Invega Trinza Adverse Reactions

Adverse events during exposure to study treatment were obtained by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardised categories using MedDRA terminology.
Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of paliperidone palmitate based on the comprehensive assessment of the available adverse event information. A causal relationship with paliperidone palmitate cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Trial Data: The data described in this section include data from two clinical trials. One was a long-term relapse-prevention/randomised withdrawal trial, in which 379 subjects with schizophrenia during the open-label phase received a single injection of INVEGA TRINZA and 160 subjects were subsequently randomised to receive at least one further dose of INVEGA TRINZA and 145 subjects received placebo during the double-blind placebo-controlled phase. The mean (Standard Deviation [SD]) duration of exposure during the double-blind phase was 150 (79) days in the placebo group and 175 (90) days in the INVEGA TRINZA group.
The second trial was a long-term double-blind, active-controlled noninferiority study, in which 1429 subjects were enrolled into the open-label phase and treated with the 1 month paliperidone palmitate injectable product. Subjects who met the randomisation criteria were randomised in a 1:1 ratio to continue on monthly injections of the 1-month paliperidone palmitate injectable product (n=512) or to switch to INVEGA TRINZA (n=504) for 48 weeks.
There also was a Phase 1 study, in which 308 subjects with schizophrenia or schizoaffective disorder received a single injection of INVEGA TRINZA concomitantly with other oral antipsychotics.
The majority of adverse reactions were mild to moderate in severity.
Adverse events reported in the long-term relapse-prevention trial are shown in Tables 5 and 6.

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Pain Assessment and Local Injection Site Reaction: In the long-term relapse prevention trial of INVEGA TRINZA in subjects with schizophrenia, the mean intensity of pain reported by subjects using a visual analog scale (0 = no pain to 100 = unbearable pain) was 16.0 for the single INVEGA TRINZA injection during the Open-label Maintenance Phase. The mean intensity of pain for INVEGA TRINZA injections was 15.8 at double-blind baseline and 15.1 at double-blind endpoint. Blinded investigators' evaluation of the injection site for induration, redness and swelling was performed over time during the Double-blind Phase. The level of redness was generally similar between the Placebo and INVEGA TRINZA groups (ie, redness being absent in 100% and ≥98% of subjects, respectively) over time. The occurrence of swelling was similar between the Placebo and INVEGA TRINZA groups (absent in ≥99% in each group) over time. Induration was absent during the entire Double-blind Phase for both groups.
In the long-term non-inferiority study, the mean intensity of pain reported by subjects ranged from 14.0 to 19.5 in subjects who received INVEGA TRINZA injections, and 14.9 to 18.4 in subjects who received 1-month paliperidone palmitate injections during the Double-blind Phase. Blinded investigators' evaluation of the injection site for induration, redness and swelling was performed over time during the Double-blind Phase. Induration, redness, and swelling were observed in ≤5% of subjects in both treatment groups and were mostly mild in nature. The level of induration, redness and swelling was generally similar between the INVEGA TRINZA and 1-month paliperidone palmitate groups over time.
Other Adverse Reactions Observed During the Clinical Trial Evaluation of Paliperidone and/or Risperidone: Paliperidone palmitate is hydrolysed to paliperidone. Paliperidone is the active metabolite of risperidone, therefore, the adverse reaction profiles of these compounds (including both the oral and injectable formulations) are relevant to one another. This subsection includes additional adverse reactions reported with paliperidone and/or risperidone in clinical trials. Table 7 lists adverse reactions that were reported with paliperidone and/or risperidone by frequency category estimated from subjects who received at least one injection of INVEGA TRINZA in two long-term, double-blind clinical trials. The following terms and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from the available data). (See Table 7.)

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Post-Marketing data: In addition to the adverse reactions reported during clinical studies and listed in Table 7, the following adverse reactions have been reported during post-marketing experience with paliperidone and/or risperidone (Table 8). In each table, the frequencies are provided according to the following convention: Very common ≥ 1/10; Common ≥ 1/100 and < 1/10; Uncommon ≥ 1/ 1000 and < 1/100; Rare ≥ 1/10000 and < 1/1000; Very rare < 1/10000, including isolated reports; Unknown cannot be estimated from the available data.
In Table 8, adverse reactions are presented by frequency category based on spontaneous reporting rates. (See Table 8.)

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Very rarely, cases of anaphylactic reaction after administration of the 1-month paliperidone palmitate injectable product have been reported during post-marketing experience in patients who have previously tolerated oral risperidone or oral paliperidone.