JURNISTA - PACKAGE LEAFLET - LEAFLETS

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Jurnista - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life

Active ingredients: Hydromorphone

Jurnista 4 mg prolonged-release tablets
Jurnista 8 mg prolonged-release tablets
Jurnista 16 mg prolonged-release tablets
Jurnista 32 mg prolonged-release tablets
Jurnista 64 mg prolonged-release tablets

Indications Why is Jurnista used? What is it for?

Jurnista contains hydromorphone hydrochloride as an active ingredient. It belongs to a group of medicines called opioid analgesics (or morphine-related pain relievers).

Jurnista is used to treat severe pain in adults.

Contraindications When Jurnista should not be used

Do not take Jurnista:

if you are allergic to hydromorphone hydrochloride or any of the other ingredients of this medicine
if you have been diagnosed with severe stenosis or blockage of the stomach and / or intestines
if you have had surgery that caused a 'blind loop' in your bowel
to treat acute pain or pain after surgery
if you have severe hepatic impairment
if you have severe breathing difficulties or severe acute asthma
if you have sudden severe abdominal (belly) pain and have not been diagnosed with the cause
if you are taking a type of antidepressant medicine called monoamine oxidase inhibitor (MAOI) or if you have taken it in the past 14 days
if you are taking buprenorphine, nalbuphine or pentazocine.

Tell your doctor if any of these apply to you.

Jurnista should not be given to women during labor or delivery or to patients in a coma.

Precautions for use What you need to know before taking Jurnista

Talk to your doctor or pharmacist before taking Jurnista. Some people need to be especially careful while taking this medicine.

Anti-doping test

The active ingredient contained in Jurnista can determine positive anti-doping tests. If he is subjected to analysis while using Jurnista, he could be disqualified from sporting activity.

For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

Children and adolescents

Jurnista is not recommended for children and adolescents under 18 years of age. Safety and efficacy in this age group are not known.

Interactions Which drugs or foods can modify the effect of Jurnista

Some medicines can affect the effect of Jurnista or make it more likely that it will cause side effects.

Do not take Jurnista if you are taking:

antidepressants called monoamine oxidase inhibitors (MAOIs) or if you have taken any in the past 14 days
other morphine-related pain relievers (buprenorphine, nalbuphine or pentazocine).

Tell your doctor if any of these apply to you.

Tell your doctor before taking Jurnista if you are taking:

any medicines that have a sedative effect or that cause drowsiness (such as sleeping pills or tranquilizers)
muscle relaxants (which may be prescribed for back pain).

Tell your doctor if you are taking, have recently taken or plan to take any other medicines.

Jurnista with alcohol

Drinking alcohol while taking Jurnista may cause drowsiness or increase the risk of serious side effects such as shortness of breath with the risk of respiratory depression and loss of consciousness. It is recommended not to drink alcohol while taking Jurnista.

Warnings It is important to know that:

Jurnista can cause serious side effects, including breathing difficulties and allergic reactions. You must be aware of these side effects or pay attention to certain signs of illness while you are taking Jurnista. See "Look out for serious side effects" in section 4.

Tell your doctor if you have, or have recently had, any of the following problems:

breathing difficulties or lung problems, including chronic obstructive pulmonary disease (COPD)
treatment with other morphine-related pain relievers
headache or head injury
chronic constipation
sudden attack of severe diarrhea
any bowel disease including obstruction or inflammatory bowel disease (IBD)
pancreatitis (inflammation of the pancreas) or diseases of the bile ducts
problems with your kidneys, liver, heart or adrenal glands
poor thyroid function (hypothyroidism)
enlarged prostate
difficulty urinating
alcoholism or drug addiction, or if you have had a severe reaction to stopping drinking alcohol (sometimes called delirium tremens)
Central Nervous System (CNS) depression
the signs include severe sleepiness, drop in body temperature and in some cases coma
fits or fits (seizures or fits)
toxic psychosis (extreme confusion)
kyphoscoliosis (abnormal curvature of the spine).

Tell your doctor:

if you are going to have a cordotomy or similar surgery to relieve pain. You should not take Jurnista shortly before or after your operation, your doctor will tell you when to stop taking Jurnista and when you can start it again, or if your dose needs to be changed.
if you are over 60 years of age. Side effects may be more likely, so your doctor may give you a low starting dose.

Constipation

Constipation (insufficient or difficult bowel movements) is a common side effect of drugs like Jurnista and is unlikely to resolve without proper treatment. Talk to your doctor or pharmacist about using a laxative (medicine to treat constipation) and stool softening substances to prevent or treat constipation while taking Jurnista.

When he goes to the bathroom

You may notice something like Jurnista's tablet in your stool. Don't worry - it's just the tablet wrapper passing through your body unchanged. It doesn't mean the tablet hasn't worked.

Pregnancy and breastfeeding

It is not recommended to use Jurnista during pregnancy. If you are pregnant, think you may be pregnant or are planning to become pregnant ask your doctor for advice.

You should not take Jurnista if you are breastfeeding, as the active substance can pass into breast milk. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Jurnista can cause drowsiness. Do not drive, operate machinery or perform hazardous work until you are certain that you are no longer subject to the action of the drug. Take special care if you change your dose or type of medicine

Jurnista prolonged-release tablets contain lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Dose, Method and Time of Administration How to use Jurnista: Posology

Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

If you are not routinely taking an opioid pain reliever, the usual starting dose of Jurnista should not exceed 8 mg each day. If you are switching from another opioid painkiller to Jurnista, your doctor may prescribe a different starting dose of Jurnista.

Your doctor may decide to increase your dose until adequate pain control is achieved, leaving an interval of at least three days between each dose increase (for example, if the first dose is taken on a Monday, the dose can be increased from Thursday).

How to take the daily tablet

Swallow the Jurnista tablet whole with a glass of water.

Do not chew, break or crush the tablet. If this happens there is a danger of overdose as the drug will be released into your body too quickly.

Do not break and inject the tablets, as some ingredients can potentially cause death if taken this way.

Try to take Jurnista at the same time every day. You can take this medicine with or without food.

Overdose What to do if you have taken too much Jurnista

If you take more Jurnista than you should

Call your doctor or nearest emergency room immediately.

If possible, tell us which and how many tablets you have taken.

In the event of an overdose, you may feel very drowsy and have difficulty breathing. The effects of overdose can become more severe, with sweating, narrowing of the pupils, hypotension, and coma (unconsciousness). In cases of severe overdose, respiratory arrest, heart attack and death are possible.

If you forget to take Jurnista

Take the next dose as soon as you remember and thereafter at the same time each day. Do not take additional tablets or a double dose to make up for a forgotten tablet. Consult your doctor or pharmacist if you are not sure what to do.

If you stop using Jurnista

When you stop taking Jurnista your doctor will gradually reduce the dose - usually by half - every two days.Once the lowest possible dose is reached, your doctor will discuss with you when to stop taking Jurnista.

when the dose of Jurnista is suddenly reduced or if treatment is stopped suddenly. Some people have withdrawal symptoms

Consult your doctor if you experience any of the following symptoms:

anxiety or irritability
large (dilated) pupils
redness or sweating
unjustified crying
nausea, vomiting or diarrhea
stomach pain or joint pain.

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

Side Effects What are the side effects of Jurnista

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

Pay attention to serious side effects

Breathing difficulties - slow or shallow breathing (respiratory depression) is termed uncommon in people taking Jurnista (may affect up to 1 in 100 people). It is more common for a certain group of people, such as the elderly or very weak people. If your breathing becomes very slow or shallow and you feel extremely tired:

keep moving and talking as much as possible
contact your doctor immediately or seek immediate medical assistance

Talk to your doctor about medicines you can use to treat respiratory depression.

Allergic reactions - are defined as uncommon in people taking Jurnista (may affect up to 1 in 100 people). The signs include:

swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing or breathing
itchy rash.

Contact your doctor immediately or seek immediate medical help if you notice any of these signs. Your doctor may decide that Jurnista is not suitable for you.

Other side effects

Very common side effects (may affect more than 1 in 10 people)

constipation, nausea, vomiting
feeling sleepy, weak or dizzy; headache.

Common side effects (may affect up to 1 in 10 people)

shortness of breath
diarrhea, stomach pain, inflammation of the stomach and intestines
indigestion, worsening of the reflux of food in the throat (heartburn), dry mouth
dehydration, decreased appetite, weight loss
seeing or hearing things that are not there (hallucinations)
feeling confused, anxious, nervous or agitated
onset of depression or worsening of depression, mood swings
feeling sleepy, trouble sleeping (insomnia), abnormal dreams
forgetfulness problems
muscle tremors or spasms, tingling or numbness of the skin, decreased sense of touch or sensation, especially of the skin
blurred vision, feeling dizzy
high blood pressure
increased sweating, itching, rash or hot flashes
pain, for example in the joints, muscles, back or limb pain
pain when urinating
strong craving for the drug after stopping (withdrawal)
swelling caused by fluid retention
fever or chills, chest discomfort
falls, bruises.

Uncommon side effects (may affect up to 1 in 100 people)

breathing difficulties (wheezing) which may be due to narrowing of the airways in the lungs
a runny nose
intestinal inflammation or blockage; pockets in the inner wall of the colon; hemorrhoids
changes in bowel movements, such as alternating constipation and diarrhea; abnormal stools for example with blood in the stool; swelling; flatulence; belching or burping
difficulty swallowing
fluid retention
increased appetite
panic attacks; paranoid feelings, apathy, feelings of discomfort or tension; cry
feeling of extreme happiness (euphoria)
decreased sexual desire
sleep disorders
brain disorders (encephalopathy)
decreased attention or awareness, difficulty concentrating, difficulty forming words or speaking
feeling faint or faint, loss of coordination, problems with balance
uncontrollable twitching, twitching or twisting movements, sudden twitching of the muscles, increased sense of touch or increased sensitivity, especially of the skin
changes in the sensation of taste
double vision, dry eye
ringing in the ear (tinnitus)
changes in your heartbeat, such as skipped, fast, or irregular beats (palpitations)
low blood pressure
redness of the skin
problems urinating, such as inability to pass urine, difficulty starting urination or increased urinary frequency
sexual problems or impotence
flu-like symptoms such as feeling hot or cold
trouble walking
feeling jittery, feeling abnormal or generally unwell
overdose of the medicine
decrease in oxygen levels in the blood, decrease in the amount of potassium in the blood, increase in the levels of liver enzymes in the blood.

Rare side effects (may affect up to 1 in 1,000 people)

fast or deep breathing (hyperventilation), sneezing
perforation of the intestine, lack of contractions of the intestinal wall, inflammation of the duodenum, anal lacerations
impaired emptying of the stomach, retention of the tablet shell in the stomach with failure to pass into the intestine, painful passing of stool
aggression
convulsions or seizures
restlessness or hyperactivity, exaggerated or increased reflexes
difficulty thinking, remembering information or solving problems
small pupils
slow heartbeat
burning sensation of the skin
feeling drunk or hangover feeling
decrease in body temperature
increase in the level of the "enzyme" amylase "in the blood
increased levels of uric acid in the blood, which can cause gout
decreased levels of sex hormones, for example decreased testosterone levels in the blood.

Other side effects have occurred but their exact frequency is unknown:

respiratory block; severe confusion; changes in the menstrual cycle.

Other side effects have occurred with other medicines that contain hydromorphone hydrochloride:

becoming dependent on the medicine (addiction) or unresponsive to the medicine (tolerance); gallstone attack.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse

By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

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 blister label and carton (EXP).

Do not store above 25oC.

Do not use Jurnista if you notice that the tablets are damaged.

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

What Jurnista contains

The active ingredient is hydromorphone hydrochloride.

The 4 mg prolonged-release tablet contains 4.36 mg and releases 4 mg of hydromorphone hydrochloride, equivalent to 3.56 mg of hydromorphone.

The 8 mg prolonged-release tablet contains 8.72 mg and releases 8 mg of hydromorphone hydrochloride, equivalent to 7.12 mg of hydromorphone.

The 16 mg prolonged-release tablet contains 16.35 mg and releases 16 mg of hydromorphone hydrochloride, equivalent to 14.24 mg of hydromorphone.

The 32 mg prolonged-release tablet contains and releases 32.00 mg of hydromorphone hydrochloride, equivalent to 28.48 mg of hydromorphone

The 64 mg prolonged-release tablet contains and releases 64.00 mg of hydromorphone hydrochloride, equivalent to 56.96 mg of hydromorphone

The excipients are:

Coated tablet core: 200K and 2000K polyethylene oxide, povidone K29-32, magnesium stearate, yellow iron oxide (E172) (4 and 32 mg tablets only), butylhydroxytoluene (E321), sodium chloride, hypromellose, black iron oxide ( E172), anhydrous lactose, cellulose acetate, macrogol 3350.

Color coating: 8 mg, 16 mg, 32 mg and 64 mg: lactose monohydrate, hypromellose, titanium dioxide (E171), glycerol triacetate, red iron oxide (E172) (8 mg) / yellow iron oxide (E172) (16 mg) / indigo carmine (E132) (64 mg). For 4 mg tablets only: hypromellose, titanium dioxide (E171), macrogol 400, yellow iron oxide (E172), red iron oxide (E172) and black iron oxide (E172).

Transparent coating: hypromellose, macrogol 400.

Printing ink: black iron oxide (E172), propylene glycol, hypromellose.

Description of the appearance of Jurnista and contents of the package

Jurnista tablets are prolonged-release. This means that the active ingredient is released gradually over time in the body after taking a tablet.

Jurnista 4 mg prolonged-release tablets: each light beige round tablet has "HM4" printed on one side in black ink
Jurnista 8 mg prolonged-release tablets: Each red round tablet has "HM8" printed on one side in black ink.
Jurnista 16 mg prolonged-release tablets: Each yellow round tablet has "HM16" printed on one side in black ink.
Jurnista 32 mg prolonged-release tablets: Each white round tablet has "HM32" printed on one side in black ink.
Jurnista 64 mg prolonged release tablets: Each blue round tablet has a "HM 64" printed on one side in black ink.

The medicine is supplied in blister packs placed in a cardboard box. Each carton contains 7, 10, 14, 20, 28, 30, 35, 40, 50, 56, 60 or 100 tablets. Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Jurnista can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction04.6 Pregnancy and lactation04.7 Effects on the ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical data of 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 HOLDER OF THE ALL AUTHORIZATION "PLACING ON MARKETING 08.0 AUTHORIZATION NUMBER" PLACING ON MARKET09.0 DATE OF PR IMA AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIOPharmaceuticals, ADDITIONAL DETAILED INSTRUCTIONS ON ESTEMPORAN PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

JURNIST EXTENDED RELEASE TABLETS

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each JURNISTA 4 mg prolonged-release tablet contains 4.36 mg of hydromorphone hydrochloride and releases 4 mg equivalent to 3.56 mg of hydromorphone.

Each JURNISTA 8 mg prolonged-release tablet contains 8.72 mg of hydromorphone hydrochloride and releases 8 mg equivalent to 7.12 mg of hydromorphone.

Each JURNISTA 16 mg prolonged-release tablet contains 16.35 mg of hydromorphone hydrochloride and releases 16 mg equivalent to 14.24 mg of hydromorphone.

Each JURNISTA 32 mg prolonged-release tablet contains and delivers 32.00 mg of hydromorphone hydrochloride, equivalent to 28.48 mg of hydromorphone.

Each JURNISTA 64 mg prolonged-release tablet contains and releases 64.00 mg of hydromorphone hydrochloride, equivalent to 56.96 mg of hydromorphone.

Excipient with known effect:

Each 4 mg tablet contains 0.01 mg of lactose.

Each 8 mg tablet contains 4.37 mg of lactose.

Each 16 mg tablet contains 6.81 mg of lactose.

Each 32 mg tablet contains 10.02 mg of lactose.

Each 64 mg tablet contains 8.03 mg of lactose.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

Prolonged-release tablets

JURNISTA 4 mg tablets: light beige, round, biconvex tablet, with "HM 4" printed on one side in black ink.

JURNISTA 8 mg tablets: red, round, biconvex tablet with "HM 8" printed on one side in black ink.

JURNISTA 16 mg tablets: yellow, round, biconvex tablet with "HM 16" printed on one side in black ink.

JURNISTA 32 mg tablets: white, round, biconvex tablet, with "HM 32" printed on one side in black ink.

JURNISTA 64 mg tablets: blue, round, biconvex tablet with "HM 64" printed on one side in black ink.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Treatment of severe pain in adults.

04.2 Posology and method of administration

Dosage

As with other opioid analgesics, safe and effective administration of JURNISTA to patients complaining of pain depends on the patient's overall assessment. The nature of the pain as well as the patient's concomitant medical condition will affect the choice of dose. Due to the different responses to opioids observed between individuals, it is recommended that all patients be given a conservative dose of opioid therapy, subsequently increased until an adequate level of analgesia is achieved, balanced by an acceptable degree of adverse reactions. .

As with any other strong opioid, appropriate prophylaxis should be considered for known adverse reactions (eg constipation).

JURNISTA should not be taken more than once every 24 hours.

Patients currently on unsystematic opioid therapy

Start of therapy - In most patients the starting dose of JURNISTA should be 8 mg taken once every 24 hours and should not exceed 8 mg. Some patients may benefit from a starting dose of 4 mg taken once every 24 hours to increase tolerability.

Titration and maintenance - After initiation of therapy, dose adjustments may be required to achieve the best balance for the patient between pain relief and side effects. If required, the dose should be adjusted upwards by 4 or 8 mg depending on the patient. response and the request for additional analgesics. Thursday) (for more information see paragraph Dose customization and therapy maintenance).

Since it is possible that with a controlled-release opioid preparation it may take longer to determine the dose for a patient to obtain "adequate analgesia, it is advisable to start treatment with conventional immediate-release preparations (for example, hydromorphone). immediate release, or immediate release morphine), then move to an appropriate total daily dose of JURNISTA For dose conversion, use the appropriate conversion table.

Patients who already receive opiates regularly

In patients currently on opioid analgesic therapy, the starting dose of JURNISTA should be based on the daily opioid dose, using standard equianalgesic doses. For opioids other than morphine, the equivalent total daily dose of morphine should first be assessed, then the table below should be used to determine the total daily dose of JURNISTA.

Conversion table: Multiplication factors for converting the daily dose of previously administered opioids into the daily dose of JURNISTA (mg /die of previous opiates x factor = mg /die by JURNISTA) Previous opiates Previous oral opiates (factor) Previous injecting opiates (factor) Morphine 0,2 0,6 Hydromorphone 1 4

There are no fixed conversion factors that can be satisfactory in all patients due to individual patient characteristics and differences in formulations. Therefore, conversion to the recommended starting doses of JURNISTA is recommended, followed by careful patient monitoring and titration.

Doses should be rounded down to the nearest dose of JURNISTA, available in 4 mg increments (4, 8, 16, 32, 64 mg tablets) as clinically indicated.

When initiating therapy with JURNISTA, all other opioid analgesic drugs taken during the day should be discontinued.

JURNISTA can also be used safely with conventional doses of non-opioid analgesics and adjuvant analgesics.

Additional analgesia

In addition to the daily administration of a "single dose of JURNISTA, it is possible to make available to all patients with chronic pain, an additional pain reliever drug for breakthrough pain, in the form of an immediate-release preparation (for example, immediate-release hydromorphone or immediate-release morphine) For the conversion step, the conversion table should be used. Individual supplemental doses of immediate-release hydromorphone or immediate-release morphine should generally not exceed 10% - 25 % of the dose of JURNISTA administered over 24 hours (see table below).

Recommended starting dose for supplemental analgesic therapy Daily dose of JURNISTA (mg) Immediate-release hydromorphone Tablet strength (mg) per dose Immediate-release morphine (mg) 4 - - 5 8 2 10 16 2 10-15 32 4 20-30 64 8 40-60

Dose customization and therapy maintenance

After initiation of therapy with JURNISTA, the dose may need to be adjusted to achieve the best balance for the patient between pain relief and opioid-associated side effects.

If the pain increases in intensity or the analgesia is inadequate, the dose may need to be increased gradually. To allow for the effects of dose modification to stabilize, the dose should be increased at a frequency not less than once every four doses (For example, if the first dose is given on Monday, the dosage can be increased no earlier than the fourth dose, which is Thursday.) Normally, increases of between 25% should be considered for each dose adjustment step. and 100% of the current daily dose of JURNISTA.

Once the patient has stabilized on a daily therapy of JURNISTA taken in a single dose, that dose can be continued until further pain relief is required. The need for ongoing opioid therapy throughout the day and dose adjustments should be reassessed periodically as needed.

Missed dose

If the patient has not taken the regularly scheduled dose of JURNISTA, he should be advised to take the next dose immediately and start a new 24-hour regimen.

Discontinuation of therapy

In patients who are physically dependent on opioids and receiving daily hydromorphone therapy, abrupt cessation of JURNISTA treatment causes withdrawal syndrome. If discontinuation of JURNISTA therapy is indicated, patients should be given a dose of JURNISTA reduced by 50% every 2 days, until the lowest possible dose is reached at which therapy can be safely stopped. If withdrawal symptoms occur, dose tapering should be discontinued. The dose should be increased slightly until opioid withdrawal symptoms disappear. Thereafter, the dose must be gradually reduced again, but with longer intervals between one dose reduction of hydromorphone and the next, or by converting it to an equianalgesic dose of another opioid, and then continued with the gradual reduction.

Use in elderly patients

The clinical picture of the elderly patient is often complex. Hydromorphone treatment should therefore be initiated with caution and the starting dose should be reduced (see section 5.2).

Renal impairment

In clinical studies, following administration of a single dose of hydromorphone immediate release tablets, the following results were observed:

• in patients with moderate renal insufficiency (clearance creatinine 40-60 ml / min), the mean concentration (plasma AUC) of hydromorphone was approximately 2 times higher than that of subjects with normal renal function, while the elimination half-life remained unchanged.

• in patients with severe renal insufficiency (clearance of creatinine

Therefore, patients with moderate renal insufficiency should start on a reduced dose and be closely monitored during the dose adjustment phase. For patients with severe renal insufficiency, a longer dose interval should be considered, as well as careful monitoring during maintenance therapy.

Hepatic impairment

In clinical studies, following administration of a single dose of hydromorphone immediate release tablets, the following results were observed:

• in patients with moderate hepatic impairment (Child-Pugh score 7-9), both the bioavailability (plasma AUC) and maximum plasma concentrations of hydromorphone were approximately 4 times higher than those of healthy controls, while the " elimination half-life was unchanged.

Therefore, patients with moderate hepatic impairment should start on a reduced dose and be closely monitored during the titration phase.

Pediatric population

The safety and efficacy of JURNISTA in children and adolescents below 18 years have not been established. No data available. JURNISTA is not recommended for use in this population.

Method of administration

Patients should be instructed to swallow the JURNISTA tablet whole, accompanied by a glass of water, at approximately the same time each day without ever chewing, dividing or crushing it. JURNISTA can be taken with or without food (see section 5.2).

04.3 Contraindications

Hypersensitivity to hydromorphone or to any of the excipients listed in section 6.1.

Patients who have undergone surgery and / or with underlying disease leading to gastrointestinal stenosis, or have "blind loops" in the gastrointestinal tract or gastrointestinal obstruction.

Treatment of acute or post-operative pain.

Patients with severely impaired liver function.

Patients with respiratory failure.

Patients with acute abdominal pain of unknown origin.

Patients with asthma.

Concomitant treatment with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing such therapy (see section 4.5).

Concomitant treatment with buprenorphine, nalbuphine or pentazocine (see section 4.5).

Patients in a state of coma.

During labor and delivery.

04.4 Special warnings and appropriate precautions for use

Hypotension

Opioid analgesics, including hydromorphone, can cause severe hypotension in patients whose ability to maintain blood pressure is impaired due to blood volume depletion or concomitant administration of drugs such as phenothiazines or general anesthetics.

Paralytic ileus

JURNISTA should not be administered in cases where there is a risk of paralytic ileus. If paralytic ileus is suspected during treatment, therapy should be discontinued.

Use before surgery

If a chordotomy or other pain relief surgery is planned, patients should not be treated with JURNISTA within 24 hours after such operations. Then, a new dose should be given, based on the change in pain relief needs, if any.

Breathing impairment

Respiratory depression is the most important risk of opiate preparations, although it is more frequent in cases of overdose, in elderly patients, in debilitated patients and in those suffering from clinical conditions accompanied by hypoxia or hypercapnia, when even moderate doses may dangerously reduce breathing. JURNISTA, like other opioids, should be used with extreme caution in patients with significantly reduced respiratory reserve or pre-existing respiratory depression, as well as in patients with chronic obstructive pulmonary disease. Severe pain antagonizes the depressive effects of opioids on breathing. However, if the pain suddenly subsides, these effects could come on quickly. Patients for whom local anesthesia procedures or other types of pain transmission pathways have been scheduled should not be treated with JURNISTA for 24 hours prior to the procedure. Concomitant administration of hydromorphone with other opioid analgesics is associated with an increased risk of respiratory failure. It is therefore important to reduce the dose of hydromorphone when co-administered with other analgesics.

Head trauma and increased intracranial pressure

The respiratory depressant effects of opioids, with carbon dioxide retention and secondary increase in cerebrospinal fluid pressure, may be markedly exacerbated in the presence of head trauma or increased intracranial pressure. Opiates produce effects that may hide the neurological signs of further increases in intracranial pressure in patients with TBI. JURNISTA should only be administered in circumstances where it is considered essential, but always with extreme caution.

Gastrointestinal tract and smooth muscle

Like other opioids, hydromorphone causes a reduction in gastrointestinal motility associated with an increase in smooth muscle tone. Constipation is a frequently reported undesirable effect in the presence of opioid treatment. prevent constipation, as well as consider the use of laxatives for prophylactic purposes. Extreme caution should be exercised in patients with chronic constipation.

Clinical or medicinal conditions that cause a sudden and appreciable decrease in gastrointestinal transit time, can cause decreased absorption of the hydromorphone contained in JURNISTA and can potentially lead to withdrawal symptoms in patients with physical dependence on opioids.

Opioid administration may obscure the diagnosis or clinical course of acute abdominal conditions. Therefore it is important to ensure that the patient is not suffering from intestinal obstruction, especially ileus, before starting treatment. Hydromorphone can also cause an increase in pressure in the biliary tract, following spasm of the sphincter of Oddi. Therefore, be careful when administering JURNISTA to patients suffering from inflammatory or obstructive intestinal disorders, from acute pancreatitis secondary to pathology of the biliary tract and in patients who are about to undergo biliary surgery.

The JURNISTA tablet is non-deformable and its shape does not change appreciably in the gastrointestinal tract. There have been rare cases of obstructive symptoms in patients with known strictures following the ingestion of drugs in non-deformable controlled-release formulations (see section 4.3).

Patients should be advised not to be alarmed if they notice the JURNISTA tablet in the stool, as it is only the indissoluble shell.

Patients with special risks

JURNISTA, like other opioid analgesics, should be administered with caution and in reduced doses in patients with renal insufficiency or mild to moderate hepatic insufficiency, adrenocortical insufficiency, myxedema, hypothyroidism, prostatic hypertrophy or urethral stricture. Care should also be taken when administering JURNISTA to patients with central nervous system (CNS) depression, kyphoscoliosis, toxic psychosis, acute alcoholism, delirium tremens or seizure disorders.

Use in elderly patients

Elderly patients are more prone to CNS adverse reactions (confusion) and gastrointestinal disturbances, as well as physiological decreased renal function. It is therefore necessary to be very careful, in addition to administering a reduced initial dose. Concomitant use of other drugs, particularly tricyclic antidepressants, increases the risk of confusion and constipation. In elderly patients, prostate gland and urinary tract disorders are often present, which contributes to an increased risk of urinary retention. The above considerations serve to underline the importance of using caution, rather than implying a limitation of opioid use in elderly patients.

Drug dependence, abuse and use with alcohol

Physical dependence is an adaptive state manifested by a specific opioid withdrawal syndrome, which can be caused by abrupt withdrawal, rapid dose reduction, decrease in blood drug levels, and / or administration of an antagonist .

In general, opioids should not be stopped abruptly (see section 4.2).

JURNISTA should be administered with caution in alcoholic or other drug addict patients due to the increased frequency of developing opioid tolerance and psychological dependence found in this patient population. With injecting abuse, the excipients of tablet can cause life-threatening complications.

Continued use of opiates, including JURNISTA, can lead to the development of tolerance and physical dependence.

Voluntary abuse of JURNISTA may occur, as occurs with other opiates, characterized by behavioral changes not found in patients whose pain is appropriately treated with JURNISTA. It is believed that only in somewhat predisposed patients can a psychological dependence or addictive effect develop, although this is not a normal or expected response during the appropriate use of opioids for pain treatment. However, even if a patient abused opioids in the past, hydromorphone or other opioids may still be indicated in the treatment of the patient's severe pain. The need to increase the dose may be due to an underlying disease and should therefore be reassessed. In most cases, the request reflects the real need for pain relief and should not be confused with inappropriate drug use.

Even if the dose is high, an increase in the dose does not correspond to a development of tolerance.

The use of hydromorphone by those who carry out sporting activities at a competitive level leads to disqualification. Hydromorphone can determine a positive anti-doping test.

The concomitant use of alcohol and JURNISTA may increase the undesirable effects of JURNISTA; concomitant use should be avoided.

Excipient of JURNISTA prolonged-release tablets

Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption syndrome should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

MAO

MAOIs, when given together with opiates, can cause CNS excitation or depression, hypotension or hypertension. JURNISTA is contraindicated in patients receiving MAOIs (see section 4.3).

Morphine agonists / antagonists

The concomitant administration of hydromorphone with morphine agonists / antagonists (buprenorphine, nalbuphine, pentazocine) may lead to a reduction of the analgesic effect by competitive blocking of receptors, with the risk of onset of withdrawal symptoms. This combination is therefore contraindicated (see section 4.3).

CNS depressants

The concomitant administration of CNS depressants such as hypnotics, sedatives, general anesthetics, antipsychotics and alcohol, may cause additive depressive effects which may result in the onset of respiratory depression, hypotension, profound sedation or coma. If this combination is indicated, it is necessary to reduce the dose of one or both agents.

Muscle relaxants

JURNISTA, like other opiates, can enhance the neuromuscular blocking action of muscle relaxants and cause an increase in the degree of respiratory depression.

Alcohol

Alcohol may enhance the pharmacodynamic effects of JURNISTA; concomitant use should be avoided.

04.6 Pregnancy and lactation

Pregnancy

There are no adequate data from the use of hydromorphone in pregnant women. While animal studies (see section 5.3) did not reveal any teratogenic effects, reproductive toxicity was observed. In animal experiments, hydromorphone has been shown to cross the placental barrier. The potential risk to the placenta is not known. man resulting from the use of opioids during pregnancy.

JURNISTA should not be administered during pregnancy and labor due to a weakening of uterine contractility and the risk of respiratory depression in the newborn. Withdrawal symptoms may be observed in infants of mothers undergoing chronic treatment.

Feeding time

In clinical studies, low concentrations of hydromorphone and other opiates have been found in breast milk. Preclinical studies have shown that hydromorphone can be found in the milk of lactating rats. JURNISTA should not be used during lactation.

Fertility

The effect of hydromorphone on human fertility has not been evaluated.

04.7 Effects on ability to drive and use machines

JURNISTA can significantly impair the ability to drive or use machines. This phenomenon is more likely at the start of therapy, following an increase in the dose or change in preparation.

04.8 Undesirable effects

Summary of the safety profile

In clinical trials with JURNISTA (n = 2,340), the most frequently reported adverse reactions were constipation (32%), nausea (29%) and vomiting (14%). They can usually be managed with dose reduction, laxatives (see sections 4.2 and 4.4) or antiemetics, as appropriate.

Somnolence, dizziness, headache and asthenia were reported in between 11% and 16% of patients.

Respiratory depression was reported in approximately 0.1% of patients.

List of adverse reactions in tabular format

The table below shows the adverse reactions observed during clinical trials and post-marketing experience with JURNISTA.

System and organ classification Adverse reactions Frequency Very Common (≥1 / 10) Common (≥1 / 100; Uncommon (≥1 / 1000; Rare (≥1 / 10,000; Very rare ( Infections and infestations Gastroenteritis Diverticulitis Disorders of the immune system Hypersensitivity Endocrine pathologies Hypogonadism Metabolism and nutrition disorders Dehydration, decreased appetite Fluid retention, increased appetite Hyperuricemia Psychiatric disorders Hallucinations, confusional state, depression, anxiety, mood changes, nervousness, restlessness, insomnia, abnormal dreams Panic attack, paranoia, apathy, dysphoria, euphoria, decreased libido, sleep disturbances Aggression Nervous system disorders Somnolence, dizziness, headache Sedation, memory problems, tremor, paraesthesia, hypoesthesia Encephalopathy, decreased level of consciousness, syncope, balance disturbances, attention disturbances, dyskinesia, dysarthria, hyperesthesia, abnormal coordination, myoclonus, crying fits, dysgeusia Convulsions, piscomotor hyperactivity, cognitive disturbances, hyperreflexia Eye disorders Blurred vision Diplopia, dry eye Miosis Ear and labyrinth disorders Dizziness Tinnitus Cardiac pathologies Tachycardia, extrasystoles, palpitations Bradycardia Vascular pathologies Hypertension, redness Hypotension Respiratory, thoracic and mediastinal disorders Dyspnea Respiratory depression, respiratory distress, bronchospasm, hypoxia, rhinorrhea Hyperventilation, sneezing Gastrointestinal disorders Constipation, nausea, vomiting Diarrhea, abdominal pain, dyspepsia, worsening of oesophageal reflux, dry mouth Diverticula, intestinal obstruction, gastrointestinal motility disorders, abdominal distension, dysphagia, haemorrhoids, hematochezia, abnormal stools, flatulence, belching, Perforation of the large intestine, ileus, anal fissures, abnormal gastric emptying, duodenitis, painful defecation, bezoar Skin and subcutaneous tissue disorders Hyperhidrosis, itching, rash Angioedema, urticaria, erythema Burning sensation of the skin Musculoskeletal and connective tissue disorders Arthralgia, myalgia, back pain, pain in extremity, muscle spasms Renal and urinary disorders Dysuria Urinary retention, hesitation in urinating, pollakiuria, disturbed urination Diseases of the reproductive system and breast Erectile dysfunction, sexual dysfunction General disorders and administration site conditions Asthenia Drug withdrawal syndrome, edema, pyrexia, chills, chest tightness, pain Flu-like syndrome, difficulty walking, feeling jittery, feeling abnormal, feeling unwell, feeling of change in body temperature Feeling drunk, confused like after a hangover Diagnostic tests Weight loss Decreased plasma potassium, increased liver enzymes Increased plasma amylase, decreased body temperature, decreased plasma testosterone Injury, poisoning and procedural complications Falls, bruises Overdose

The following additional adverse reactions have been reported with other hydromorphone hydrochloride formulations: dependence, drug tolerance and biliary colic.

The following events have been reported in the literature, the frequency of which is unknown: respiratory failure, delirium and amenorrhea.

Respiratory depression

Respiratory depression may be more likely in some patient subgroups (see section 4.4).

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

04.9 Overdose

Overdose with hydromorphone is characterized by respiratory depression, somnolence leading to stupor and coma, musculoskeletal flaccidity, cold skin, contraction of the pupils and sometimes, tachycardia and hypotension. In the event of a severe overdose, apnea, circulatory collapse, cardiac arrest and death can occur.

In the treatment of overdose, attention should first be paid to re-establishing "adequate respiratory function, keeping the airway open and establishing assisted and controlled ventilation."

Supportive measures (oxygen, vasopressors) are needed to manage shock and pulmonary edema, which can follow overdose. Cardiac arrest and arrhythmias may require heart massage or defibrillation.

In cases of severe overdose, specific antidotes such as naloxone and nalmefene should be used to manage respiratory depression (see the prescribing information for the specific opioid antagonist for details of proper use). The effect of naloxone is relatively short, so the patient should be carefully monitored until breathing stabilizes. JURNISTA releases hydromorphone for approximately 24 hours. This should be taken into account in treatment planning. Naloxone should not be administered in the absence of respiratory depression. clinically significant or circulatory depression due to opioid intake. Naloxone should be administered with caution in patients with suspected physical dependence on hydromorphone, as rapid antagonism of an opioid, including hydromorphone, can precipitate withdrawal symptoms.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: analgesics; natural alkaloids of opium, ATC code: N02AA03.

Hydromorphone is a semi-synthetic derivative of morphine.

Like other opiates, hydromorphone exerts its main pharmacological effects on the CNS and smooth muscle. These effects are expressed and modulated by binding to specific opioid receptors. Hydromorphone is primarily a µ-receptor agonist, with a weak affinity for κ receptors. Analgesia occurs as a consequence of the binding of hydromorphone to the µ receptors of the CNS. Although estimates vary (2 to 10 times), hydromorphone taken by mouth appears to be about 5 times more potent (by weight) than morphine and has a shorter duration of action. Respiratory depression arises primarily from direct action on the brain's respiratory control centers. Opiates can cause nausea and vomiting due to direct stimulation of chemoreceptors for emesis in the posterior region of the marrow.

05.2 "Pharmacokinetic properties

Absorption

After a single oral administration of JURNISTA prolonged-release tablets, plasma concentrations gradually increase over 6-8 hours and subsequently remain constant for approximately 18-24 hours; the mean values of Tmax were approximately between 13 and 16 hours. This demonstrates that, as desired, hydromorphone is released steadily from the drug formulation, with continued absorption throughout the intestinal tract for approximately 24 hours, compatible with once daily administration. The absolute mean bioavailability of hydromorphone after a single dose of 8, 16 or 32 mg of JURNISTA is between 22% and 26%. Co-administration of JURNISTA with a high-fat meal has no effect on the absorption of hydromorphone.

Steady-state plasma concentrations are approximately double those observed after administration of the first dose, and steady state is achieved at the fourth dose of JURNISTA. No time-dependent changes in pharmacokinetics were observed with multiple dose administration. At steady state JURNISTA, administered once daily, maintained plasma concentrations of hydromorphone within the same concentration range as an immediate-release tablet administered 4 times daily at the same overall daily dose and decreased periodic fluctuations in plasma concentrations of the immediate-release tablets. The degree of fluctuations in steady-state plasma concentrations over a 24 hour period (calculated as (Cmax (ss) - Cmin (ss)) / Cavg (ss) x 100%) was lower with JURNISTA (83%) in comparison with the total fluctuations of immediate-release tablets (147%). At steady state, the AUC of hydromorphone contained in JURNISTA is equivalent to that observed for immediate release tablets.

Distribution

Plasma protein binding is low (

Biotransformation

Glucuronidation is the main metabolic pathway and the primary metabolite is hydromorphone-3-glucuronide, which has a release time in plasma similar to that of hydromorphone. Unlike morphine, 6-glucuronide is not produced.

Linearity

For the controlled-release tablet, linear pharmacokinetics have been demonstrated over the dose range 4-64 mg, with dose proportional increases in plasma concentrations (Cmax) and overall concentration (AUC).

Elderly patients

The effect of age on the pharmacokinetic profile after a single dose of immediate-release hydromorphone shows a 14% reduction in Cmax and a modest (11%) increase in AUC in elderly compared to young patients. There was no difference in Tmax. An increased sensitivity of elderly subjects cannot be excluded. In general, dose selection for an elderly patient should be made with caution, usually starting at the lowest level of the dose range, as decreased liver, kidney or heart function may occur more frequently in this patient population. , concomitant diseases or the use of other drugs.

Sex

Plasma concentrations and pharmacokinetic parameters of hydromorphone after administration of JURNISTA are comparable in male and female subjects.

Renal impairment

Renal impairment affected the pharmacokinetic profile of hydromorphone and its metabolites, hydromorphone-3-glucuronide and 3-sulfate after administration of a single oral dose of immediate-release tablets. The effects of renal impairment on hydromorphone pharmacokinetics were represented by two- and four-fold increases in the bioavailability of hydromorphone, with moderate and severe impairment, respectively. Substantial changes in the elimination kinetics of hydromorphone-3-glucuronide were also observed in the severely impaired group, although hemodialysis was effective in reducing plasma levels of both hydromorphone and its metabolites. doses refer to section 4.2.

Hepatic impairment

In studies using a single oral administration of conventional (immediate-release) tablets, hepatic impairment reduced the first pass metabolism of hydromorphone, resulting in a four-fold increase in plasma levels of hydromorphone in subjects with grade hepatic dysfunction. moderate See section 4.2 for dosing recommendations.

Alcohol

In a study comparing the absorption of hydromorphone after administration of JURNISTA in combination with 240 ml of 4%, 20% and 40% alcohol, Cmax increased on average by 17, 31 and 28% respectively under conditions fasting while this absorption was less affected after the meal with increases of 14, 14 and 10% respectively. The mean Tmax (fed and fasted) after 4, 20 and 40% alcohol intake was 12-16 hours and with 0% alcohol it was 16 hours. There was no effect on AUC values in both fasting and post-meal cases. Thanks to JURNISTA's OROS tablet technology, prolonged release properties are maintained in the presence of alcohol. For pharmacodynamic interactions see section 4.4.

05.3 Preclinical safety data

Non-clinical data following oral administration of hydromorphone reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and fertility. A slight but significant reduction in implantation was observed in rats. at a dose of 6.25 mg / kg / day, a dose that produces toxicity in the mother during the mating period. The plasma exposure (AUC) to hydromorphone at this dose was 135 ng / hour / ml, providing a 1.5-fold higher safety factor than human exposure (AUC) based on mean daily dose. Neonatal viability and survival were reduced in pre-weaning rats at the mother's oral daily dose of 6.25 mg / kg. The latter appears to be a class effect of opioid analgesics.

Long-term studies of hydromorphone showed no evidence of carcinogenic effects after daily oral administration for 2 years in mice and rats. Steady-state plasma exposure (AUC, ng.hr/mL) of hydromorphone was approximately 0.46-fold in mice and 3-fold greater than human exposure after a single 64 mg dose of JURNISTA.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Core of the coated tablet

200K polyethylene oxide

Povidone K29-32

Magnesium stearate

Yellow iron oxide E172 (only for 4 and 32 mg tablets)

Butylhydroxytoluene E321

Polyethylene oxide 2000K

Sodium chloride

Hypromellose

Black iron oxide E172

Anhydrous lactose

Cellulose acetate

Macrogol 3350

Colored coating

8 mg, 16 mg, 32 mg and 64 mg: Lactose monohydrate, hypromellose, titanium dioxide E171, glycerol triacetate, red iron oxide E172 (8 mg) / yellow iron oxide E172 (16 mg) / indigo carmine E132 (64 mg).

4 mg: hypromellose, titanium dioxide E171, macrogol 400, yellow iron oxide E172, red iron oxide E172 and black iron oxide E172.

Transparent coating

Hypromellose

Macrogol 400

Printing ink

Black iron oxide E172

Propylene glycol

Hypromellose