CCDS: 20 April 2009 Page 1 of 37 PACKAGE INSERT

CCDS: 20 April 2009 Page 1 of 37

PACKAGE INSERT

SCHEDULING STATUS

Schedule 6

PROPRIETARY NAME AND DOSAGE FORM

JURNISTA® 4 mg extended-release tablets



Contains the antioxidant, butylated hydroxytoluene.

COMPOSITION

Each JURNISTA 4 mg extended-release tablet contains 4,36 mg and delivers 4 mg hydromorphone

hydrochloride, equivalent to 3,56 mg hydromorphone base.





PHARMACOLOGICAL CLASSIFICATION

A.2.9 Other Analgesics

PHARMACOLOGICAL ACTION

Pharmacodynamic Properties

Hydromorphone is a semi-synthetic morphine derivative. Hydromorphone exerts its principal

pharmacological effects on the CNS and smooth muscle. These effects are expressed and modulated by

binding to specific opioid receptors. Hydromorphone is principally an agonist of -receptors, showing a

weak affinity for -receptors. Analgesia occurs as a consequence of the binding of hydromorphone to the

-receptors of the CNS.


Although estimates vary (from 2 to 10 times), hydromorphone appears to be approximately 5 times as

potent (by weight) as morphine and has a shorter duration of effect. Respiratory depression occurs

principally by direct action on the cerebral respiratory control centers. Hydromorphone may cause nausea

and vomiting due to direct stimulation of the chemoreceptors for emesis in the posterior area of the

medulla.

Pharmacokinetic Properties

Following a single oral dose of JURNISTA extended-release tablets, plasma concentrations gradually

increase over 6 to 8 hours thereafter concentrations are sustained for approximately 18 - 24 hours post-

dose; the mean Tmax values were approximately 13 – 16 hours. Hydromorphone is released in a

consistent manner from the dosage form, with drug absorption continuing throughout the intestinal tract for

approximately 24 hours, consistent with once-daily dosing. The mean absolute bioavailability of

hydromorphone after a single dose of 8 mg, 16 mg or 32 mg of JURNISTA ranged from 22 % to 26 %.

The concomitant administration of JURNISTA with a high fat meal has no effect on the absorption of

hydromorphone.

Steady state plasma concentrations are approximately twice those observed following the first dose, and

steady state is reached by the fourth dose of JURNISTA. No time dependent change in pharmacokinetics

was seen with multiple dosing.

Plasma protein binding is low (< 30 %). Glucuronidation is the main metabolic pathway and the principal

metabolite is hydromorphone 3-glucuronide, which follows a similar time course to hydromorphone in

plasma. Unlike morphine, no 6-glucuronide is produced. Linear pharmacokinetics has been

demonstrated for the (extended release) tablet over the dose range 4 to 64 mg, with dose proportional

increase in plasma concentrations (Cmax) and overall exposure (AUC).


The effect of age on the single-dose pharmacokinetics of hydromorphone immediate-release resulted in a

14 % decrease in Cmax and a modest increase (11 %) in AUC in the elderly compared to the young. No

difference in Tmax was observed. Greater sensitivity of older individuals cannot be excluded. In general,

dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing

range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant

disease or other drug therapy in this population.

JURNISTA plasma concentrations and pharmacokinetic parameters are comparable in male and female

subjects. Population pharmacokinetics analysis revealed no evidence of race-related differences in the

pharmacokinetics of hydromorphone.

In studies, that used single oral dosing with conventional (immediate release) tablets, hepatic impairment

reduces the first-pass metabolism of hydromorphone such that four-fold higher plasma levels of

hydromorphone are seen in subjects with moderate hepatic dysfunction. Renal impairment affected the

pharmacokinetics of hydromorphone and its metabolites hydromorphone 3-glucuronide and 3-sulphate.

The effects of renal impairment on hydromorphone pharmacokinetics were two-fold and four-fold

increases in hydromorphone bioavailability in moderate and severe impairment, respectively. There were

also substantial changes in hydromorphone 3-glucuronide elimination kinetics for the severe impairment

group, although haemodialysis was effective at reducing plasma levels of both hydromorphone and

metabolites. See section DOSAGE AND DIRECTIONS FOR USE for recommendations on dosage.

In a study comparing hydromorphone absorption with JURNISTA when taken with 240 mL of 4 %, 20 %

and 40 % alcohol, Cmax increased on average by 17, 31, and 28 % respectively in the fasting state and

was less affected in the fed state with increases of 14, 14, and 10 %, respectively. Median Tmax (fasted

and fed) with 4, 20 and 40 % alcohol was 12 - 16 h and with 0 % alcohol was 16 h. No effect was seen on

AUC values both in the fed and fasted state. Due to the OROS®

technology in JURNISTA, the extended-

release properties of JURNISTA are maintained in the presence of alcohol. For the pharmacodynamic

interactions (see Special Warnings and Precautions for use).


INDICATIONS

Treatment of severe chronic intractable pain.

CONTRA-INDICATIONS

JURNISTA is contraindicated in:

Patients with a known hypersensitivity to hydromorphone or to any of the excipients.

Patients who have had surgical procedures and/or underlying disease that would result in

narrowing of the gastrointestinal tract, or have “blind loops” of the gastrointestinal tract or

gastrointestinal obstruction.

The management of acute or post-operative pain.

Patients with severely decreased liver function.

Patients with respiratory insufficiency.

Patients with acute abdominal pain of unknown origin.

Patients with status asthmaticus.

Concomitant treatment with MAO-inhibitors or within 14 days of stopping such treatment.

Concomitant treatment with buprenorphine, nalbuphine or pentazocine.

Patients in a coma state.

Children, pre-term newborn infants, or during labour for delivery of pre-term newborn infants.

WARNINGS

JURNISTA may cause severe hypotension in an individual whose ability to maintain blood pressure is

compromised by a depleted blood volume or concomitant administration of drugs such as phenothiazines

or general anesthetics.

JURNISTA should not be used in situations with risk of paralytic ileus. If during treatment, paralytic ileus is

suspected, the treatment should be stopped.


In the case of planned chordotomy or other pain-relieving operations, patients should not be treated with

JURNISTA within 24 hours after the operation. Thereafter, a new dose should be used in accordance with

the change needed for pain relief, if needed.

Impaired respiration:

Respiratory depression is the most important hazard of hydromorphone preparations but occurs most

frequently in overdose situations, in the elderly, in the debilitated, and in those suffering from conditions

accompanied by hypoxia or hypercapnia when even moderate doses may dangerously decrease

respiration.

JURNISTA should be used with extreme caution in patients having a substantially decreased respiratory

reserve or pre-existing respiratory depression and in patients with chronic obstructive pulmonary disease.

Severe pain antagonises the respiratory depressant effects of opioids. However, should pain suddenly

subside, these effects may rapidly become manifest. Patients who are scheduled for regional anaesthetic

procedures or other interruptions of pain transmission pathways should not receive JURNISTA within 24

hours of the procedure. Concomitant administration of hydromorphone with other opioid analgesics is

associated with an increased risk of respiratory failure. Therefore, it is important to reduce the dose of

hydromorphone, when other analgesics are given concomitantly.

Head injury and increased intracranial pressure:

The respiratory depressant effects of JURNISTA with carbon dioxide retention and secondary elevation of

cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury or raised

intracranial pressure. JURNISTA produces effects, which may obscure neurological signs of further

increases in intracranial pressure in patients with head injuries. JURNISTA should only be administered

under such circumstances when considered essential and then with extreme caution.

Gastrointestinal tract and other smooth muscle:


Hydromorphone causes a reduction in gastrointestinal motility associated with an increase in smooth

muscle tone. Constipation is a frequent side effect reported with the treatment with opioids. Patients

should be advised on measures to prevent constipation and prophylactic laxative use should be

considered. Extra caution should be used in patients with chronic constipation.

Clinical conditions or medicinal products that cause a sudden and significant shortening of gastrointestinal

transit time may result in decreased hydromorphone absorption with JURNISTA and may potentially lead

to withdrawal symptoms in patients with a physical dependence on opioids.

The administration of JURNISTA may obscure the diagnosis or clinical course of acute abdominal

conditions. Therefore it is important to make sure that the patient is not suffering from intestinal occlusion,

especially of the ileus before initiation of treatment. Hydromorphone also can cause an increase in biliary

tract pressure as a result of spasm in the sphincter of Oddi. Caution should therefore be exercised in the

administration of JURNISTA to patients with inflammatory or obstructive bowel disorders, acute

pancreatitis secondary to biliary tract disease and in patients about to undergo biliary surgery.

The JURNISTA tablet is non deformable and does not appreciably change in shape in the GI tract. There

have been very rare reports of obstructive symptoms in patients with known strictures in association with

ingestion of medicinal products in non deformable controlled-release formulations (see CONTRA-

INDICATIONS). Patients should be advised not to be alarmed if they notice what appears to be the

JURNISTA tablet in their stools, as it is simply the non-dissolvable shell.

INTERACTIONS

Monoamine oxidase inhibitors (MAOIs) may cause CNS excitation or depression, hypotension or

hypertension if co-administered with opioids. JURNISTA is contraindicated for patients taking MAOIs.

The concomitant use of hydromorphone with morphine agonist/antagonists (buprenorphine, nalbuphine,

petazocine) could lead to a reduction of the analgesic effect by competitive blocking of receptors, thus

leading to risk of withdrawal symptoms, therefore this combination is contraindicated.


The concomitant use of central nervous system depressants such as hypnotics, sedatives, general

anaesthetics, antipsychotics and alcohol may cause additive depressant effects, and respiratory

depression, hypotension and profound sedation or coma may occur. When this combination is indicated,

the dose of one or both agents should be reduced.

JURNISTA may enhance the neuromuscular blocking action of muscle relaxants and cause an increased

degree of respiratory depression.

The concomitant use of alcohol should be avoided. Alcohol increases the sedative effect of

hydromorphone.

PREGNANCY AND LACTATION

Pregnancy:

No clinical data on exposed pregnancies are available. While animal studies have revealed no teratogenic

effects, reproductive toxicity has been observed. Hydromorphone has been shown to cross the placental

barrier in experimental animals. The potential risk for humans from use of opiates during pregnancy is

unknown.

JURNISTA should not be used during pregnancy and labour due to impaired uterine contractility and the

risk of neonatal respiratory depression. Withdrawal symptoms may be observed in the newborn of

mothers undergoing chronic treatment.

Lactation:

Low concentrations of hydromorphone and other opioid analgesics have been detected in human milk in

clinical studies. Preclinical studies have shown that hydromorphone can be detected in milk of lactating

rats. JURNISTA should not be used during breast-feeding.

DOSAGE AND DIRECTIONS FOR USE


Safe and effective administration of JURNISTA to patients with pain depends upon a comprehensive

assessment of the patient. The nature of the pain as well as the concurrent medical status of the patient

will affect selection of the dose.

Owing to the varied response observed to opioids between individuals, it is recommended that all patients

be started at the lowest appropriate dose of opioid therapy and titrated to an adequate level of analgesia,

balanced against an acceptable frequency of adverse reactions.

Appropriate prophylaxis for known adverse reactions (for example constipation), should be instituted with

initiation of therapy.

Patients should be instructed to swallow the JURNISTA tablet whole with a glass of water, at

approximately the same time each day, and never to chew, divide, or crush it.

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

If the patient did not take the regularly scheduled dose of JURNISTA, the patient should be instructed to

take the next dose immediately and start a new 24-hour regimen.

Patients currently not routinely receiving opioids:

The initial dose in patients currently not routinely receiving opioids should not exceed 8 mg every 24

hours. Some patients may benefit from an initial titration dose of 4 mg every 24 hours to improve

tolerability. The dose may be titrated upwards, if required, in increments of either 4 or 8 mg depending on

response and supplementary analgesic requirements. Dose should not be titrated more frequently than

every 2 days.

Patients currently receiving opioids regularly:

In patients currently taking opioid analgesics, the starting dose of JURNISTA should be based on the prior

daily opioid dose, using standard equianalgesic ratios. For opioids other than morphine, first estimate the


equivalent total daily dose of morphine, then use the table (1a) below to determine the equivalent total

daily dose of JURNISTA.

Table 1a:

Conversion Table: Multiplication Factors for Converting the Daily Dose of Prior Opioids to the Daily Dose

of JURNISTA (mg/day Prior Opioid x Factor = mg/day JURNISTA):

Prior Opioid Oral Prior Opioid (factor) Parenteral Prior Opioid (factor)

Morphine 0,2 0,6

Hydromorphone 1 4

No fixed conversion ratio is likely to be satisfactory in all patients, due to individual patient and formulation

differences. Therefore conversion to the recommended starting dose of JURNISTA should be followed by

close patient monitoring and titration. Dosages should be rounded down to the closest dose of JURNISTA

available in 4 mg increments (4, 8, 16, 32, 64 mg tablets), as clinically indicated.

Discontinue all other around-the-clock opioid analgesic medications when JURNISTA therapy is initiated.

Supplemental Analgesia:

In addition to once daily JURNISTA therapy, supplemental breakthrough pain medication in the form of

immediate release preparations (e.g. immediate release morphine) could be made available to all patients

with chronic pain. For conversion, the conversion table should be used. Individual supplemental doses of

immediate release morphine should generally not exceed 10 % to 25 % of the JURNISTA dose.

Individualisation of Dosage and Maintenance of Therapy:

After initiation of therapy with JURNISTA, dose adjustments may be necessary to obtain the patient’s best

balance between pain relief and opioid-related side effects.

If the pain increases in severity or analgesia is inadequate, a gradual increase in dosage may be required.

In order to allow the effects of the dose change to stabilise, the dosage should be increased no more


frequently than every two days. As a guideline, dosage increases of 25 %-100 % of the current daily dose

of JURNISTA should be considered for each titration step.

Once patients become stable on once-daily JURNISTA therapy, the dose may be continued for as long as

pain relief is necessary. The continued need for around-the-clock opioid therapy and adjustments in

therapy should be reassessed periodically as appropriate.

Use in children:

JURNISTA is not recommended for use in children and adolescents below age 18 due to insufficient data

on safety and efficacy.

Use in the elderly:

The medical setting of the elderly is often complex. Therefore, treatment with JURNISTA should be

initiated cautiously, and the initial dose should be reduced.

Renal and hepatic impairment:

Following single dose administration of hydromorphone immediate release tablets, the following results

were observed in clinical studies:

In patients with moderate hepatic insufficiency (scoring 7-9 on Child-Pugh rating scale) both

exposure (plasma AUC) and peak plasma concentrations of hydromorphone were approximately

4-times higher compared with healthy controls and elimination half-life was unaltered.

In patients with moderate renal insufficiency (creatinine clearance of 40-60 mL/min), exposure

(plasma AUC) to hydromorphone was 2-times higher than in those with normal renal function and

elimination half-life was unaltered.

In patients with severe renal insufficiency (creatinine clearance < 30 mL/min), exposure (plasma

AUC) to hydromorphone was approximately 4-times greater than in those with normal renal

function and elimination half-life 3-times longer.

Therefore, patients with either moderate hepatic or renal insufficiency should be started on a reduced dose

and closely monitored during dose titration. In patients with severe renal insufficiency an increased dosing


interval should also be considered and these patients should in addition be monitored during maintenance

therapy for development of opioid-related adverse reactions.

Cessation of Therapy:

In patients who are physically dependent and receiving daily administration of hydromorphone, abrupt

discontinuation of treatment with JURNISTA will result in symptoms of withdrawal syndrome. If cessation

of therapy with JURNISTA is indicated, patients should therefore have their JURNISTA dose reduced by

50 % every 2 days until the lowest possible dose is reached, at which time therapy may be safely

discontinued. If symptoms of withdrawal appear, tapering should be stopped. The dose should be slightly

increased until the signs and symptoms of opioid withdrawal disappear. Tapering should then begin again

but with longer periods of time between each JURNISTA dose reduction, or before converting to an

equianalgesic dose of another opioid to continue tapering.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS

Side-effects

Adverse Drug Reactions

In clinical trials with JURNISTA (n = 1684), the most commonly reported ADRs were opioid-related GI

events of constipation, nausea, and vomiting. They can usually be managed by dose reduction, laxatives

or anti-emetics, as appropriate.

The table below shows the adverse drug reactions (ADRs) observed with JURNISTA and those that have been

reported with other hydromorphone hydrochloride formulations. If the JURNISTA and hydromorphone

hydrochloride frequencies were different, the higher frequency of both databases was used.

Table 2: Adverse Drug Reactions in JURNISTA treated patients.

System Organ

Class

Adverse Drug Reaction Frequency

Very Common

(> 1/10)

Common

(1/100 to <1/10)

Uncommon

(1/1000 to <1/100)

Rare

( 1/10,000

to <1/1000)



System Organ

Class


Very Common

(> 1/10)

Common

(1/100 to <1/10)

Uncommon

(1/1000 to <1/100)

Rare

( 1/10,000

to <1/1000)

Infections and

infestations

Diverticulitis, Gastroenteritis

Endocrine disorders Hypogonadism

Metabolism and

nutrition disorders

Anorexia

Dehydration

appetite

Fluid retention

Hyperuricaemia

Psychiatric

disorders

Insomnia

Anxiety

Confusional state

Nervousness

Abnormal dreams

Depression

Mood alterations

Restlessness

Hallucination

Decreased libido

Panic attack

Paranoia

Aggression

Crying

Listless

Drug tolerance*

Dysphoria

Euphoric mood

Dependence*

Nervous system

disorders

Somnolence

Dizziness

Headache

Memory impairment

Hypoaesthesia

Paraesthesia

Tremor or involuntary

muscle contractions

Sedation

Disturbance in

attention

Dysgeusia

Myoclonus

Abnormal coordination

Dyskinesia

Syncope

Dysarthria

Balance disorder

Depressed level of

consciousness

Hyperaesthesia

Encephalopathy

Cognitive disorder

Psychomotor hyperactivity

Fits/convulsions

Hyperreflexia

Eye disorders Visual disorders s.a.

blurred vision

Miosis,

Diplopia

Dry eye

Ear and labyrinth

disorders

Vertigo Tinnitus

Cardiac Disorders Tachycardia Palpitations

Extrasystoles

Bradycardia

Vascular disorders Hypotension

Flushing

Hypertension



System Organ

Class


Very Common

(> 1/10)

Common

(1/100 to <1/10)

Uncommon

(1/1000 to <1/100)

Rare

( 1/10,000

to <1/1000)

Respiratory,

thoracic and

mediastinal

disorders

Dyspnoea Respiratory distress

Rhinorrhoea

Hypoxia

Bronchospasm

Hyperventilation

Sneezing

Gastrointestinal

disorders

Constipation

Nausea

Vomiting

Dry mouth

Diarrhoea

Abdominal pain

Dyspepsia

Dysphagia

Flatulence

Abdominal distension,

Haemorrhoids

Haematochezia

Abnormal faeces

Intestinal obstruction

Diverticulum

Eructation

Gastrointestinal motility

disorder

Large intestine perforation

in pancreatic

enzymes*

Anal fissure

Bezoar

Duodenitis

Ileus

Impaired gastric

emptying

Painful

defaecation

Hepatobiliary

disorders

Biliary colic

Skin and

subcutaneous

tissue disorders

Hyperhidrosis

Pruritus

Rash

Eczema* Reddening of

face/erythema

Musculoskeletal

and connective

tissue disorders

Muscle spasms

Back pain

Arthralgia

Pain in extremity

Myalgia

Renal and urinary

disorders

Urinary retention

Dysuria

Micturition disorder

Urinary hesitation

Pollakiuria

Reproductive

system and breast

disorders

Erectile dysfunction /

impotence

Sexual dysfunction

General disorders

and administration

site conditions

Asthenia Oedema

Drug withdrawal

syndrome

Pyrexia

Pain

Chest discomfort

Chills

Feeling abnormal

Malaise

Difficulty in walking

Feeling jittery

Hangover

Feeling drunk

Feeling hot and

cold

Hypothermia



System Organ

Class


Very Common

(> 1/10)

Common

(1/100 to <1/10)

Uncommon

(1/1000 to <1/100)

Rare

( 1/10,000

to <1/1000)

Investigations Weight decreased Oxygen saturation

Blood potassium

Hepatic enzyme

Blood amylase

Blood

testosterone

Injury, poisoning

and procedural

complications

Fall

Contusion

Overdose

* Adverse drug reaction (ADR) reported with other hydromorphone HCl formulations.

The following terms of unknown frequencies have been reported in the literature:

Respiratory failure; delirium and amenorrhea. Respiratory depression may be more likely in certain

subgroups of patients (see WARNINGS).

Special Precautions

Special risk patients:

JURNISTA should be administered with caution and in reduced dosages in patients with moderate to

severe renal or mild to moderate hepatic insufficiency, adrenocortical insufficiency, myxedema,

hypothyroidism, prostatic hypertrophy or urethral stricture. Caution should also be exercised in the

administration of JURNISTA to patients with CNS depression, kyphoscoliosis, toxic psychosis, acute

alcoholism, delirium tremens, or convulsive disorders.

Use in the Elderly:

Elderly are more prone to CNS adverse effects (confusion) and gastrointestinal disturbances, and

physiological reduction of the renal function. Therefore, extra caution should be shown, and the initial

dose should be reduced. Concomitant use of other medications, especially tricyclic antidepressants,

increases the risk of confusion and constipation. Diseases of the prostate gland and the urinary tract are

often seen in the elderly. This contributes to the increased risk of urinary retention. The above


considerations should stress the importance of caution rather than imply a restriction of the use of

hydromorphone in the elderly.

Drug dependence:

JURNISTA should be used with caution in patients with alcoholism and other drug dependencies due to

the increased frequency of opioid tolerance and psychological dependence observed in these patient

populations. With abuse by parenteral route, the tablet excipients may be fatal.

With the continued use of JURNISTA, the development of tolerance and physical dependence may be

expected.

The deliberate abuse of JURNISTA may occur and is characterized by changes in behaviour, which are

not seen in patients whose pain is treated appropriately with JURNISTA. The development of

psychological dependence or an addictive effect is believed to occur only in individuals who may be

predisposed in some way and is not a normal or expected response to the appropriate administration of

opioids for pain management. However, even if a patient has misused opioids in the past, JURNISTA or

other opioids could still be indicated in the treatment of moderate to severe pain in the patient. A

requirement for an increase in dose may be due to the underlying pathology and should be re-evaluated.

In most cases the request for higher doses reflects a real need for pain relief and should not be mistaken

for inappropriate medication use.

Use of JURNISTA in connection with sporting will imply disqualification.

Since alcohol increases the sedative effect of hydromorphone concomitant use of JURNISTA and alcohol

should be avoided.

Reactions to Excipients


An excipient of JURNISTA, butylated hydroxytoluene, is known to be an irritant to the eyes, skin and

mucous membranes.

Effects on Ability to Drive and Use Machines

JURNISTA can have a major influence on the ability to drive and use machines. This is particularly likely

at the start of therapy, following an increase in dose or change of preparation.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

JURNISTA overdose is characterized by respiratory depression, drowsiness which progresses to stupor

and coma, musculoskeletal flaccidity, cold skin, contracted pupils and, at times, tachycardia and

hypotension. In cases of severe overdose, apnoea, circulatory collapse, cardiac arrest and death may

occur.

In the treatment of overdose, primary attention should be given to the reestablishment of adequate

respiratory exchange keeping the airway open and instituting assisted or controlled ventilation. If the oral

ingestion was recent, gastric contents may be emptied by gastric lavage, as indicated.

Supportive measures (including oxygen and, vasopressors) should be used to manage the shock and

pulmonary edema, which potentially accompany overdose. Cardiac arrest and arrhythmias may require

cardiac 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 opioids antagonist for

details of proper use).

The effect of naloxone is relatively short, therefore, the patient should be carefully monitored until

respiration has stabilised.


JURNISTA will release hydromorphone for approximately 24 hours. This should be taken into account in

determining the treatment. Opioid antagonists should not be given in the absence of clinically significant

respiratory depression, or circulatory depression because of opioids. Opioid antagonists should be

administered with caution to patients suspected to be physically dependent on hydromorphone, since

rapid reversal of an opioid, including hydromorphone, may precipitate symptoms of withdrawal.

IDENTIFICATION

JURNISTA 4 mg extended-release tablet: pale beige, round, biconvex tablet, with ‘HM 4’ printed in black

ink on one side.

JURNISTA 8 mg extended-release tablet: red, round, biconvex tablet, with ‘HM 8’ printed in black ink on

one side.

JURNISTA 16 mg extended-release tablet: yellow, round, biconvex tablet, with ‘HM 16’ printed in black ink

on one side.

PRESENTATION

JURNISTA extended-release tablets are packed in opaque PVC/Aclar blisters, heat-sealed to aluminium

foil. One or more blisters are packed into an outer carton.

Each carton contains 14 or 28 tablets.

STORAGE INSTRUCTIONS

Store below 25 C.

Blisters must be kept in the cartons until required for use.

KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER(s)

JURNISTA 4 mg: 41/2.9/1136

JURNISTA 8 mg: 41/2.9/1130

JURNISTA 16 mg: 41/2.9/1131


NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION

JANSSEN PHARMACEUTICA (PTY) LTD

(Reg. No. 1980/011122/07)

Building 6, Country Club Estate,

21 Woodlands Drive,

Woodmead,

2191

www.janssen.co.za

DATE OF PUBLICATION OF THE PACKAGE INSERT

October 2010

http://www.janssen.co.za/


VOUBILJET

SKEDULERINGSTATUS

Skedule 6

EIENDOMSNAAM EN DOSEERVORM

JURNISTA® 4 mg verlengde-vrystelling tablette



Bevat die antioksidant, gebutileerde hidroksietolueen.

SAMESTELLING

Elke JURNISTA 4 mg verlengde-vrystelling tablet bevat 4,36 mg en lewer 4 mg hidromorfoonhidrochloried,

ekwivalent aan 3,56 mg hidromorfoon basis.





FARMAKOLOGIESE KLASSIFIKASIE

A.2.9 Ander Analgetika

FARMAKOLOGIESE WERKING

Farmakodinamiese eienskappe

Hidromorfoon is ’n semi-sintetiese morfienderivaat. Die belangrikste farmakologiese werking van

hidromorfoon vind plaas in die SSS en gladde spiere. Hierdie werksaamhede word uitgedruk en

gemoduleer deur binding aan spesifieke opioïedreseptore. Hidromorfoon is hoofsaaklik ’n agonis van -

reseptors en toon ’n swak affiniteit vir -reseptore. Analgesie ontstaan as ’n gevolg van die binding van

hidromorfoon aan die -reseptore van die SSS.


Alhoewel skattings wissel (van 2 tot 10 keer), wil dit voorkom asof JURNISTA ongeveer 5 keer so kragtig

is (volgens massa) as morfien en ’n korter duur van werking het. Respiratoriese onderdrukking kom

hoofsaaklik voor deur direkte werking op die serebrale respiratoriese beheersentrum. Hidromorfoon kan

naarheid en braking veroorsaak as gevolg van direkte stimulasie van die chemoreseptore vir emese in die

posterior streek van die medulla.

Farmakokinetiese eienskappe

Na ’n enkele orale dosis JURNISTA verlengde-vrystelling tablette neem plasmakonsentrasies geleidelik

toe vir 6 tot 8 uur daarna en word volgehou vir ongeveer 18 - 24 uur na dosering; die gemiddelde Tmaks

waardes was ongeveer 13 – 16 uur. Hidromorfoon word bestendig vrygestel uit die doseringsvorm, met

volgehoue geneesmiddel-absorpsie regdeur die dermkanaal vir ongeveer 24 uur, wat steekhoudend is met

een-keer-daaglikse dosering. Die gemiddelde absolute biobeskikbaarheid van hidromorfoon na ’n enkele

dosis van 8 mg, 16 mg of 32 mg JURNISTA het gereik van 22 % tot 26 %.

Die gesamentlike toediening van JURNISTA met ’n hoëvet maaltyd het geen effek op die absorpsie van

hidromorfoon nie.

Bestendige toestand plasmakonsentrasies is ongeveer twee keer soveel as wat waargeneem is met die

eerste dosis en bestendige toestand word bereik teen die vierde dosis van JURNISTA. Geen

tydsafhanklike verandering in farmakokinetika is met veelvuldige dosisse waargeneem nie.

Plasma proteïenbinding is gering (< 30 %). Glukuronidasie is die belangrikste metaboliese weg en die

belangrikste metaboliet is hidromorfoon 3-glukuronied, wat ’n soortgelyke tydsverloop het as hidromorfoon

in plasma. In teenstelling met morfien, word geen 6-glukuronied geproduseer nie. Lineêre

farmakokinetika is aangetoon vir die ER (“Extended Release”) tablet oor die dosis reikwydte 4 tot 64 mg,

met dosis-proporsionele toename in plasmakonsentrasie (Kmaks) en algehele blootstelling (AOK).


Die effek van ouderdom op die enkeldosis farmakokinetika van hidromorfoon onmiddellike-vrystelling het

gelei tot ’n 14 % afname in Kmaks en ’n matige toename (11 %) in AOK by die bejaarde, vergeleke met

jongmense. Geen verskil in Tmaks is waargeneem nie. Verhoogde gevoeligheid by ouer individue kan nie

uitgesluit word nie. Oor die algemeen moet die keuse van ’n dosis vir ’n bejaarde pasiënt versigtig

geskied, gewoonlik deur te begin aan die lae kant van die doseringsreeks, wat die hoër frekwensie van

verminderde lewer, nier of hartfunksie en/of gesamentlike siekte of ander geneesmiddelterapie by hierdie

populasie weerspieël.

JURNISTA plasmakonsentrasies en farmakokinetiese parameters is vergelykbaar by manlike en vroulike

pasiënte. Populasie farmakokinetiese analise het geen bewys opgelewer van rasverwante verskille in die

farmakokinetika van hidromorfoon na toediening nie.

In navorsingstudies waar enkele orale dosering met konvensionele (onmiddellike vrystelling) tablette

gebruik is, verminder lewerinkorting die eerste-deurgangsmetabolisme van hidromorfoon tot so ’n mate dat

viervoudige hoër plasmavlakke van hidromorfoon by pasiënte met matige lewerdisfunksie waargeneem

word. Nierinkorting affekteer die farmakokinetika van hidromorfoon en die metaboliete daarvan,

hidromorfoon 3-glukuronied en 3-sulfaat. Die effekte van nierinkorting op hidromorfoon farmakokinetika

was onderskeidelik tweevoudige en viervoudige toenames in hidromorfoon biobeskikbaarheid by matige

en ernstige inkorting. Daar was ook aansienlike veranderinge in die hidromorfoon 3-glukuronied

eliminasie-kinetika vir die groep met ernstige inkorting, alhoewel hemodialise doeltreffend was om

plasmavlakke van beide hidromorfoon en metaboliete te verlaag. Sien afdeling DOSIS EN

GEBRUIKSAANWYSINGS vir aanbevelings oor die dosering.

In ’n navorsingstudie waar absorpsie van hidromorfoon met JURNISTA vergelyk is toe dit geneem is met

240 mL alkohol 4 %, 20 % en 40 %, het die Kmaks gemiddeld toegeneem met onderskeidelik 17, 31 en

28 % in die vastende toestand en was dit minder aangetas in die gevoede toestand met onderskeidelike

toenames van 14, 14 en 10 %. Die mediane Tmax (vastend en gevoed) met 4, 20 en 40 % alkohol was 12 -

16 h en met 0 % alkohol was 16 h. Geen effek is waargeneem op AOK waardes by sowel die gevoede as

die vastende toestand nie. Te danke aan die OROS®

-tegnologie van JURNISTA word die uitgebreide-


vrystellingseienskappe JURNISTA volgehou in die teenwoordigheid van alkohol. Vir die

farmakodinamiese interaksies (sien Waarskuwings en Spesiale voorsorgmaatreëls vir gebruik).

INDIKASIES

Behandeling van ernstige chroniese halsstarrige pyn.

KONTRAÏNDIKASIES

JURNISTA word teenaangedui by:

Pasiënte met ’n bekende hipersensitiwiteit vir hidromorfoon of vir enige van die bestanddele.

Pasiënte wat chirurgiese prosedures ondergaan het en/of ’n onderliggende siekte het wat kan lei

tot vernouing van die gastroïntestinale weg, stagnante derms of gastroïntestinale obstruksie.

Die beheer van akute of post-operatiewe pyn.

Pasiënte met ernstige verminderde lewerfunksie.

Pasiënte met respiratoriese ontoereikendheid.

Pasiënte met akute abdominale pyn van onbekende oorsprong.

Pasiënte met langdurige bronchospasma (status asthmaticus).

Gesamentlike behandeling met MAO-remmers of binne 14 dae wat sodanige behandeling gestaak

is.

Gesamentlike behandeling met buprenorfien, nalbufien of pentasoksien.

Pasiënte in ’n komateuse toestand.

Kinders, vroeggebore babas, of tydens kraam vir die verlossing van voortydige pasgebore babas.

WAARSKUWINGS

JURNISTA kan ernstige hipotensie veroorsaak by ’n individu by wie die vermoë om die bloeddruk te

reguleer deur ’n verminderde bloedvolume of gesamentlike toediening van geneesmiddels soos

fenotiasiene of algemene narkosemiddels aangetas is.

JURNISTA moet nie gebruik word by situasies waar daar ’n risiko vir paralitiese ileus is nie. Indien daar

tydens behandeling paralitiese ileus vermoed word, moet die behandeling gestaak word.


In die geval van beplande chordotomie of ander pynverligtende operasies moet pasiënte nie binne 24 uur

van die operasie met JURNISTA behandel word nie. Daarna kan ’n nuwe dosis vir pynverligting gebruik

word, in ooreenstemming met die behoefte aan verandering, indien nodig.

Belemmerde asemhaling:

Respiratoriese onderdrukking is die belangrikste gevaar van hidromorfoon preparate, maar dit kom

meestal by oordoseringsituasies voor, by die bejaarde, by die verswakte persoon en by diegene wat ly aan

toestande wat gepaard gaan met hipoksie of hiperkapnie, wanneer selfs matige dosisse die respirasie

gevaarlik kan laat afneem.

JURNISTA moet met uiterste versigtigheid gebruik word by pasiënte met ’n aansienlik verlaagde

respiratoriese reserwe of voorafbestaande respiratoriese onderdrukking en by pasiënte met chroniese

obstruktiewe pulmonêre siekte.

Erge pyn antagoniseer die respiratoriese onderdrukkende effekte van opioïede. Indien pyn egter skielik

opklaar, kan hierdie effek skielik na vore tree. Pasiënte wat geskeduleer word vir streeks-narkotiese

prosedures of ander onderbrekings van pyn-oordrag weë moet nie JURNISTA binne 24 uur van die

prosedure ontvang nie. Gesamentlike toediening van hidromorfoon met ander opioïed-analgetika word

geassosieer met ’n verhoogde risiko vir respiratoriese versaking. Gevolglik is dit belangrik om die

hidromorfoon dosis te verminder wanneer ander analgetika gesamentlik gegee word.

Kopbesering en verhoogde intrakraniale druk:

Die respiratories onderdrukkende effekte van JURNISTA met koolsuurgas-retensie en sekondêre

verhoging van serebrospinale vloeistofdruk kan aansienlik sterker word in die teenwoordigheid van

kopbesering of verhoogde intrakraniale drukking. JURNISTA produseer effekte wat neurologiese tekens

kan verbloem of wat intrakraniale druk meer kan verhoog by pasiënte met hoofbeserings. JURNISTA

moet slegs toegedien word onder sodanige omstandighede waar dit noodsaaklik geag word en dan slegs

met buitengewone versigtigheid.


Gastroïntestinale weg en ander gladde spiere:

Hidromorfoon veroorsaak ’n afname in gastroïntestinale motiliteit, geassosieer met ’n toename in

gladdespier tonus. Hardlywigheid is ’n gereelde newe-effek wat aangemeld word by behandeling met

opioïede. Pasiënte moet geadviseer word oor maatreëls om hardlywigheid te voorkom en die gebruik van

voorkomende lakseermiddels moet oorweeg word. Spesiale voorsorg moet gebruik word by pasiënte met

chroniese hardlywigheid.

Kliniese toestande of medisinale produkte wat ’n skielike en beduidende verkorting van gastroïntestinale

deurgangstyd veroorsaak, kan lei tot verminderde hidromorfoon absorpsie met JURNISTA en kan

potensieel lei tot onttrekkingsimptome by pasiënte met ’n fisiese afhanklikheid van opioïede.

Die toediening van JURNISTA kan die diagnose of kliniese verloop van akute abdominale toestande

aantas. Dit is gevolglik belangrik om voor aanvang van behandeling te verseker dat die pasiënt nie aan

inwendige verstopping, veral van die ileus, ly nie. Hidromorfoon kan ook ’n toename in galbuisdruk

veroorsaak as gevolg van spasma in die sfinkter van Oddi. Versigtigheid moet gevolglik uitgeoefen word

by die toediening van JURNISTA aan pasiënte met inflammatoriese of obstruktiewe dermsiektes, akute

pankreatitis sekondêr tot galbuis siekte en by pasiënte wat op die punt staan om gal-chirurgie te

ondergaan.

Die JURNISTA tablet is nie vervormbaar nie en verander nie veel van vorm in die SVK nie. Daar was baie

seldsame berigte van obstruktiewe simptome by pasiënte met bekende strikture in assosiasie met die

inname van medisinale produkte by nie-vervormbare beheerde-vrystelling formulerings (sien

KONTRAÏNDIKASIES). Pasiënte moet aangeraai word om nie te skrik as hulle in hul stoelgang iets

gewaar wat soos ’n JURNISTA tablet lyk nie, aangesien dit slegs die onoplosbare dop is.

INTERAKSIES


Monoamien-oksidase inhibeerders (MAOIs) kan SSS prikkeling of depressie veroorsaak, hipotensie of

hipertensie, indien saam met opioïede toegedien. JURNISTA word teenaangedui by pasiënte wat MAOIs

neem.

Die gesamentlike gebruik van hidromorfoon met morfien agoniste/antagoniste (buprenorfien, nalbufien,

pentasosien) kan lei tot ’n afname in die analgetiese effek deur kompetitiewe blokkering van die reseptore

en sodoende ’n risiko van onttrekkingsimptome laat ontstaan; gevolglik word hierdie kombinasie

teenaangedui.

Die gesamentlike gebruik van sentrale senuweestelsel onderdrukkers soos hipnotika, bedaarmiddels,

algemene narkosemiddels, antipsigotiese middels en alkohol kan additiewe onderdrukkende effekte en

respiratoriese onderdrukking, hipotensie veroorsaak en intense kalmering of koma kan voorkom. Indien

hierdie kombinasie aangedui word, moet die dosis van een of albei middels verminder word.

JURNISTA kan die neuromuskulêre blokkeringswerking van spierverslappers versterk en ’n verhoogde

graad van respiratoriese onderdrukking veroorsaak.

Die gesamentlike gebruik van alkohol moet vermy word. Alkohol verhoog die kalmerende effek van

hidromorfoon.

SWANGERSKAP EN LAKTASIE

Swangerskap:

Geen kliniese data is beskikbaar oor swangerskappe wat blootgestel is nie. Alhoewel daar nie met

dierestudies enige teratogeniese effekte getoon is nie, is reproduktiewe toksisiteit waargeneem. Daar is

aangetoon dat hidromorfoon die plasentale skans kruis by proefdiere. Die potensiële risiko vir die mens

met die gebruik van opiate tydens swangerskap is onbekend.


JURNISTA moet nie tydens swangerskap en geboorte gebruik word nie as gevolg van belemmerde

kontraktiliteit van die uterus en die risiko vir neonatale respiratoriese onderdrukking. Onttrekkingsimptome

kan waargeneem word by die pasgeborenes van moeders wat chroniese behandeling ondergaan.

Laktasie:

Lae konsentrasies hidromorfoon en ander opioïede analgetika is in mens melk tydens kliniese

navorsingstudies waargeneem. Pre-kliniese navorsingstudies het getoon dat hidromorfoon in borsmelk

van lakterende rotte waargeneem kan word. JURNISTA moet nie tydens borsvoeding gebruik word nie.

DOSIS EN GEBRUIKSAANWYSINGS

Veilige en doeltreffende toediening van JURNISTA aan pasiënte met pyn hang af van ’n omvattende

evaluering van die pasiënt. Die aard van die pyn sowel as die gelyktydige mediese status van die pasiënt

sal die seleksie van die dosis bepaal.

As gevolg van die verskil in respons tussen individue op opioïede, word dit aanbeveel dat alle pasiënte

begin met die laagste toepaslike dosis opioïed-behandeling en getitreer word tot by ’n voldoende vlak van

analgesie, gebalanseer ten opsigte van ’n aanvaarbare frekwensie van newe-effekte.

Geskikte profilakse vir bekende newe-effekte (byvoorbeeld konstipasie) moet met aanvang van

behandeling ingestel word.

Pasiënte moet ingelig word om die JURNISTA tablet heel in te sluk met ’n glas water, ongeveer dieselfde

tyd elke dag en om dit nooit te kou, deel of breek nie.

JURNISTA moet nie meer as een keer elke 24 uur geneem word nie

Indien die pasiënt nie gereeld die geskeduleerde dosis JURNISTA geneem het nie, moet die pasiënt die

volgende dosis dadelik neem en ’n nuwe 24-uur regimen begin.


Pasiënte wat tans nie gereeld opioïede middels gebruik nie:

Die aanvanklike dosis vir pasiënte wat tans nie gereeld opioïede ontvang nie, moet nie meer wees as

8 mg elke 24 uur nie. Sommige pasiënte kan voordeel trek uit ’n aanvanklike titrasiedosis van 4 mg elke

24 uur om verdraagsaamheid te verbeter. Die dosis kan indien nodig opwaarts getitreer word, met

inkremente van 4 mg of 8 mg, afhangende van die respons en aanvullende analgetiese behoeftes. Die

dosis moet nie meer dikwels as elke 2 dae getitreer word nie.

Pasiënte wat tans gereeld opioïede ontvang:

By pasiënte wat tans ’n opioïed-analgetikum neem, moet die aanvangsdosis van JURNISTA gebaseer

word op die vorige daaglikse opioïed dosis, met behulp van standaard “equianalgesic ratios”

(gelykwaardige analgesie-verhoudings). Vir opioïede, behalwe morfien, bepaal eers die ekwivalente

daaglikse dosis van morfien, gebruik dan die tabel (1a) hieronder om die ekwivalente daaglikse dosis

JURNISTA te bepaal.

Tabel 1a:

Omskakelingstabel: Vermenigvuldigingsfaktore vir die omskakeling van daaglikse dosis van vorige

opioïed na daaglikse dosis JURNISTA (mg/dag Vorige Opioïed x Faktor = mg/dag JURNISTA)

Vorige Opioïed Orale Vorige Opioïed (faktor) Parenterale Vorige Opioïed (faktor)

Morfien 0,2 0,6

Hidromorfoon 1 4

Geen vaste omrekeningsverhouding sal waarskynlik by alle pasiënte bevredigend wees nie, te wyte aan

die individuele pasiënt en formuleringsverskille. Gevolglik moet omskakeling na die aanbevole

aanvangsdosis van JURNISTA gevolg word deur sorgvuldige pasiënt-monitering en titrasie.

Dosisse moet afgerond word tot die naaste dosis van JURNISTA wat beskikbaar is in 4 mg inkremente (4,

8, 16, 32, 64 mg tablette), soos klinies aangedui.

Staak alle ander deurlopende opioïed analgetiese medikasies wanneer daar met JURNISTA behandeling

begin word.


Aanvullende Analgesie:

Bo en behalwe een keer daaglikse JURNISTA behandeling, kan aanvullende deurbraak pynmedikasie in

die vorm van onmiddellik-vrygestelde preparate (bv. onmiddellike vrystelling morfien) beskikbaar gemaak

word aan alle pasiënte met chroniese pyn. Die omrekeningstabel moet gebruik word vir omskakeling.

Individuele aanvullende dosisse van onmiddellik vrystelling morfien moet gewoonlik nie 10 % tot 25 % van

die JURNISTA dosis oorskry nie.

Individualisering van dosering en instandhoudingsterapie:

Na aanvang van behandeling met JURNISTA kan dosis aanpassings nodig wees om die pasiënt se beste

balans tussen verligting van pyn en opioïed-verwante newe-effekte te bereik.

Indien die pyn toeneem in erns of analgesie onvoldoende is, kan ’n geleidelik verhoging van dosis benodig

word. Ten einde die effek van die verandering in dosis toe te laat om te stabiliseer, moet die dosis nie

meer dikwels as elke twee dae verhoog word nie. As ’n riglyn kan dosisverhogings van 25 %-100 % van

die huidige daaglikse dosis van JURNISTA oorweeg word met elke titrasiestap.

Sodra pasiënte gestabiliseer is op een-keer-daaglikse JURNISTA terapie, kan die dosis volgehou word

solank as wat pynverligting nodig is. Die voortgesette behoefte aan deurlopende opioïed behandeling en

aanpassings in terapie moet periodiek revalueer word, soos toepaslik.

Gebruik by kinders:

JURNISTA word nie aanbeveel vir gebruik by kinders en adolessente onder 18 jaar oud nie, as gevolg van

onvoldoende data oor veiligheid en doeltreffendheid.

Gebruik by bejaardes:

Die mediese opset van die bejaarde is dikwels kompleks. Gevolglik moet behandeling met JURNISTA

versigtig begin word en die aanvanklike dosis moet verminder word.

Nier- en lewerinkorting:


Na enkel dosis toediening van hidromorfoon onmiddellike vrystelling tablette, is die volgende resultate in

kliniese proewe waargeneem:

By pasiënte met matige lewerinkorting (telling 7-9 op Child-Pugh taksering skaal) was beide

blootstelling (plasma AOK) en piek plasmakonsentrasies van hidromorfoon ongeveer 4-keer hoër

vergeleke met gesonde kontroles en die eliminasie-halfleeftyd was onveranderd.

By pasiënte met matige nierinkorting (kreatinienopklaring 40-60 mL/min), was die blootstelling

(plasma AOK) aan hidromorfoon 2-keer hoër as by diegene met ’n normale nierfunksie en

eliminasie-halfleeftyd was onveranderd.

By pasiënte met ernstige nierinkorting (kreatinien-opklaring < 30 mL/min), was blootstelling

(plasma AOK) aan hidromorfoon ongeveer 4-keer hoër as by diegene met normale nierfunksie en

eliminasie-halfleeftyd 3-keer langer.

Gevolglik moet pasiënte met matige lewer- of nierinkorting begin word met ’n verminderde dosis en

noukeurige monitering tydens dosistitrasie. By pasiënte met ernstige nierinkorting moet ’n verhoogde

dosis interval ook oorweeg word en hierdie pasiënte moet ook tydens instandhoudingsterapie gemoniteer

word vir die ontwikkeling van opioïed-verwante newe-effekte.

Staking van behandeling:

By pasiënte wat fisies afhanklik is en daaglikse toediening van hidromorfoon ontvang, sal skielike

onttrekking van behandeling met JURNISTA aanleiding gee tot simptome van onttrekkingsindroom. Indien

staking van behandeling met JURNISTA aangedui word, moet pasiënte dus hulle JURNISTA dosis elke 2

dae met 50 % verminder totdat die laagste moontlike dosis bereik word, wanneer terapie veilig gestaak

kan word. Indien simptome van onttrekking voorkom, moet afskaling gestaak word. Die dosis moet dan

effens verhoog word totdat die tekens en simptome van opioïed-onttrekking verdwyn. Afskaling moet dan

weer begin maar met langer tydperke tussen elke JURNISTA dosis-vermindering, of voordat oorgeskakel

word na ’n gelykwaardige analgetiese dosis van ’n ander opioïed, waarmee dan aangegaan word met

afskaling.


NEWE-EFFEKTE EN SPESIALE VOORSORGMAATREËLS

Newe-effekte

Ongunstige Geneesmiddelreaksies (OGRs)

In kliniese proewe met JURNISTA (n = 1684), was die mees algemeen aangemelde OGRs opioïed-

verwante GI voorvalle van hardlywigheid, naarheid en braking. Dit kan gewoonlik beheer word deur die

dosis te verlaag, lakseermiddels of anti-emetika, soos van toepassing.

Die onderstaande tabel dui die ongunstige geneesmiddelreaksies (OGRs) wat met JURNISTA

waargeneem is aan en die wat met ander hidromorfoonhidrochloried formulerings aangemeld is. Indien

JURNISTA en hidromorfoonhidrochloried frekwensies verskil, was die hoogste frekwensie van elke

databasis gebruik.

Tabel 2: Ongunstige Geneesmiddelreaksies by JURNISTA behandelde pasiënte.

Orgaan

Sisteemklas Ongunstige Geneesmiddelreaksie Frekwensie

Baie Algemeen

( 1/10)

Algemeen

(1/100 tot <1/10)

Ongewoon

(1/1000 tot <1/100)

Seldsaam

( 1/10,000 tot

<1/1000)

Infeksies en infestasies Divertikulitis, Gastroënteritis

Endokriensiektes Hipogonadisme

Metabolisme en

voedingsiektes

Anoreksie

Dehidrasie

eetlus

Vloeistof retensie

Hiperurisemie

Psigiatriese siektes Slaaploosheid

Angs

Verwarde toestand

Senuweeagtigheid

Abnormale drome

Depressie

Gemoed skommeling

Rusteloosheid

Hallusinasie

Afname in libido

Paniek aanval

Paranoia

Aggressie

Huil

Lusteloosheid

Geneesmiddel toleransie*

Disforie

Euforiese bui

Afhanklikheid*



Orgaan


Baie Algemeen

( 1/10)

Algemeen

(1/100 tot <1/10)

Ongewoon

(1/1000 tot <1/100)

Seldsaam

( 1/10,000 tot

<1/1000)

Senuweestelsel

siektes

Slaapsug Duiseligheid

Hoofpyn

Geheue inkorting

Hipoëstesie

Parestesie

Tremor of onwillekeurige

spierkontraksies

Sedasie

Aandagversteuring

Disgeusie

Mioklonus

Abnormale koördinasie

Diskinesie

Sinkopee

Disartrie

Balansversteuring

Onderdrukte vlak van bewussyn

Hiperestesie

Enkefalopatie

Kognitiewe versteuring

Psigomotoriese hiperaktiwiteit

Toeval/konvulsies

Hiper refleksie

Oogsiektes Visuele versteurings bv.

dowwe visie

Miose

Diplopie

Droë oog

Oor- en doolhof siektes Vertigo Tinnitus

Hartsiektes Tagikardie Palpitasies

Ekstrasistolie

Bradikardie

Vaatsiektes Hipotensie

Gloede

Hipertensie

Respiratoriese, bors-

en mediastinum

siektes

Dispnee Respiratoriese nood

Rinorree

Hipoksie

Brongospasma

Hiperventilasie

Nies



Orgaan


Baie Algemeen

( 1/10)

Algemeen

(1/100 tot <1/10)

Ongewoon

(1/1000 tot <1/100)

Seldsaam

( 1/10,000 tot

<1/1000)

Gastroïntestinale

siektes

Konstipasie

Naarheid

Braking

Droë mond

Diarree

Buikpyn

Dispepsie

Disfagie

Winderigheid

Abdominale opsetting

Aambeie

Hematochesie

Abnormale feses

Inwendige obstruksie

Divertikel

Eruktasie

Gastroïntestinale

motiliteitsversteuring

Dikderm perforasie

in pankreatiese

ensieme*

Anale fissuur

Besoar

Duodenitis

Ileus

Belemmerde maag

lediging

Pynlike defekasie

Hepatobiliêre siektes

Gal koliek

Vel- en onderhuidse

weefsel siektes

Hiperhidrose

Pruritus

Uitslag

Ekseem*

Rooi gesig/ eriteem

Skeletspier en

bindweefsel siektes

Spier spasmas

Rugpyn

Artralgie

Pyn in ledemate

Mialgie

Nier- en

urienwegsiektes

Urinêre retensie

Disurie

Mikturisie siekte

Urinêre huiwering

Pollakurie

Voortplantingstelsel en

borssiektes

Ereksie disfunksie / impotensie

Seksuele disfunksie



Orgaan


Baie Algemeen

( 1/10)

Algemeen

(1/100 tot <1/10)

Ongewoon

(1/1000 tot <1/100)

Seldsaam

( 1/10,000 tot

<1/1000)

Algemene siektes en

toestande by die plek

van toediening

Astenie

Edeem

Geneesmiddel onttrekking

sindroom

Pireksie

Pyn

Bors ongemak

Koue rillings

Abnormale gevoel

Siektegevoel

Probleme met loop

Angstige gevoel

Babalaas gevoel

Dronk gevoel

Warm en koue

gevoel

Hipotermie

Ondersoeke Gewig verminder

Suurstof saturasie

Bloed kalium

Lewerensieme

Bloed amilase

Bloed testosteroon

Besering, vergiftiging

en prosedure-

komplikasie

Val

Verwarring

Oordosering

* Ongunstige geneesmiddelreaksie (OGR) aangemeld met ander hidromorfoon HCl formulerings.

Die volgende terme van onbekende frekwensie is in die literatuur aangemeld:

Respiratoriese versaking; delirium en amenorree. Respiratoriese onderdrukking kan moontlik meer

waarskynlik wees by sekere subgroepe pasiënte (sien WAARSKUWINGS).

Spesiale Voorsorgmaatreëls

Spesiale risiko pasiënte:

JURNISTA moet met versigtigheid toegedien word en teen verlaagde dosisse aan pasiënte met matige tot

ernstige nierinkorting, of ligte tot matige lewerinkorting, bynier ontoereikendheid, miksedeem,

hipotiroïdisme, prostaat hipertrofie of uretrale vernouing. Versigtigheid moet ook uitgeoefen word by die


toediening van JURNISTA aan pasiënte met SSS onderdrukking, kifoskoliose, toksies psigose, akute

alkoholisme, delirium tremens, of konvulsiewe afwykings.

Gebruik by die bejaarde:

Bejaardes is meer geneig om SSS newe-effekte (verwarring), gastroïntestinale versteurings en fisiologiese

vermindering van nierfunksie te ervaar. Gevolglik moet spesiale aandag aan hulle gegee word en die

aanvanklike dosis moet verminder word. Gesamentlike gebruik van ander medikasies, veral trisikliese

antidepressante, verhoog die risiko vir verwarring en hardlywigheid. Siektes van die prostaatklier en die

urienweg kom dikwels voor by bejaardes. Dit dra by tot die verhoogde risiko vir urinêre retensie. Die

bogenoemde oorwegings behoort die belangrikheid te beklemtoon van versigtigheid eerder as om ’n

beperking te plaas op die gebruik van hidromorfoon by die bejaarde.

Geneesmiddel afhanklikheid:

JURNISTA moet met versigtigheid gebruik word by pasiënte met alkoholisme en ander geneesmiddel

afhanklikhede, as gevolg van die verhoogde frekwensie van opioïed toleransie en psigologiese

afhanklikheid wat by hierdie pasiënt populasies waargeneem word. Met misbruik per parenterale roete,

kan die tablet bestanddele noodlottig wees.

Met die volgehoue gebruik van JURNISTA kan die ontwikkeling van toleransie en sielkundige

afhanklikheid verwag word.

Die opsetlike misbruik van JURNISTA kan voorkom en word gekenmerk deur veranderings in gedrag, wat

nie waargeneem word by pasiënte wie se pyn behoorlik met JURNISTA behandel word nie. Daar word

gereken dat die ontwikkeling van sielkundige afhanklikheid of ’n verslawende effek slegs by individue

voorkom wat op die een of ander wyse daartoe gepredisponeer is en dit is nie ’n normale of verwagte

respons op die gepaste toediening van opioïede vir beheer van pyn nie. Indien ’n pasiënt egter in die

verlede opioïede misbruik het, kan JURNISTA of ander opioïede egter steeds aangedui wees by die

behandeling van matige tot ernstige pyn by die pasiënt. ’n Behoefte vir die verhoging van die dosis kan te

wyte wees aan die onderliggende patologie en moet revalueer word.


In die meeste gevalle weerspieël die versoek om hoër dosisse ’n werklike behoefte aan verligting van die

pyn en moet dit nie verkeerdelik geïnterpreteer word as ontoepaslike gebruik van medikasie nie.

Gebruik van JURNISTA in sportverband sal diskwalifikasie meebring.

Aangesien alkohol die kalmerende effek van hidromorfoon versterk, moet gelyktydige gebruik van

JURNISTA en alkohol vermy word.

Reaksies op bestanddele

’n Bestanddeel van JURNISTA, gebutileerde hidroksietolueen, is ’n bekende prikkelstof vir die oë, vel en

slymvliese.

Effekte op die vermoë om te bestuur en masjinerie te gebruik

JURNISTA kan ’n belangrike invloed uitoefen op die vermoë om te bestuur en masjinerie te gebruik. Dit is

veral waarskynlik aan die begin van behandeling, na ’n toename in dosis, of verandering van

geneesmiddel.

BEKENDE SIMPTOME VAN OORDOSERING EN BESONDERHEDE VAN DIE BEHANDELING

DAARVAN

JURNISTA oordosering word gekenmerk deur respiratoriese onderdrukking, lomerigheid wat vorder tot

beneweling en koma, skeletspier slapheid, koue vel, saamgetrekte pupille en, somtyds, tagikardie en

hipotensie. In gevalle van erge oordosering, kan apnee, bloedsomloop ineenstorting, hartstilstand en

dood voorkom.

Met die behandeling van oordosering moet daar hoofsaaklik aandag geskenk word aan die herinstelling

van voldoende respiratoriese uitruiling, deur die lugweg oop te hou en deur die instelling van

ondersteunde of beheerde ventilasie. Indien die orale inname onlangs was, kan die maaginhoud deur

maagspoeling geledig word, soos aangedui.


Ondersteunende maatreëls (insluitende suurstof en vasopressors) moet gebruik word om die skok en

pulmonêre edeem, wat moontlik gepaard gaan met oordosering, te beheer. Hartstilstand en aritmie kan

hartmassering of defibrillasie benodig.

In gevalle van ernstige oordosering, kan spesifieke teenmiddels soos naloksoon en nalmefeen gebruik

word om respiratoriese onderdrukking te beheer (sien in die voorskrifinligting van die spesifieke opioïed-

antagonis vir besonderhede oor die korrekte gebruik).

Die effek van naloksoon is relatief kort, gevolglik moet die pasiënt noukeurig gemoniteer word totdat

asemhaling gestabiliseer het.

JURNISTA sal hidromorfoon vir ongeveer 24 uur vrystel. Dit moet in gedagte gehou word wanneer die

behandeling bepaal word. Opioid antagoniste moet nie gegee word indien tekens van klinies beduidende

respiratoriese onderdrukking voorkom of ineenstorting van die bloedsomloop as gevolg van opioïede nie.

Opioid antagoniste moet met versigtigheid toegedien word aan pasiënte wie vermoedelik fisies afhanklik is

aan hidromorfoon, aangesien vinnige omkering van ’n opioïed, insluitende hidromorfoon, simptome van

onttrekking kan veroorsaak.

IDENTIFIKASIE

JURNISTA 4 mg verlengde-vrystelling tablet: ligbeige, ronde, bikonvekse tablet, bedruk ‘HM 4’ met swart

ink aan die een kant.

JURNISTA 8 mg verlengde-vrystelling tablet: rooi, ronde, bikonvekse tablet, bedruk ‘HM 8’ met swart ink

aan die een kant.

JURNISTA 16 mg verlengde-vrystelling tablet: geel, ronde, bikonvekse tablet, bedruk met ‘HM 16’ in swart

ink aan die een kant.

AANBIEDING


JURNISTA verlengde-vrystelling tablette word verpak in ondeursigtige PVC/Aclar stolpstroke, verseël aan

aluminiumfoelie. Een of meer stolpstrokies word verpak in ’n karton.

Elke karton bevat 14 or 28 tablette.

BERGINGSAANWYSINGS

Bewaar onder 25 C.

Stolpstrokies moet in die karton gehou word totdat dit benodig word vir gebruik.

HOU BUITE BEREIK VAN KINDERS

REGISTRASIENOMMERS

JURNISTA 4 mg: 41/2.9/1136

JURNISTA 8 mg: 41/2.9/1130

JURNISTA 16 mg: 41/2.9/1131

NAAM EN BESIGHEIDSADRES VAN DIE HOUER VAN DIE REGISTRASIESERTIFIKAAT

JANSSEN PHARMACEUTICA (PTY) LTD

(Reg. No. 1980/011122/07)

Building 6, Country Club Estate,

21 Woodlands Drive,

Woodmead,

2191

www.janssen.co.za

DATUM VAN PUBLIKASIE VAN HIERDIE VOUBILJET

Oktober 2010

http://www.janssen.co.za/

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