CCDS: 20 April 2009 Page 1 of 37 PACKAGE INSERT ...
Transcript of 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
JURNISTA® 8 mg extended-release tablets
JURNISTA® 16 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.
Each JURNISTA 8 mg extended-release tablet contains 8,72 mg and delivers 8 mg hydromorphone
hydrochloride, equivalent to 7,12 mg hydromorphone base.
Each JURNISTA 16 mg extended-release tablet contains 16,35 mg and delivers 16 mg hydromorphone
hydrochloride, equivalent to 14,24 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.
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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).
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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).
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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.
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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:
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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.
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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
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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
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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
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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
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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)
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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)
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
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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)
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
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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)
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
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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
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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.
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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
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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
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VOUBILJET
SKEDULERINGSTATUS
Skedule 6
EIENDOMSNAAM EN DOSEERVORM
JURNISTA® 4 mg verlengde-vrystelling tablette
JURNISTA® 8 mg verlengde-vrystelling tablette
JURNISTA® 16 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.
Elke JURNISTA 8 mg verlengde-vrystelling tablet bevat 8,72 mg en lewer 8 mg hidromorfoonhidrochloried,
ekwivalent aan 7,12 mg hidromorfoon basis.
Elke JURNISTA 16 mg verlengde-vrystelling tablet bevat 16,35 mg en lewer 16 mg hidromorfoonhidrochloried,
ekwivalent aan 14,24 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.
CCDS: 20 April 2009 Page 20 of 37
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).
CCDS: 20 April 2009 Page 21 of 37
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-
CCDS: 20 April 2009 Page 22 of 37
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.
CCDS: 20 April 2009 Page 23 of 37
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.
CCDS: 20 April 2009 Page 24 of 37
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
CCDS: 20 April 2009 Page 25 of 37
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.
CCDS: 20 April 2009 Page 26 of 37
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.
CCDS: 20 April 2009 Page 27 of 37
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.
CCDS: 20 April 2009 Page 28 of 37
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:
CCDS: 20 April 2009 Page 29 of 37
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.
CCDS: 20 April 2009 Page 30 of 37
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*
CCDS: 20 April 2009 Page 31 of 37
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)
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
CCDS: 20 April 2009 Page 32 of 37
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)
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
CCDS: 20 April 2009 Page 33 of 37
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)
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
CCDS: 20 April 2009 Page 34 of 37
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.
CCDS: 20 April 2009 Page 35 of 37
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.
CCDS: 20 April 2009 Page 36 of 37
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
CCDS: 20 April 2009 Page 37 of 37
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