Israel - English - Ministry of Health
Palladone Injection 10 mg/ml
Solution for injection
IM, SC, IV
Narcotic prescription required
Each 2 ml ampoule contains: Hydromorphone HCl 20 mg (10mg/ml).
Palladone Injection also contains citric acid 2 mg/ml and tri-sodium citrate dihydrate 2.28 mg/ml
Palladone Injection contains no preservatives.
The solution is clear and colorless.
Hydromorphone is a semisynthetic opioid agonist analgesic that acts primarily at the mu opiate
receptor. Opiate receptors in the central nervous system mediate analgesic activity. Opioid
agonists occupy the same receptors as endogenous opioid peptides (enkephalins or endorphins),
and both may alter the central release of neurotransmitters from afferent nerves sensitive to
noxious stimuli. Opioid antagonists block the opiate receptor, inhibit the pharmacological
activity of the agonist and will precipitate withdrawal in dependent patients.
Hydromorphone has similar pharmacological and pharmacokinetic properties to morphine to
which it is chemically related. Hydromorphone is recognized by the World Health Organization
as an alternative opioid to morphine for severe pain. This is important since one of the
cornerstones of severe pain management is opioid rotation. Opioid rotation consists of
switching a patient from one opioid to another in order to achieve adequate analgesia with few
side effects. In particular, hydromorphone may have a better side effect profile than morphine
in some individuals, producing less severe constipation and vomiting. In the post-operative
setting as well, hydromorphone is a suitable alternative to morphine, especially in patients with
a history of an unsatisfactory response to morphine e.g. excessive vomiting.
There are several administration techniques for parenteral delivery of hydromorphone,
including a single or double injection (e.g. post-operative), multiple intermittent bolus injections
(e.g. in the cancer patient), or continuous infusion with or without bolus as-needed injections
(e.g. in the cancer patient requiring exceptionally high doses). Patient controlled analgesia (PCA)
is becoming increasingly widespread using on-demand patient-controlled boluses and a lockout
period, with or without an underlying continuous basal infusion.
Hydromorphone is suitable for either bolus injection or continuous infusion. However, the
10 mg/ml concentrated formulation is only indicated for patients already receiving opioids and
will generally be useful for continuous infusion in patients with chronic pain. For bolus
injections, patients with acute pain, or opioid-naive patients, hydromorphone at a concentration
of 10mg/ml is not generally appropriate.
In patients with chronic pain, parenteral opioid infusions should generally be reserved for
patients in whom oral opioids fail to provide adequate analgesia and/or are associated with
unacceptable side effects. Hydromorphone represents an excellent choice for either continuous
intravenous (IV) or subcutaneous (SC) opioid infusion. Hydromorphone is 5-7 times more potent
than morphine and 5 times more soluble. Therefore, when administering an opioid via SC
infusion, hydromorphone affords potent analgesia using a much smaller volume of infusion.
Hydromorphone delivered SC is also less cumbersome and requires fewer changes in needle
sites, an important practical consideration.
The analgesic action of parenteral hydromorphone administered as a bolus is generally apparent
within 15 minutes. Peak analgesic effect occurs at 15-30 minutes following IV therapy, 30-60
minutes following intramuscular (IM) therapy, and 30-90 minutes following SC therapy.
Duration of action is 4-5 hours following IM or SC administration and 2-3 hours following IV
administration. A 10 mg IM injection of morphine is approximately equivalent to a 1.5 mg IM
injection of hydromorphone.
Relief of moderate to severe pain such as that due to surgery or cancer.
Hypersensitivity to hydromorphone or to any of the other ingredients.
Respiratory depression with hypoxia or elevated carbon dioxide levels in the blood in the
absence of resuscitative equipment, status asthmaticus , upper airway obstruction.
Concurrent monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy.
Due to the high concentration, this formulation is contraindicated:
In all patients who are not already receiving large amounts of opioids.
For use during obstetric labor.
For use during Pregnancy.
In children and in all other patients who cannot reliably participate in the correct
assessment of their own pain relief.
Warnings and precautions
Palladone Injection 10 mg/ml is a highly concentrated solution of hydromorphone intended for
use in patients already receiving opioids.
Like other opioids, continuing use of hydromorphone may result in physical dependence,
tolerance, and, in susceptible individuals, psychological dependence.
Physical dependence and tolerance are expected to occur with chronic opioid therapy, but both
are distinct entities from psychological (psychogenic) dependence.
Physical dependence is the adaptation of the body to the presence of an opioid drug. This
involves physiological changes that explain two phenomena frequently seen with long-term
opioid treatment: tolerance and the withdrawal syndrome.
Tolerance is defined as the need to administer a higher dose of the opioid to maintain the same
level of analgesia. For most patients, the first indication of tolerance is a decrease in the
duration of analgesia for a given dose and the appearance of breakthrough pain. Tolerance may
be confused with an increase in the pain intensity of the disease itself (which is the most
common reason an increase in dosage is indicated). Irrespective of the underlying cause, it is
recommended that the dose be increased and the patient re-titrated until the pain is again
Withdrawal symptoms, sometimes called the opioid abstinence syndrome, are those manifested
by a patient upon cessation of treatment or rapid reduction of dosage. In its mildest form, the
opioid abstinence syndrome may be confused with viral, influenza-like syndromes.
In severe withdrawal, early symptoms include yawning, lacrimation, rhinorrhea, restless or "yen
sleep", and perspiration. These may be followed by mydriasis, piloerection, flushing,
tachycardia, twitching, tremor, restlessness, instability, and anorexia. Ultimately, symptoms
include muscle spasm, fever, nausea, diarrhea, vomiting, and spontaneous orgasm.
Opioid abstinence syndrome has been well described in the literature and the severity of the
syndrome in a particular patient can vary from mild discomfort to potential cardiovascular
Without treatment most observable symptoms resolve in 5-14 days. A period of “subacute
withdrawal” lasting up to 6 months has also been described in which previously dependent
patients experience difficulty concentrating, insomnia, irritability, myalgias and autonomic
The severity of the abstinence syndrome is related to the degree of dependence, the abruptness
of withdrawal, and the drug used. In general, withdrawal symptoms develop at the time the
next dose would originally have been given. For hydromorphone, they gradually increase in
intensity, reaching a maximum at 24-72 hours and subsiding over 5-10 days.
If a reduction in dosage is required, the opioid abstinence syndrome can usually be avoided by
gradually decreasing the dosage in the following fashion. Half the prior daily dosage should be
given for the first 2 days. This should be reduced by 25% every 2 days thereafter, until the daily
dosage is 1.5 mg parenteral hydromorphone. The drug may be discontinued after 2 days on this
Various regimens have been described for treatment of severe abstinence syndrome, including
but not limited to methadone substitution, clonidine, benzodiazepines, and phenothiazines.
Supportive care is essential and associated symptoms, such as dehydration and gastrointestinal
(GI) disturbances, should be treated accordingly.
Withdrawal precipitated by the administration of an opioid antagonist is manifested by the
onset of symptoms within minutes, reaching maximum intensity within 30 minutes. Do not
administer an opioid antagonist as a means of detecting dependence. If an opioid antagonist
must be used to treat serious respiratory depression in a physically dependent patient,
administer with extreme care.
Physical dependence does not imply psychological dependence.
Psychological dependence is a pattern of compulsive drug use characterized by a craving for an
opioid and the need to use the opioid for effects other than pain relief.
This type of dependence is extremely rare in patients taking opioids for the relief of severe pain.
It is very occasionally seen in patients who have previously used psychoactive substances for
recreational purposes. This must not be confused with the behavior of patients whose pain is
inadequately treated, who will also manifest drug-seeking behavior. For these patients titration
to pain-controlling dosage is required.
Use in drug and alcohol-dependent patients
Hydromorphone has an abuse profile similar to other strong opioids. Hydromorphone may be
sought and abused by people with latent or manifest addiction disorders. Hydromorphone
should be used with caution in patients with alcoholism and other drug dependencies due to the
increased frequency of opioid tolerance, physical and psychological dependence observed in
these patient populations. Abuse of hydromorphone in combination with other CNS depressant
drugs can result in serious risks to the patient.
Because of the tendency of hydromorphone to produce respiratory depression and its capacity
to elevate cerebrospinal fluid pressure, it should be used with extreme caution, if at all, in the
presence of head injury, other intracranial lesions or a pre-existing increase in intracranial
pressure, since both of these adverse reactions may be markedly exaggerated. Opioid agonists
like hydromorphone may interfere with evaluation of CNS functions, especially relative to
consciousness levels, pupillary changes, and respiratory depression, thereby masking the
clinical course and neurologic signs of further increase in intracranial pressure
in patients with
head injuries. In such cases, hydromorphone must be used with extreme caution and only
when it is absolutely essential.
The major risk of opioid excess is respiratory depression. Respiratory depression 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 therapeutic doses may
dangerously decrease pulmonary ventilation.
Hydromorphone should be used with extreme caution, if at all, in patients with
impairment of pulmonary function, acute asthma, chronic obstructive pulmonary disease or cor-
pulmonale, a decreased respiratory reserve (as in emphysema, kyphoscoliosis or severe obesity),
pre-existing respiratory depression, hypoxia or hypercapnia. In such patients even therapeutic
doses of opioids may decrease respiratory drive while simultaneously increasing airway
resistance to the point of apnea.
Opioids may cause severe hypotension in the postoperative patient, or in those whose ability to
maintain blood pressure is compromised by hypovolemia or concurrent administration of
phenothiazines or general anesthetics. Opioids may produce orthostatic hypotension in
Hydromorphone, like all opioid analgesics, should be administered with caution to patients in
circulatory shock since vasodilation produced by the drug may further reduce cardiac output and
Hyperalgesia that will not respond to a further dose increase of hydromorphone may occur, in
particular, at high doses. A hydromorphone dose reduction or change in opioid may be required.
Patients receiving opioids on a chronic basis and who undergo cordotomy or any other pain-
relieving surgical procedure should be monitored closely for respiratory depression, and the
hydromorphone dosage should be titrated to the new post-operative requirement.
Long term carcinogenicity studies have not been performed.
Hydromorphone was non-genotoxic in the Ames test and the in vivo mouse micronucleus assay
but positive in mouse lymphoma assay with metabolic activation. Similar findings have been
reported with other opioid analgesics such as codeine and oxycodone.
Effects on fertility
No effects have been observed on male or female fertility or sperm parameters in rats.
Use in Pregnancy
Safety of use in pregnancy has not been established. The placental transfer of opioids is rapid.
Maternal addiction following illicit use, resulting in withdrawal symptoms in the neonate, is well
documented. Withdrawal symptoms include irritability, excessive crying, yawning, sneezing,
increased respiratory rate, tremors, hyperreflexia, fever, vomiting, increased stools and diarrhea.
These symptoms usually appear during the first days of life. Palladone injection 10 mg/ml is
contraindicated during pregnancy.
Use in Labor
Due to the high concentration, this formulation is contraindicated for use during labor (see
Use in Breastfeeding
Ordinarily, nursing should not be undertaken while a patient is receiving Palladone Injection
since hydromorphone may be excreted in maternal milk.
Use in Pediatrics
Due to the high concentration of the 10mg/ml injection, this formulation is contraindicated in
children and in all other patients who cannot reliably participate in the correct assessment of
their own pain relief (see Contraindications). Safety and effectiveness in children have not been
established. Paradoxical excitation is more likely to occur in pediatric patients receiving opioid
Use in the Elderly
Elderly subjects have been shown to have at least twice the sensitivity (as measured by EEG
changes) of young adults to some opioids.
Hydromorphone should be used with caution in the elderly, and the initial dose should be
reduced. The elderly may require a lower dosage than adults to achieve adequate analgesia.
Some elderly patients may be sensitive to the respiratory depressant effect of hydromorphone
and should be monitored closely during therapy initiation and any subsequent dosage increase.
The diagnosis or clinical course of acute abdominal conditions may be obscured by opioids.
Exercise caution (and reduced initial dose) in elderly and debilitated patients and in patients
sensitive to CNS depressants, including those with cardiovascular disease, myxoedema or
hypothyroidism, acute alcoholism, delirium tremens, cerebral arteriosclerosis, fever,
adrenocortical insufficiency e.g. Addison's disease, prostatic hypertrophy or
urethral stricture, toxic psychosis, CNS depression, coma, gallbladder/biliary tract/pancreas
dysfunction including pancreatitis, or a history of drug abuse.
Renal and hepatic dysfunction may cause a prolonged duration of action and a cumulative
effect. Hence, care should be exercised in these conditions, particularly with repeated dosing.
Seizures may become aggravated, or may occur in individuals without a history of convulsive
disorders. Patients with known seizure disorders should be carefully observed.
The cough reflex is suppressed.
Exercise caution when using opioid analgesics in patients with pulmonary disease.
Use with caution in patients with atrial flutter and other supraventricular tachycardias. Vagolytic
action may increase the ventricular response rate.
Use in surgery: Palladone should be used with caution pre- or intra- operatively and within the
first 24 hours post-operatively.
Exercise caution when using opioid analgesics especially following gastrointestinal tract surgery
as opioids are known to impair intestinal motility and should not be used until the physician is
assured of normal bowel function. Should paralytic ileus be suspected or occur during use,
Palladone should be discontinued immediately).
used with caution in patients
requiring biliary tract procedures since it may cause spasm of the sphincter of Oddi.
Driving and operating dangerous machinery
Hydromorphone may impair mental and/or physical ability required for the performance of
potentially hazardous tasks (e.g. the drug may produce drowsiness or dizziness).Therefore,
patients should be warned that their ability to perform potentially hazardous tasks requiring
mental alertness or physical coordination, such as driving a vehicle or operating machinery,
may be impaired.
Hydromorphone should not be given to patients taking non-selective MAOIs or within 14 days
of stopping such treatment.
Administration of an opioid antagonist such as naloxone or naltrexone will block the therapeutic
effect of hydromorphone, and will precipitate withdrawal symptoms in patients physically
dependent on opioids; such symptoms may persist for up to 48 hours and be difficult to reverse.
Similarly, administration of a mixed agonist/antagonist opioid analgesic (e.g. pentazocine,
buprenorphine) to a patient receiving therapy with a pure agonist opioid such as
hydromorphone may reduce the analgesic effect, or precipitate withdrawal.
Use with caution and in reduced dosage in patients concurrently receiving other opioid
analgesics, general anesthetics, antihistamines, phenothiazines, barbiturates,
tranquilizers, sedative-hypnotics, antidepressants, antiemetics and other CNS depressants
including alcohol, anticholinergics or neuromuscular blocking agents. Concurrent therapy may
increase the risk of respiratory depression, hypotension, profound sedation, coma, severe
constipation, or urinary retention.
When such combined therapy is contemplated, the dose of one or both agents should be
reduced, however hydromorphone should not be taken with alcohol.
Concurrent use of opioid analgesics with antidiarrheals may increase the risk of severe
constipation, as well as CNS depression.
Patients receiving concurrent antihypertensive medication and opioid analgesics should be
monitored closely, due to the increased risk of orthostatic hypotension.
Case reports have described CNS toxicity (confusion, disorientation, respiratory depression,
apnea, seizures) following concurrent administration of cimetidine and opioid analgesics, though
no clear-cut cause and effect relationship has been established.
Because opioids may increase biliary tract pressure with resultant increases in plasma amylase
or lipase, measurements of these enzymes may be unreliable for 24 hours following
The adverse effects of hydromorphone are similar to those of other opioid agonist analgesics,
and represent established pharmacological effects of the drug class. The major hazards include
respiratory depression and apnea. To a lesser degree, circulatory depression, respiratory
arrest, shock and cardiac arrest have occurred.
Adverse effects reported commonly (frequency > 1%) seem to be more prominent in
ambulatory patients and in those not experiencing severe pain. Syncopal reactions and related
symptoms in ambulatory patients may be alleviated if the patient lies down.
Very common (≥ 1/10)
(≥ 1/100 to < 1/10)
(≥ 1/1,000 to <1/100)
(≥ 1/10,000 to < 1/1,000)
(cannot be estimated from the available data)
bradycardia, hypertension, palpitation, tachycardia
blurred vision, diplopia, miosis, visual impairment
abdominal pain, dry mouth, vomiting
cramps, diarrhea, dysgeusia (taste alteration), paralytic ileus
General disorders and administration site conditions
asthenia, injection site reactions (following parenteral administration)
chills, drug tolerance, drug withdrawal syndrome, peripheral
oedema, fatigue, malaise
biliary colic, increased hepatic enzymes
Immune system disorders
anaphylactic reactions, hypersensitivity reactions (including
Metabolism and nutrition disorders
Nervous system disorders
headache, light-headedness, sedation
convulsions, dyskinesia, faintness, hyperalgesia, increased intracranial
pressure, myoclonus, uncoordinated muscle movement, muscle rigidity,
paraesthesia, syncope, tremor, weakness
anxiety, confusional state, dysphoria, euphoria, insomnia, nervousness
agitation, drug dependence, alterations of mood (apprehension,
depression, floating feelings), transient hallucinations, disorientation,
Renal and urinary disorders
antidiuretic effects, urinary hesitancy
Reproductive system and breast disorders
Respiratory, thoracic and mediastinal disorders
bronchospasm, dyspnoea, laryngospasm, respiratory depression
Skin and subcutaneous tissue disorders
hyperhidrosis (sweating), pruritus, rash
urticaria and other skin rashes
In clinical trials, neither local tissue irritation nor induration was observed at the site of
subcutaneous injection; pain at the injection site was rarely observed.
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the
National Regulation by using an online form
Dosage and Administration
Because of its high concentration, the delivery of precise doses of Palladone Injection 10 mg/ml
may be difficult if low doses of hydromorphone are required. Therefore, Palladone Injection
10mg/ml should be used only if the amount of hydromorphone required can be delivered
accurately with this formulation. Similarly, Palladone Injection 10mg/ml is not generally
recommended for single-dose administration due to the very large amount of hydromorphone
in the ampoule and the associated risk of overdosage.
Palladone concentrated preservative-free Injection 10 mg/ml is intended for IV, SC (and rarely
IM) administration only in patients already receiving opioids. In most cases, these patients will
have chronic, not acute pain. Patients with severe chronic pain should receive opioids on a
regular time schedule (round-the-clock) so that they remain free of pain, rather than on an as-
needed basis after pain recurs.
Because this formulation of hydromorphone is highly concentrated, a smaller injection volume
can be used than with other parenteral opioid formulations. Discomfort associated with the SC
(or IM) injection of an unusually large volume of solution can therefore be avoided.
For the correct and effective use of hydromorphone it is critical to adjust the dosing regimen for
each patient individually, according to the severity of pain, the patient's metabolism, previous
history of analgesic therapy, concurrent medications and response to hydromorphone. The
following dosage recommendations are, therefore, only suggested approaches to what is
actually a series of clinical decisions in the management of pain of an individual patient.
For patients with severe chronic pain in whom the oral route is not feasible, parenteral opioids
are needed. Since intermittent injections are expensive, uncomfortable, induce "clock
watching" and are associated with the "bolus effect" (peak levels associated with intolerable
adverse effects and trough levels associated with inadequate analgesia), continuous IV or SC
infusions are preferable. Continuous IV infusions (CIVI) are suitable for patients who already
require IV access and maintenance for other reasons. In home-based patients in particular, it is
rarely feasible to maintain peripheral IV access for continuous IV infusions. Thus, continuous IV
infusions are usually considered when patients have an indwelling central venous port or other
long-term venous access device. In most other patients, continuous SC infusions (CSCI) using
relatively small, portable programmable infusion pumps attached to a 27-gauge butterfly needle
placed SC, are an excellent alternative to CIVI. CSCI does not require IV access or the need for
continuous nursing care, enhances patient mobility and is not associated with potentially
dangerous complications, e.g. sepsis. However, in CSCI, skin irritation at the infusion site must be
monitored and the infusion site rotated accordingly, e.g. every 7 days. The anterior chest wall,
abdominal wall and subclavicular region are popular sites for the SC infusion.
A. Initial Dosage and Rescue Medication
For patients transferring from morphine or oral hydromorphone to Palladone Injection,
conversion factors should be used to convert the previous 24-hour opioid use to a parenteral
hydromorphone equivalent. (For patients receiving opioids other than morphine or
hydromorphone, standard equianalgesic tables should be consulted to determine the equivalent
24-hour opioid dose in parenteral morphine equivalents. Then follow the steps below for
Calculate the total daily dosage (mg) of each opioid (around-the-clock plus rescue doses).
Multiply the daily dose of each prior opioid by the appropriate multiplication factor from the
table for oral and/or parenteral forms, adding the results to obtain the equivalent total daily
hydromorphone parenteral dose. For CIVI, the daily parenteral hydromorphone dose should be
added to solution (e.g. 500 ml saline) and delivered over the ensuing 24 hours (e.g. 20 ml/hour).
A loading bolus of 2 mg may be given by slow IV injection at the start of the infusion. For CSCI,
the daily parenteral hydromorphone dose should be divided into 24 to obtain the initial hourly
infusion rate and the pump/infusion device set accordingly.
An hourly volume of 5 ml, and preferably 2 ml, should not be exceeded.
Multiplication Factors for Converting to Parenteral Hydromorphone
(mg/day prior opioid X factor = mg/day parenteral hydromorphone)
For example, a patient receiving 240 mg oral morphine daily (120 mg twice daily) who is being
switched to Palladone Injection:
240 mg X 0.05 = 12 mg daily parenteral hydromorphone
12 mg ÷ 24 hr = 0.5 mg/hr hydromorphone
The conversion table is only meant to serve as a guide. It should be noted that the above table is
based on a hydromorphone:morphine ratio of 7.5:1. However, recent studies have indicated
that in some patients the ratio may approximate 4:1. Therefore, the above table presents a
conservative starting dose, and consideration should be given to early upward titration in a
significant portion of patients. In the rare patient receiving very large opioid doses,
consideration should be given to the potential for incomplete cross tolerance. When converting
these patients to hydromorphone therapy, the starting dose estimated by the conversion ratio
may need to be decreased. For patients who have experienced intolerable side effects on their
previous opioid, consideration should be given to decreasing the initial hydromorphone infusion
rate by 50%. In all circumstances, the patient's response following conversion from other opioids
must be carefully monitored and the dosage of Palladone Injection adjusted accordingly. (Note:
The table should not be used for converting patients from hydromorphone to other opioids.)
Following initiation of the infusion and after any subsequent changes in the infusion rate that
are substantial, the patient should be monitored closely for several hours in a setting where an
opioid antagonist, oxygen and resuscitative equipment, and personnel trained in their use, are
Arrangements for rescue medication for breakthrough pain should always be ensured.
Rescue medication should always preferably consist of the same opioid administered through
the same route of administration. For continuous infusions, the size of the rescue dose should
be 50-100% of the hourly dose, and rescue doses should be available every 60 minutes. An initial
loading dose equivalent to the rescue dose should be given at the start of the infusion to reduce
the time before reaching steady state. Both the initial bolus and the rescue doses can be
administered using the same site of infusion via a three-way stopcock or via a PCA device with a
B. Titration to Pain Control
Adjustments of the initial dosage should be made to obtain an appropriate balance between
pain relief and opioid adverse experiences. The optimal dose is that which maintains adequate
analgesia with no or controllable side effects. Adequate analgesia is generally considered to be
mild or no pain with the regular use of no more than two doses of supplemental analgesia per
24 hours. If the initial dose provides inadequate analgesia, the dose should be titrated upwards
and the patient should be assessed.
The number of daily rescue doses required by the patient is a useful guide for the escalation of
the baseline continuous infusion. For example, a patient receiving hydromorphone 4 mg/hr by
continuous infusion who requires 6 supplemental doses of 4 mg should have the infusion
increased to 5 mg/h with a concurrent increase in the rescue dose to 5 mg.
4 mg/h X 24 hours = 96 mg via continuous infusion
96 mg + 24 mg rescue medication = 120 mg total daily dose
120 mg/day ÷ 24 hours = 5 mg/h
If significant adverse events occur before the therapeutic goal of mild or no pain is achieved, the
events should be treated aggressively. Once adverse events are under control, upward titration
can continue to an acceptable level of pain control. Patients with good pain relief who develop
intolerable side effects should have the infusion decreased by 25-50% with further titration up
or down depending on the response. Whenever the adverse experiences cannot be controlled
or tolerated, opioid rotation should be considered.
C. Maintenance of Therapy
During the course of treatment the patient may experience a recurrence of pain due to an
increase in the level of pain because of disease progression or due to the development of
tolerance. Regardless of the reason, the hydromorphone dose should be increased and the
patient re-titrated as outlined above in order to re-establish pain control. As there is no upper
limit to the amount of hydromorphone that may be given in intractable oncologic pain, the
quantity administered should be that which produces adequate analgesia.
Patients who undergo pain-relieving procedures (e.g. nerve blocks, cordotomy) should be
reassessed following the procedure to determine whether further treatment with Palladone
Injection is indicated. If so, the dosage should be adjusted to the new post-operative
Hydromorphone 10 mg/ml should not generally be used for bolus injections. In the occasional
patient in whom this therapy is appropriate, bolus injections should preferably be administered
either IV or SC. Repeated IM injections are painful and should be avoided. Repeated bolus IV or
SC injections can be considered if the oral route becomes unavailable for a short period.
However, for longer periods, continuous infusions are preferable to repeated bolus injections
(see above). (Note: If an infusion device is not available, hydromorphone can be administered SC
as intermittent four-hourly injections via a 27-gauge butterfly needle left in situ for several
Since rapid IV injections of opioids can cause serious adverse reactions, IV injections should be
administered in a dilute solution slowly, over a period of several minutes. An opioid antagonist
and equipment for artificial ventilation should be available.
Serious overdosage with hydromorphone is characterised by respiratory depression
(reduced respiratory rate and/or tidal volume, cyanosis), extreme somnolence, progressing
to stupor or coma, skeletal muscle flaccidity, cold and/or clammy skin, pupillary constriction,
and possibly bradycardia, hypotension and death. Severe overdose may result in apnoea,
pulmonary oedema, circulatory collapse and death.
The primary concern in the treatment of opioid overdose is immediate supportive therapy with
the establishment of adequate respiratory exchanges through the provision of, and
maintenance of, adequate ventilation - patients may need ventilatory support up to and
including endotracheal intubation and controlled ventilation. Adequate body temperature and
fluid balance should be maintained. Oxygen, intravenous fluids, vasopressors and other
supportive measures should be used as indicated.
Tolerance to the respiratory and CNS-depressant effects of opioids develops concomitantly
with tolerance to the analgesic effects, therefore making respiratory depression unlikely in an
opioid-tolerant patient taking the usual therapeutic doses of hydromorphone. Activated
charcoal may reduce absorption of the drug if given within one to two hours after ingestion.
A potentially serious recent oral ingestion of hydromorphone, if suspected, may be treated
with activated charcoal in a patient who is fully conscious with an intact gag reflex or a secured
airway. Initial dose of charcoal is 30 to 100 g in adults and 1 - 2 g/kg in children and is given as
a slurry via nasogastric tube. In patients who are not fully conscious or have an impaired gag
reflex, consideration should be given to administering activated charcoal via a nasogastric tube,
once the airway is protected.
If there are signs of clinically significant respiratory or cardiovascular depression, the use of
an opioid antagonist such as naloxone should be considered.
Caution should always be observed when using an opioid antagonist for the treatment of
suspected hydromorphone overdose as the duration of action of hydromorphone may exceed
that of the antagonist. Continuing surveillance is mandatory to prevent recurrence of
respiratory depression and supportive care - including ventilatory and circulatory
resuscitation/support when indicated - should always be provided. Additional doses of
antagonist may be given as indicated by the clinical situation.
Opioid antagonists such as naloxone may precipitate an acute abstinence syndrome in opioid-
dependent patients and should be carefully titrated to the desired degree of reversal. The
severity of an abstinence syndrome precipitated by administration of an opioid antagonist is
contingent upon the degree of dependence and the dose of antagonist given. Too rapid or
complete reversal may induce nausea, vomiting, sweating and circulatory stress and may
reverse the desirable therapeutic effects (analgesia) as well.
Toxicity may result from overdosage but because of the great interindividual variation in
sensitivity to opioids it is difficult to determine an exact dose of any opioid that is toxic or
lethal. The toxic effects and signs of overdosage may be less pronounced than expected, when
pain and /or tolerance are manifest.
Protect from light and store below 25
C. Discard any unused portion. Do not autoclave. Protect
Parenteral solutions should be inspected visually for particulate matter and discoloration prior
to administration whenever container and solution permit. Do not use if the solution is not clear
and colorless or if it contains a precipitate.
Hydromorphone has been reported to be physically or chemically incompatible with solutions
containing cefazolin, cloxacillin sodium, diazepam, dimenhydrinate, gallium nitrate, haloperidol,
heparin sodium, hyaluronidase, soluble barbiturates, phenobarbitol sodium, phenytoin sodium,
prochlorperazine edisylate, sodium bicarbonate, sargramostim, or thiopental sodium.
Each ampoule of Palladone Injection 10mg/ml contains a large amount of potent narcotic that
may be potentially abused. Due to the limited indications for this product, the risk of overdosage
and risk of its diversion and abuse, it is recommended that special measures be taken to control
this product within the hospital or clinic. Accidental dermal exposure should be treated by the
removal of any contaminated clothing and rinsing the affected area with water.
2 ml amber ampoules.
Each box contains 5 ampoules.
Rafa Laboratories Ltd. P.O.Box 405, Jerusalem 9100301
Registration number: 105 43 28474
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