Description
Release form
Suspension for intramuscular administration of prolonged action
Packaging
0.75 ml syringe.
Pharmacological action
Xeplion is an antipsychotic (antipsychotic).
Pharmacodynamics
Paliperidone palmitate is hydrolyzed to paliperidone. The latter is a central active antagonist of predominantly serotonin 5-HT2A receptors, as well as dopamine D2 receptors, adrenergic 1- and 2 receptors and H1-histamine receptors. Paliperidone does not bind to cholinergic m-receptors and adrenergic 1- and 2 receptors. The pharmacological activity of the (+) and (-) enantiomers of paliperidone is quantitatively and qualitatively the same.
The therapeutic efficacy of schizophrenia is believed to be due to the combined blockade of D2 and 5-HT2A receptors.
Pharmacokinetics
Absorption and distribution of
Due to the extremely low solubility of paliperidone in water, palmitate after intramuscular administration slowly dissolves and is absorbed into the systemic circulation. After a single intramuscular injection, the concentration of paliperidone in the blood plasma slowly increases, reaching a maximum 13-14 days (median) after administration to the deltoid muscle and 13-17 days after administration to the gluteus maximus. The release of a substance is detected already on the 1st day and persists for at least 126 days. The release characteristics of the active component and the dosing schedule of the drug Xeplion provide long-term maintenance of therapeutic concentration. After a single dose of 25 – 150 mg into the deltoid muscle, the maximum concentration (Cmax) is on average 28% higher than after insertion into the gluteus muscle. At the beginning of therapy, administration of the drug to the deltoid muscle helps to achieve a faster therapeutic concentration of paliperidone (150 mg on the 1st day and 100 mg on the 8th day) than administration to the gluteus maximus. After repeated injections, the difference in exposure is less obvious. The average ratio of the maximum and equilibrium concentrations of paliperidone after 4 injections of Xeplion at a dose of 100 mg in the gluteus muscle was 1.8, and after administration in the deltoid muscle, it was 2.2. At paliperidone doses of 25-150 mg, the area under the concentration-time curve (AUC) of paliperidone changed in proportion to the dose, and Cmax at doses greater than 50 mg increased to a lesser extent than in proportion to the dose.
The median elimination half-life of paliperidone after administration of the drug Xeplion in doses of 25-150 mg ranged from 25 to 49 days.
After administration of the drug (-) – the enantiomer of paliperidone partially turns into the (+) – enantiomer, and the ratio of AUC (+) – and (-) – enantiomers is approximately 1.6-1.8.
In a population analysis, the apparent distribution volume of paliperidone was 391 l. paliperidone binds to plasma proteins by 74%.
Metabolism and excretion of
A week after a single oral administration of 1 mg of 14C-paliperidone with immediate release of the active component in the urine, 59% of the administered dose is excreted unchanged, which indicates the absence of a significant metabolism of the drug in the liver. About 80% of the administered radioactivity was found in urine and 11% in feces. There are 4 known ways of drug metabolism in vivo, but none of them determines the metabolism of more than 6.5% of the administered dose: dealkylation, hydroxylation, dehydrogenation, cleavage of the benzisoxazole group. Although in vitro studies suggest a certain role for the isoenzymes of CYP2D6 and CYP3A4 in the metabolism of paliperidone, there is no evidence of a significant role of these isoenzymes in the metabolism of paliperidone in vivo. Population pharmacokinetic analysis did not reveal a noticeable difference in paliperidone clearance after oral administration of the drug by people with active and weak CYP2D6 metabolism. In vitro studies using human liver microsomes have shown that paliperidone does not significantly inhibit drug metabolism by the isoenzymes CYP1A2, CYP2A6, CYP2D6, CYP2E1, CYP3A4 and CYP3A5.
In in vitro studies, paliperidone showed the properties of a P-glycoprotein substrate, and in high concentrations, the properties of a weak P-glycoprotein inhibitor. There is no relevant data in vivo, and the clinical significance of this information is unclear.
In general, the concentration of paliperidone in the blood plasma during the load period after the intramuscular administration of the drug Xeplion lay in the same range as after the administration of the prolonged-acting paliperidone orally with the release of the active component in doses between 6 and 12 mg. The used paliperidone loading scheme ensures that the concentration is maintained in this range even at the end of the interdose interval (day 8 and 36). Individual differences in the pharmacokinetics of paliperidone after administration of the drug Xeplion in different patients were less than after oral administration of paliperidone prolonged action. Due to the difference in the nature of the change in the median concentration of paliperidone in blood plasma when using two drugs, caution should be exercised with a direct comparison of their pharmacokinetics.
Special categories of patients
Impaired liver function.
Paliperidone does not undergo significant metabolism in the liver. Although the use of the drug Xeplion in patients with impaired liver function of mild or moderate severity has not been studied, with such violations of the liver, dose adjustment is not required. In the study, the use of paliperidone orally in patients with impaired liver function of moderate severity (Child-Pugh class B), the concentration of free paliperidone in blood plasma was the same as in healthy volunteers. In patients with severe hepatic impairment, the use of paliperidone has not been studied.
Impaired renal function.
For patients with mild renal impairment, the dose of paliperidone should be reduced. Xeplion is not recommended for patients with impaired renal function of moderate severity. The distribution of paliperidone was studied after a single oral administration of a 3 mg prolonged-release paliperidone tablet in patients with varying degrees of renal impairment. With a decrease in creatinine clearance (CC), the excretion of paliperidone was weakened: with impaired renal function of mild severity (CC 50-80 ml / min) – 32%, with moderate severity (CC 30-50 ml / min) – 64%, in severe cases (CC 10-30 ml / min) – by 71%, bringing AUC0- increased in comparison with healthy volunteers, respectively, 1.5, 2.6 and 4.8 times. Based on the small amount of data on the use of the drug Xeplion in patients with impaired renal function and the results of pharmacokinetics modeling, the recommended loading dose of paliperidone for such patients is 75 mg on the 1st and 8th day after that monthly (every 4 weeks ) 50 mg are administered.
elderly patients.
Age per se is not a factor requiring dose adjustment. However, such a correction may be required due to an age-related decrease in QC.
race.
A population-based pharmacokinetic analysis of paliperidone oral test results did not reveal differences in the pharmacokinetics of paliperidone after administration of the drug by people of different races.
Paul
No clinically significant differences in the pharmacokinetics of paliperidone in men and women were found.
The effect of smoking on the pharmacokinetics of the drug.
According to in vitro studies using human liver microsomes, paliperidone is not a substrate of CYP1A2, therefore smoking should not affect the pharmacokinetics of paliperidone. In accordance with these in vitro data, a population pharmacokinetic analysis did not reveal differences in the pharmacokinetics of paliperidone in smokers and non-smokers.
Contraindications
Hypersensitivity to paliperidone or any component of the drug Xeplion.
Since paliperidone is an active metabolite of risperidone, Xeplion is contraindicated in patients with known hypersensitivity to risperidone.
Caution
Orthostatic hypotension
With alpha-blocker activity, paliperidone in some patients may cause orthostatic hypotension. Xeplion should be used with caution in patients with cardiovascular diseases (for example, heart failure, myocardial infarction or myocardial ischemia, impaired cardiac conduction), cerebrovascular disorders or conditions predisposing to lower blood pressure (for example, dehydration, decreased circulating blood volume, use antihypertensive drugs).
Seizures
Like other antipsychotics, Xeplion should be used with caution in patients with a history of seizures or other conditions in which the seizure threshold may decrease.
Regulation of body temperature
With the use of antipsychotics, a deterioration in the body’s ability to lower body temperature is associated. Caution is advised when prescribing the drug Xeplion to patients who may be exposed to effects that increase body temperature, for example, intense physical exertion, high ambient temperature, exposure to drugs with m-anticholinergic activity, and dehydration.
QT Interval
As with other antipsychotics, caution should be exercised when prescribing Xeplion to patients with a history of arrhythmia or congenital lengthening of the QT interval, or taking drugs that extend the QT interval.
Considering the effects of paliperidone on the central nervous system (CNS), it is necessary to use Xeplion with caution in combination with other drugs acting on the central nervous system and alcohol. Paliperidone may attenuate the effects of levodopa and dopamine agonists.
Caution should be exercised when prescribing Xeplion to elderly patients with dementia, patients with Parkinson’s disease, or dementia with Levy bodies.
Pregnancy and lactation
Pregnancy
Safety of using the drug Xeplion intramuscularly or paliperidone orally during pregnancy in humans has not been established. When using high doses of paliperidone, a slight increase in fetal mortality in animals was observed orally. When administered intramuscularly, xeplion did not affect rat pregnancy, but high doses were toxic to pregnant females. Dosages of paliperidone by ingestion and Xeplion by intramuscular injection, which create concentrations exceeding the maximum therapeutic doses in humans by 20-22 times and 6 times, respectively, did not affect the offspring of laboratory animals. Xeplion can be used during pregnancy only if the intended benefit to the mother outweighs the potential risk to the fetus. The effect of the drug Xeplion on labor and delivery in humans is unknown.
The use of antipsychotics in the last trimester of pregnancy is accompanied by the development of reversible extrapyramidal disorders in newborns.
Breastfeeding
In studies of the use of paliperidone in animals and risperidone in humans, excretion of paliperidone with breast milk has been found. Therefore, women receiving Xeplion should not breast-feed their children.
Special instructions
QT interval
Caution should be exercised when using paliperidone in patients with a known cardiovascular disease or with a prolonged QT interval in history, as well as with the combined use of drugs, which can lead to a prolongation of the QT interval.
Malignant antipsychotic syndrome
With the use of antipsychotics, including paliperidone, the development of malignant antipsychotic syndrome (ZNS), characterized by hyperthermia, muscle rigidity, instability of the autonomic nervous system, impaired consciousness and increased concentration of serum creatine phosphokinase, has been reported. In addition, myoglobinuria (rhabdomyolysis) and acute renal failure can be observed. With the appearance of symptoms suggesting ZNS, all antipsychotics, including Xeplion, are canceled.
Tardive dyskinesia
The use of drugs with the properties of dopamine receptor antagonists is accompanied by the development of tardive dyskinesia, characterized by rhythmic, involuntary movements, mainly the tongue and / or facial muscles. If symptoms of tardive dyskinesia appear, consider discontinuing all antipsychotics, including Xeplion.
Hyperglycemia and diabetes mellitus
During treatment with Xeplion, hyperglycemia, diabetes mellitus and exacerbation of existing diabetes mellitus were observed. Establishing the relationship between the use of atypical antipsychotic drugs and impaired glucose metabolism is complicated by the increased risk of diabetes in patients with schizophrenia and the prevalence of diabetes in the general population. Given these factors, the relationship between the use of atypical antipsychotic drugs and the development of side effects associated with hyperglycemia has not been fully established. All patients should be clinically monitored for symptoms of hyperglycemia and diabetes mellitus (see the section “Side effects”).
Weight gain
A significant increase in body weight was observed with atypical antipsychotics. It is necessary to control the body weight of patients.
Hyperprolactinemia
Tissue culture studies indicate that human breast tumor growth may be stimulated by prolactin. Despite the fact that so far in clinical and epidemiological studies have not been shown a direct relationship with the use of antipsychotics, caution should be exercised when using paliperidone in patients with possible prolactin-dependent tumors.
Orthostatic hypotension
With alpha blocker activity, paliperidone in some patients may cause orthostatic hypotension. Xeplion should be used with caution in patients with cardiovascular diseases (for example, heart failure, myocardial infarction or myocardial ischemia, impaired cardiac conduction), cerebrovascular disorders or conditions predisposing to lower blood pressure (for example, dehydration, decreased circulating blood volume, use antihypertensive drugs).
Seizures
Like other antipsychotics, Xeplion should be used with caution in patients with a history of seizures or other conditions in which the seizure threshold may decrease.
Renal failure
The concentration of paliperidone in plasma is increased in patients with impaired renal function. In patients with impaired renal function, a dose adjustment is recommended. Xeplion is not recommended for patients with moderate or severe renal impairment (creatinine clearance <50 ml / min) Hepatic insufficiency The use of Xeplion in patients with severe hepatic impairment (class C on the Child-Pugh scale) has not been studied. Caution should be exercised when using paliperidone in such patients. Elderly patients with dementia A cross-sectional analysis of research results showed increased mortality in elderly patients with dementia who received atypical antipsychotics, including risperidone, aripiprazole, olanzapine and quetiapine, compared with placebo. Among patients receiving risperidone and placebo, mortality was 4% and 3.1%, respectively. The use of the drug Xeplion in elderly patients with dementia has not been studied. Since paliperidone is an active metabolite of risperidone, experience with risperidone should be considered. For elderly patients with dementia taking risperidone, there was an increased mortality in patients taking furosemide and risperidone, compared with the group taking only risperidone and the group taking only furosemide. No pathophysiological mechanisms explaining this observation have been established. Nevertheless, special care should be taken when prescribing the drug in such cases. No increase in mortality was found in patients concomitantly taking other diuretics along with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be closely monitored in elderly patients with dementia. Cerebrovascular accident Placebo-controlled studies found an increased incidence of cerebrovascular accident (transient and stroke), including fatalin elderly patients with dementia who received some atypical antipsychotics, including risperidone, aripiprazole and olanzapine, compared with placebo. Leukopenia, neutropenia, agranulocytosis Leukopenia, neutropenia and agranulocytosis were noted with the use of antipsychotic drugs, including when using the drug Xeplion. Agranulocytosis was very rare during post-marketing observations. Patients with a clinically significant decrease in the history of leukocytes or drug-dependent leukopenia / neutropenia are advised to conduct a complete blood count during the first months of therapy, discontinuation of treatment with Xeplion should be considered at the first clinically significant decrease in the number of leukocytes in the absence of other possible causes. Patients with clinically significant neutropenia are advised to observe for fever or symptoms of infection and begin treatment immediately if such symptoms occur. Patients with severe neutropenia (an absolute neutrophil count of less than 1 x 109 / L) should stop using Xeplion until the white blood cell count returns to normal. Venous thromboembolism Cases of venous thromboembolism have been reported with antipsychotic drugs. Since patients taking antipsychotic drugs often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Xeplion, and preventive measures should be taken. Parkinson ² ¢s disease and dementia with Levi bodies The doctor must compare the risk and benefits of using antipsychotics, including Xeplion, in patients with Parkinson ² ¢s disease or dementia with Levi bodies, since both of these categories of patients may be at increased risk of developing malignant neuroleptic syndrome (ZNS) and the risk of hypersensitivity to antipsychotics. Manifestations of hypersensitivity may include confusion, dullness of pain sensitivity, instability of the posture with frequent falls, and extrapyramidal symptoms. Priapism There is evidence of the ability of drugs with alpha-blocker properties to cause priapism. Priapism is registered as part of post-marketing control of paliperidone. Effect on the regulation of body temperature With the use of antipsychotics, a deterioration in the body’s ability to lower body temperature is associated. Caution is advised when prescribing the drug Xeplion to patients who may be exposed to effects that increase body temperature, for example, intense physical exertion, high ambient temperature, exposure to drugs with m anticholinergic activity, and dehydration. Antiemetic effect An antiemetic effect has been found in preclinical studies of paliperidone. The appearance of this effect in a patient may mask the signs and symptoms of an overdose of certain drugs or, for example, conditions such as bowel obstruction, Reye’s syndrome, or a brain tumor. Introduction With intramuscular administration, care should be taken to avoid accidental entry of the drug into a blood vessel. Intraoperative Flaccid Iris Syndrome (ISDS) ISDR was observed during surgery for cataracts in patients receiving therapy with 1-adrenoreceptor antagonists such as Xeplion. ISDS increases the risk of complications associated with the organ of vision during and after surgery. The doctor conducting such an operation should be informed in advance that the patient has been taking or is currently taking drugs with antagonist activity of 1-adrenergic receptors. The potential benefit of discontinuing therapy with 1-adrenergic antagonists before surgery is not established, and should be assessed taking into account the risks associated with discontinuation of antipsychotic therapy. Influence on driving a car and working with mechanisms Xeplion may interfere with actions requiring concentration and speed of psychomotor reactions, and may affect vision. Therefore, patients should be advised not to drive vehicles and moving machinery until their individual sensitivity is established. Composition Active substance: 100 mg of paliperidone in 1 ml of suspension (equivalent to 156 mg of paliperidone palmitate). Excipients: polysorbate 20, macrogol 4000 (polyethylene glycol 4000), citric acid monohydrate, sodium hydrogen phosphate, sodium dihydrogen phosphate monohydrate, sodium hydroxide, water for injection. Side effects Most of the unwanted side reactions (NDP) were mild or moderate. The following are adverse reactions observed in patients. The frequency of adverse reactions was classified as follows: very frequent (? 10%), frequent (? 1% and <10%), infrequent (? 0.1% and Infections: frequent - upper respiratory tract infections. Metabolic disorders: infrequent – decrease appetite, increased appetite. Psychiatric disorders: very frequent – insomnia frequent – agitation, nightmares infrequent – anxiety. Disorders of the nervous system: very frequent – headache, frequent akathisia, dizziness, extrapyramidal symptoms, drowsiness, infrequent – cramps, postural dizziness, salivation, dysarthria, dyskinesia, dystonia, malignant antipsychotic syndrome, lethargy, oromandibular dystonia, parkinsonism, psychomotor hyperreactivity. Ophthalmic disorders: infrequent – oculogyric crisis, involuntary movement of the eyeball, blurred visual perception. Disorders of the organ of hearing and balance: infrequent – vertigo. Disorders from the cardiovascular system: frequent – increased blood pressure infrequent – bradycardia, blockade of the bundle of His bundle, postural orthostatic tachycardia syndrome, tachycardia, orthostatic hypotension. Gastrointestinal disturbances: frequent – pain in the upper abdomen, constipation, diarrhea, dry oral mucosa, nausea, toothache, vomiting, infrequent discomfort in the abdomen, hypersecretion of saliva, discomfort in the stomach. Disorders from the musculoskeletal system and connective tissue: frequent – pain in the limbs. Disturbances from the skin: infrequent – generalized itching, rash. Reproductive system disorderss and mammary glands: infrequent – amenorrhea, erectile dysfunction, galactorrhea, gynecomastia, irregular menstruation, sexual dysfunction. Other: frequent – asthenic disorders, weakness, local reactions (pain, itching, tightening at the injection site), weight gain. Changes in laboratory parameters: Infrequent – an increase in the concentration of serum prolactin, cholesterol and glucose in the blood. Side effects of paliperidone for oral administration The following are side effects recorded when using paliperidone for oral administration: Disorders of the immune system: anaphylactic reaction Disorders of the nervous system: major and minor seizures, tremor Disorders of the cardiovascular systems: atrioventricular block I degree, palpitations, sinus arrhythmia, sinus tachycardia, decreased blood pressure, myocardial ischemia Disorders from the musculoskeletal system and connective tissue: muscle stiffness Disorders from the reproductive system and mammary glands: priapism, discharge from nipples Other: peripheral edema : changes in the electrocardiogram (ECG) Risperidone safety data Paliperidone is an active metabolite of risperidone. The nature of the release of the active substance and the pharmacokinetics of paliperidone after administration of the drug Xeplion differ significantly from those after oral administration of risperidone preparations with immediate release of the active substance or risperidone for intramuscular administration of a prolonged action. Information on the safety of risperidone for oral administration and risperidone for injection of prolonged action, obtained in clinical studies and as part of post-marketing monitoring of drug use, is given in the instructions for medical use of these drugs. Drug interactions Paliperidone may increase the QT interval, so it should be combined with caution with other drugs that increase the QT interval (antiarrhythmic drugs, including quinidine, procainamide, amiodarone, sotalol antipsychotic drugs, chloridazprom) antibiotics, including gatifloxacin, moxifloxacin. Since paliperidone palmitate is hydrolyzed to paliperidone, when assessing the possibility of drug interaction, consider the results of paliperidone studies for oral administration The ability of the drug Xeplion to influence other drugs is not expected that paliperidone will exhibit a clinically significant pharmacokinetic interaction with drugs metabolized by isoenzymes of the cytochrome P450 system. In vitro studies using human liver microsomes have shown that paliperidone does not significantly impair the metabolism of substances by the isoenzymes CYP1A2, CYP2A6, CYP2C8 / 9/10, CYP2D6, CYP2E1, CYP3A4 and CYP3A5. Therefore, it is not expected that paliperidone will clinically significantly reduce the clearance of drugs metabolized by these isoenzymes. It is also not expected that paliperidone will exhibit the properties of an isoenzyme inducer, as in in vitro studies, paliperidone did not induce the activity of CYPA2, CYPC19 or CYP3A4 isoenzymes. Paliperidone in high concentrations is a weak inhibitor of P-glycoprotein. However, there are no in vivo data in this regard, and the clinical significance of this phenomenon is unknown. Considering the effect of paliperidone on the central nervous system, Xeplion should be used with caution in combination with other centrally acting drugs and alcohol. Paliperidone may attenuate the effect of levodopa and dopamine receptor agonists. Due to the ability of the drug Xeplion to cause orthostatic hypotension, an additive enhancement of this effect may be observed when using the drug Xeplion in conjunction with other drugs with this ability. The ability of other drugs to influence Xeplion Paliperidone is not a substrate of the isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19 and CYP3A5. This suggests a low probability of interaction with inhibitors and inducers of these isoenzymes. Although in vitro studies show the possibility of minimal involvement of CYP2D6 and CYP3A4 in paliperidone metabolism, there is currently no evidence that these enzymes can play a significant role in paliperidone metabolism in vitro or in vivo. In vitro studies indicate that paliperidone is a substrate of P-glycoprotein. Paliperidone is metabolized to a limited extent by the CYP2D6 isoenzyme. In a study of the interaction of paliperidone for oral administration with an active CYP2D6 inhibitor paroxetine in healthy volunteers, no clinically significant change in the pharmacokinetics of paliperidone was found. Administration of paliperidone with prolonged release of the active component (1 time per day) orally simultaneously with carbamazepine (200 mg 2 times per day) led to a decrease in the average C max and AUC of paliperidone by about 37%. This decrease is largely due to an increase in renal clearance of paliperidone by 35%, probably due to the activation of renal P-glycoprotein by carbamazepine. A very small decrease in the amount of the drug excreted through the kidneys unchanged suggests that carbamazepine only weakly affects mediated through metabolism in the liver or bioavailability of paliperidone. At the beginning of the use of carbamazepine, the dose of Xeplion should be reviewed and, if necessary, increased. On the contrary, when canceling carbamazepine, the dose of Xeplion should be reviewed and, if necessary, reduced. Paliperidone at physiological pH is a cation and is mainly excreted unchanged through the kidneys – half by filtration and half by active secretion. The simultaneous use of trimethoprim, which inhibits the active cation transport system in the kidneys, did not affect the pharmacokinetics of paliperidone. The use of the drug Xeplion with risperidone The use of the drug Xeplion together with risperidone has not been studied. Since paliperidone is an active metabolite of risperidone, with the simultaneous use of the drug Xeplion and risperidone, an increase in the concentration of paliperidone in blood plasma should be considered. Overdose Because Xeplion is intended for use by paramedics, the likelihood of overdose by patients is low. Symptoms In general, the expected signs and symptoms correspond to an increase in known pharmacological tachycardia, an action to decrease paliperidone, arterial i. pressure, drowsiness, inhibition, QT interval lengthening, extrapyramidal symptoms. In the case of acute overdose, the possibility of patients receiving several drugs should be considered. Treatment When assessing the need for treatment and recovery of patients, the long-term release of the active substance and the long half-life of paliperidone should be considered. There is no specific antidote for paliperidone. General supportive measures should be taken, airway patency, adequate lung ventilation and oxygen saturation should be maintained and maintained. Cardiovascular function monitoring should be started immediately, including ongoing ECG monitoring to detect possible arrhythmia. When blood pressure and circulatory collapse decrease, appropriate measures should be taken, for example, intravenous injection of solutions and / or sympathomimetics. When developing severe extrapyramidal symptoms, anticholinergic drugs are used. Care should be taken to carefully monitor the patient’s condition before recovering. Storage Conditions At a temperature not exceeding 30 ° C. Keep out of reach of children. Shelf life 2 years. Deystvuyushtee substance Paliperidone Terms and conditions prescription dosage form injection Possible product names Ksepleion 75 mg / 0.75 ml No. 1 syringe + needles Ksepleion suspension w / m prolong action 75mg / 0 , 75ml syringe No. 1 KSEPLION SUSP. V / M ENTER. PROLONG. ACTION 75MG / 0.75ML SYRINGE 0, 75ML No. 1 (KIT WITH 2 NEEDLES) Kseplion suspension for in / mouse. Introduction. prologue. action 75 mg / 0.75 ml syringe 1 pc. Xeplion syringe, 75 mg / 0.75 ml Janssen Pharmaceutical N.V., Belgium
