 mL x 1's. 75 mg/0.75 mL x 1's. 100 mg/mL x 1's. 150 mg/1.5 mL x 1's.
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