Trevicta

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

TREVICTA 175 mg prolonged release suspension for injection
TREVICTA 263 mg prolonged release suspension for injection
TREVICTA 350 mg prolonged release suspension for injection
TREVICTA 525 mg prolonged release suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

175 mg prolonged release suspension for injection

Each pre-filled syringe contains 273 mg paliperidone palmitate equivalent to 175 mg paliperidone.

263 mg prolonged release suspension for injection

Each pre-filled syringe contains 410 mg paliperidone palmitate equivalent to 263 mg paliperidone.

350 mg prolonged release suspension for injection

Each pre-filled syringe contains 546 mg paliperidone palmitate equivalent to 350 mg paliperidone.

525 mg prolonged release suspension for injection

Each pre-filled syringe contains 819 mg paliperidone palmitate equivalent to 525 mg paliperidone.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Prolonged release suspension for injection.
The suspension is white to off-white. The suspension is pH neutral (approximately 7.0).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

TREVICTA, a 3-monthly injection, is indicated for the maintenance treatment of schizophrenia in 
adult patients who are clinically stable on 1-monthly paliperidone palmitate injectable product (see
section 5.1).

4.2 Posology and method of administration

Posology

Patients who are adequately treated with 1-monthly paliperidone palmitate injectable (preferably for 
four months or more) and do not require dose adjustment may be switched to 3-monthly paliperidone
palmitate injection.

TREVICTA should be initiated in place of the next scheduled dose of 1-monthly paliperidone 
palmitate injectable (± 7 days). The TREVICTA dose should be based on the previous 1-monthly
paliperidone palmitate injectable dose using a 3.5-fold higher dose shown in the following table:



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TREVICTA doses for patients adequately treated with 1-monthly paliperidone palmitate 
injectable

If the last dose of 1-monthly paliperidone 
palmitate injectable is

Initiate TREVICTA at the following dose

50 mg 175 mg
75 mg 263 mg
100 mg 350 mg
150 mg 525 mg

There is no equivalent dose of TREVICTA for the 25 mg dose of 1-monthly paliperidone palmitate 
injectable which was not studied.

Following the initial TREVICTA dose, TREVICTA should be administered by intramuscular injection 
once every 3 months (± 2 weeks, see also Missed dose section).

If needed, dose adjustment of TREVICTA can be made every 3 months in increments within the range 
of 175 mg to 525 mg based on individual patient tolerability and/or efficacy. Due to the long-acting 
nature of TREVICTA, the patient’s response to an adjusted dose may not be apparent for several 
months (see section 5.2). If the patient remains symptomatic, they should be managed according to 
clinical practice.

Switching from other antipsychotic medicinal products
Patients should not be switched directly from other antipsychotics as 3-monthly paliperidone palmitate 
injectable should only be initiated after the patient is stabilised on the 1-monthly paliperidone 
palmitate injectable.

Switching from TREVICTA to other antipsychotic medicinal products
If TREVICTA is discontinued, its prolonged release characteristics must be considered.

Switching from TREVICTA to 1-monthly paliperidone palmitate injectable
For switching from TREVICTA to 1-monthly paliperidone palmitate injectable, 1-monthly
paliperidone palmitate injectable should be administered at the time the next TREVICTA dose was to 
be administered using a 3.5-fold lower dose shown in the following table. The initiation dosing as 
described in the prescribing information for 1-monthly paliperidone palmitate injectable is not 
required. The 1-monthly paliperidone palmitate injectable should then continue to be dosed at monthly 
intervals as described within its prescribing information.

Doses of 1-monthly paliperidone palmitate injectable for patients switching from TREVICTA
If the last dose of TREVICTA is Initiate 1-monthly paliperidone palmitate 

injectable 3 months later at the following dose
175 mg 50 mg
263 mg 75 mg
350 mg 100 mg
525 mg 150 mg

Switching from TREVICTA to oral daily paliperidone prolonged release tablets
For switching from TREVICTA to paliperidone prolonged release tablets, the daily dosing of 
paliperidone prolonged release tablets should be started 3 months after the last TREVICTA dose and 
treatment continued with paliperidone prolonged release tablets as described in the table below. The 
following table provides recommended dose conversion regimens to allow patients previously 
stabilised on different doses of TREVICTA to attain similar paliperidone exposure with paliperidone 
prolonged release tablets.



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Doses of paliperidone prolonged release tablets for patients switching from TREVICTA*

Last TREVICTA dose
(Week 0)

Week number after last TREVICTA dose
Week 12 to Week 18, 

inclusive
Week 19 to Week 24, 

inclusive
From Week 25

onwards
Daily dose of paliperidone prolonged release tablets

175 mg 3 mg 3 mg 3 mg
263 mg 3 mg 3 mg 6 mg
350 mg 3 mg 6 mg 9 mg
525 mg 6 mg 9 mg 12 mg

* All doses of once daily paliperidone prolonged release tablets should be individualised to the specific patient, taking 
into consideration variables such as reasons for switching, response to previous paliperidone treatment, severity of 
psychotic symptoms, and/or propensity for side effects.

Missed dose

Dosing window
TREVICTA should be injected once every 3 months. To avoid a missed dose of TREVICTA patients 
may be given the injection up to 2 weeks before or after the 3-month time point.

Missed doses
If scheduled dose is missed and the time since 

last injection is
Action

> 3½ months up to 4 months The injection should be administered as soon as 
possible and then resume the 3-monthly
injection schedule.

4 months to 9 months Use the recommended re-initiation regimen 
shown in the table below.

> 9 months Re-initiate treatment with 1-monthly
paliperidone palmitate injectable as described in 
the prescribing information for that product. 
TREVICTA can then be resumed after the 
patient has been adequately treated with 
1-monthly paliperidone palmitate injectable 
preferably for four months or more.

Recommended re-initiation regimen after missing 4 months to 9 months of TREVICTA

If the last dose of 
TREVICTA was

Administer 1-monthly paliperidone palmitate 
injectable, two doses one week apart (into 

deltoid muscle)

Then administer 
TREVICTA (into 
deltoida or gluteal 

muscle)
Day 1 Day 8 1 month after day 8

175 mg 50 mg 50 mg 175 mg
263 mg 75 mg 75 mg 263 mg
350 mg 100 mg 100 mg 350 mg
525 mg 100 mg 100 mg 525 mg

a
See also Information intended for medical or healthcare professionals for deltoid injection needle selection based on 
body weight.

Special populations

Elderly
Efficacy and safety in elderly > 65 years have not been established.

In general, recommended dosing of TREVICTA for elderly patients with normal renal function is the 
same as for younger adult patients with normal renal function. As elderly patients may have reduced 
renal function, see Renal impairment below for dosing recommendations in patients with renal 
impairment.



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Renal impairment
TREVICTA has not been studied in patients with renal impairment (see section 5.2). For patients with
mild renal impairment (creatinine clearance ≥ 50 to < 80 mL/min), dose should be adjusted and the 
patient stabilised using 1-monthly paliperidone palmitate injectable, and then transitioned to 
TREVICTA.

TREVICTA is not recommended in patients with moderate or severe renal impairment (creatinine 
clearance < 50 mL/min).

Hepatic impairment
TREVICTA has not been studied in patients with hepatic impairment. Based on experience with oral 
paliperidone, no dose adjustment is required in patients with mild or moderate hepatic impairment. As 
paliperidone has not been studied in patients with severe hepatic impairment, caution is recommended 
in such patients (see section 5.2).

Paediatric population
The safety and efficacy of TREVICTA in children and adolescents < 18 years of age have not been 
established. No data are available.

Method of administration

TREVICTA is intended for intramuscular use only. It must not be administered by any other route. 
Each injection must be administered only by a health care professional giving the full dose in a single 
injection. It should be injected slowly, deep into the deltoid or gluteal muscle. A switch from gluteal to 
deltoid (and vice versa) should be considered for future injection in the event of injection site 
discomfort (see section 4.8).

TREVICTA must be administered using only the thin wall needles that are provided in the 
TREVICTA pack. Needles from the 1-monthly paliperidone palmitate injectable pack or other 
commercially available needles must not be used when administering TREVICTA (see Information 
intended for medical or health care professionals).

The contents of the pre-filled syringe should be inspected visually for foreign matter and 
discolouration prior to administration. It is important to shake the syringe vigorously with the tip 
up and a loose wrist for at least 15 seconds to ensure a homogeneous suspension. TREVICTA 
should be administered within 5 minutes after shaking. If more than 5 minutes pass before 
injection, shake vigorously again for at least 15 seconds to re-suspend the medicinal product. (See 
Information intended for medical or health care professionals).

Deltoid muscle administration
The specified needle for administration of TREVICTA into the deltoid muscle is determined by the 
patient’s weight.
 For those ≥ 90 kg, the thin wall 1½ inch, 22 gauge (0.72 mm x 38.1 mm) needle should be used.
 For those < 90 kg, the thin wall 1 inch, 22 gauge (0.72 mm x 25.4 mm) needle should be used.

It should be administered into the centre of the deltoid muscle. Deltoid injections should be alternated 
between the two deltoid muscles.

Gluteal muscle administration
The needle to be used for administration of TREVICTA into the gluteal muscle is the thin wall 
1½ inch, 22 gauge (0.72 mm x 38.1 mm) needle regardless of body weight. It should be administered
into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between 
the two gluteal muscles.



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Incomplete administration
To avoid incomplete administration of TREVICTA, the pre-filled syringe must be shaken vigorously 
for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension 
(see Information intended for medical or health care professionals).

However, in the event of an incompletely injected dose, the dose remaining in the syringe should not 
be re-injected and another dose should not be given since it is difficult to estimate the proportion of the 
dose actually administered. The patient should be closely monitored and managed as clinically 
appropriate until the next scheduled 3-monthly injection of TREVICTA.

4.3 Contraindications

Hypersensitivity to the active substance, to risperidone or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Use in patients who are in an acutely agitated or severely psychotic state

TREVICTA should not be used to manage acutely agitated or severely psychotic states when 
immediate symptom control is warranted.

QT interval

Caution should be exercised when paliperidone is prescribed in patients with known cardiovascular 
disease or family history of QT prolongation, and in concomitant use with other medicinal products 
thought to prolong the QT interval.

Neuroleptic malignant syndrome

Neuroleptic Malignant Syndrome (NMS), characterised by hyperthermia, muscle rigidity, autonomic 
instability, altered consciousness, and elevated serum creatine phosphokinase levels has been reported 
to occur with paliperidone. Additional clinical signs may include myoglobinuria (rhabdomyolysis) and
acute renal failure. If a patient develops signs or symptoms indicative of NMS, paliperidone should be 
discontinued. Consideration should be given to the long-acting nature of TREVICTA.

Tardive dyskinesia/extrapyramidal symptoms

Medicinal products with dopamine receptor antagonistic properties have been associated with the 
induction of tardive dyskinesia characterised by rhythmical, involuntary movements, predominantly of 
the tongue and/or face. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all 
antipsychotics, including paliperidone, should be considered. Consideration should be given to the 
long-acting nature of TREVICTA.

Caution is warranted in patients receiving both, psychostimulants (e.g., methylphenidate) and 
paliperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both 
medicinal products. Gradual withdrawal of stimulant treatment is recommended (see section 4.5).

Leucopenia, neutropenia, and agranulocytosis

Events of leucopenia, neutropenia, and agranulocytosis have been reported with paliperidone. Patients 
with a history of a clinically significant low white blood cell count (WBC) or a drug-induced 
leucopenia/neutropenia should be monitored during the first few months of therapy and 
discontinuation of TREVICTA should be considered at the first sign of a clinically significant decline 
in WBC in the absence of other causative factors. Patients with clinically significant neutropenia 
should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if 
such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count 



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< 1 x 109/L) should discontinue TREVICTA and have their WBC followed until recovery. 
Consideration should be given to the long-acting nature of TREVICTA.

Hypersensitivity reactions

Hypersensitivity reactions can occur even in patients who have previously tolerated oral risperidone or 
oral paliperidone (see section 4.8).

Hyperglycaemia and diabetes mellitus

Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes, including diabetic coma 
and ketoacidosis, have been reported with paliperidone. Appropriate clinical monitoring is advisable in 
accordance with utilised antipsychotic guidelines. Patients treated with TREVICTA should be 
monitored for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) 
and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.

Weight gain

Significant weight gain has been reported with TREVICTA use. Weight should be monitored 
regularly.

Use in patients with prolactin-dependent tumours

Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by 
prolactin. Although no clear association with the administration of antipsychotics has so far been 
demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant 
medical history. Paliperidone should be used with caution in patients with a pre-existing tumour that 
may be prolactin-dependent.

Orthostatic hypotension

Paliperidone may induce orthostatic hypotension in some patients based on its alpha-adrenergic 
blocking activity. In the clinical trials of TREVICTA, 0.3% of subjects reported orthostatic 
hypotension related adverse reaction. TREVICTA should be used with caution in patients with known 
cardiovascular disease (e.g., heart failure, myocardial infarction or ischaemia, conduction 
abnormalities), cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., 
dehydration and hypovolemia).

Seizures

TREVICTA should be used cautiously in patients with a history of seizures or other conditions that 
potentially lower the seizure threshold.

Renal impairment

The plasma concentrations of paliperidone are increased in patients with renal impairment. For 
patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min), dose should 
be adjusted and the patient stabilised using 1-monthly paliperidone palmitate injectable, then 
transitioned to TREVICTA. TREVICTA is not recommended in patients with moderate or severe 
renal impairment (creatinine clearance < 50 mL/min). (See sections 4.2 and 5.2).

Hepatic impairment

No data are available in patients with severe hepatic impairment (Child-Pugh class C). Caution is 
recommended if paliperidone is used in such patients.



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Elderly patients with dementia

TREVICTA has not been studied in elderly patients with dementia. TREVICTA is not recommended 
to treat elderly patients with dementia due to increased risk of overall mortality and cerebrovascular 
adverse reactions.

The experience from risperidone cited below is considered valid also for paliperidone.

Overall mortality
In a meta-analysis of 17 controlled clinical trials, elderly patients with dementia treated with other 
atypical antipsychotics, including risperidone, aripiprazole, olanzapine, and quetiapine had an 
increased risk of mortality compared to placebo. Among those treated with risperidone, the mortality 
was 4% compared with 3.1% for placebo.

Cerebrovascular adverse reactions
An approximately 3-fold increased risk of cerebrovascular adverse reactions has been seen in 
randomised placebo-controlled clinical trials in the dementia population with some atypical 
antipsychotics, including risperidone, aripiprazole, and olanzapine. The mechanism for this increased 
risk is not known.

Parkinson’s disease and dementia with Lewy bodies

Physicians should weigh the risks versus the benefits when prescribing TREVICTA to patients with 
Parkinson’s disease or Dementia with Lewy Bodies (DLB) since both groups may be at increased risk 
of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotics. 
Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with 
frequent falls, in addition to extrapyramidal symptoms.

Priapism

Antipsychotic medicinal products (including paliperidone) with alpha-adrenergic blocking effects 
have been reported to induce priapism. Patients should be informed to seek urgent medical care in case 
that priapism has not been resolved within 4 hours.

Body temperature regulation

Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic 
medicinal products. Appropriate care is advised when prescribing TREVICTA to patients who will be 
experiencing conditions which may contribute to an elevation in core body temperature, e.g., 
exercising strenuously, exposure to extreme heat, receiving concomitant medicinal products with 
anticholinergic activity or being subject to dehydration.

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with antipsychotic medicinal products. 
Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible 
risk factors for VTE should be identified before and during treatment with TREVICTA and 
preventative measures undertaken.

Antiemetic effect

An antiemetic effect was observed in preclinical studies with paliperidone. This effect, if it occurs in 
humans, may mask the signs and symptoms of overdosage with certain medicinal products or of 
conditions such as intestinal obstruction, Reye’s syndrome and brain tumour.



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Administration

Care must be taken to avoid inadvertent injection of TREVICTA into a blood vessel.

Intraoperative floppy iris syndrome

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients 
treated with medicinal products with alpha 1a-adrenergic antagonist effect, such as TREVICTA (see 
section 4.8).

IFIS may increase the risk of eye complications during and after the operation. Current or past use of 
medicinal products with alpha 1a-adrenergic antagonist effect should be made known to the 
ophthalmic surgeon in advance of surgery. The potential benefit of stopping alpha 1 blocking therapy 
prior to cataract surgery has not been established and must be weighed against the risk of stopping the 
antipsychotic therapy.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially 
sodium-free.

4.5 Interaction with other medicinal products and other forms of interaction

Caution is advised when prescribing TREVICTA with medicinal products known to prolong the QT
interval, e.g., class IA antiarrhythmics (e.g., quinidine, disopyramide) and class III antiarrhythmics
(e.g., amiodarone, sotalol), some antihistaminics, some antibiotics (e.g., fluoroquinolones), some other 
antipsychotics and some antimalarials (e.g., mefloquine). This list is indicative and not exhaustive.

Potential for TREVICTA to affect other medicines

Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicinal 
products that are metabolised by cytochrome P450 isozymes.

Given the primary central nervous system (CNS) effects of paliperidone (see section 4.8), TREVICTA 
should be used with caution in combination with other centrally acting medicinal products, e.g., 
anxiolytics, most antipsychotics, hypnotics, opiates, etc. or alcohol.

Paliperidone may antagonise the effect of levodopa and other dopamine agonists. If this combination 
is deemed necessary, particularly in end-stage Parkinson’s disease, the lowest effective dose of each 
treatment should be prescribed.

Because of its potential for inducing orthostatic hypotension (see section 4.4), an additive effect may 
be observed when TREVICTA is administered with other medicinal products that have this potential, 
e.g., other antipsychotics, tricyclics.

Caution is advised if paliperidone is combined with other medicinal products known to lower the 
seizure threshold (i.e., phenothiazines or butyrophenones, tricyclics or SSRIs, tramadol, mefloquine, 
etc.).

Co-administration of oral paliperidone prolonged release tablets at steady-state (12 mg once daily) 
with divalproex sodium prolonged release tablets (500 mg to 2,000 mg once daily) did not affect the 
steady-state pharmacokinetics of valproate.

No interaction study between TREVICTA and lithium has been performed, however, a 
pharmacokinetic interaction is not likely to occur.



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Potential for other medicines to affect TREVICTA

In vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone 
metabolism, but there are no indications in vitro nor in vivo that these isozymes play a significant role 
in the metabolism of paliperidone. Concomitant administration of oral paliperidone with paroxetine, a 
potent CYP2D6 inhibitor, showed no clinically significant effect on the pharmacokinetics of 
paliperidone.

Co-administration of oral paliperidone prolonged 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. A minor decrease in the amount of 
active substance excreted unchanged in the urine suggests that there was little effect on the CYP 
metabolism or bioavailability of paliperidone during carbamazepine co-administration. Larger 
decreases in plasma concentrations of paliperidone could occur with higher doses of carbamazepine. 
On initiation of carbamazepine, the dose of TREVICTA should be re-evaluated and increased if 
necessary. Conversely, on discontinuation of carbamazepine, the dose of TREVICTA should be 
re-evaluated and decreased if necessary. Consideration should be given to the long-acting nature of 
TREVICTA.

Co-administration of a single dose of an oral paliperidone prolonged release tablet 12 mg with 
divalproex sodium prolonged release tablets (two 500 mg tablets once daily) resulted in an increase of 
approximately 50% in the Cmax and AUC of paliperidone, likely as a result of increased oral
absorption. Since no effect on the systemic clearance was observed, a clinically significant interaction 
would not be expected between divalproex sodium prolonged release tablets and TREVICTA 
intramuscular injection. This interaction has not been studied with TREVICTA.

Concomitant use of TREVICTA with risperidone or oral paliperidone

Since paliperidone is the major active metabolite of risperidone, caution should be exercised when 
TREVICTA is co-administered with risperidone or with oral paliperidone for extended periods of 
time. Safety data involving concomitant use of TREVICTA with other antipsychotics is limited.

Concomitant use of TREVICTA with psychostimulants

The combined use of psychostimulants (e.g. methylphenidate) with paliperidone can lead to
extrapyramidal symptoms upon change of either or both treatments (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data from the use of paliperidone during pregnancy. Intramuscularly injected 
paliperidone palmitate and orally administered paliperidone were not teratogenic in animal studies, but 
other types of reproductive toxicity were seen (see section 5.3). Neonates exposed to paliperidone 
during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or 
withdrawal symptoms that may vary in severity and duration following delivery. There have been 
reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding 
disorder. Consequently, newborns should be monitored carefully. TREVICTA should not be used 
during pregnancy unless clearly necessary.

Since paliperidone has been detected in plasma up to 18 months after a single dose of TREVICTA, 
consideration should be given to the long-acting nature of TREVICTA as maternal exposure to 
TREVICTA before and during pregnancy may lead to adverse reactions in the newborn child.



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Breast-feeding

Paliperidone is excreted in the breast milk to such an extent that effects on the breast-fed infant are 
likely if therapeutic doses are administered to breast-feeding women. Since paliperidone has been 
detected in plasma up to 18 months after a single dose administration of TREVICTA, consideration 
should be given to the long-acting nature of TREVICTA as breastfed infants may be at risk even from 
TREVICTA administration long before breast-feeding. TREVICTA should not be used while 
breast-feeding.

Fertility

There were no relevant effects observed in the non-clinical studies.

4.7 Effects on ability to drive and use machines

Paliperidone can have minor or moderate influence on the ability to drive and use machines due to 
potential nervous system and visual effects, such as sedation, somnolence, syncope, vision blurred (see 
section 4.8). Therefore, patients should be advised not to drive or operate machines until their 
individual susceptibility to TREVICTA is known.

4.8 Undesirable effects

Summary of the safety profile

The most frequently observed adverse drug reactions reported in ≥ 5% of patients in two double-blind
controlled clinical trials of TREVICTA were weight increased, upper respiratory tract infection, 
anxiety, headache, insomnia, and injection site reaction.

Tabulated list of adverse reactions

The following are all ADRs that were reported with paliperidone by frequency category estimated 
from paliperidone palmitate 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).

System organ class Adverse drug reaction
Frequency

Very 
common

Common Uncommon Rare Not knowna

Infections and 
infestations

upper respiratory tract 
infection, urinary tract 
infection, influenza

pneumonia, 
bronchitis, 
respiratory tract 
infection, sinusitis, 
cystitis, ear 
infection, 
tonsillitis, 
onychomycosis, 
cellulitis

eye infection, 
acarodermatitis, 
subcutaneous 
abscess

Blood and 
lymphatic system 
disorders

white blood cell 
count decreased, 
thrombocytopenia, 
anaemia

neutropenia, 
eosinophil count 
increased

agranulocytosis

Immune system 
disorders

hypersensitivity anaphylactic 
reaction

Endocrine 
disorders

hyperprolactinaemiab inappropriate 
antidiuretic 
hormone secretion, 
glucose urine 
present



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Metabolism and 
nutrition disorders

hyperglycaemia, weight 
increased, weight 
decreased, decreased 
appetite,

diabetes mellitusd, 
hyperinsulinaemia, 
increased appetite, 
anorexia, blood 
triglycerides 
increased, blood 
cholesterol 
increased

diabetic 
ketoacidosis, 
hypoglycaemia, 
polydipsia

water intoxication

Psychiatric 
disorders

insomniae agitation, depression, 
anxiety

sleep disorder, 
mania, libido 
decreased, 
nervousness, 
nightmare

catatonia, 
confusional state, 
somnambulism, 
blunted affect, 
anorgasmia

sleep-related 
eating disorder

Nervous system 
disorders

parkinsonism
c
, 

akathisia
c
, sedation/ 

somnolence, dystonia
c
, 

dizziness, dyskinesia
c
, 

tremor, headache

tardive dyskinesia, 
syncope, 
psychomotor 
hyperactivity, 
dizziness postural, 
disturbance in 
attention, 
dysarthria, 
dysgeusia, 
hypoaesthesia, 
paraesthesia

neuroleptic 
malignant 
syndrome, cerebral 
ischaemia,
unresponsive to 
stimuli, loss of 
consciousness, 
depressed level of 
consciousness,
convulsione, 
balance disorder,
coordination 
abnormal,

diabetic coma, 
head titubation

Eye disorders vision blurred, 
conjunctivitis, dry 
eye

glaucoma, eye 
movement 
disorder, eye 
rolling, 
photophobia, 
lacrimation 
increased, ocular 
hyperaemia

floppy iris 
syndrome
(intraoperative)

Ear and labyrinth 
disorders

vertigo, tinnitus, 
ear pain

Cardiac disorders tachycardia atrioventricular 
block, conduction 
disorder, 
electrocardiogram 
QT prolonged, 
postural orthostatic 
tachycardia 
syndrome, 
bradycardia, 
electrocardiogram 
abnormal, 
palpitations

atrial fibrillation, 
sinus arrhythmia

Vascular disorders hypertension hypotension, 
orthostatic 
hypotension

venous thrombosis, 
flushing

pulmonary 
embolism, 
ischaemia

Respiratory, 
thoracic and 
mediastinal 
disorders

cough, nasal congestion dyspnoea, 
respiratory tract 
congestion, 
wheezing, 
pharyngolaryngeal 
pain, epistaxis

sleep apnoea 
syndrome, 
pulmonary 
congestion, rales

hyperventilation, 
pneumonia 
aspiration, 
dysphonia

Gastrointestinal 
disorders

abdominal pain, 
vomiting, nausea, 
constipation, diarrhoea, 
dyspepsia, toothache

abdominal 
discomfort, 
gastroenteritis,
dysphagia, dry 
mouth, flatulence

pancreatitis, 
swollen tongue, 
faecal 
incontinence, 
faecaloma, cheilitis

intestinal 
obstruction, ileus

Hepatobiliary 
disorders

transaminases increased gamma-glutamyltr
ansferase 
increased, hepatic 
enzyme increased

jaundice



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Skin and 
subcutaneous 
tissue disorders

urticaria, pruritus, 
rash, alopecia, 
eczema, dry skin, 
erythema, acne

drug eruption, 
hyperkeratosis, 
dandruff

angioedema, skin 
discolouration, 
seborrhoeic 
dermatitis

Musculoskeletal 
and connective 
tissue disorders

musculoskeletal pain, 
back pain, arthralgia

blood creatine 
phosphokinase 
increased, muscle 
spasms, joint 
stiffness, muscular 
weakness, neck 
pain

rhabdomyolysis, 
joint swelling

posture abnormal

Renal and urinary 
disorders

urinary 
incontinence, 
pollakiuria, 
dysuria

urinary retention

Pregnancy, 
puerperium and 
perinatal 
conditions

drug withdrawal 
syndrome 
neonatal
(see section 4.6)

Reproductive 
system and breast 
disorders

amenorrhoea,
galactorrhoea

erectile 
dysfunction, 
ejaculation 
disorder,
menstrual
disordere, 
gynaecomastia, 
sexual 
dysfunction, breast 
pain

breast discomfort, 
breast 
engorgement, 
breast enlargement, 
vaginal discharge

priapism

General disorders 
and administration 
site conditions

pyrexia, asthenia, 
fatigue, injection site 
reaction

face oedema, 

oedema
e
, body 

temperature 
increased, gait 
abnormal, chest 
pain, chest 
discomfort, 
malaise, induration

hypothermia, 
chills, thirst, drug 
withdrawal 
syndrome, 
injection site 
abscess, injection 
site cellulitis, 
injection site cyst, 
injection site 
haematoma

body temperature 
decreased, 
injection site 
necrosis, injection 
site ulcer

Injury, poisoning 
and procedural 
complications

fall

a
The frequency of adverse reactions is qualified as “not known” because they were not observed in paliperidone 
palmitate clinical trials. They were either derived from spontaneous post-marketing reports and frequency cannot be 
determined, or they were derived from risperidone (any formulation) or oral paliperidone clinical trials data and/or 
post-marketing reports.

b
Refer to ‘Hyperprolactinaemia’ below.

c
Refer to ‘Extrapyramidal symptoms’ below.

d
In placebo-controlled trials, diabetes mellitus was reported in 0.32% in subjects treated with 1-monthly paliperidone 
palmitate injectable compared to a rate of 0.39% in placebo group. Overall incidence from all clinical trials was 0.65%
in all subjects treated 1-monthly paliperidone palmitate injectable.

e
Insomnia includes: initial insomnia, middle insomnia; Convulsion includes: grand mal convulsion; Oedema 
includes: generalised oedema, oedema peripheral, pitting oedema Menstrual disorder includes: menstruation delayed, 
menstruation irregular, oligomenorrhoea.

Undesirable effects noted with risperidone formulations

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.



14

Description of selected adverse reactions

Anaphylactic reaction
Rarely, cases of anaphylactic reaction after injection with 1-monthly paliperidone palmitate injectable 
have been reported during post-marketing experience in patients who have previously tolerated oral 
risperidone or oral paliperidone (see section 4.4).

Injection site reactions
In clinical trials of TREVICTA, 5.3% of subjects reported injection site related adverse reaction. None 
of these events were serious or led to discontinuation. Based on the investigators’ ratings, induration, 
redness, and swelling were absent or mild in ≥ 95% of the assessments. Subject-rated injection site 
pain based on a visual analogue scale was low and decreased in intensity over time.

Extrapyramidal symptoms (EPS)
In the clinical trials of TREVICTA, akathisia, dyskinesia, dystonia, parkinsonism, and tremor were 
reported in 3.9%, 0.8%, 0.9%, 3.6%, and 1.4% of subjects, respectively.

Extrapyramidal symptoms (EPS) included a pooled analysis of the following terms: parkinsonism 
(includes extrapyramidal disorder, extrapyramidal symptoms, on and off phenomenon, Parkinson’s 
disease, parkinsonian crisis, salivary hypersecretion, musculoskeletal stiffness, parkinsonism, 
drooling, cogwheel rigidity, bradykinesia, hypokinesia, masked facies, muscle tightness, akinesia, 
nuchal rigidity, muscle rigidity, parkinsonian gait, glabellar reflex abnormal, and parkinsonian rest 
tremor), akathisia (includes akathisia, restlessness, hyperkinesia, and restless leg syndrome), 
dyskinesia (dyskinesia, chorea, movement disorder, muscle twitching, choreoathetosis, athetosis, and 
myoclonus), dystonia (includes dystonia, cervical spasm, emprosthotonus, oculogyric crisis, 
oromandibular dystonia, risus sardonicus, tetany, hypertonia, torticollis, muscle contractions 
involuntary, muscle contracture, blepharospasm, oculogyration, tongue paralysis, facial spasm, 
laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue spasm, and 
trismus), and tremor.

Weight gain
In the long-term randomised withdrawal study, abnormal increases of ≥ 7% in body weight from 
double-blind baseline to double-blind end point were reported for 10% subjects in the TREVICTA 
group and 1% subjects in the placebo group. Conversely, abnormal decreases in body weight (≥ 7%) 
from double-blind baseline to double-blind end point were reported for 1% subjects in the TREVICTA 
group and 8% subjects in the placebo group. The mean changes in body weight from double-blind 
baseline to double-blind end point were +0.94 kg and -1.28 kg for the TREVICTA and placebo
groups, respectively.

Hyperprolactinaemia
During the double-blind phase of the long-term randomised withdrawal study, elevations of prolactin 
to above the reference range (> 13.13 ng/mL in males and > 26.72 ng/mL in females) were noted in a 
higher percentage of males and females in the TREVICTA group than in the placebo group (9% vs. 
3% and 5% vs. 1%, respectively). In the TREVICTA group, the mean change from double-blind 
baseline to double-blind end point was +2.90 ng/mL for males (vs. -10.26 ng/mL in the placebo group) 
and +7.48 ng/mL for females (vs. -32.93 ng/mL in the placebo group). One female (2.4%) in the 
TREVICTA group experienced an adverse reaction of amenorrhea, while no potentially prolactin 
related adverse reactions were noted among females in the placebo group. There were no potentially 
prolactin related adverse reactions among males in either group.

Class effects

QT prolongation, ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), sudden 
unexplained death, cardiac arrest, and Torsade de pointes may occur with antipsychotics.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein 
thrombosis, have been reported with antipsychotic medicinal products (frequency unknown).



15

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medical product is important. It allows 
continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are 
asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

4.9 Overdose

Symptoms

In general, expected signs and symptoms are those resulting from an exaggeration of paliperidone’s 
known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension, QT 
prolongation, and extrapyramidal symptoms. Torsade de pointes and ventricular fibrillation have been 
reported in a patient in the setting of overdose with oral paliperidone. In the case of acute overdose, 
the possibility of multiple drug involvement should be considered.

Management

Consideration should be given to the long-acting nature of the medicinal product and the long 
elimination half-life of paliperidone when assessing treatment needs and recovery. There is no specific 
antidote to paliperidone. General supportive measures should be employed. Establish and maintain a 
clear airway and ensure adequate oxygenation and ventilation.

Cardiovascular monitoring should commence immediately and should include continuous 
electrocardiographic monitoring for possible arrhythmias. Hypotension and circulatory collapse should 
be treated with appropriate measures such as intravenous fluid and/or sympathomimetic agents. In 
case of severe extrapyramidal symptoms, anticholinergic agents should be administered. Close 
supervision and monitoring should continue until the patient recovers.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Psycholeptics, other antipsychotics. ATC code: N05AX13

TREVICTA contains a racemic mixture of (+)- and (-)-paliperidone.

Mechanism of action

Paliperidone is a selective blocking agent of monoamine effects, whose pharmacological properties 
are different from that of traditional neuroleptics. Paliperidone binds strongly to serotonergic 5-HT2-
and dopaminergic D2-receptors. Paliperidone also blocks alpha 1-adrenergic receptors and slightly 
less, H1-histaminergic and alpha 2-adrenergic receptors. The pharmacological activity of the (+)- and 
(-)-paliperidone enantiomers are qualitatively and quantitatively similar.

Paliperidone is not bound to cholinergic receptors. Even though paliperidone is a strong 
D2-antagonist, which is believed to relieve the symptoms of schizophrenia, it causes less catalepsy and 
decreases motor functions less than traditional neuroleptics. Dominating central serotonin antagonism 
may reduce the tendency of paliperidone to cause extrapyramidal side effects.

Clinical efficacy

The efficacy of TREVICTA in the maintenance treatment of schizophrenia in subjects who have been 
adequately treated for at least four months with 1-monthly paliperidone palmitate injectable and the
last two doses of the same dosage strength was evaluated in one long-term randomised withdrawal 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


16

double-blind, placebo-controlled study and one long-term double-blind, active-controlled, 
non-inferiority study. For both studies, the primary outcome was based on relapse.

In the long-term randomised withdrawal study, 506 adult subjects who met DSM-IV criteria for 
schizophrenia were enrolled into the open-label transition phase and treated with flexible doses of 
1-monthly paliperidone palmitate injectable administered into the deltoid or gluteal muscle 
(50-150 mg) for 17 weeks (dose adjustments occurred at weeks 5 and 9). A total of 379 subjects then 
received a single dose of TREVICTA in either the deltoid or gluteal muscle in the open-label 
stabilisation phase (dose was a 3.5 multiple of the last dose of 1-monthly paliperidone palmitate). 
Subjects who were considered clinically stable at the end of the 12-week stabilisation phase were then 
randomised 1:1 to TREVICTA or placebo in a variable duration double-blind phase (the dose of 
TREVICTA was the same as the last dose received during the stabilisation phase; this dose remained 
fixed throughout the double-blind phase). In this period, 305 symptomatically stable subjects were 
randomised to continue treatment with TREVICTA (n = 160) or placebo (n = 145) until relapse, early 
withdrawal, or the end of study. The primary efficacy variable was time to first relapse. The study was 
terminated on the basis of a pre-planned interim analysis conducted when 283 subjects had been 
randomised and 42 relapse events had been observed.

Based on the final analysis (N = 305), 42 subjects (29.0%) in the placebo group and 14 subjects 
(8.8%) in the TREVICTA group had experienced a relapse event during the double blind phase. The 
hazard ratio was 3.81 (95% CI: 2.08, 6.99) indicating a 74% decrease in relapse risk with TREVICTA 
compared to placebo. A Kaplan Meier plot of time to relapse by treatment group is shown in Figure 1. 
There was a significant difference (p < 0.0001) between the two treatment groups in the time to 
relapse in favour of TREVICTA. The time to relapse of the placebo group (median 395 days) was 
significantly shorter than for the TREVICTA group (the median could not be estimated due to the low 
percentage of subjects with relapse [8.8%]).

Time(days) since Randomization

28 56 84 112 140 168 196 224 252 280 308 336 364 392 420 448

E
s
ti
m

a
te

d
 P

e
rc

e
n
t 
o

f 
S

u
b
je

c
ts

 W
it
h
o

u
t 
R

e
la

p
s
e

0

20

40

60

80

100

     Placebo (N=145)

TREVICTA (N=160) logrank test, p-value<0.0001

Figure 1: Kaplan-Meier plot of time to relapse – Final analysis

In the non-inferiority study, 1,429 acutely ill subjects (baseline mean PANSS total score: 85.7) who 
met DSM-IV criteria for schizophrenia were enrolled into the open-label phase and treated with
1-monthly paliperidone palmitate injectable for 17 weeks. The dose could be adjusted (i.e., 50 mg, 
75 mg, 100 mg, or 150 mg) at the week 5 and 9 injections and the injection site could be deltoid or 
gluteal. For subjects that met randomisation criteria at weeks 14 and 17, 1,016 were randomised in a 
1:1 ratio to continue on monthly injections of 1-monthly paliperidone palmitate injectable or to switch 
to TREVICTA with a 3.5 multiple of the week 9 and 13 dose of 1-monthly paliperidone palmitate 
injectable for 48 weeks. Subjects received TREVICTA once every 3 months and received 



17

placebo-injectable medication for the other months to maintain the blind. The primary efficacy 
endpoint of the study was the percentage of subjects who had not relapsed at the end of the 48-week 
double-blind phase based on the Kaplan-Meier 48-week estimate (TREVICTA: 91.2%, 1-monthly
paliperidone palmitate injectable: 90.0%). The median time to relapse in either group could not be 
estimated due to low percentage of subjects with relapse. The difference (95% CI) between the 
treatment groups was 1.2% (-2.7%, 5.1%), meeting non-inferiority criterion based on a margin of 
-10%. Thus, the TREVICTA treatment group was non-inferior to 1-monthly paliperidone palmitate 
injectable. Improvements in functioning, as measured by the Personal and Social Performance scale 
(PSP), which was observed during the open-label stabilisation phase were maintained during the 
double-blind phase for both treatment groups.

Figure 2: Kaplan-Meier plot of time to relapse comparing TREVICTA and 1-monthly paliperidone 
palmitate injectable

The efficacy results were consistent across population subgroups (gender, age, and race) in both 
studies.

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with 
TREVICTA in all subsets of the paediatric population in schizophrenia. See section 4.2 for 
information on paediatric use.

5.2 Pharmacokinetic properties

Absorption and distribution

Due to its extremely low water solubility, the 3-monthly formulation of paliperidone palmitate 
dissolves slowly after intramuscular injection before being hydrolysed to paliperidone and absorbed 
into the systemic circulation. The release of the active substance starts as early as day 1 and lasts for as 
long as 18 months.

The data presented in this paragraph are based on a population pharmacokinetic analysis. Following a 
single intramuscular dose of TREVICTA, the plasma concentrations of paliperidone gradually rise to 
reach maximum plasma concentrations at a median Tmax of 30-33 days. Following intramuscular 
injection of TREVICTA at doses of 175-525 mg in the deltoid muscle, on average, an 11-12% higher 
Cmax was observed compared with injection in the gluteal muscle. The release profile and dosing 
regimen of TREVICTA results in sustained therapeutic concentrations. The total exposure of 
paliperidone following TREVICTA administration was dose-proportional over a 175-525 mg dose 
range, and approximately dose-proportional for Cmax. The mean steady-state peak:trough ratio for a 
TREVICTA dose was 1.6 following gluteal administration and 1.7 following deltoid administration.



18

The plasma protein binding of racemic paliperidone is 74%.

Following administration of TREVICTA, the (+) and (-) enantiomers of paliperidone interconvert, 
reaching an AUC (+) to (-) ratio of approximately 1.7-1.8.

Biotransformation and elimination

In a study with oral immediate release 14C-paliperidone, one week following administration of a single 
oral dose of 1 mg immediate release 14C-paliperidone, 59% of the dose was excreted unchanged into 
urine, indicating that paliperidone is not extensively metabolised in the liver. Approximately 80% of 
the administered radioactivity was recovered in urine and 11% in the faeces. Four metabolic pathways 
have been identified in vivo, none of which accounted for more than 10% of the dose: dealkylation, 
hydroxylation, dehydrogenation, and benzisoxazole scission. Although in vitro studies suggested a 
role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, there is no evidence in vivo that 
these isozymes play a significant role in the metabolism of paliperidone. Population pharmacokinetics 
analyses indicated no discernible difference on the apparent clearance of paliperidone after 
administration of oral paliperidone between extensive metabolisers and poor metabolisers of CYP2D6 
substrates. In vitro studies in human liver microsomes showed that paliperidone does not substantially 
inhibit the metabolism of medicines metabolised by cytochrome P450 isozymes, including CYP1A2, 
CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5.

In vitro studies have shown that paliperidone is a P-gp substrate and a weak inhibitor of P-gp at high 
concentrations. No in vivo data are available and the clinical relevance is unknown.

Based on population pharmacokinetic analysis, the median apparent half-life of paliperidone following 
TREVICTA administration over the dose range of 175-525 mg ranged from 84-95 days following 
deltoid injections and 118-139 days following gluteal injections.

Long-acting 3-monthly paliperidone palmitate injection versus other paliperidone formulations

TREVICTA is designed to deliver paliperidone over a 3-month period, while 1-monthly paliperidone 
palmitate injection is administered on a monthly basis. TREVICTA, when administered at doses that 
are 3.5-fold higher than the corresponding dose of 1-monthly paliperidone palmitate injection (see 
section 4.2), results in paliperidone exposures similar to those obtained with corresponding monthly 
doses of 1-monthly paliperidone palmitate injection and corresponding once daily doses of 
paliperidone prolonged release tablets. The exposure range for TREVICTA is encompassed within the 
exposure range for the approved dose strengths of paliperidone prolonged release tablets.

Hepatic impairment

Paliperidone is not extensively metabolised in the liver. Although TREVICTA was not studied in 
patients with hepatic impairment, no dose adjustment is required in patients with mild or moderate 
hepatic impairment. In a study with oral paliperidone in subjects with moderate hepatic impairment 
(Child-Pugh class B), the plasma concentrations of free paliperidone were similar to those of healthy 
subjects. Paliperidone has not been studied in patients with severe hepatic impairment.

Renal impairment

TREVICTA has not been systematically studied in patients with renal impairment. The disposition of 
a single oral dose of a paliperidone 3 mg prolonged release tablet was studied in subjects with varying 
degrees of renal function. Elimination of paliperidone decreased with decreasing estimated creatinine 
clearance. Total clearance of paliperidone was reduced in subjects with impaired renal function by 
32% on average in mild (CrCl = 50 to < 80 mL/min), 64% in moderate (CrCl = 30 to < 50 mL/min), 
and 71% in severe (CrCl = 10 to < 30 mL/min) renal impairment, corresponding to an average 
increase in exposure (AUCinf) of 1.5, 2.6, and 4.8-fold, respectively, compared to healthy subjects.



19

Elderly

Population pharmacokinetics analysis showed no evidence of age related pharmacokinetics 
differences.

Body mass index (BMI)/body weight

Lower Cmax was observed in overweight and obese subjects. At apparent steady-state with 
TREVICTA, the trough concentrations were similar among normal, overweight, and obese subjects.

Race

Population pharmacokinetics analysis showed no evidence of race related pharmacokinetics 
differences.

Gender

Population pharmacokinetics analysis showed no evidence of gender related pharmacokinetics 
differences.

Smoking status

Based on in vitro studies utilising human liver enzymes, paliperidone is not a substrate for CYP1A2; 
smoking should, therefore, not have an effect on the pharmacokinetics of paliperidone. Effect of 
smoking on the pharmacokinetics of paliperidone was not studied with TREVICTA. A population 
pharmacokinetic analysis based on data with oral paliperidone prolonged release tablets showed a 
slightly lower exposure to paliperidone in smokers compared with non-smokers. The difference is not 
likely to be of clinical relevance.

5.3 Preclinical safety data

Repeat-dose toxicity studies of intramuscularly injected paliperidone palmitate (the 1-monthly
formulation) and orally administered paliperidone in rat and dog showed mainly pharmacological 
effects, such as sedation and prolactin-mediated effects on mammary glands and genitals. In animals 
treated with paliperidone palmitate an inflammatory reaction was seen at the intramuscular injection 
site. Occasionally abscess formation occurred.

In rat reproduction studies with oral risperidone, which is extensively converted to paliperidone in rats 
and humans, adverse effects were seen on the birth weight and survival of the offspring. No 
embryotoxicity or malformations were observed following intramuscular administration of 
paliperidone palmitate to pregnant rats up to the highest dose (160 mg/kg/day) corresponding to 
2.2 times the exposure level in humans at the maximum recommended dose of 525 mg. Other 
dopamine antagonists, when administered to pregnant animals, have caused negative effects on 
learning and motor development in the offspring.

Paliperidone palmitate and paliperidone were not genotoxic. In oral carcinogenicity studies of 
risperidone in rats and mice, increases in pituitary gland adenomas (mouse), endocrine pancreas 
adenomas (rat), and mammary gland adenomas (both species) were seen. The carcinogenic potential 
of intramuscularly injected paliperidone palmitate was assessed in rats. There was a statistically 
significant increase in mammary gland adenocarcinomas in female rats at 10, 30 and 60 mg/kg/month. 
Male rats showed a statistically significant increase in mammary gland adenomas and carcinomas at 
30 and 60 mg/kg/month which is 0.6 and 1.2 times the exposure level at the maximum recommended 
human 525 mg dose. These tumours can be related to prolonged dopamine D2-antagonism and 
hyperprolactinemia. The relevance of these tumour findings in rodents in terms of human risk is 
unknown.



20

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Polysorbate 20
Polyethylene glycol 4000
Citric acid monohydrate
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

2 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Pre-filled syringe (cyclic-olefin-copolymer) with a plunger stopper, backstop, and tip cap (bromobutyl 
rubber) with a thin wall 22G 1½ inch (0.72 mm x 38.1 mm) safety needle and a thin wall 22G 1 inch 
(0.72 mm x 25.4 mm) safety needle.

Pack sizes:
Pack contains 1 pre-filled syringe and 2 needles

6.6 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

Full instructions for use and handling of TREVICTA are provided in the package leaflet (See 
Information intended for medical or health care professionals).

7. MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/971/007
EU/1/14/971/008
EU/1/14/971/009
EU/1/14/971/010



21

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 05 December 2014
Date of latest renewal:

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

http://www.ema.europa.eu/


22

ANNEX II

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 
SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT



23

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release

Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk Management Plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.



24

ANNEX III

LABELLING AND PACKAGE LEAFLET



25

A. LABELLING



26

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

TREVICTA 175 mg prolonged release suspension for injection
paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 175 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: polysorbate 20, polyethylene glycol 4000, citric acid monohydrate, sodium dihydrogen 
phosphate monohydrate, sodium hydroxide, water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection
1 pre-filled syringe
2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

Administer every 3 months

Shake syringe vigorously for at least 15 seconds

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



27

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/971/007

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

trevicta 175 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:



28

NN:



29

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

TREVICTA 175 mg injection
paliperidone
IM

2. METHOD OF ADMINISTRATION

Shake vigorously

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

175 mg

6. OTHER



30

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

TREVICTA 263 mg prolonged release suspension for injection
paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 263 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: polysorbate 20, polyethylene glycol 4000, citric acid monohydrate, sodium dihydrogen 
phosphate monohydrate, sodium hydroxide, water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection
1 pre-filled syringe
2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

Administer every 3 months

Shake syringe vigorously for at least 15 seconds

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



31

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/971/008

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

trevicta 263 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA
PC:
SN:
NN:



32

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

TREVICTA 263 mg injection
paliperidone
IM

2. METHOD OF ADMINISTRATION

Shake vigorously

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

263 mg

6. OTHER



33

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

TREVICTA 350 mg prolonged release suspension for injection
paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 350 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: polysorbate 20, polyethylene glycol 4000, citric acid monohydrate, sodium dihydrogen 
phosphate monohydrate, sodium hydroxide, water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection
1 pre-filled syringe
2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

Administer every 3 months

Shake syringe vigorously for at least 15 seconds

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



34

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/971/009

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

trevicta 350 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA
PC:
SN:
NN:



35

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

TREVICTA 350 mg injection
paliperidone
IM

2. METHOD OF ADMINISTRATION

Shake vigorously

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

350 mg

6. OTHER



36

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

TREVICTA 525 mg prolonged release suspension for injection
paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 525 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: polysorbate 20, polyethylene glycol 4000, citric acid monohydrate, sodium dihydrogen 
phosphate monohydrate, sodium hydroxide, water for injections

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection
1 pre-filled syringe
2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

Administer every 3 months

Shake syringe vigorously for at least 15 seconds

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



37

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/971/010

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

trevicta 525 mg

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA
PC:
SN:
NN:



38

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

TREVICTA 525 mg injection
paliperidone
IM

2. METHOD OF ADMINISTRATION

Shake vigorously

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

525 mg

6. OTHER



39

B. PACKAGE LEAFLET



40

Package leaflet: Information for the user

TREVICTA 175 mg prolonged release suspension for injection
TREVICTA 263 mg prolonged release suspension for injection
TREVICTA 350 mg prolonged release suspension for injection
TREVICTA 525 mg prolonged release suspension for injection

paliperidone

Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What TREVICTA is and what it is used for
2. What you need to know before you use TREVICTA
3. How to use TREVICTA
4. Possible side effects
5. How to store TREVICTA
6. Contents of the pack and other information

1. What TREVICTA is and what it is used for

TREVICTA contains the active substance paliperidone which belongs to the class of antipsychotic 
medicines and is used as a maintenance treatment for the symptoms of schizophrenia in adult patients.

If you have responded well to treatment with paliperidone palmitate injection given once a month, 
your doctor may start treatment with TREVICTA.

Schizophrenia is a disease with “positive” and “negative” symptoms. Positive means an excess of 
symptoms that are not normally present. For example, a person with schizophrenia may hear voices or 
see things that are not there (called hallucinations), believe things that are not true (called delusions), 
or feel unusually suspicious of others. Negative means a lack of behaviours or feelings that are 
normally present. For example, a person with schizophrenia may appear withdrawn and may not 
respond at all emotionally or may have trouble speaking in a clear and logical way. People with this 
disease may also feel depressed, anxious, guilty, or tense.

TREVICTA can help alleviate the symptoms of your disease and reduce the chance of your symptoms 
coming back.

2. What you need to know before you use TREVICTA

Do not use TREVICTA
- if you are allergic to paliperidone or any of the other ingredients of this medicine (listed in 

section 6).
- if you are allergic to another antipsychotic medicine including the substance risperidone.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using TREVICTA.
This medicine has not been studied in elderly patients with dementia. However, elderly patients with 
dementia, who are treated with other similar types of medicine, may have an increased risk of stroke 
or death (see section 4).



41

All medicines have side effects and some of the side effects of this medicine can worsen the symptoms 
of other medical conditions. For that reason, it is important to discuss with your doctor any of the 
following conditions which can potentially worsen during treatment with this medicine:

- if you have Parkinson’s disease
- if you have ever been diagnosed with a condition whose symptoms include high temperature 

and muscle stiffness (also known as Neuroleptic Malignant Syndrome)
- if you have ever experienced twitching or jerking movements that you cannot control in your 

face, tongue, or other parts of your body (Tardive Dyskinesia)
- if you know that you have had low levels of white blood cells in the past (which may or may not 

have been caused by other medicines)
- if you are diabetic or prone to diabetes
- if you have had breast cancer or a tumour in the pituitary gland in your brain
- if you have a heart disease or heart disease treatment that makes you prone to low blood 

pressure
- if you have low blood pressure when you stand up or sit up suddenly
- if you have a history of seizures
- if you have kidney problems
- if you have liver problems
- if you have prolonged and/or painful erection
- if you have problems with controlling body temperature or overheating
- if you have an abnormally high level of the hormone prolactin in your blood or if you have a 

possible prolactin-dependent tumour
- if you or someone else in your family has a history of blood clots, as antipsychotics have been 

associated with formation of blood clots.

If you have any of these conditions, please talk to your doctor as he/she may want to adjust your dose 
or monitor you for a while.

As dangerously low numbers of a certain type of white blood cell needed to fight infection in your 
blood has been seen very rarely with patients taking this medicine, your doctor may check your white 
blood cell counts.

Even if you have previously tolerated oral paliperidone or risperidone, rarely allergic reactions occur 
after receiving injections of TREVICTA. Seek medical attention right away if you experience a rash, 
swelling of your throat, itching, or problems breathing as these may be signs of a serious allergic 
reaction.

This medicine may cause you to gain weight. Significant weight gain may be bad for your health. 
Your doctor should regularly measure your body weight.

As diabetes mellitus or worsening of pre-existing diabetes mellitus have been seen with patients taking 
this medicine, your doctor should check for signs of high blood sugar. In patients with pre-existing 
diabetes mellitus blood glucose should be monitored regularly.

Since this medicine may reduce your urge to vomit, there is a chance that it may mask the body’s 
normal response to ingestion of toxic substances or other medical conditions.

During an operation on the eye for cloudiness of the lens (cataract), the pupil (the black circle in the 
middle of your eye) may not increase in size as needed. Also, the iris (the coloured part of the eye) 
may become floppy during surgery and that may lead to eye damage. If you are planning to have an 
operation on your eye, make sure you tell your eye doctor that you are taking this medicine.

Children and adolescents
Do not use this medicine in children and adolescents under 18 years of age. It is not known if it is safe 
and effective in these patients.



42

Other medicines and TREVICTA
Tell your doctor if you are taking, have recently taken or might take any other medicines.

Taking this medicine with carbamazepine (an anti-epileptic and mood stabiliser) may require a change 
to your dose of this medicine.

Since this medicine works primarily in the brain, using other medicines that work in the brain can 
cause an exaggeration of side effects such as sleepiness or other effects on the brain such as other 
psychiatric medications, opioids, antihistamines and sleep medication.

Since this medicine can lower blood pressure, care should be taken when this medicine is used with 
other medicines that lower blood pressure.

This medicine can reduce the effect of medicines against Parkinson’s disease and restless legs 
syndrome (e.g., levodopa).

This medicine may cause an electrocardiogram (ECG) abnormality demonstrating a long time for an 
electrical impulse to travel through a certain part of the heart (known as “QT prolongation”). Other 
medicines that have this effect include some medicines used to treat the rhythm of the heart or to treat 
infection, and other antipsychotics.

If you have a history of seizures, this medicine may increase your chance of experiencing them. Other 
medicines that have this effect include some medicines used to treat depression or to treat infection, 
and other antipsychotics.

TREVICTA should be used with caution with medicines that increase the activity of the central 
nervous system (psychostimulants such as methylphenidate).

TREVICTA with alcohol
Alcohol should be avoided.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask
your doctor or pharmacist for advice before taking this medicine. You should not use this medicine 
during pregnancy unless this has been discussed with your doctor. The following symptoms may occur 
in newborn babies of mothers that have used paliperidone in the last trimester (last three months of 
their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, agitation, breathing problems, 
and difficulty in feeding. If your baby develops any of these symptoms seek medical attention for your 
baby.

This medicine can pass from mother to baby through breast milk and may harm the baby. Therefore, 
you should not breast-feed when using this medicine.

Driving and using machines
Dizziness, extreme tiredness and vision problems may occur during treatment with this medicine (see 
section 4). This should be considered in cases where full alertness is required, e.g., when driving a car 
or handling machines.

TREVICTA contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’.



43

3. How to use TREVICTA

This medicine is administered by your doctor or other health care professional. Your doctor will tell 
you when you need your next injection. It is important not to miss your scheduled dose. If you cannot 
keep your appointment with the doctor, make sure you call him right away so another appointment can 
be made as soon as possible.

You will receive an injection of TREVICTA in the upper arm or buttocks once every 3 months.

Depending on your symptoms, your doctor may increase or decrease the amount of medicine you 
receive at the time of your next scheduled injection.

Patients with kidney problems
If you have mild kidney problems your doctor will determine the appropriate dose of TREVICTA 
based on the dose of 1-monthly paliperidone palmitate injectable that you have been receiving. If you 
have moderate or severe kidney problems this medicine should not be used.

Elderly
Your doctor will determine your dose of this medicine if your kidney function is reduced.

If you are given more TREVICTA than needed
This medicine will be given to you under medical supervision; it is, therefore, unlikely that you will be 
given too much.

Patients who have been given too much paliperidone may experience the following symptoms:
drowsiness or sedation, fast heart rate, low blood pressure, an abnormal electrocardiogram (electrical 
tracing of the heart), or slow or abnormal movements of the face, body, arms or legs.

If you stop using TREVICTA
If you stop receiving your injections, your symptoms of schizophrenia may get worse. You should not 
stop using this medicine unless told to do so by your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you:
 experience blood clots in the veins, especially in the legs (symptoms include swelling, pain, and 

redness in the leg), which may travel through blood vessels to the lungs causing chest pain and 
difficulty breathing. If you notice any of these symptoms seek medical advice immediately.

 have dementia and experience a sudden change in your mental state or sudden weakness or 
numbness of your face, arms or legs, especially on one side, or slurred speech, even for a short 
period of time. These may be signs of a stroke.

 experience fever, muscle stiffness, sweating or a lowered level of consciousness (a disorder 
called “Neuroleptic Malignant Syndrome”). Immediate medical treatment may be needed

 are a man and experience prolonged or painful erection. This is called priapism. Immediate 
medical treatment may be needed.

 experience involuntary rhythmic movements of the tongue, mouth and face. Withdrawal of 
paliperidone may be needed.

 experience a severe allergic reaction characterised by fever, swollen mouth, face, lip or tongue, 
shortness of breath, itching, skin rash and sometimes drop in blood pressure (amounting to an 
‘anaphylactic reaction’). Even if you have previously tolerated oral risperidone or oral 
paliperidone, rarely allergic reactions occur after receiving injections of paliperidone.



44

 are planning to have an operation on your eye, make sure you tell your eye doctor that you are 
taking this medicine. During an operation on the eye for cloudiness of the lens (cataract), the iris 
(the coloured part of the eye) may become floppy during surgery (known as “floppy iris 
syndrome”) that may lead to eye damage.

 are aware of having dangerously low numbers of a certain type of white blood cell needed to 
fight infection in your blood.

The following side effects may happen:

Very common side effects: may affect more than 1 in 10 people
 difficulty falling or staying asleep.

Common side effects: may affect up to 1 in 10 people
 common cold symptoms, urinary tract infection, feeling like you have the flu
 TREVICTA can raise your levels of a hormone called "prolactin" found on a blood test (which 

may or may not cause symptoms). When symptoms of high prolactin occur, they may include: 
(in men) breast swelling, difficulty in getting or maintaining erections, or other sexual 
dysfunction; (in women) breast discomfort, leakage of milk from the breasts, missed menstrual 
periods, or other problems with your cycle.

 high blood sugar, weight gain, weight loss, decreased appetite
 irritability, depression, anxiety
 feeling restless
 parkinsonism: This condition may include slow or impaired movement, sensation of stiffness or 

tightness of the muscles (making your movements jerky), and sometimes even a sensation of 
movement "freezing up" and then restarting. Other signs of parkinsonism include a slow 
shuffling walk, a tremor while at rest, increased saliva and/or drooling, and a loss of expression 
on the face.

 restlessness, feeling sleepy, or less alert
 dystonia: This is a condition involving slow or sustained involuntary contraction of muscles. 

While it can involve any part of the body (and may result in abnormal posture), dystonia often 
involves muscles of the face, including abnormal movements of the eyes, mouth, tongue or jaw.

 dizziness
 dyskinesia: This is a condition involving involuntary muscle movements, and can include 

repetitive, spastic or writhing movements, or twitching.
 tremor (shaking)
 headache
 rapid heart rate
 high blood pressure
 cough, stuffy nose
 abdominal pain, vomiting, nausea, constipation, diarrhoea, indigestion, toothache
 increased liver transaminases in your blood
 bone or muscle ache, back pain, joint pain
 loss of menstrual periods, leakage of milk from the breasts
 fever, weakness, fatigue (tiredness)
 a reaction at the injection site, including itching, pain or swelling.

Uncommon side effects: may affect up to 1 in 100 people
 pneumonia, infection of the chest (bronchitis), infection of the breathing passages, sinus 

infection, bladder infection, ear infection, tonsillitis, fungal infection of the nails, infection of 
the skin

 white blood cell count decreased, decrease in the type of white blood cells that help to protect 
you against infection, decrease in platelets (blood cells that help you stop bleeding), anaemia

 allergic reaction
 diabetes or worsening of diabetes, increased insulin (a hormone that controls blood sugar levels) 

in your blood



45

 increased appetite
 loss of appetite resulting in malnutrition and low body weight
 high blood triglycerides (a fat), increased cholesterol in your blood
 sleep disorder, elated mood (mania), decreased sexual drive, nervousness, nightmares
 tardive dyskinesia (twitching or jerking movements that you cannot control in your face, tongue, 

or other parts of your body). Tell your doctor immediately if you experience involuntary 
rhythmic movements of the tongue, mouth and face. Withdrawal of this medicine may be 
needed.

 fainting, a restless urge to move parts of your body, dizziness upon standing, disturbance in
attention, problems with speech, loss or abnormal sense of taste, reduced sensation of skin to 
pain and touch, a sensation of tingling, pricking, or numbness of skin

 blurry vision, eye infection or "pink eye", dry eye
 sensation of spinning (vertigo), ringing in the ears, ear pain
 an interruption in conduction between the upper and lower parts of the heart, abnormal electrical 

conduction of the heart, prolongation of the QT interval from your heart, rapid heartbeat upon 
standing, slow heart rate, abnormal electrical tracing of the heart (electrocardiogram or ECG), a 
fluttering or pounding feeling in your chest (palpitations)

 low blood pressure, low blood pressure upon standing (consequently, some people taking this 
medicine may feel faint, dizzy, or may pass out when they stand up or sit up suddenly)

 shortness of breath, congestion of breathing passages, wheezing, sore throat, nosebleeds
 abdominal discomfort, stomach or intestinal infection, difficulty swallowing, dry mouth, 

excessive passing of gas or wind
 increased GGT (a liver enzyme called gamma-glutamyltransferase) in your blood, increased 

liver enzymes in your blood
 hives (or "nettle rash"), itching, rash, hair loss, eczema, dry skin, skin redness, acne
 an increase of CPK (creatine phosphokinase) in your blood, an enzyme which is sometimes

released with muscle breakdown
 muscle spasms, joint stiffness, muscle weakness, neck pain
 incontinence (lack of control) of urine, frequent passing of urine, pain when passing urine
 erectile dysfunction, ejaculation disorder, missed menstrual periods or other problems with your 

cycle (females), development of breasts in men, sexual dysfunction, breast pain
 swelling of the face, mouth, eyes, or lips, swelling of the body, arms, or legs
 an increase in body temperature
 a change in the way you walk
 chest pain, chest discomfort, feeling unwell
 hardening of the skin
 fall.

Rare side effects: may affect up to 1 in 1,000 people
 eye infection
 skin inflammation caused by mites, abscess under the skin
 increase in eosinophils (a type of white blood cell) in your blood
 inappropriate secretion of a hormone that controls urine volume
 sugar in the urine
 life threatening complications of uncontrolled diabetes
 low blood sugar
 excessive drinking of water
 confusion
 not moving or responding while awake (catatonia)
 sleep walking
 lack of emotion
 inability to reach orgasm
 neuroleptic malignant syndrome (confusion, reduced or loss of consciousness, high fever, and 

severe muscle stiffness), blood vessel problems in the brain, including sudden loss of blood 
supply to brain (stroke or "mini" stroke), unresponsive to stimuli, loss of consciousness, low 



46

level of consciousness, convulsion (fits), balance disorder
 abnormal coordination
 glaucoma (increased pressure within the eyeball)
 problems with movement of your eyes, eye rolling, oversensitivity of the eyes to light, increased 

tears, redness of the eyes
 atrial fibrillation (an abnormal heart rhythm), irregular heart beat
 blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 

the leg). If you notice any of these symptoms seek medical advice immediately
 flushing
 trouble breathing during sleep (sleep apnoea)
 lung congestion
 crackly lung sounds
 inflammation of the pancreas, swollen tongue, stool incontinence, very hard stool
 chapped lips
 rash on skin related to drug, thickening of skin, dandruff
 joint swelling
 inability to pass urine
 breast discomfort, enlargement of the glands in your breasts, breast enlargement
 vaginal discharge
 very low body temperature, chills, feeling thirsty
 symptoms of drug withdrawal
 accumulation of pus caused by infection at injection site, deep skin infection, a cyst at the 

injection site, bruising at injection site.

Not known: frequency cannot be estimated from the available data
 dangerously low numbers of a certain type of white blood cell needed to fight infection in your 

blood
 severe allergic reaction characterised by fever, swollen mouth, face, lip or tongue, shortness of 

breath, itching, skin rash and sometimes drop in blood pressure
 dangerously excessive intake of water
 sleep-related eating disorder
 coma due to uncontrolled diabetes
 shaking of the head
 blood clot in the lungs causing chest pain and difficulty in breathing. If you notice any of these 

symptoms seek medical advice immediately.
 fast, shallow breathing, pneumonia caused by inhaling food, voice disorder
 decreased oxygen in parts of your body (because of decreased blood flow)
 a blockage in the bowels, lack of bowel movement that causes blockage
 yellowing of the skin and the eyes (jaundice)
 serious allergic reaction with swelling that may involve the throat and lead to difficulty 

breathing
 skin discolouration, flaky, itchy scalp or skin
 abnormal posture
 newborn babies born to mothers who have taken TREVICTA during pregnancy may experience 

side effects of the drug and/or withdrawal symptoms, such as irritability, slow, or sustained 
muscle contractions, shaking, sleepiness, breathing, or feeding problems

 priapism (a prolonged penile erection that may require surgical treatment)
 a decrease in body temperature
 dead skin cells at injection site, an ulcer at injection site.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


47

5. How to store TREVICTA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to 
the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What TREVICTA contains
The active substance is paliperidone.
Each TREVICTA 175 mg pre-filled syringe contains 273 mg paliperidone palmitate.
Each TREVICTA 263 mg pre-filled syringe contains 410 mg paliperidone palmitate.
Each TREVICTA 350 mg pre-filled syringe contains 546 mg paliperidone palmitate.
Each TREVICTA 525 mg pre-filled syringe contains 819 mg paliperidone palmitate.

The other ingredients are:
Polysorbate 20
Polyethylene glycol 4000
Citric acid monohydrate
Sodium dihydrogen phosphate monohydrate
Sodium hydroxide (for pH adjustment)
Water for injections

What TREVICTA looks like and contents of the pack
TREVICTA is a white to off-white prolonged release suspension for injection in a pre-filled syringe 
that your doctor or nurse will shake vigorously to resuspend the suspension before it is given as an 
injection.

Each pack contains 1 pre-filled syringe and 2 needles.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Janssen-Cilag International NV
Turnhoutseweg 30
B-2340 Beerse
Belgium

Manufacturer
Janssen Pharmaceutica NV
Turnhoutseweg 30
B-2340 Beerse
Belgium



48

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder.

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11

Lietuva
UAB “JOHNSON & JOHNSON”
Tel: +370 5 278 68 88

България
”Джонсън & Джонсън България” ЕООД
Тел.:+359 2 489 94 00

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11

Česká republika
Janssen-Cilag s.r.o.
Tel:+420 227 012 227

Magyarország
Janssen-Cilag Kft.
Tel.:+36 1 884 2858

Danmark
Janssen-Cilag A/S
Tlf: +45 45 94 82 82

Malta
AM MANGION LTD.
Tel: +356 2397 6000

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137-955-955

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111

Eesti
UAB “JOHNSON & JOHNSON” Eesti filiaal
Tel.: +372 617 7410

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε
Tηλ: +30 210 80 90 000

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00

France
Janssen-Cilag
Tel: 0 800 25 50 75 / +33 1 55 00 40 03

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00

Ísland
Janssen-Cilag AB
C/o Vistor hf
Sími: +354 535 7000

Slovenská republika
Johnson & Johnson s.r.o.
Tel: +421 232 408 400

Italia
Janssen-Cilag SpA
Tel: +39 02 2510 1

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300



49

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Tηλ: +357 22 207 700

Sverige
Janssen-Cilag AB
Tel: +46 8 626 50 00

Latvija
UAB “JOHNSON & JOHNSON” filiāle Latvijā
Tel: +371 6789 3561

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

http://www.ema.europa.eu/


50

Information intended for medical or health care professionals

The following information is intended for medical or healthcare professionals only and should 
be read by the medical or healthcare professional in conjunction with the full prescribing 
information (Summary of Product Characteristics).

Administer every 3 months

Shake syringe vigorously for at least 15 seconds

For intramuscular injection only. Do not administer by any other route.

Important
Read complete instructions prior to use. TREVICTA requires close attention to these step-by-step 
Instructions for Use to help ensure successful administration.
TREVICTA should be administered by a healthcare professional as a single injection. DO NOT
divide dose into multiple injections.
TREVICTA is intended for intramuscular use only. Inject slowly, deep into the muscle taking care to 
avoid injection into a blood vessel.

Dosing
TREVICTA should be administered once every 3 months.

Preparation
Peel off the tab label from the syringe and place in patient record.
TREVICTA requires longer and more vigorous shaking than 1-monthly paliperidone palmitate 
injectable. Shake the syringe vigorously, with the syringe tip pointing up, for at least 15 seconds 
within 5 minutes prior to administration (see Step 2).

Thin Wall Safety Needle Selection
Thin wall (TW) safety needles are designed to be used with TREVICTA. It is important to only use 
the needles provided in the TREVICTA pack.



51

Dose pack contents



52

Needle selection is determined by injection site and patient weight.

If administering a Deltoid injection

If patient weighs:
Less than 90 kg

pink hub

90 kg or more
yellow hub

If administering a Gluteal injection

Regardless of patient weight:
yellow hub

Select needle1

Immediately discard the unused needle in an approved sharps 
container. Do not save for future use.



53

Prepare for injection2

Proceed to the next step 
immediately after shaking. If more 
than 5 minutes pass before 
injection, shake vigorously, with 
the syringe tip pointing up, again
for at least 15 seconds to re-suspend 
the medication.

SHAKE VIGOROUSLY for at 
least 15 seconds
With the syringe tip pointing up,
SHAKE VIGOROUSLY with a loose 
wrist for at least 15 seconds to ensure 
a homogeneous suspension.
NOTE: This medicine requires 
longer and more vigorous shaking 
than 1-monthly paliperidone palmitate 
injectable.



54

Check suspension

After shaking the syringe for at least 15 seconds, check the appearance of the suspension in the 
viewing window.
The suspension should appear uniform and milky white in colour.
It is also normal to see small air bubbles.

Open needle pouch and remove cap

First, open needle pouch by peeling the cover back half way. Place on a clean surface.
Then, holding the syringe upright, twist and pull the rubber cap to remove.

Grasp needle pouch

Fold back needle cover and plastic tray. Then, firmly grasp the needle sheath through the pouch, as 
shown.



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Attach needle

With your other hand, hold the syringe by the luer connection and attach it to the safety needle with a 
gentle clockwise twisting motion.
Do not remove the pouch until the syringe and needle are securely attached.

Remove needle sheath

Pull the needle sheath away from the needle in a straight motion.
Do not twist the sheath, as this may loosen the needle from the syringe.

Remove air bubbles

Hold the syringe upright and tap gently to make any air bubbles rise to the top.
Slowly and carefully press plunger rod upward to remove air.



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Inject dose

Slowly inject the entire contents of the syringe intramuscularly, deep into the selected deltoid or 
gluteal muscle.
Do not administer by any other route.

Secure needle

After the injection is complete, use your thumb or a flat surface to secure the needle in the safety 
mechanism. The needle is secure when a “click” sound is heard.

Inject3

After injection4



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Dispose properly

Dispose of the syringe and unused needle in an approved sharps container.

Thin wall safety needles are designed specifically for use with 
TREVICTA. Unused needle should be discarded and not saved for 
future use.


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET