Summary

• INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. INVEGA SUSTENNA is not approved for use in patients with dementia-related psychosis.¹
  • Patients with Parkinson’s Disease or Dementia with Lewy Bodies can experience increased sensitivity to INVEGA SUSTENNA and may be at an increased risk of neuroleptic malignant syndrome.²
• Clinical studies of INVEGA SUSTENNA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.³
• This drug is known to be substantially excreted by the kidney and clearance is decreased in patients with renal impairment, who should be given reduced doses. Because elderly patients are more likely to have decreased renal function, adjust dose based on renal function.³
• INVEGA SUSTENNA has not been systematically studied in patients with renal impairment. For patients with mild renal impairment (creatinine clearance [CrCl] ≥50 mL/min to <80 mL/min), initiate INVEGA SUSTENNA with a dose of 156 mg on treatment day 1 and 117 mg one week later. Administer both doses in the deltoid muscle. Thereafter, follow with the recommended monthly maintenance dose of 78 mg, administered in either the deltoid or gluteal muscle. Adjust monthly maintenance dose based on tolerability and/or efficacy within the strengths of 39 mg, 78 mg, 117 mg, or 156 mg.^2,3
• INVEGA SUSTENNA is not recommended in patients with moderate or severe renal impairment (CrCl <50 mL/min).³

DOSAGE STRENGTH INFORMATION

Doses of paliperidone palmitate extended-release injectable suspension may be expressed in milligram equivalents of paliperidone (active moiety) or milligrams of paliperidone palmitate. Dosage information in this response has been converted to mg of paliperidone palmitate to reflect the commercially available dosage strengths in the United States. The conversion factor from mg eq. to mg is 1.56.

• INVEGA SUSTENNA doses expressed as 39, 78, 117, 156, and 234 mg of paliperidone palmitate are equal to 25, 50, 75, 100, and 150 mg eq., respectively.

PUBLISHED LITERATURE

Meta-Analysis

Gopal et al (2013)⁴ conducted a meta-analysis of 64 randomized, double-blind, placebo- or active-controlled clinical trials evaluating the occurrence of cardiac treatment-emergent adverse events (TEAEs) and effect on QT interval, and a cumulative review of post-marketing safety data. Three groups were analyzed: risperidone oral or long-acting injection (LAI) (n=2958) or paliperidone oral or LAI (n=3554); placebo (n=3517); or active control (n=1061). Most results were reported as pooled data for risperidone and paliperidone; oral forms were studied in 56/64 trials. Of the patients in the placebo-controlled studies who had a recorded medical history, 77% of elderly patients and 20% of non-elderly patients had a history of cardiovascular disease. In the total study population, the point estimate for the odds ratio was numerically higher in elderly (≥65 years) vs non-elderly (<65 years) patients for cardiac arrhythmias, cardiac failure, torsades/QT prolongation, cerebrovascular disorders, embolic/thrombotic events, and convulsions, but not ischemic heart disease. Maximum QTc (Fridericia's formula) increases from baseline of <30 ms, 30-60 ms, and >60 ms occurred in 82.4%, 17.6%, and 0%, respectively, of paliperidone patients >74 years old (n=17), vs 93.9%, 6.0%, and 0.1% of paliperidone patients 30-74 years old (n=2546), and vs 100%, 0%, and 0% of placebo-treated patients >74 years old (n=4) in the paliperidone studies.

Case Reports

Rama Raj et al (2015)⁵ reported the efficacy and safety of INVEGA SUSTENNA in a 68-year-old female with a 45-year history of treatment-resistant schizophrenia. The patient experienced relapses on her current treatment regimen of clozapine (250 mg), zuclopenthixol LAI (400 mg) and sodium valproate (1000 mg) secondary to noncompliance and alcohol bingeing. Due to her refractory symptoms, INVEGA SUSTENNA was initiated (234 mg day 1, 156 mg day 8; deltoid muscle; maintenance: 156 mg monthly) in place of zuclopenthixol-LAI. Overall, the patient’s Positive and Negative Syndrome Scale total score improved from 67 at baseline to 49 at week 28, with reductions occurring as early as week 4. Improvements in her mental state and a reduction in relapses were also noted. Barnes Akathisia Rating Scale scores decreased from 3 to 0 by week 4, resulting in resolution of akathisia, possibly related to immediate past use of zuclopenthixol. Improvement in Simpson-Angus Scale and WHO Quality of Life BREF scores were also observed at the 28 week endpoint. The patient experienced an increase in fasting blood glucose from 9.5 mmol/L at baseline to 13.4 mmol/L at week 28. However, the patient was noted as having underlying diabetes and was also noncompliant with her diabetes medication. From baseline to endpoint, prolactin levels increased from 514 µmol/L to 1025 µmol/L, respectively; no prolactin-related adverse events were reported. QTc intervals increased from baseline to endpoint (446 vs 488, respectively); no ventricular arrhythmias were detected. Weight increased from 91.6 kg at baseline to 94.2 kg at endpoint.

Coffey (2012)⁶ reported a case of a 79-year-old female with paranoid schizophrenia who initiated treatment with INVEGA SUSTENNA with a dose of 234 mg, followed by 156 mg one week later, followed by 117 mg monthly, increased to 156 mg monthly. The patient had previously been treated with multiple oral and injectable medications, including quetiapine, clozapine, ziprasidone, haloperidol, fluphenazine, risperidone, and aripiprazole. The patient had no history of parkinsonism, dystonia, or catatonia. Twenty-four hours after the sixth monthly 156-mg injection, the patient developed encephalopathy and catatonia, with motor symptoms including rigidity of all four extremities, neck, and jaw; posturing; Gegenhalten; and bilateral upper extremity resting tremor. The rigidity, posturing, and Gegenhalten were resolved by a continuous lorazepam infusion of 16 mg per 24 hours, but the response was otherwise incomplete. Bromocriptine 5 mg every 6 hours had no measurable benefit. Electroconvulsive therapy (ECT) (four times per week) was initiated 21 days after the syndrome onset. After two treatments, the motor features had resolved, but the other symptoms persisted. After 10 additional treatments, ECT was discontinued; mild rigidity recurred; posturing, Gegenhalten, and tremor did not recur; the patient died from respiratory distress one month later.

Singh and Williams (2012)⁷ reported a case of a 76-year-old woman with a 40-year history of schizophrenia who was switched from risperidone long-acting injection (RLAI) to INVEGA SUSTENNA. The patient had been stable for four years on RLAI 50 mg every two weeks but complained of the frequency of visits and injection pain. The patient was switched to INVEGA SUSTENNA 156 mg every 4 weeks. After three weeks, the patient's mental state began to deteriorate with re-emergence of auditory hallucinations, delusions, a decline in self-care, and sleep disturbance. She was hospitalized, and INVEGA SUSTENNA was increased to 234 mg every four weeks and supplemented with oral risperidone 2 mg/day. The patient improved and returned to independent living, and the oral risperidone was discontinued shortly after discharge. Two months later, the patient relapsed again, experienced psychotic symptoms and diminished self-care, and was readmitted. RLAI was restarted with oral risperidone supplementation and her symptoms improved over the course of three weeks. The patient was discharged and the oral risperidone was discontinued, but RLAI was increased to 75 mg every two weeks for symptom control. The authors noted no further readmissions and no medical problems or stressors to account for the relapses.

UNPUBLISHED LITERATURE

Samtani et al (2009)⁸ presented a poster describing the use of INVEGA SUSTENNA in an elderly population. Pharmacokinetic simulations depict that the INVEGA SUSTENNA dose should be adjusted in the elderly population according to renal function status. In general, recommended dosing of INVEGA SUSTENNA for patients >60 years with normal renal function is the same as for younger adult patients (18–60 years) with normal renal function. Since patients >60 years are more likely to have decreased renal function, dose adjustment may be required because of age-related decreases in CrCL.

There was an expected age-related decline in renal function (i.e. CrCL) with increasing age. The distribution of CrCL in the two important age groups is shown in the Figure: Distribution of Creatinine Clearance in the Population-Pharmacokinetic Database for Patients Aged 18-60 vs >60 years, for the population-pharmacokinetic database. This resulted in a difference in PK profiles for the two age groups (18−60 years vs >60 years) (Figure: Age Has Very Little Independent Impact on the Pharmacokinetics of Paliperidone Palmitate and is Considered to be of No Clinical Significance [A]). However, after correcting for the decline in renal function, the difference in PK across ages was minimal (Figure: Age Has Very Little Independent Impact on the Pharmacokinetics of Paliperidone Palmitate and is Considered to be of No Clinical Significance [B]).

other relevant literature

A 5-year, retrospective, cross-sectional study evaluated the use of LAI antipsychotics in elderly patients in an Australian psychogeriatric service is referenced for your convenience.⁹

A real-world study using multi-state Medicaid claims databases (2017-2021) examined 528 elderly patients (≥65 years of age; female, 59%; average age, 70.4 years) with schizophrenia or related disorders. The most prescribed LAI antipsychotics was INVEGA SUSTENNA (~35%), followed by haloperidol decanoate (~24%) and risperidone microspheres (~15%).¹⁰

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 27 August 2024.