Paliperidone Janssen-Cilag International

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 25 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 50 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 75 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 100 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 150 mg prolonged release suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

25 mg prolonged release suspension for injection

Each pre-filled syringe contains 39 mg paliperidone palmitate equivalent to 25 mg paliperidone.

50 mg prolonged release suspension for injection

Each pre-filled syringe contains 78 mg paliperidone palmitate equivalent to 50 mg paliperidone.

75 mg prolonged release suspension for injection

Each pre-filled syringe contains 117 mg paliperidone palmitate equivalent to 75 mg paliperidone.

100 mg prolonged release suspension for injection

Each pre-filled syringe contains 156 mg paliperidone palmitate equivalent to 100 mg paliperidone.

150 mg prolonged release suspension for injection

Each pre-filled syringe contains 234 mg paliperidone palmitate equivalent to 150 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

Paliperidone Janssen-Cilag International is indicated for maintenance treatment of schizophrenia in 
adult patients stabilised with paliperidone or risperidone.

In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or 
risperidone, Paliperidone Janssen-Cilag International may be used without prior stabilisation with oral 
treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is 
needed.



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4.2 Posology and method of administration

Posology

Recommended initiation of Paliperidone Janssen-Cilag International is with a dose of 150 mg on 
treatment day 1 and 100 mg one week later (day 8), both administered in the deltoid muscle in order to 
attain therapeutic concentrations rapidly (see section 5.2). The third dose should be administered one 
month after the second initiation dose. The recommended monthly maintenance dose is 75 mg; some 
patients may benefit from lower or higher doses within the recommended range of 25 to 150 mg based 
on individual patient tolerability and/or efficacy. Patients who are overweight or obese may require 
doses in the upper range (see section 5.2). Following the second initiation dose, monthly maintenance 
doses can be administered in either the deltoid or gluteal muscle.

Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the 
prolonged release characteristics of Paliperidone Janssen-Cilag International should be considered (see 
section 5.2), as the full effect of maintenance doses may not be evident for several months.

Switching from oral prolonged release paliperidone or oral risperidone to Paliperidone Janssen-
Cilag International
Paliperidone Janssen-Cilag International should be initiated as described at the beginning of 
section 4.2 above. During monthly maintenance treatment with Paliperidone Janssen-Cilag 
International, patients previously stabilised on different doses of paliperidone prolonged release tablets 
can attain similar paliperidone steady-state exposure by injection. The Paliperidone Janssen-Cilag 
International maintenance doses needed to attain similar steady-state exposure are shown as follows:

Doses of paliperidone prolonged release tablets and Paliperidone Janssen-Cilag International
needed to attain similar steady-state paliperidone exposure during maintenance treatment

Previous paliperidone
prolonged release tablet dose

Paliperidone Janssen-Cilag International
injection

3 mg daily 25-50 mg monthly
6 mg daily 75 mg monthly
9 mg daily 100 mg monthly
12 mg daily 150 mg monthly

Previous oral paliperidone or oral risperidone can be discontinued at the time of initiation of treatment 
with Paliperidone Janssen-Cilag International. Some patients may benefit from gradual withdrawal.
Some patients switching from higher paliperidone oral doses (e.g., 9-12 mg daily) to gluteal injections 
with Paliperidone Janssen-Cilag International may have lower plasma exposure during the first 
6 months after the switch. Therefore, alternatively, it could be considered to give deltoid injections for 
the first 6 months.

Switching from risperidone long acting injection to Paliperidone Janssen-Cilag International
When switching patients from risperidone long acting injection, initiate Paliperidone Janssen-Cilag 
International therapy in place of the next scheduled injection. Paliperidone Janssen-Cilag International
should then be continued at monthly intervals. The one-week initiation dosing regimen including the 
intramuscular injections (day 1 and 8, respectively) as described in section 4.2 above is not required.
Patients previously stabilised on different doses of risperidone long acting injection can attain similar 
paliperidone steady-state exposure during maintenance treatment with Paliperidone Janssen-Cilag 
International monthly doses according to the following:

Doses of risperidone long acting injection and Paliperidone Janssen-Cilag International
needed to attain similar paliperidone exposure at steady-state

Previous risperidone long acting injection dose
Paliperidone Janssen-Cilag International

injection
25 mg every 2 weeks 50 mg monthly

37.5 mg every 2 weeks 75 mg monthly
50 mg every 2 weeks 100 mg monthly



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Discontinuation of antipsychotic medicinal products should be made in accordance with appropriate 
prescribing information. If Paliperidone Janssen-Cilag International is discontinued, its prolonged
release characteristics must be considered. The need for continuing existing extrapyramidal symptoms 
(EPS) medicine should be re-evaluated periodically.

Missed doses

Avoiding missed doses
It is recommended that the second initiation dose of Paliperidone Janssen-Cilag International be given 
one week after the first dose. To avoid a missed dose, patients may be given the second dose 4 days 
before or after the one-week (day 8) time point. Similarly, the third and subsequent injections after the 
initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients 
may be given the injection up to 7 days before or after the monthly time point.

If the target date for the second Paliperidone Janssen-Cilag International injection (day 8 ± 4 days) is 
missed, the recommended reinitiation depends on the length of time which has elapsed since the 
patient's first injection.

Missed second initiation dose (< 4 weeks from first injection)
If less than 4 weeks have elapsed since the first injection, then the patient should be administered the 
second injection of 100 mg in the deltoid muscle as soon as possible. A third Paliperidone 
Janssen-Cilag International injection of 75 mg in either the deltoid or gluteal muscles should be 
administered 5 weeks after the first injection (regardless of the timing of the second injection). The 
normal monthly cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on 
individual patient tolerability and/or efficacy should be followed thereafter.

Missed second initiation dose (4-7 weeks from first injection)
If 4 to 7 weeks have elapsed since the first injection of Paliperidone Janssen-Cilag International, 
resume dosing with two injections of 100 mg in the following manner:
1. a deltoid injection as soon as possible
2. another deltoid injection one week later
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed second initiation dose (> 7 weeks from first injection)
If more than 7 weeks have elapsed since the first injection of Paliperidone Janssen-Cilag International, 
initiate dosing as described for the initial recommended initiation of Paliperidone Janssen-Cilag 
International above.

Missed monthly maintenance dose (1 month to 6 weeks)
After initiation, the recommended injection cycle of Paliperidone Janssen-Cilag International is 
monthly. If less than 6 weeks have elapsed since the last injection, then the previously stabilised dose 
should be administered as soon as possible, followed by injections at monthly intervals.

Missed monthly maintenance dose (> 6 weeks to 6 months)
If more than 6 weeks have elapsed since the last injection of Paliperidone Janssen-Cilag International,
the recommendation is as follows:

For patients stabilised with doses of 25 to 100 mg
1. a deltoid injection as soon as possible at the same dose the patient was previously stabilised on
2. another deltoid injection (same dose) one week later (day 8)
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

For patients stabilised with 150 mg
1. a deltoid injection as soon as possible at the 100 mg dose



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2. another deltoid injection one week later (day 8) at the 100 mg dose
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed monthly maintenance dose (> 6 months)
If more than 6 months have elapsed since the last injection of Paliperidone Janssen-Cilag 
International, initiate dosing as described for the initial recommended initiation of Paliperidone 
Janssen-Cilag International above.

Special populations

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

In general, recommended dosing of Paliperidone Janssen-Cilag International for elderly patients with 
normal renal function is the same as for younger adult patients with normal renal function. However, 
because elderly patients may have diminished renal function, dose adjustment may be necessary (see 
Renal impairment below for dosing recommendations in patients with renal impairment).

Renal impairment
Paliperidone Janssen-Cilag International has not been systematically studied in patients with renal 
impairment (see section 5.2). For patients with mild renal impairment (creatinine clearance ≥ 50 to
< 80 mL/min), recommended initiation of Paliperidone Janssen-Cilag International is with a dose of 
100 mg on treatment day 1 and 75 mg one week later, both administered in the deltoid muscle. The 
recommended monthly maintenance dose is 50 mg with a range of 25 to 100 mg based on patient 
tolerability and/or efficacy.

Paliperidone Janssen-Cilag International is not recommended in patients with moderate or severe renal 
impairment (creatinine clearance < 50 mL/min) (see section 4.4).

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 Paliperidone Janssen-Cilag International in children and adolescents 
< 18 years of age have not been established. No data are available.

Method of administration

Paliperidone Janssen-Cilag International is intended for intramuscular use only. It must not be 
administered by any other route. It should be injected slowly, deep into the deltoid or gluteal muscle. 
Each injection should be administered by a health care professional. Administration should be in a 
single injection. The dose should not be given in divided injections.

The day 1 and day 8 initiation doses must each be administered in the deltoid muscle in order to attain 
therapeutic concentrations rapidly (see section 5.2). Following the second initiation dose, monthly 
maintenance doses can be administered in either the deltoid or gluteal muscle. A switch from gluteal 
to deltoid (and vice versa) should be considered in the event of injection site pain if the injection site 
discomfort is not well tolerated (see section 4.8). It is also recommended to alternate between left and
right sides (see below).

For instructions for use and handling of Paliperidone Janssen-Cilag International, see package leaflet 
(information intended for medical or healthcare professionals).



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Deltoid muscle administration
The recommended needle size for initial and maintenance administration of Paliperidone 
Janssen-Cilag International into the deltoid muscle is determined by the patient’s weight. For those 
≥ 90 kg, the 1½ inch, 22 gauge needle (38.1 mm x 0.72 mm) is recommended. For those < 90 kg, the 
1-inch, 23 gauge needle (25.4 mm x 0.64 mm) is recommended. Deltoid injections should be 
alternated between the two deltoid muscles.

Gluteal muscle administration
The recommended needle size for maintenance administration of Paliperidone Janssen-Cilag 
International into the gluteal muscle is the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm). 
Administration should be made into the upper-outer quadrant of the gluteal area. Gluteal injections 
should be alternated between the two gluteal muscles.

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

Paliperidone Janssen-Cilag International 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.

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.

Caution is warranted in patients receiving both, psychostimulants (e.g., methylphenidate) and 
paliperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both
medications. 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 
Janssen-Cilag International. Agranulocytosis has been reported very rarely (< 1/10,000 patients) 
during post-marketing surveillance. 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 Paliperidone Janssen-Cilag International should be 
considered at the first sign of a clinically significant decline in WBC in the absence of other causative 



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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 < 1 x 109/L) should discontinue Paliperidone 
Janssen-Cilag International and have their WBC followed until recovery.

Hypersensitivity reactions

Anaphylactic reactions in patients who have previously tolerated oral risperidone or oral paliperidone 
have been rarely reported during post-marketing experience (see sections 4.1 and 4.8).

If hypersensitivity reactions occur, discontinue use of Paliperidone Janssen-Cilag International; initiate 
general supportive measures as clinically appropriate and monitor the patient until signs and 
symptoms resolve (see sections 4.3 and 4.8).

Hyperglycaemia and diabetes mellitus

Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes including diabetic coma 
and ketoacidosis, have been reported during treatment with paliperidone. Appropriate clinical 
monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with 
Paliperidone Janssen-Cilag International 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 Paliperidone Janssen-Cilag International 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-blocking activity.
Based on pooled data from the three placebo-controlled, 6-week, fixed-dose trials with oral 
paliperidone prolonged release tablets (3, 6, 9, and 12 mg), orthostatic hypotension was reported by 
2.5% of subjects treated with oral paliperidone compared with 0.8% of subjects treated with placebo. 
Paliperidone Janssen-Cilag International 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

Paliperidone Janssen-Cilag International 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 and 
therefore, dose adjustment is recommended in patients with mild renal impairment. Paliperidone 



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Janssen-Cilag International 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.

Elderly patients with dementia

Paliperidone Janssen-Cilag International has not been studied in elderly patients with dementia. 
Paliperidone Janssen-Cilag International should be used with caution in elderly patients with dementia 
with risk factors for stroke.

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 Paliperidone Janssen-Cilag 
International 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 risperidone) with alpha-adrenergic blocking effects have 
been reported to induce priapism. During post-marketing surveillance, priapism has also been reported 
with oral paliperidone, which is the active metabolite of risperidone. 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 Paliperidone Janssen-Cilag 
International 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 Paliperidone Janssen-Cilag 
International and preventative measures undertaken.



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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.

Administration

Care must be taken to avoid inadvertent injection of Paliperidone Janssen-Cilag International 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 Paliperidone 
Janssen-Cilag International (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 Paliperidone Janssen-Cilag International 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 other antipsychotics 
and some antimalarials (e.g. mefloquine). This list is indicative and not exhaustive.

Potential for Paliperidone Janssen-Cilag International to affect other medicines

Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicinal 
products that are metabolised by cytochrome P-450 isozymes.

Given the primary central nervous system (CNS) effects of paliperidone (see section 4.8), Paliperidone 
Janssen-Cilag International 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 Paliperidone Janssen-Cilag International is administered with other therapeutic 
agents 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.).



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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 Paliperidone Janssen-Cilag International and lithium has been 
performed, however, a pharmacokinetic interaction is not likely to occur.

Potential for other medicines to affect Paliperidone Janssen-Cilag International

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 Paliperidone Janssen-Cilag International should be 
re-evaluated and increased if necessary. Conversely, on discontinuation of carbamazepine, the dose of 
Paliperidone Janssen-Cilag International should be re-evaluated and decreased if necessary.

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 Paliperidone 
Janssen-Cilag International intramuscular injection. This interaction has not been studied with 
Paliperidone Janssen-Cilag International.

Concomitant use of Paliperidone Janssen-Cilag International with risperidone or with oral 
paliperidone

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

Concomitant use of Paliperidone Janssen-Cilag International 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 



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disorder. Consequently, newborns should be monitored carefully. Paliperidone Janssen-Cilag 
International should not be used during pregnancy unless clearly necessary.

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. Paliperidone Janssen-Cilag 
International 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 Paliperidone Janssen-Cilag International is known.

4.8 Undesirable effects

Summary of the safety profile

The adverse drug reactions (ADRs) most frequently reported in clinical trials were insomnia, 
headache, anxiety, upper respiratory tract infection, injection site reaction, parkinsonism, weight 
increased, akathisia, agitation, sedation/somnolence, nausea, constipation, dizziness, musculoskeletal 
pain, tachycardia, tremor, abdominal pain, vomiting, diarrhoea, fatigue, and dystonia. Of these, 
akathisia and sedation/somnolence appeared to be dose-related.

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

parkinsonismc, 
akathisiac, 
sedation/somnolence, 
dystoniac, dizziness, 
dyskinesiac, 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-
glutamyltransferase 
increased, hepatic 
enzyme increased

jaundice

Skin and 
subcutaneous 
tissue disorders

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

drug eruption, 
hyperkeratosis, 
dandruff

angioedema, skin 
discolouration, 
seborrhoeic 
dermatitis



13

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, oedemae, 
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 these 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 Paliperidone Janssen-Cilag International-treated 

subjects compared to a rate of 0.39% in placebo group. Overall incidence from all clinical trials was 0.65% in all paliperidone 
palmitate-treated subjects

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.

Description of selected adverse reactions

Anaphylactic reaction
Rarely, cases of anaphylactic reaction after injection with Paliperidone Janssen-Cilag International
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
The most commonly reported injection site related adverse reaction was pain. The majority of these 
reactions were reported to be of mild to moderate severity. Subject evaluations of injection site pain 
based on a visual analogue scale tended to lessen in frequency and intensity over time in all Phase 2 
and 3 studies with Paliperidone Janssen-Cilag International. Injections into the deltoid were perceived 
as slightly more painful than corresponding gluteal injections. Other injection site reactions were 
mostly mild in intensity and included induration (common), pruritus (uncommon) and nodules (rare).



14

Extrapyramidal symptoms (EPS)
EPS included a pooled analysis of the following terms: parkinsonism (includes 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, muscle twitching, 
choreoathetosis, athetosis, and myoclonus), dystonia (includes dystonia, 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. It should be noted that a broader spectrum of symptoms are included that do 
not necessarily have an extrapyramidal origin.

Weight gain
In the 13-week study involving the 150 mg initiation dosing, the proportion of subjects with an 
abnormal weight increase ≥ 7% showed a dose-related trend, with a 5% incidence rate in the placebo 
group compared with rates of 6%, 8% and 13% in the Paliperidone Janssen-Cilag International 25 mg, 
100 mg, and 150 mg groups, respectively.

During the 33-week open-label transition/maintenance period of the long-term recurrence prevention 
trial, 12% of Paliperidone Janssen-Cilag International-treated subjects met this criterion (weight gain 
of ≥ 7% from double-blind phase to endpoint); the mean (SD) weight change from open-label baseline 
was + 0.7 (4.79) kg.

Hyperprolactinaemia
In clinical trials, median increases in serum prolactin were observed in subjects of both genders who 
received Paliperidone Janssen-Cilag International. Adverse reactions that may suggest increase in 
prolactin levels (e.g., amenorrhoea, galactorrhoea, menstrual disturbances, gynaecomastia) were 
reported overall in < 1% of subjects.

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).

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.

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


15

Management

Consideration should be given to the prolonged release 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

Paliperidone Janssen-Cilag International 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 positive 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

Acute treatment of schizophrenia
The efficacy of Paliperidone Janssen-Cilag International in the acute treatment of schizophrenia was 
established in four short-term (one 9-week and three 13-week) double-blind, randomised, 
placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria 
for schizophrenia. The fixed doses of Paliperidone Janssen-Cilag International in these studies were 
given on days 1, 8, and 36 in the 9-week study, and additionally on day 64 of the 13-week studies. No 
additional oral antipsychotic supplementation was needed during the acute treatment of schizophrenia 
with Paliperidone Janssen-Cilag International. The primary efficacy endpoint was defined as a 
decrease in Positive and Negative Syndrome Scale (PANSS) total scores as shown in the table below. 
The PANSS is a validated multi-item inventory composed of five factors to evaluate positive 
symptoms, negative symptoms, disorganised thoughts, uncontrolled hostility/excitement and 
anxiety/depression. Functioning was evaluated using the Personal and Social Performance (PSP) scale. 
The PSP is a validated clinician rated scale that measures personal and social functioning in four 
domains: socially useful activities (work and study), personal and social relationships, self-care and 
disturbing and aggressive behaviours.

In a 13-week study (n = 636) comparing three fixed doses of Paliperidone Janssen-Cilag International
(initial deltoid injection of 150 mg followed by 3 gluteal or deltoid doses of either 25 mg/4 weeks, 
100 mg/4 weeks or 150 mg/4 weeks) to placebo, all three doses of Paliperidone Janssen-Cilag 
International were superior to placebo in improving the PANSS total score. In this study, both the 



16

100 mg/4 weeks and 150 mg /4 weeks, but not the 25 mg/4 weeks, treatment groups demonstrated 
statistical superiority to placebo for the PSP score. These results support efficacy across the entire 
duration of treatment and improvement in PANSS and was observed as early as day 4 with significant 
separation from placebo in the 25 mg and 150 mg Paliperidone Janssen-Cilag International groups by 
day 8.

The results of the other studies yielded statistically significant results in favour of Paliperidone 
Janssen-Cilag International, except for the 50 mg dose in one study (see table below).

Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score - Change From Baseline to 
End Point- LOCF for Studies R092670-SCH-201, R092670-PSY-3003, R092670-PSY-3004 and 

R092670-PSY-3007: Primary Efficacy Analysis Set
Placebo 25 mg 50 mg 100 mg 150 mg

R092670-PSY-3007*
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 160
86.8 (10.31)
-2.9 (19.26)

--

n = 155
86.9 (11.99)
-8.0 (19.90)

0.034
--

n = 161
86.2 (10.77)
-11.6 (17.63)

< 0.001

n = 160
88.4 (11.70)
-13.2 (18.48)

< 0.001

R092670-PSY-3003
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 132
92.4 (12.55)
-4.1 (21.01)

--
--

n = 93
89.9 (10.78)
-7.9 (18.71)

0.193

n = 94
90.1 (11.66)
-11.0 (19.06)

0.019

n = 30
92.2 (11.72)
-5.5 (19.78)

--

R092670-PSY-3004
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 125
90.7 (12.22)
-7.0 (20.07)

--

n = 129
90.7 (12.25)
-13.6 (21.45)

0.015

n = 128
91.2 (12.02)
-13.2 (20.14)

0.017

n = 131
90.8 (11.70)
-16.1 (20.36)

< 0.001
--

R092670-SCH-201
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 66
87.8 (13.90)
6.2 (18.25)

--
--

n = 63
88.0 (12.39)
-5.2 (21.52)

0.001

n = 68
85.2 (11.09)
-7.8 (19.40)

< 0.0001
--

* For Study R092670-PSY-3007 an initiation dose of 150 mg was given to all subjects in the Paliperidone Janssen-Cilag 
International treatment groups on day 1 followed by the assigned dose afterwards.

Note: Negative change in score indicates improvement.

Maintaining symptom control and delaying relapse of schizophrenia
The efficacy of Paliperidone Janssen-Cilag International in maintaining symptomatic control and 
delaying relapse of schizophrenia was established in a longer-term double-blind, placebo-controlled, 
flexible-dose study involving 849 non-elderly adult subjects who met DSM-IV criteria for 
schizophrenia. This study included a 33-week open-label acute treatment and stabilisation phase, a 
randomised, double-blind placebo-controlled phase to observe for relapse, and a 52-week open-label 
extension period. In this study, doses of Paliperidone Janssen-Cilag International included 25, 50, 75, 
and 100 mg administered monthly; the 75 mg dose was allowed only in the 52-week open-label 
extension. Subjects initially received flexible doses (25-100 mg) of Paliperidone Janssen-Cilag 
International during a 9-week transition period, followed by a 24-week maintenance period, where 
subjects were required to have a PANSS score of ≤ 75. Dosing adjustments were only allowed in the 
first 12 weeks of the maintenance period. A total of 410 stabilised patients were randomised to either 
Paliperidone Janssen-Cilag International (median duration 171 days [range 1 day to 407 days]) or to 
placebo (median duration 105 days [range 8 days to 441 days]) until they experienced a relapse of 
schizophrenia symptoms in the variable length double-blind phase. The trial was stopped early for 
efficacy reasons as a significantly longer time to relapse (p < 0.0001, Figure 1) was seen in patients 
treated with Paliperidone Janssen-Cilag International compared to placebo (hazard ratio = 4.32; 95% 
CI: 2.4-7.7).



17

Figure 1: Kaplan-Meier Plot of Time to Relapse – Interim Analysis (Intent-to-Treat Interim 
Analysis Set)

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with 
Paliperidone Janssen-Cilag International 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

Paliperidone palmitate is the palmitate ester prodrug of paliperidone. Due to its extremely low water 
solubility, paliperidone palmitate dissolves slowly after intramuscular injection before being 
hydrolysed to paliperidone and absorbed into the systemic circulation. Following a single 
intramuscular dose, the plasma concentrations of paliperidone gradually rise to reach maximum 
plasma concentrations at a median Tmax of 13 days. The release of the active substance starts as early 
as day 1 and lasts for at least 4 months.

Following intramuscular injection of single doses (25-150 mg) in the deltoid muscle, on average, a 
28% higher Cmax was observed compared with injection in the gluteal muscle. The two initial deltoid 
intramuscular injections of 150 mg on day 1 and 100 mg on day 8 help attain therapeutic 
concentrations rapidly. The release profile and dosing regimen of Paliperidone Janssen-Cilag 
International results in sustained therapeutic concentrations. The total exposure of paliperidone 
following Paliperidone Janssen-Cilag International administration was dose-proportional over a 
25-150 mg dose range, and less than dose-proportional for Cmax for doses exceeding 50 mg. The mean 
steady-state peak:trough ratio for a Paliperidone Janssen-Cilag International dose of 100 mg was 1.8 
following gluteal administration and 2.2 following deltoid administration. The median apparent 
half-life of paliperidone following Paliperidone Janssen-Cilag International administration over the 
dose range of 25-150 mg ranged from 25-49 days.



18

The absolute bioavailability of paliperidone palmitate following Paliperidone Janssen-Cilag 
International administration is 100%.

Following administration of paliperidone palmitate the (+) and (-) enantiomers of paliperidone 
interconvert, reaching an AUC (+) to (-) ratio of approximately 1.6-1.8.

The plasma protein binding of racemic paliperidone is 74%.

Biotransformation and elimination

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 6.5% 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 medicinal products
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.

Long acting paliperidone palmitate injection versus oral prolonged release paliperidone

Paliperidone Janssen-Cilag International is designed to deliver paliperidone over a monthly period 
while prolonged release oral paliperidone is administered on a daily basis. The initiation regimen for 
Paliperidone Janssen-Cilag International (150 mg/100 mg in the deltoid muscle on day 1/day 8) was 
designed to rapidly attain steady-state paliperidone concentrations when initiating therapy without the 
use of oral supplementation.

In general, overall initiation plasma levels with Paliperidone Janssen-Cilag International were within 
the exposure range observed with 6-12 mg prolonged release oral paliperidone. The use of the 
Paliperidone Janssen-Cilag International initiation regimen allowed patients to stay in this exposure 
window of 6-12 mg prolonged release oral paliperidone even on trough pre-dose days (day 8 and 
day 36). Because of the difference in median pharmacokinetic profiles between the two medicinal
products, caution should be exercised when making a direct comparison of their pharmacokinetic 
properties.

Hepatic impairment

Paliperidone is not extensively metabolised in the liver. Although Paliperidone Janssen-Cilag 
International was not studied on 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

The disposition of a single oral dose paliperidone 3 mg prolonged release tablet was studied in 
subjects with varying degrees of renal function. Elimination of paliperidone decreased with decreasing 



19

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. Based on a limited number of observations with Paliperidone Janssen-Cilag International in 
subjects with mild renal impairment and pharmacokinetic simulations, a reduced dose is recommended 
(see section 4.2).

Elderly

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

Body mass index (BMI)/body weight

Pharmacokinetic studies with paliperidone palmitate have shown somewhat lower (10-20%) plasma 
concentrations of paliperidone in patients who are overweight or obese in comparison with normal
weight patients (see section 4.2).

Race

Population pharmacokinetics analysis of data from studies with oral paliperidone revealed no evidence 
of race-related differences in the pharmacokinetics of paliperidone following Paliperidone 
Janssen-Cilag International administration.

Gender

No clinically significant differences were observed between men and women.

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 Paliperidone Janssen-Cilag 
International. 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 unlikely to be of clinical relevance.

5.3 Preclinical safety data

Repeat-dose toxicity studies of intramuscularly injected paliperidone palmitate (the 1-month 
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 
4.1 times the exposure level in humans at the maximum recommended dose of 150 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 



20

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 1.2 and 2.2 times the exposure level at the maximum recommended 
human 150 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.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Polysorbate 20
Polyethylene glycol 4000
Citric acid monohydrate
Disodium hydrogen phosphate anhydrous
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

Do not store above 30°C.

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 22G 1½-inch safety needle (0.72 mm x 38.1 mm) and a 23G 1-inch safety needle
(0.64 mm x 25.4 mm).

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

6.6 Special precautions for disposal

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

7. MARKETING AUTHORISATION HOLDER

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



21

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1453/001
EU/1/20/1453/002
EU/1/20/1453/003
EU/1/20/1453/004
EU/1/20/1453/005

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 

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

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 150 mg and Paliperidone Janssen-Cilag International 100 mg
prolonged release suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each pre-filled syringe contains 156 mg paliperidone palmitate equivalent to 100 mg paliperidone.
Each pre-filled syringe contains 234 mg paliperidone palmitate equivalent to 150 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

Paliperidone Janssen-Cilag International is indicated for maintenance treatment of schizophrenia in 
adult patients stabilised with paliperidone or risperidone.

In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or 
risperidone, Paliperidone Janssen-Cilag International may be used without prior stabilisation with oral 
treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is 
needed.

4.2 Posology and method of administration

Posology

Recommended initiation of Paliperidone Janssen-Cilag International is with a dose of 150 mg on 
treatment day 1 and 100 mg one week later (day 8), both administered in the deltoid muscle in order to 
attain therapeutic concentrations rapidly (see section 5.2). The third dose should be administered one 
month after the second initiation dose. The recommended monthly maintenance dose is 75 mg; some 
patients may benefit from lower or higher doses within the recommended range of 25 to 150 mg based 
on individual patient tolerability and/or efficacy. Patients who are overweight or obese may require 
doses in the upper range (see section 5.2). Following the second initiation dose, monthly maintenance 
doses can be administered in either the deltoid or gluteal muscle.

Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the 
prolonged release characteristics of Paliperidone Janssen-Cilag International should be considered (see 
section 5.2), as the full effect of maintenance doses may not be evident for several months.

Switching from oral prolonged release paliperidone or oral risperidone to Paliperidone Janssen-
Cilag International
Paliperidone Janssen-Cilag International should be initiated as described at the beginning of 
section 4.2 above. During monthly maintenance treatment with Paliperidone Janssen-Cilag 
International, patients previously stabilised on different doses of paliperidone prolonged release tablets 
can attain similar paliperidone steady-state exposure by injection. The Paliperidone Janssen-Cilag 
International maintenance doses needed to attain similar steady-state exposure are shown as follows:



23

Doses of paliperidone prolonged release tablets and Paliperidone Janssen-Cilag International
needed to attain similar steady-state paliperidone exposure during maintenance treatment

Previous paliperidone
prolonged release tablet dose

Paliperidone Janssen-Cilag International
injection

3 mg daily 25-50 mg monthly
6 mg daily 75 mg monthly
9 mg daily 100 mg monthly
12 mg daily 150 mg monthly

Previous oral paliperidone or oral risperidone can be discontinued at the time of initiation of treatment 
with Paliperidone Janssen-Cilag International. Some patients may benefit from gradual withdrawal.
Some patients switching from higher paliperidone oral doses (e.g., 9-12 mg daily) to gluteal injections 
with Paliperidone Janssen-Cilag International may have lower plasma exposure during the first 
6 months after the switch. Therefore, alternatively, it could be considered to give deltoid injections for 
the first 6 months.

Switching from risperidone long acting injection to Paliperidone Janssen-Cilag International
When switching patients from risperidone long acting injection, initiate Paliperidone Janssen-Cilag 
International therapy in place of the next scheduled injection. Paliperidone Janssen-Cilag International
should then be continued at monthly intervals. The one-week initiation dosing regimen including the 
intramuscular injections (day 1 and 8, respectively) as described in section 4.2 above is not required.
Patients previously stabilised on different doses of risperidone long acting injection can attain similar
paliperidone steady-state exposure during maintenance treatment with Paliperidone Janssen-Cilag 
International monthly doses according to the following:

Doses of risperidone long acting injection and Paliperidone Janssen-Cilag International
needed to attain similar paliperidone exposure at steady-state

Previous risperidone long acting injection dose
Paliperidone Janssen-Cilag International

injection
25 mg every 2 weeks 50 mg monthly

37.5 mg every 2 weeks 75 mg monthly
50 mg every 2 weeks 100 mg monthly

Discontinuation of antipsychotic medicinal products should be made in accordance with appropriate 
prescribing information. If Paliperidone Janssen-Cilag International is discontinued, its prolonged
release characteristics must be considered. The need for continuing existing extrapyramidal symptoms 
(EPS) medicine should be re-evaluated periodically.

Missed doses

Avoiding missed doses
It is recommended that the second initiation dose of Paliperidone Janssen-Cilag International be given 
one week after the first dose. To avoid a missed dose, patients may be given the second dose 4 days 
before or after the one-week (day 8) time point. Similarly, the third and subsequent injections after the 
initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients 
may be given the injection up to 7 days before or after the monthly time point.

If the target date for the second Paliperidone Janssen-Cilag International injection (day 8 ± 4 days) is 
missed, the recommended reinitiation depends on the length of time which has elapsed since the 
patient's first injection.

Missed second initiation dose (< 4 weeks from first injection)
If less than 4 weeks have elapsed since the first injection, then the patient should be administered the 
second injection of 100 mg in the deltoid muscle as soon as possible. A third Paliperidone Janssen-
Cilag International injection of 75 mg in either the deltoid or gluteal muscles should be administered 
5 weeks after the first injection (regardless of the timing of the second injection). The normal monthly 



24

cycle of injections in either the deltoid or gluteal muscle of 25 mg to 150 mg based on individual 
patient tolerability and/or efficacy should be followed thereafter.

Missed second initiation dose (4-7 weeks from first injection)
If 4 to 7 weeks have elapsed since the first injection of Paliperidone Janssen-Cilag International, 
resume dosing with two injections of 100 mg in the following manner:
1. a deltoid injection as soon as possible
2. another deltoid injection one week later
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed second initiation dose (> 7 weeks from first injection)
If more than 7 weeks have elapsed since the first injection of Paliperidone Janssen-Cilag International, 
initiate dosing as described for the initial recommended initiation of Paliperidone Janssen-Cilag 
International above.

Missed monthly maintenance dose (1 month to 6 weeks)
After initiation, the recommended injection cycle of Paliperidone Janssen-Cilag International is 
monthly. If less than 6 weeks have elapsed since the last injection, then the previously stabilised dose 
should be administered as soon as possible, followed by injections at monthly intervals.

Missed monthly maintenance dose (> 6 weeks to 6 months)
If more than 6 weeks have elapsed since the last injection of Paliperidone Janssen-Cilag International, 
the recommendation is as follows:

For patients stabilised with doses of 25 to 100 mg
1. a deltoid injection as soon as possible at the same dose the patient was previously stabilised on
2. another deltoid injection (same dose) one week later (day 8)
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

For patients stabilised with 150 mg
1. a deltoid injection as soon as possible at the 100 mg dose
2. another deltoid injection one week later (day 8) at the 100 mg dose
3. resumption of the normal monthly cycle of injections in either the deltoid or gluteal muscle of 

25 mg to 150 mg based on individual patient tolerability and/or efficacy.

Missed monthly maintenance dose (> 6 months)
If more than 6 months have elapsed since the last injection of Paliperidone Janssen-Cilag 
International, initiate dosing as described for the initial recommended initiation of Paliperidone 
Janssen-Cilag International above.

Special populations

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

In general, recommended dosing of Paliperidone Janssen-Cilag International for elderly patients with 
normal renal function is the same as for younger adult patients with normal renal function. However, 
because elderly patients may have diminished renal function, dose adjustment may be necessary (see 
Renal impairment below for dosing recommendations in patients with renal impairment).

Renal impairment
Paliperidone Janssen-Cilag International has not been systematically studied in patients with renal 
impairment (see section 5.2). For patients with mild renal impairment (creatinine clearance ≥ 50 to 
< 80 mL/min), recommended initiation of Paliperidone Janssen-Cilag International is with a dose of 
100 mg on treatment day 1 and 75 mg one week later, both administered in the deltoid muscle. The 



25

recommended monthly maintenance dose is 50 mg with a range of 25 to 100 mg based on patient 
tolerability and/or efficacy.

Paliperidone Janssen-Cilag International is not recommended in patients with moderate or severe renal 
impairment (creatinine clearance < 50 mL/min) (see section 4.4).

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 Paliperidone Janssen-Cilag International in children and adolescents 
< 18 years of age have not been established. No data are available.

Method of administration

Paliperidone Janssen-Cilag International is intended for intramuscular use only. It must not be 
administered by any other route. It should be injected slowly, deep into the deltoid or gluteal muscle. 
Each injection should be administered by a health care professional. Administration should be in a 
single injection. The dose should not be given in divided injections.

The day 1 and day 8 initiation doses must each be administered in the deltoid muscle in order to attain 
therapeutic concentrations rapidly (see section 5.2). Following the second initiation dose, monthly 
maintenance doses can be administered in either the deltoid or gluteal muscle. A switch from gluteal 
to deltoid (and vice versa) should be considered in the event of injection site pain if the injection site 
discomfort is not well tolerated (see section 4.8). It is also recommended to alternate between left and 
right sides (see below).

For instructions for use and handling of Paliperidone Janssen-Cilag International, see package leaflet 
(information intended for medical or healthcare professionals).

Deltoid muscle administration
The recommended needle size for initial and maintenance administration of Paliperidone Janssen-
Cilag International into the deltoid muscle is determined by the patient’s weight. For those ≥ 90 kg, 
the 1½ inch, 22 gauge needle (38.1 mm x 0.72 mm) is recommended. For those < 90 kg, the 1-inch, 
23 gauge needle (25.4 mm x 0.64 mm) is recommended. Deltoid injections should be alternated 
between the two deltoid muscles.

Gluteal muscle administration
The recommended needle size for maintenance administration of Paliperidone Janssen-Cilag 
International into the gluteal muscle is the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm). 
Administration should be made into the upper-outer quadrant of the gluteal area. Gluteal injections 
should be alternated between the two gluteal muscles.

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

Paliperidone Janssen-Cilag International should not be used to manage acutely agitated or severely 
psychotic states when immediate symptom control is warranted.



26

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.

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.

Caution is warranted in patients receiving both, psychostimulants (e.g., methylphenidate) and 
paliperidone concomitantly, as extrapyramidal symptoms could emerge when adjusting one or both 
medications. 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 Janssen-
Cilag International. Agranulocytosis has been reported very rarely (< 1/10,000 patients) during 
post-marketing surveillance. 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 Paliperidone Janssen-Cilag International 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 < 1 x 109/L) should discontinue Paliperidone Janssen-
Cilag International and have their WBC followed until recovery.

Hypersensitivity reactions

Anaphylactic reactions in patients who have previously tolerated oral risperidone or oral paliperidone 
have been rarely reported during post-marketing experience (see sections 4.1 and 4.8).

If hypersensitivity reactions occur, discontinue use of Paliperidone Janssen-Cilag International; initiate
general supportive measures as clinically appropriate and monitor the patient until signs and 
symptoms resolve (see sections 4.3 and 4.8).

Hyperglycaemia and diabetes mellitus

Hyperglycaemia, diabetes mellitus, and exacerbation of pre-existing diabetes including diabetic coma 
and ketoacidosis, have been reported during treatment with paliperidone. Appropriate clinical 
monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with 
Paliperidone Janssen-Cilag International 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.



27

Weight gain

Significant weight gain has been reported with Paliperidone Janssen-Cilag International 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-blocking activity.
Based on pooled data from the three placebo-controlled, 6-week, fixed-dose trials with oral 
paliperidone prolonged release tablets (3, 6, 9, and 12 mg), orthostatic hypotension was reported by 
2.5% of subjects treated with oral paliperidone compared with 0.8% of subjects treated with placebo. 
Paliperidone Janssen-Cilag International 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

Paliperidone Janssen-Cilag International 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 and 
therefore, dose adjustment is recommended in patients with mild renal impairment. Paliperidone 
Janssen-Cilag International 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.

Elderly patients with dementia

Paliperidone Janssen-Cilag International has not been studied in elderly patients with dementia. 
Paliperidone Janssen-Cilag International should be used with caution in elderly patients with dementia 
with risk factors for stroke.

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.



28

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 Paliperidone Janssen-Cilag 
International 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 risperidone) with alpha-adrenergic blocking effects have 
been reported to induce priapism. During post-marketing surveillance, priapism has also been reported 
with oral paliperidone, which is the active metabolite of risperidone. 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 Paliperidone Janssen-Cilag 
International 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 Paliperidone Janssen-Cilag 
International 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.

Administration

Care must be taken to avoid inadvertent injection of Paliperidone Janssen-Cilag International 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 Paliperidone 
Janssen-Cilag International (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 



29

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 Paliperidone Janssen-Cilag International 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 other antipsychotics 
and some antimalarials (e.g. mefloquine). This list is indicative and not exhaustive.

Potential for Paliperidone Janssen-Cilag International to affect other medicines

Paliperidone is not expected to cause clinically important pharmacokinetic interactions with medicinal 
products that are metabolised by cytochrome P-450 isozymes.

Given the primary central nervous system (CNS) effects of paliperidone (see section 4.8), Paliperidone 
Janssen-Cilag International 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 Paliperidone Janssen-Cilag International is administered with other therapeutic 
agents 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 Paliperidone Janssen-Cilag International and lithium has been 
performed, however, a pharmacokinetic interaction is not likely to occur.

Potential for other medicines to affect Paliperidone Janssen-Cilag International

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. 



30

On initiation of carbamazepine, the dose of Paliperidone Janssen-Cilag International should be 
re-evaluated and increased if necessary. Conversely, on discontinuation of carbamazepine, the dose of 
Paliperidone Janssen-Cilag International should be re-evaluated and decreased if necessary.

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 Paliperidone 
Janssen-Cilag International intramuscular injection. This interaction has not been studied with 
Paliperidone Janssen-Cilag International.

Concomitant use of Paliperidone Janssen-Cilag International with risperidone or with oral 
paliperidone

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

Concomitant use of Paliperidone Janssen-Cilag International 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. Paliperidone Janssen-Cilag 
International should not be used during pregnancy unless clearly necessary.

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. Paliperidone Janssen-Cilag 
International 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 Paliperidone Janssen-Cilag International is known.



31

4.8 Undesirable effects

Summary of the safety profile

The adverse drug reactions (ADRs) most frequently reported in clinical trials were insomnia, 
headache, anxiety, upper respiratory tract infection, injection site reaction, parkinsonism, weight 
increased, akathisia, agitation, sedation/somnolence, nausea, constipation, dizziness, musculoskeletal 
pain, tachycardia, tremor, abdominal pain, vomiting, diarrhoea, fatigue, and dystonia. Of these, 
akathisia and sedation/somnolence appeared to be dose-related.

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

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

parkinsonismc, 
akathisiac, 
sedation/somnolence, 
dystoniac, dizziness, 
dyskinesiac, 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



32

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-
glutamyltransferase 
increased, hepatic 
enzyme increased

jaundice

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



33

General disorders 
and 
administration 
site conditions

pyrexia, asthenia, 
fatigue, injection site 
reaction

face oedema, oedemae, 
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 these 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 Paliperidone Janssen-Cilag International-treated 

subjects compared to a rate of 0.39% in placebo group. Overall incidence from all clinical trials was 0.65% in all paliperidone 
palmitate -treated subjects

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.

Description of selected adverse reactions

Anaphylactic reaction
Rarely, cases of anaphylactic reaction after injection with Paliperidone Janssen-Cilag International
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
The most commonly reported injection site related adverse reaction was pain. The majority of these 
reactions were reported to be of mild to moderate severity. Subject evaluations of injection site pain 
based on a visual analogue scale tended to lessen in frequency and intensity over time in all Phase 2 
and 3 studies with Paliperidone Janssen-Cilag International. Injections into the deltoid were perceived 
as slightly more painful than corresponding gluteal injections. Other injection site reactions were 
mostly mild in intensity and included induration (common), pruritus (uncommon) and nodules (rare).

Extrapyramidal symptoms (EPS)
EPS included a pooled analysis of the following terms: parkinsonism (includes 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, muscle twitching, 
choreoathetosis, athetosis, and myoclonus), dystonia (includes dystonia, 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. It should be noted that a broader spectrum of symptoms are included that do
not necessarily have an extrapyramidal origin.



34

Weight gain
In the 13-week study involving the 150 mg initiation dosing, the proportion of subjects with an 
abnormal weight increase ≥ 7% showed a dose-related trend, with a 5% incidence rate in the placebo
group compared with rates of 6%, 8% and 13% in the Paliperidone Janssen-Cilag International 25 mg, 
100 mg, and 150 mg groups, respectively.

During the 33-week open-label transition/maintenance period of the long-term recurrence prevention 
trial, 12% of Paliperidone Janssen-Cilag International-treated subjects met this criterion (weight gain 
of ≥ 7% from double-blind phase to endpoint); the mean (SD) weight change from open-label baseline 
was + 0.7 (4.79) kg.

Hyperprolactinaemia
In clinical trials, median increases in serum prolactin were observed in subjects of both genders who 
received Paliperidone Janssen-Cilag International. Adverse reactions that may suggest increase in 
prolactin levels (e.g., amenorrhoea, galactorrhoea, menstrual disturbances, gynaecomastia) were 
reported overall in < 1% of subjects.

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).

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 prolonged release 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.

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


35

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Paliperidone Janssen-Cilag International 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 positive 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

Acute treatment of schizophrenia
The efficacy of Paliperidone Janssen-Cilag International in the acute treatment of schizophrenia was 
established in four short-term (one 9-week and three 13-week) double-blind, randomised, 
placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria 
for schizophrenia. The fixed doses of Paliperidone Janssen-Cilag International in these studies were 
given on days 1, 8, and 36 in the 9-week study, and additionally on day 64 of the 13-week studies. No 
additional oral antipsychotic supplementation was needed during the acute treatment of schizophrenia
with Paliperidone Janssen-Cilag International. The primary efficacy endpoint was defined as a 
decrease in Positive and Negative Syndrome Scale (PANSS) total scores as shown in the table below. 
The PANSS is a validated multi-item inventory composed of five factors to evaluate positive 
symptoms, negative symptoms, disorganised thoughts, uncontrolled hostility/excitement and 
anxiety/depression. Functioning was evaluated using the Personal and Social Performance (PSP) scale.
The PSP is a validated clinician rated scale that measures personal and social functioning in four 
domains: socially useful activities (work and study), personal and social relationships, self-care and 
disturbing and aggressive behaviours.

In a 13-week study (n = 636) comparing three fixed doses of Paliperidone Janssen-Cilag International
(initial deltoid injection of 150 mg followed by 3 gluteal or deltoid doses of either 25 mg/4 weeks, 
100 mg/4 weeks or 150 mg/4 weeks) to placebo, all three doses of Paliperidone Janssen-Cilag 
International were superior to placebo in improving the PANSS total score. In this study, both the 
100 mg/4 weeks and 150 mg /4 weeks, but not the 25 mg/4 weeks, treatment groups demonstrated 
statistical superiority to placebo for the PSP score. These results support efficacy across the entire 
duration of treatment and improvement in PANSS and was observed as early as day 4 with significant 
separation from placebo in the 25 mg and 150 mg Paliperidone Janssen-Cilag International groups by 
day 8.

The results of the other studies yielded statistically significant results in favour of Paliperidone 
Janssen-Cilag International, except for the 50 mg dose in one study (see table below).



36

Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Total Score - Change From Baseline to 
End Point- LOCF for Studies R092670-SCH-201, R092670-PSY-3003, R092670-PSY-3004 and 

R092670-PSY-3007: Primary Efficacy Analysis Set
Placebo 25 mg 50 mg 100 mg 150 mg

R092670-PSY-3007*
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 160
86.8 (10.31)
-2.9 (19.26)

--

n = 155
86.9 (11.99)
-8.0 (19.90)

0.034
--

n = 161
86.2 (10.77)
-11.6 (17.63)

< 0.001

n = 160
88.4 (11.70)
-13.2 (18.48)

< 0.001

R092670-PSY-3003
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 132
92.4 (12.55)
-4.1 (21.01)

--
--

n = 93
89.9 (10.78)
-7.9 (18.71)

0.193

n = 94
90.1 (11.66)
-11.0 (19.06)

0.019

n = 30
92.2 (11.72)
-5.5 (19.78)

--

R092670-PSY-3004
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 125
90.7 (12.22)
-7.0 (20.07)

--

n = 129
90.7 (12.25)
-13.6 (21.45)

0.015

n = 128
91.2 (12.02)
-13.2 (20.14)

0.017

n = 131
90.8 (11.70)
-16.1 (20.36)

< 0.001
--

R092670-SCH-201
Mean baseline (SD)
Mean change (SD)
P-value (vs. Placebo)

n = 66
87.8 (13.90)
6.2 (18.25)

--
--

n = 63
88.0 (12.39)
-5.2 (21.52)

0.001

n = 68
85.2 (11.09)
-7.8 (19.40)

< 0.0001
--

* For Study R092670-PSY-3007 an initiation dose of 150 mg was given to all subjects in the Paliperidone Janssen-Cilag 
International treatment groups on day 1 followed by the assigned dose afterwards.

Note: Negative change in score indicates improvement.

Maintaining symptom control and delaying relapse of schizophrenia
The efficacy of Paliperidone Janssen-Cilag International in maintaining symptomatic control and 
delaying relapse of schizophrenia was established in a longer-term double-blind, placebo-controlled, 
flexible-dose study involving 849 non-elderly adult subjects who met DSM-IV criteria for 
schizophrenia. This study included a 33-week open-label acute treatment and stabilisation phase, a 
randomised, double-blind placebo-controlled phase to observe for relapse, and a 52-week open-label 
extension period. In this study, doses of Paliperidone Janssen-Cilag International included 25, 50, 75, 
and 100 mg administered monthly; the 75 mg dose was allowed only in the 52-week open-label 
extension. Subjects initially received flexible doses (25-100 mg) of Paliperidone Janssen-Cilag 
International during a 9-week transition period, followed by a 24-week maintenance period, where 
subjects were required to have a PANSS score of ≤ 75. Dosing adjustments were only allowed in the 
first 12 weeks of the maintenance period. A total of 410 stabilised patients were randomised to either 
Paliperidone Janssen-Cilag International (median duration 171 days [range 1 day to 407 days]) or to 
placebo (median duration 105 days [range 8 days to 441 days]) until they experienced a relapse of 
schizophrenia symptoms in the variable length double-blind phase. The trial was stopped early for 
efficacy reasons as a significantly longer time to relapse (p < 0.0001, Figure 1) was seen in patients 
treated with Paliperidone Janssen-Cilag International compared to placebo (hazard ratio = 4.32; 95% 
CI: 2.4-7.7).



37

Figure 1: Kaplan-Meier Plot of Time to Relapse – Interim Analysis (Intent-to-Treat Interim
Analysis Set)

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of studies with 
Paliperidone Janssen-Cilag International 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

Paliperidone palmitate is the palmitate ester prodrug of paliperidone. Due to its extremely low water 
solubility, paliperidone palmitate dissolves slowly after intramuscular injection before being 
hydrolysed to paliperidone and absorbed into the systemic circulation. Following a single 
intramuscular dose, the plasma concentrations of paliperidone gradually rise to reach maximum 
plasma concentrations at a median Tmax of 13 days. The release of the active substance starts as early 
as day 1 and lasts for at least 4 months.

Following intramuscular injection of single doses (25-150 mg) in the deltoid muscle, on average, a 
28% higher Cmax was observed compared with injection in the gluteal muscle. The two initial deltoid 
intramuscular injections of 150 mg on day 1 and 100 mg on day 8 help attain therapeutic 
concentrations rapidly. The release profile and dosing regimen of Paliperidone Janssen-Cilag 
International results in sustained therapeutic concentrations. The total exposure of paliperidone 
following Paliperidone Janssen-Cilag International administration was dose-proportional over a 
25-150 mg dose range, and less than dose-proportional for Cmax for doses exceeding 50 mg. The mean 
steady-state peak:trough ratio for a Paliperidone Janssen-Cilag International dose of 100 mg was 1.8 
following gluteal administration and 2.2 following deltoid administration. The median apparent 
half-life of paliperidone following Paliperidone Janssen-Cilag International administration over the 
dose range of 25-150 mg ranged from 25-49 days.



38

The absolute bioavailability of paliperidone palmitate following Paliperidone Janssen-Cilag
International administration is 100%.

Following administration of paliperidone palmitate the (+) and (-) enantiomers of paliperidone 
interconvert, reaching an AUC (+) to (-) ratio of approximately 1.6-1.8.

The plasma protein binding of racemic paliperidone is 74%.

Biotransformation and elimination

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 6.5% 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 medicinal products 
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.

Long acting paliperidone palmitate injection versus oral prolonged release paliperidone

Paliperidone Janssen-Cilag International is designed to deliver paliperidone over a monthly period 
while prolonged release oral paliperidone is administered on a daily basis. The initiation regimen for 
Paliperidone Janssen-Cilag International (150 mg/100 mg in the deltoid muscle on day 1/day 8) was 
designed to rapidly attain steady-state paliperidone concentrations when initiating therapy without the 
use of oral supplementation.

In general, overall initiation plasma levels with Paliperidone Janssen-Cilag International were within 
the exposure range observed with 6-12 mg prolonged release oral paliperidone. The use of the 
Paliperidone Janssen-Cilag International initiation regimen allowed patients to stay in this exposure 
window of 6-12 mg prolonged release oral paliperidone even on trough pre-dose days (day 8 and 
day 36). Because of the difference in median pharmacokinetic profiles between the two medicinal 
products, caution should be exercised when making a direct comparison of their pharmacokinetic 
properties.

Hepatic impairment

Paliperidone is not extensively metabolised in the liver. Although Paliperidone Janssen-Cilag
International was not studied on 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

The disposition of a single oral dose paliperidone 3 mg prolonged release tablet was studied in 
subjects with varying degrees of renal function. Elimination of paliperidone decreased with decreasing 



39

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. Based on a limited number of observations with Paliperidone Janssen-Cilag International in 
subjects with mild renal impairment and pharmacokinetic simulations, a reduced dose is recommended 
(see section 4.2).

Elderly

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

Body mass index (BMI)/body weight

Pharmacokinetic studies with paliperidone palmitate have shown somewhat lower (10-20%) plasma 
concentrations of paliperidone in patients who are overweight or obese in comparison with normal 
weight patients (see section 4.2).

Race

Population pharmacokinetics analysis of data from studies with oral paliperidone revealed no evidence 
of race-related differences in the pharmacokinetics of paliperidone following Paliperidone 
Janssen-Cilag International administration.

Gender

No clinically significant differences were observed between men and women.

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 Paliperidone Janssen-Cilag 
International. 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 unlikely to be of clinical relevance.

5.3 Preclinical safety data

Repeat-dose toxicity studies of intramuscularly injected paliperidone palmitate (the 1-month 
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 
4.1 times the exposure level in humans at the maximum recommended dose of 150 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 



40

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 1.2 and 2.2 times the exposure level at the maximum recommended 
human 150 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.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Polysorbate 20
Polyethylene glycol 4000
Citric acid monohydrate
Disodium hydrogen phosphate anhydrous
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

Do not store above 30°C.

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 22G 1½-inch safety needle (0.72 mm x 38.1 mm) and a 23G 1-inch safety needle 
(0.64 mm x 25.4 mm).

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

Treatment initiation pack:
Each pack contains 1 pack of Paliperidone Janssen-Cilag International 150 mg and 1 pack of 
Paliperidone Janssen-Cilag International 100 mg.

6.6 Special precautions for disposal

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

7. MARKETING AUTHORISATION HOLDER

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



41

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1453/006

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 

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/


42

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



43

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 (PSURs)

The requirements for submission of PSURs 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 Marketing Authorization Holder (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.



44

ANNEX III

LABELLING AND PACKAGE LEAFLET



45

A. LABELLING



46

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 25 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 25 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, 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

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

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.



47

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/1/20/1453/001 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



48

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

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

Paliperidone Janssen-Cilag International 25 mg injection
Paliperidone
IM

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

25 mg

6. OTHER



49

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 50 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 50 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, 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

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

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.



50

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/1/20/1453/002 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



51

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

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

Paliperidone Janssen-Cilag International 50 mg injection
Paliperidone
IM

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

50 mg

6. OTHER



52

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 75 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 75 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, 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

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

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.



53

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/1/20/1453/003 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



54

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

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

Paliperidone Janssen-Cilag International 75 mg injection
Paliperidone
IM

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

75 mg

6. OTHER



55

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 100 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 100 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, 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

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

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.



56

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/1/20/1453/004 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



57

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

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

Paliperidone Janssen-Cilag International 100 mg injection
Paliperidone
IM

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

100 mg

6. OTHER



58

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 150 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 150 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, 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

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

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.



59

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/1/20/1453/005 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



60

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

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

Paliperidone Janssen-Cilag International 150 mg injection
Paliperidone
IM

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

150 mg

6. OTHER



61

PARTICULARS TO APPEAR ON THE OUTER PACKAGING
TREATMENT INITIATION PACK
OUTER LABEL (WITH BLUE BOX)

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 150 mg
Paliperidone Janssen-Cilag International 100 mg
prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Paliperidone Janssen-Cilag International 150 mg: Each pre-filled syringe contains paliperidone 
palmitate equivalent to 150 mg paliperidone.
Paliperidone Janssen-Cilag International 100 mg: Each pre-filled syringe contains paliperidone 
palmitate equivalent to 100 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, Sodium hydroxide, Water for 
injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection.
Treatment initiation pack
Each pack contains 2 pre-filled syringes:
1 pre-filled syringe of paliperidone 150 mg and 2 needles
1 pre-filled syringe of paliperidone 100 mg and 2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

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



62

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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/1/20/1453/006 

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:



63

NN:



64

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON (150 mg PRE-FILLED SYRINGE, COMPONENT OF 
TREATMENT INITIATION PACK - WITHOUT BLUE BOX)

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 150 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 150 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, Sodium hydroxide, Water for 
injections.

4. PHARMACEUTICAL FORM AND CONTENTS

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

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

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

8. EXPIRY DATE

EXP



65

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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/1/20/1453/006

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted



66

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARDBOARD CARTON (100 mg PRE-FILLED SYRINGE, COMPONENT OF 
TREATMENT INITIATION PACK - WITHOUT BLUE BOX)

1. NAME OF THE MEDICINAL PRODUCT

Paliperidone Janssen-Cilag International 100 mg prolonged release suspension for injection
Paliperidone

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each pre-filled syringe contains paliperidone palmitate equivalent to 100 mg paliperidone.

3. LIST OF EXCIPIENTS

Excipients: Polysorbate 20, Polyethylene glycol 4000, Citric acid monohydrate, Disodium hydrogen 
phosphate anhydrous, Sodium dihydrogen phosphate monohydrate, Sodium hydroxide, Water for 
injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Prolonged release suspension for injection
Day 8
1 pre-filled syringe
2 needles

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Intramuscular use

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

8. EXPIRY DATE

EXP



67

9. SPECIAL STORAGE CONDITIONS

Do not store above 30°C.

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/1/20/1453/006

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted



68

B. PACKAGE LEAFLET



69

Package leaflet: Information for the user

Paliperidone Janssen-Cilag International 25 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 50 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 75 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 100 mg prolonged release suspension for injection
Paliperidone Janssen-Cilag International 150 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 Paliperidone Janssen-Cilag International is and what it is used for
2. What you need to know before you use Paliperidone Janssen-Cilag International
3. How to use Paliperidone Janssen-Cilag International
4. Possible side effects
5. How to store Paliperidone Janssen-Cilag International
6. Contents of the pack and other information

1. What Paliperidone Janssen-Cilag International is and what it is used for

Paliperidone Janssen-Cilag International 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 stabilised on paliperidone or risperidone.

If you have shown responsiveness to paliperidone or risperidone in the past and have mild to moderate 
symptoms your doctor may start treatment with Paliperidone Janssen-Cilag International without prior 
stabilisation with paliperidone or risperidone.

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.

Paliperidone Janssen-Cilag International can help alleviate the symptoms of your disease and stop 
your symptoms from coming back.

2. What you need to know before you use Paliperidone Janssen-Cilag International

Do not use Paliperidone Janssen-Cilag International
- if you are allergic to paliperidone or to 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 Paliperidone Janssen-Cilag International.



70

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, possible side effects).

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 abnormal movements of the tongue or face (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 epilepsy
- if you have kidney problems
- if you have liver problems
- if you have prolonged and/or painful erection
- if you have problems with controlling core 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 Paliperidone Janssen-Cilag International. 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 adversely affect 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
This medicine is not for people who are under 18 years old.



71

Other medicines and Paliperidone Janssen-Cilag International
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, interference from 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 are prone to develop convulsions, 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.

Paliperidone Janssen-Cilag International should be used with caution with medicines that increase the 
activity of the central nervous system (psychostimulants such as methylphenidate).

Paliperidone Janssen-Cilag International 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 you may need to contact your 
doctor.

This medicine can pass from mother to baby through breast milk and may harm the baby. Therefore, 
you should not breastfeed 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.

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



72

3. How to use Paliperidone Janssen-Cilag International

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 the first injection (150 mg) and second injection (100 mg) of this medicine in the 
upper arm approximately one week apart. Thereafter, you will receive an injection (ranging from
25 mg to 150 mg) in either the upper arm or buttocks once a month.

If your doctor is switching you from risperidone long acting injection to this medicine, you will 
receive the first injection of this medicine (ranging from 25 mg to 150 mg) in either the upper arm or 
buttocks on the date that your next injection was scheduled. Thereafter, you will receive an injection 
(ranging from 25 mg to 150 mg) in either the upper arm or buttocks once a month.

Depending on your symptoms, your doctor may increase or decrease the amount of medicine you 
receive by one dose level at the time of your scheduled monthly injection.

Patients with kidney problems
Your doctor may adjust your dose of this medicine based on your kidney function. If you have mild 
kidney problems your doctor may give you a lower dose. If you have moderate or severe kidney 
problems this medicine should not be used.

Elderly
Your doctor may reduce your dose of this medicine if your kidney function is reduced.

If you are given more Paliperidone Janssen-Cilag International 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 Paliperidone Janssen-Cilag International
If you stop receiving your injections, you will lose the effects of the medicine. You should not stop 
using this medicine unless told to do so by your doctor as your symptoms may return.

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.



73

 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.

 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
 Paliperidone Janssen-Cilag International 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
 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, fungal infection of the nails, tonsillitis, infection of 



74

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
 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
 not moving or responding while awake (catatonia)
 confusion



75

 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 
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
 breakdown of muscle fibers and pain in muscles (rhabdomyolysis)
 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 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.
 decreased oxygen in parts of your body (because of decreased blood flow)
 fast, shallow breathing, pneumonia caused by inhaling food, voice disorder
 a blockage in the bowels, lack of bowel muscle 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 Paliperidone Janssen-Cilag International

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)



76

 a decrease in body temperature
 dead skin cells at the injection site and an ulcer at the 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.

5. How to store Paliperidone Janssen-Cilag International

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.

Do not store above 30°C.

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 Paliperidone Janssen-Cilag International contains
The active substance is paliperidone.
Each Paliperidone Janssen-Cilag International 25 mg pre-filled syringe contains 39 mg paliperidone 
palmitate.
Each Paliperidone Janssen-Cilag International 50 mg pre-filled syringe contains 78 mg paliperidone 
palmitate.
Each Paliperidone Janssen-Cilag International 75 mg pre-filled syringe contains 117 mg paliperidone 
palmitate.
Each Paliperidone Janssen-Cilag International 100 mg pre-filled syringe contains 156 mg paliperidone 
palmitate.
Each Paliperidone Janssen-Cilag International 150 mg pre-filled syringe contains 234 mg paliperidone 
palmitate.

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

What Paliperidone Janssen-Cilag International looks like and contents of the pack
Paliperidone Janssen-Cilag International is a white to off-white prolonged release suspension for 
injection in a pre-filled syringe.

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

Treatment initiation pack:
Each pack contains 1 pack of Paliperidone Janssen-Cilag International 150 mg and 1 pack of 
Paliperidone Janssen-Cilag International 100 mg.

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


77

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

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 4594 8282

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



78

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

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: +371 678 93561

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/


79

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).

The suspension for injection is for single use only. It should be inspected visually for foreign matter 
before administration. Do not use if the syringe is not visually free of foreign matter.

The pack contains a pre-filled syringe and 2 safety needles (a 1½-inch 22 gauge needle [38.1 mm x 
0.72 mm] and a 1-inch 23 gauge needle [25.4 mm x 0.64 mm]) for intramuscular injection. 
Paliperidone Janssen-Cilag International is also available in a Treatment initiation pack which contains 
two pre-filled syringes (150 mg + 100 mg) and 2 additional safety needles.

1. Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous 
suspension.

2. Select the appropriate needle.

The first initiation dose of Paliperidone Janssen-Cilag International (150 mg) is to be 
administered on Day 1 in the DELTOID muscle using the needle for DELTOID injection. The 
second initiation dose of Paliperidone Janssen-Cilag International (100 mg) is to also be 
administered in the DELTOID muscle one week later (Day 8) using the needle for DELTOID 
injection.



80

If the patient is being switched from risperidone long acting injection to Paliperidone Janssen-
Cilag International, the first injection of Paliperidone Janssen-Cilag International (ranging from 
25 mg to 150 mg) can be administered in either the DELTOID or GLUTEAL muscle using the 
appropriate needle for the injection site at the time of the next scheduled injection.

Thereafter, the monthly maintenance injections can be administered in either the DELTOID or 
GLUTEAL muscle using the appropriate needle for the injection site.

For DELTOID injection, if the patient weighs < 90 kg, use the 1-inch, 23 gauge needle 
(25.4 mm x 0.64 mm) (needle with blue coloured hub); if the patient weighs ≥ 90 kg, use the 
1½-inch, 22 gauge needle (38.1 mm x 0.72 mm) (needle with grey coloured hub).

For GLUTEAL injection, use the 1½-inch, 22 gauge needle (38.1 mm x 0.72 mm) (needle with 
grey coloured hub).

3. While holding the syringe upright, remove the rubber tip cap with a twisting motion.

4. Peel the safety needle blister pouch half way open. Grasp the needle sheath using the plastic 
peel pouch. Attach the safety needle to the luer connection of the syringe with an easy 
clockwise twisting motion.

5. Pull the needle sheath away from the needle with a straight pull. Do not twist the sheath as the 
needle may be loosened from the syringe.



81

6. Bring the syringe with the attached needle in upright position to de-aerate. De-aerate the syringe 
by moving the plunger rod carefully forward.

7. Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal muscle 
of the patient. Do not administer intravascularly or subcutaneously.

8. After the injection is complete, use either thumb or finger of one hand (8a, 8b) or a flat surface 
(8c) to activate the needle protection system. The system is fully activated when a ‘click’ is 
heard. Discard the syringe with needle appropriately.



82

8a

8b

8c

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


	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