MORPHINE HP 25 - 25MG/ML SOLUTION

Canada - English - Health Canada

Buy It Now

Active ingredient:
MORPHINE SULFATE
Available from:
SANDOZ CANADA INCORPORATED
ATC code:
N02AA01
INN (International Name):
MORPHINE
Dosage:
25MG
Pharmaceutical form:
SOLUTION
Composition:
MORPHINE SULFATE 25MG
Administration route:
INTRAMUSCULAR
Units in package:
1/4ML
Prescription type:
Narcotic (CDSA I)
Therapeutic area:
OPIATE AGONISTS
Product summary:
Active ingredient group (AIG) number: 0104545005; AHFS: 28:08.08
Authorization status:
APPROVED
Authorization number:
00676411
Authorization date:
2005-08-04

Documents in other languages

PRODUCT MONOGRAPH

INCLUDING PATIENT MEDICATION INFORMATION

MORPHINE HP 25

Morphine sulfate injection USP

25 mg/mL

MORPHINE HP 50

Morphine sulfate injection USP

50 mg/mL

Narcotic Analgesic

Sandoz Canada Inc.

110 rue de Lauzon

Date of Revision: May 17, 2019

Boucherville, QC, Canada

J4B 1E6

Submission Control No: 221205

Morphine HP 25 / Morphine HP 50

Page 2 of 31

Table of Contents

PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3

SUMMARY PRODUCT INFORMATION ....................................................................... 3

INDICATIONS AND CLINICAL USE ............................................................................. 3

CONTRAINDICATIONS .................................................................................................. 3

WARNINGS AND PRECAUTIONS ................................................................................. 4

ADVERSE REACTIONS ................................................................................................. 12

DRUG INTERACTIONS ................................................................................................. 14

DOSAGE AND ADMINISTRATION ............................................................................. 15

OVERDOSAGE ............................................................................................................... 19

ACTION AND CLINICAL PHARMACOLOGY ........................................................... 20

STORAGE AND STABILITY ......................................................................................... 21

SPECIAL HANDLING INSTRUCTIONS ...................................................................... 21

DOSAGE FORMS, COMPOSITION AND PACKAGING ............................................ 21

PART II: SCIENTIFIC INFORMATION ............................................................................... 23

REFERENCES ................................................................................................................. 23

PART III: PATIENT MEDICATION INFORMATION ....................................................... 24

Morphine HP 25 / Morphine HP 50

Page 3 of 31

N

MORPHINE HP 25 /

N

MORPHINE HP 50

Morphine sulfate injection USP

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form /

Strength

Nonmedicinal Ingredients

Intramuscular,

intravenous, and

subcutaneous

Sterile solution /

25 mg/mL, and

50 mg/mL

Sodium chloride, sulfuric acid and/or sodium

hydroxide and water for injection

INDICATIONS AND CLINICAL USE

Adults

Morphine HP 25 and Morphine HP 50 (morphine sulfate injection USP) used without dilution

are indicated for the relief of severe pain in patients who require subcutaneously or

intramuscularly administered narcotics in doses higher than those usually needed.

For the relief of severe pain, Morphine HP 25 and Morphine HP 50 may also be diluted and

administered by intravenous infusion.

Morphine HP 25 and Morphine HP 50 are not indicated as an as-needed (prn) analgesic.

Geriatrics (> 65 years of age)

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, concomitant disease or other drug therapy.

Pediatrics (< 18 years of age)

The safety and efficacy of morphine sulfate have not been studied in the pediatric population.

Therefore, the use of Morphine HP 25 and Morphine HP 50 are not recommended in patients

under 18 years of age.

CONTRAINDICATIONS

Patients who are hypersensitive to the active substance morphine sulfate or other opioid

analgesics or to any ingredient in the formulation. For a complete listing, see the

DOSAGE FORMS, COMPOSITION AND PACKAGING section of the Product

Monograph.

Morphine HP 25 / Morphine HP 50

Page 4 of 31

In patients with known or suspected mechanical gastrointestinal obstruction (e.g., bowel

obstruction or strictures) or any diseases/conditions that affect bowel transit (e.g., ileus of

any type).

Patients with suspected surgical abdomen, after biliary tract surgery or surgical

anastomosis (e.g., acute appendicitis or pancreatitis).

Patients with mild pain that can be managed with other pain medications.

Patients with acute or severe bronchial asthma, chronic obstructive airway, or status

asthmaticus.

Heart failure secondary to chronic lung disease or cardiac arrhythmias.

Patients with acute respiratory depression, elevated carbon dioxide levels in the blood

and cor pulmonale.

Patients with acute alcoholism, delirium tremens, and convulsive disorders.

Patients with severe CNS depression, increased cerebrospinal or intracranial pressure,

and head injury or brain tumor.

Patients taking monoamine oxidase (MAO) inhibitors (or within 14 days of such

therapy).

WARNINGS AND PRECAUTIONS

SERIOUS WARNINGS AND PRECAUTIONS

Morphine HP 25 and Morphine HP 50 are highly concentrated solutions of morphine.

They should be used without dilution only in narcotic-tolerant patient requiring high doses

of opiate agonists. Do not confuse Morphine HP 25 and Morphine HP 50 with the standard

dosage strengths of parenteral morphine, since overdose and death could result.

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended

doses, and because of the risks of overdose and death with immediate release opioid

formulations, Morphine HP 25 and Morphine HP 50 should only be used in patients for

whom alternative treatment options (e.g., non-opioid analgesics) are ineffective, not

tolerated, or would be otherwise inadequate to provide appropriate management of pain

(see DOSAGE AND ADMINISTRATION).

Addiction, Abuse, and Misuse

Morphine HP 25 and Morphine HP 50 poses risks of opioid addiction, abuse, and misuse,

which can lead to overdose and death. Each patient’s risk should be assessed prior to

prescribing Morphine HP 25 and Morphine HP 50 and all patients should be monitored

regularly for the development of these behaviours or conditions (see WARNINGS AND

PRECAUTIONS, Abuse and Misuse). Morphine HP 25 and Morphine HP 50 should be

stored securely to avoid theft or misuse.

Life-threatening Respiratory Depression: OVERDOSE

Serious, life-threatening, or fatal respiratory depression may occur with use of Morphine HP

25 and Morphine HP 50. Infants exposed in-utero or through breast milk are at risk of life-

Morphine HP 25 / Morphine HP 50

Page 5 of 31

threatening respiratory depression upon delivery or when nursed. Patients should be

monitored for respiratory depression, especially during initiation of Morphine HP 25 and

Morphine HP 50 or following a dose increase. Further, instruct patients of the hazards

related to taking opioids including fatal overdose.

Accidental Exposure

Accidental exposure of even one dose of Morphine HP 25 and Morphine HP 50 especially by

children, can result in a fatal overdose of morphine sulfate (see DOSAGE AND

ADMINISTRATION, Disposal, for instructions on proper disposal).

Neonatal Opioid Withdrawal Syndrome

Prolonged maternal use of Morphine HP 25 and Morphine HP 50 during pregnancy can

result in neonatal opioid withdrawal syndrome, which may be life-threatening (see

WARNINGS AND PRECAUTIONS, Neonatal Opioid Withdrawal Syndrome (NOWS)).

Interaction with Alcohol

Caution should be observed when administering Morphine HP 25 and Morphine HP 50 to

patients who have been or are taking alcohol. Morphine HP 25 and Morphine HP 50 should

be avoided as it may result in dangerous additive effects, causing serious injury or death (see

WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS).

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS)

depressants, including alcohol, may result in profound sedation, respiratory depression,

coma, and death (see WARNINGS AND PRECAUTIONS, Neurologic and DRUG

INTERACTIONS).

Reserve concomitant prescribing of Morphine HP 25/Morphine HP 50 and

benzodiazepines or other CNS depressants for use in patients for whom alternative

treatment options are inadequate.

Limit dosages and durations to the minimum required.

Follow patients for signs and symptoms of respiratory depression and sedation.

General

Morphine HP 25 and Morphine HP 50 should be stored securely to avoid theft or misuse.

Morphine HP 25 and Morphine HP 50 should only be prescribed by persons

knowledgeable in the continuous administration of potent opioids, in the management of

patients receiving potent opioids for the treatment of pain, and in the detection and

management of respiratory depression, including the use of opioid antagonists.

Patients should be cautioned not to consume alcohol while taking Morphine HP 25 and

Morphine HP 50 as they may increase the chance of experiencing serious adverse events,

including death.

Hyperalgesia that will not respond to a further dose increase of morphine sulfate can occur at

Morphine HP 25 / Morphine HP 50

Page 6 of 31

particularly high doses. A morphine sulfate dose reduction or change in opioid may be required.

Do not use unless solution is clear and package is undamaged (see DOSAGE AND

ADMINISTRATION). Morphine products may discolor over a period of time. No loss of

analgesic potency and no increase in toxicity has ever been demonstrated for such discolored

solutions.

Abuse and Misuse

Like all opioids, Morphine HP 25 and Morphine HP 50 are a potential drug of abuse and misuse,

which can lead to overdose and death. Therefore, Morphine HP 25 and Morphine HP 50 should

be prescribed and handled with caution.

Patients should be assessed for their clinical risks for opioid abuse or addiction prior to being

prescribed opioids. All patients receiving opioids should be routinely monitored for signs of

misuse and abuse.

Opioids, such as Morphine HP 25 and Morphine HP 50 should be used with particular care in

patients with a history of alcohol and illicit/prescription drug abuse. However, concerns about

abuse, addiction, and diversion should not prevent the proper management of pain.

Carcinogenesis and Mutagenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic or the

mutagenic potential of morphine. No long-term follow-up studies of patients receiving morphine

epidurally have been conducted

Cardiovascular

Morphine sulfate administration may result in severe hypotension in patients whose ability to

maintain adequate blood pressure is compromised by reduced blood volume, or concurrent

administration of drugs such as phenothiazines and other tranquilizers, sedative/hypnotics,

tricyclic antidepressants or general anesthetics. Morphine sulfate may produce orthostatic

hypotension in ambulatory patients. These patients should be monitored for signs of hypotension

after initiating or titrating the dose of Morphine HP 25 and Morphine HP 50.

The use of Morphine HP 25 and Morphine HP 50 in patients with circulatory shock should be

avoided as it may cause vasodilation that can further reduce cardiac output and blood pressure.

Rapid intravenous injection of opioid analgesics increases the possibility of hypotension and

respiratory depression and should be avoided (see DOSAGE AND ADMINISTRATION).

Because of possible vagolytic action that may produce a significant increase in the ventricular

response rate, morphine should be used with caution in patients with atrial flutter and other

supraventricular tachycardias.

Dependence/Tolerance

Morphine HP 25 / Morphine HP 50

Page 7 of 31

As with other opioids, tolerance and physical dependence may develop upon repeated

administration of Morphine HP 25 and Morphine HP 50 and there is a potential for development

of psychological dependence.

Physical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic

exposure to an opioid, and are separate and distinct from abuse and addiction. Tolerance, as well

as physical dependence, may develop upon repeated administration of opioids, and are not by

themselves evidence of an addictive disorder or abuse.

Patients on prolonged therapy should be tapered gradually from the drug if it is no longer

required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of

therapy or upon administration of an opioid antagonist. Some of the symptoms that may be

associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea,

goosebumps, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing,

tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in

sweating, palpitations, unexplained fever, weakness and yawning (see ADVERSE REACTIONS;

DOSAGE AND ADMINISTRATION, Adjustment or Reduction of Dosage).

Use in Drug and Alcohol Addiction

Morphine HP 25 and Morphine HP 50 are opioids with no approved use in the management of

addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active

or in remission is for the management of pain requiring opioid analgesia. Patients with a history

of addiction to drugs or alcohol may be at higher risk of becoming addicted to Morphine HP 25

and Morphine HP 50; extreme caution and awareness are warranted to mitigate the risk.

Endocrine

Adrenal Insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more

often following greater than one month of use. Presentation of adrenal insufficiency may include

non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness,

dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis

with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with

physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow

adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.

Other opioids may be tried as some cases reported use of a different opioid without recurrence of

adrenal insufficiency. The information available does not identify any particular opioids as being

more likely to be associated with adrenal insufficiency.

Gastrointestinal Effects

Morphine sulfate and other morphine-like opioids have been shown to decrease bowel motility.

Morphine sulfate may obscure the diagnosis or clinical course of patients with acute abdominal

conditions (see CONTRAINDICATIONS).

Neonatal Opioid Withdrawal Syndrome (NOWS)

Prolonged maternal use of opioids during pregnancy can result in withdrawal signs in the

neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults,

may be life-threatening.

Morphine HP 25 / Morphine HP 50

Page 8 of 31

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep

pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset,

duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid

used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug

by the newborn.

Morphine HP 25 and Morphine HP 50 are not recommended to be used in pregnant women,

unless, in the judgement of the physician, the potential benefits outweigh the risks. If Morphine

HP 25 and Morphine HP 50 were used during pregnancy, special attention to NOWS is

warranted.

Neurologic

Interactions with Central Nervous System Depressants (including benzodiazepines and

alcohol): Morphine HP 25 and Morphine HP 50 should be used with caution and in a reduced

dosage during concomitant administration of other opioid analgesics, general anesthetics,

phenothiazines and other tranquilizers, sedative-hypnotics, tricyclic antidepressants,

antipsychotics, antihistamines, benzodiazepines, centrally-active anti-emetics and other CNS

depressants. Respiratory depression, hypotension and profound sedation, coma or death may

result.

Observational studies have demonstrated that concomitant use of opioid analgesics and

benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics

alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with

the concomitant use of other CNS depressant drugs with opioid analgesics (see DRUG

INTERACTIONS). If the decision is made to prescribe a benzodiazepine or other CNS

depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and

minimum durations of concomitant use. In patients already receiving an opioid analgesic,

prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in

the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated

in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial

dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for

signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when

Morphine HP 25 and Morphine HP 50 are used with benzodiazepines or other CNS depressants

(including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery

until the effects of concomitant use of the benzodiazepine or other CNS depressant have been

determined. Screen patients for risk of substance use disorders, including opioid abuse and

misuse, and warn them of the risk for overdose and death associated with the use of additional

CNS depressants including alcohol and illicit drugs (see DRUG INTERACTIONS).

Morphine HP 25 and Morphine HP 50 should not be administered to patients who have been or

are consuming alcohol as it may increase the chance of experiencing dangerous side effects,

including death (see CONTRAINDICATIONS; ADVERSE REACTIONS, Sedation; and DRUG

INTERACTIONS).

Morphine HP 25 / Morphine HP 50

Page 9 of 31

Severe pain antagonizes the subjective and respiratory depressant actions of opioid analgesics.

Should pain suddenly subside, these effects may rapidly become manifest.

Morphine may aggravate pre-existing convulsions in patients with convulsive disorders. If

dosage is escalated substantially above recommended levels because of tolerance development,

convulsions may occur in individuals without a history of convulsive disorders.

Head Injury:

The respiratory depressant effects of morphine sulfate, and the capacity to elevate cerebrospinal

fluid pressure, may be greatly increased in the presence of an already elevated intracranial

pressure produced by trauma, other intracranial lesions, or a pre-existing increase in

intracranial pressure. Also, morphine sulfate may produce confusion, miosis, vomiting and other

side effects which obscure the clinical course of patients with head injury. In such patients,

morphine sulfate must be used with extreme caution and only if it is judged essential (see

CONTRAINDICATIONS).

Serotonin Syndrome: Morphine HP 25 and Morphine HP 50 could cause a rare but potentially

life-threatening condition resulting from concomitant administration of serotonergic drugs (e.g.

anti-depressants, migraine medications). Treatment with the serotoninergic drug should be

discontinued if such events (characterized by clusters of symptoms such as hyperthermia,

rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental

status changes including confusion, irritability, extreme agitation progressing to delirium and

coma) occur and supportive symptomatic treatment should be initiated. Morphine HP 25 and

Morphine HP 50 should not be used in combination with MAO inhibitors or serotonin-precursors

(such as L-tryptophan, oxitriptan) and should be used with caution in combination with other

serotonergic drugs (triptans, certain tricyclic antidepressants, lithium, tramadol, St. John’s Wort)

due to the risk of serotonergic syndrome (see DRUG INTERACTIONS).

Peri-Operative Considerations

Morphine HP 25 and Morphine HP 50 are not indicated for pre-emptive analgesia

(administration pre-operatively for the management of post-operative pain).

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

treated with Morphine HP 25 and Morphine HP 50 for at least 24 hours before the operation and

Morphine HP 25 and Morphine HP 50 should not be used in the immediate post-operative

period.

Physicians should individualize treatment, moving from parenteral to oral analgesics as

appropriate. Thereafter, if Morphine HP 25 and Morphine HP 50 are to be continued after the

patient recovers from the post-operative period, a new dosage should be administered in

accordance with the changed need for pain relief. The risk of withdrawal in opioid-tolerant

patients should be addressed as clinically indicated.

The administration of analgesics in the peri-operative period should be managed by healthcare

providers with adequate training and experience (e.g., by an anesthesiologist).

Morphine HP 25 / Morphine HP 50

Page 10 of 31

Morphine sulfate and other morphine-like opioids have been shown to decrease bowel motility.

Ileus is a common post-operative complication, especially after intra-abdominal surgery with

opioid analgesia. Caution should be taken to monitor for decreased bowel motility in post-

operative patients receiving opioids. Standard supportive therapy should be implemented.

Morphine HP 25 and Morphine HP 50 should not be used in the early post-operative period (12

to 24 hours post-surgery) unless the patient is ambulatory and gastrointestinal function is normal.

Psychomotor Impairment

Morphine HP 25 and Morphine HP 50 may impair the mental and/or physical abilities needed for

certain potentially hazardous activities such as driving a car or operating machinery. Patients

should be cautioned accordingly. Patients should also be cautioned about the combined effects of

morphine sulfate with other CNS depressants, including other opioids, phenothiazine,

sedative/hypnotics and alcohol.

Respiratory

Respiratory Depression: Dose related respiratory depression is produced by morphine acting

directly on brain stem respiratory centers (see WARNINGS AND PRECAUTIONS). Morphine

also affects centers controlling respiratory rhythm and may produce irregular or periodic

breathing. Serious, life-threatening, or fatal respiratory depression has been reported with the use

of opioids, even when used as recommended. Respiratory depression from opioid use, if not

immediately recognized and treated, may lead to respiratory arrest and death. Management of

respiratory depression may include close observation, supportive measures, and use of opioid

antagonists, depending on the patient’s clinical status. Morphine HP 25 and Morphine HP 50

should be used with extreme caution in patients with substantially decreased respiratory reserve,

pre-existing respiratory depression, hypoxia or hypercapnia (see CONTRAINDICATIONS).

While serious, life-threatening, or fatal respiratory depression can occur at any time during the

use of Morphine HP 25 and Morphine HP 50 the risk is greatest during the initiation of therapy

or following a dose increase. Patients should be closely monitored for respiratory depression

when initiating therapy with Morphine HP 25 and Morphine HP 50 and following dose

increases. If significant respiratory depression occurs, it may be reversed by the use of naloxone

hydrochloride (see OVERDOSAGE).

Life-threatening respiratory depression is more likely to occur in the elderly, cachectic, or

debilitated patients because they may have altered pharmacokinetics or altered clearance

compared to younger, healthier patients.

To reduce the risk of respiratory depression, proper dosing and titration of Morphine HP 25 and

Morphine HP 50 are essential. Overestimating the Morphine HP 25 and Morphine HP 50 dose

when converting patients from another opioid product can result in a fatal overdose with the first

dose. In these patients, the use of non-opioid analgesics should be considered, if feasible (see

WARNINGS AND PRECAUTIONS, Special Populations, Special Risk Groups; and DOSAGE

AND ADMINISTRATION).

Indiscriminate use of morphine in patients with asthma or pulmonary emphysema may, due to its

drying action upon the respiratory tract mucosa, precipitate severe respiratory insufficiency

Morphine HP 25 / Morphine HP 50

Page 11 of 31

resulting from increased viscosity of bronchial secretions and suppression of the cough reflex.

Morphine HP 25 and Morphine HP 50 should be used with great caution in patients having an

acute asthmatic attack.

Use in Patients with Chronic Pulmonary Disease: Monitor patients with significant chronic

obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased

respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly

when initiating therapy and titrating with Morphine HP 25 and Morphine HP 50 as in these

patients, even at usual therapeutic doses of Morphine HP 25 and Morphine HP 50 may decrease

respiratory drive to the point of apnea while simultaneously increasing airway resistance. In

these patients, use of alternative non-opioid analgesics should be considered, if possible. The use

of Morphine HP 25 and Morphine HP 50 are contraindicated in patients with acute or severe

bronchial asthma, chronic obstructive airway, or status asthmaticus (see

CONTRAINDICATIONS).

Sexual Function/Reproduction

Long-term use of opioids may be associated with decreased sex hormone levels and symptoms

such as low libido, erectile dysfunction, or infertility (see ADVERSE REACTIONS, Post-

Marketing Experience).

Special Populations

Special Risk Groups: Morphine sulfate should be administered with caution to patients with

impaired hepatic or renal function, a history of alcohol and drug abuse and in a reduced dosage

to elderly or debilitated patients, and in patients with severely impaired pulmonary function,

Addison’s disease, hypothyroidism, myxedema, toxic psychosis, prostatic hypertrophy or

urethral stricture.

Pregnant Women: Studies in human have not been conducted. Morphine sulfate crosses the

placental barrier and are not recommended to be administered to pregnant women unless in the

judgement of the physician, potential benefits outweigh the risks.

Morphine sulfate administered a short time (i.e., up to 4 hours) prior to delivery to women with

no history of chronic abuse or dependence has been associated with a delay in initial respiration

and transient respiratory depression in the neonate. Respiratory depression may be produced in

the neonate.

Prolonged maternal use of opioids during pregnancy can result in withdrawal signs in the

neonate. Neonatal Opioid Withdrawal Syndrome (NOWS), unlike opioid withdrawal syndrome

in adults, may be life-threatening (see WARNINGS AND PRECAUTIONS, Neonatal Opioid

Withdrawal Syndrome (NOWS)).

Pregnant women using opioids should not discontinue their medication abruptly as this can cause

pregnancy complication such as miscarriage or still-birth. Tapering should be slow and under

medical supervision to avoid serious adverse events to the fetus.

Labour, Delivery and Nursing Women: Since opioids can cross the placental barrier and are

Morphine HP 25 / Morphine HP 50

Page 12 of 31

excreted in breast milk, Morphine HP 25 and Morphine HP 50 are not recommended to be used

in nursing women and during labour and delivery unless, in the judgement of the physician, the

potential benefits outweigh the risks. Life-threatening respiratory depression may occur in the

infant if opioids are administered to the mother. Naloxone, a drug that counters the effects of

opioids, should be readily available if Morphine HP 25 and Morphine HP 50 are used in this

population.

Occasionally, morphine sulfate may prolong labour through actions which temporarily reduce

the strength, duration and frequency of uterine contraction. However, this effect is not consistent

and may be offset by an increased rate of cervical dilation, which tends to shorten labour.

Morphine HP 25 and Morphine HP 50 should be used with caution in women delivering

premature infants since respiratory depression in the neonate may occur. Neonates whose

mothers received morphine sulfate during labor should be observed closely for signs of

respiratory depression. A specific opioid antagonist, naloxone, is available for reversal of

morphine-induced respiratory depression in the neonate.

Pediatrics (< 18 years of age): The safety and efficacy of morphine sulfate have not been

studied in the pediatric population. Therefore, use of Morphine HP 25 and Morphine HP 50 are

not recommended in patients under 18 years of age.

Geriatrics (> 65 years of age): In general, dose selection for an elderly patient should be

cautious, usually starting at the low end of the dosing range and titrate slowly, reflecting the

greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or

other drug therapy (see DOSAGE AND ADMINISTRATION).

Patients with Hepatic or Renal Impairment:

Elimination half-life may be prolonged in patients with reduced metabolic rates and with hepatic

or renal dysfunction. Therefore, care should be exercised in administering Morphine HP 25 and

Morphine HP 50 in these conditions, particularly with repeated dosing.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Adverse effects of morphine sulfate are similar to those of other opioid analgesics, and represent

an extension of pharmacological effects of the drug class. The major hazards of opioids include

respiratory and central nervous system depression and to a lesser degree, circulatory depression,

respiratory arrest, shock and cardiac arrest.

The most frequently observed adverse effects of morphine sulfate are lightheadedness, dizziness,

sedation, nausea, vomiting, constipation and sweating. These effects seem to be more prominent

in ambulatory patients and in those who are not suffering severe pain. In such individuals, lower

doses may be advisable. Some adverse effects may be alleviated in the ambulatory patient if he

lies down. Other adverse effects include the following:

Morphine HP 25 / Morphine HP 50

Page 13 of 31

Central Nervous System:

Sedation, drowsiness, mental clouding, dizziness, lethargy, impairment of mental and physical

performance, anxiety, convulsion, fear, miosis, dysphoria, psychic dependence, and mood

changes.

Gastrointestinal System:

Nausea, vomiting, increased pressure in the biliary tract, constipation.

Cardiovascular System:

Orthostatic hypotension, fainting, tachycardia, peripheral circulatory collapse, and cardiac arrest

have occurred after rapid intravenous injection.

Genitourinary System:

Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported.

Other:

Flushing, sweating, pruritus, allergic reactions, suppressed cough reflex.

Sedation: Sedation is a common side effect of opioid analgesics, especially in opioid naïve

individuals. Sedation may also occur partly because patients often recuperate from prolonged

fatigue after the relief of persistent pain. Most patients develop tolerance to the sedative effects

of opioids within three to five days and, if the sedation is not severe, will not require any

treatment except reassurance. If excessive sedation persists beyond a few days, the dose of the

opioid should be reduced and alternate causes investigated. Some of these are: concurrent CNS

depressant medication, hepatic or renal dysfunction, brain metastases, hypercalcemia and

respiratory failure. If it is necessary to reduce the dose, it can be carefully increased again after

three or four days if it is obvious that the pain is not being well controlled. Dizziness and

unsteadiness may be caused by postural hypotension, particularly in elderly or debilitated

patients, and may be alleviated if the patient lies down.

Nausea and Vomiting: Nausea is a common side effect on initiation of therapy with opioid

analgesics and is thought to occur by activation of the chemoreceptor trigger zone, stimulation of

the vestibular apparatus and through delayed gastric emptying. The prevalence of nausea

declines following continued treatment with opioid analgesics. When instituting therapy with an

opioid for chronic pain, the routine prescription of an antiemetic should be considered. In the

cancer patient, investigation of nausea should include such causes as constipation, bowel

obstruction, uremia, hypercalcemia, hepatomegaly, tumor invasion of celiac plexus and

concurrent use of drugs with emetogenic properties. Persistent nausea which does not respond to

dosage reduction may be caused by opioid-induced gastric stasis and may be accompanied by

other symptoms including anorexia, early satiety, vomiting and abdominal fullness. These

symptoms respond to chronic treatment with gastrointestinal prokinetic agents.

Constipation: Practically all patients become constipated while taking opioids on a persistent

basis. In some patients, particularly the elderly or bedridden, fecal impaction may result. It is

essential to caution the patients in this regard and to institute an appropriate regimen of bowel

management at the start of prolonged opioid therapy. Stimulant laxatives, stool softeners, and

Morphine HP 25 / Morphine HP 50

Page 14 of 31

other appropriate measures should be used as required. As fecal impaction may present as

overflow diarrhea, the presence of constipation should be excluded in patients on opioid therapy

prior to initiating treatment for diarrhea.

Post-Marketing Experience

Androgen deficiency: Chronic use of opioids may influence the hypothalamic-pituitary-gonadal

axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile

dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of

hypogonadism is unknown because the various medical, physical, lifestyle, and psychological

stressors that may influence gonadal hormone levels have not been adequately controlled for in

studies conducted to date. Patients presenting with symptoms of androgen deficiency should

undergo laboratory evaluation.

DRUG INTERACTIONS

Interaction with Benzodiazepines and Other Central Nervous System (CNS) Depressants:

Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS

depressants (e.g. other opioids, sedatives/hypnotics, antidepressants, anxiolytics, tranquilizers,

muscle relaxants, general anesthetics, antipsychotics, phenothiazines, neuroleptics,

antihistamines, antiemetics, and alcohol) and beta-blockers, increases the risk of respiratory

depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs

for use in patients for whom alternative treatment options are inadequate. Limit dosages and

durations to the minimum required. Follow patients closely for signs of respiratory depression

and sedation (see WARNINGS AND PRECAUTIONS, Neurologic, Interactions with Central

Nervous System Depressants (including benzodiazepines and alcohol) and Psychomotor

Impairment). Morphine HP 25 and Morphine HP 50 should not be consumed with alcohol as it

may increase the chance of experiencing dangerous side effects.

Incompatibility:

Morphine sulfate are incompatible with admixtures of soluble barbiturates, chlorothiazide,

aminophylline, heparin, meperidine, methicillin, phenytoin, sodium bicarbonate, iodide,

sulfadiazine and sulfisoxazole.

Drug-Drug Interactions

Morphine analgesia may be decreased when given concomitantly with phenothiazines. When

such combined therapy is contemplated, the dose of one or both agents should be appropriately

adjusted. Coadministration of morphine with a serotonergic agent, such as a Selective Serotonin

Re-uptake Inhibitor or a Serotonin Norepinephrine Re-uptake Inhibitor, may increase the risk of

serotonin syndrome, a potentially life-threatening condition (see WARNINGS AND

PRECAUTIONS).

Drug-Lifestyle Interactions

The concomitant use of alcohol should be avoided (see WARNINGS AND PRECAUTIONS,

General).

Morphine HP 25 / Morphine HP 50

Page 15 of 31

DOSAGE AND ADMINISTRATION

Morphine HP 25 and Morphine HP 50 should only be used in patients for whom

alternative treatment options are ineffective or not tolerated (e.g., non-opioid analgesics).

For acute pain, it is recommended that Morphine HP 25 and Morphine HP 50 be used for a

maximum of 7 days at the lowest dose that provides adequate pain relief.

All doses of opioids carry an inherent risk of fatal or non-fatal adverse events. This risk is

increased with higher doses. For the management of chronic non-cancer, non-palliative pain, it is

recommended that 90 mg (90 morphine milligram equivalent) of Morphine HP 25 or Morphine

HP 50 not be exceeded. Each patient should be assessed for their risk prior to prescribing

Morphine HP 25 or Morphine HP 50, as the likelihood of experiencing serious adverse events

can depend upon the type of opioid, duration of treatment, level of pain as well as the patient’s

own level of tolerance. In addition, the level of pain should be assessed routinely to confirm the

most appropriate dose and the need for further use of Morphine HP 25 or Morphine HP 50 (see

DOSAGE AND ADMINISTRATION, Adjustment or Reduction of Dosage).

Dosing Considerations

Morphine HP 25 and Morphine HP 50 (morphine sulfate injection USP) should be used with

caution within 12 hours pre-operatively and within the first 12-24 hours post-operatively (see

WARNINGS AND PRECAUTIONS, Peri-operative Considerations).

Morphine HP 25 and Morphine HP 50 are not indicated for rectal administration

Rapid intravenous injection of opioid analgesics increases the possibility of hypotension and

respiratory depression.

Because Morphine HP 25 and Morphine HP 50 contain 25 mg/mL and 50 mg/mL of morphine

respectively, a smaller injection volume can be used to avoid the discomfort associated with

subcutaneous intramuscular injection of larger volumes of solution.

Recommended Dose and Dosage Adjustment

Morphine HP 25 and Morphine HP 50, used without dilution are indicated for the relief of severe

pain in narcotic-tolerant patients and therefore are not to be given to patients who are not already

receiving large doses of narcotics.

The initial dosage should be based on the preceding (or previous) morphine or other narcotic

regimen used by the patient. If the patient is being changed from a less concentrated morphine

injection, similar doses should be used depending on the patient’s clinical response to the drug. If

the patient is being changed from one narcotic analgesic to the other, the dose should be adjusted

according to the severity of pain and the patient's clinical response. There can be considerable

variability in both the dosage requirement and the patient's response.

Morphine HP 25 / Morphine HP 50

Page 16 of 31

If Morphine HP 25 or Morphine HP 50 are substituted for a different narcotic analgesic, the

appropriate starting dose must be determined.

Following are the equivalence of commonly used narcotic analgesics (Table 1), and comparison

of effects of strong analgesics used in the treatment of cancer pain (Table 2).

Opioid Rotation

Conversion ratios for opioids are subject to variations in kinetics governed by genetics and other

factors. When switching from one opioid to another, consider reducing the calculated dose by

25-50% to minimize the risk of overdose. Subsequently, up-titrate the dose, as required, to reach

the appropriate maintenance dose.

Table 1 - OPIOID ANALGESICS: APPROXIMATE ANALGESIC EQUIVALENCES

1

DRUG

Equivalent Dose (mg)

2

(compared to morphine 10 mg IM)

Duration of

Action (Hours)

Strong Opioid Agonists:

Morphine

Oxycodone

Hydromorphone

Anileridine

Levorphanol

Meperidine

Oxymorphone

Methadone

Heroin

Weak Opioid Agonists:

Codeine

Propoxyphene

Mixed Agonist-Antagonists

7

:

Pentazocine

Nalbuphine

Butorphanol

Parenteral

5 - 8

Oral

5 (rectal)

10 - 15

3 - 4

2 - 4

2 - 4

2 - 3

4 - 8

1 - 3

3 - 4

3 - 4

3 - 4

2 - 4

3 - 4

3 - 6

3 - 4

Footnotes:

References:

Expert Advisory Committee on the Management of Severe Chronic Pain in Cancer Patients, Health and Welfare

Canada. Cancer pain: A monograph on the management of cancer pain. Ministry of Supplies and Services Canada,

1987. Cat. No. H42-2/5-1984E.

Foley KM. The treatment of cancer pain. N Engl J. Med 1985; 313(2): 84-95.

Aronoff GM, Evans WO. Pharmacological management of chronic pain: A review. In: Aronoff GM, editor.

Evaluation and treatment of chronic pain. 2nd ed. Baltimore (MD); Williams and Wilkins; 1992. p. 359-68.

Cherny NI Portenoy RK. Practical issues in the management of cancer pain. In: Wall PD, Melzack R, editors.

Textbook of pain. 3rd ed. New York: Churchill Livingstone; 1994. p. 1437-67.

Most of the data were derived from single-dose, acute pain studies and should be considered an approximation

for selection of doses when treating chronic pain. As analgesic conversion factors are approximate and patient

response may vary, dosing should be individualized according to relief of pain and side effects. Because of

incomplete cross-tolerance, dose reductions of 25% to 50% of the equianalgesic dose may be appropriate in

some patients when converting from one opioid to another, particularly at high doses.† Upward titration may be

required to reach appropriate maintenance doses.

†Levy MH. Pharmacologic treatment of cancer pain. N Engl J Med 1996;335:1124-1132.

Morphine HP 25 / Morphine HP 50

Page 17 of 31

For acute pain, the oral or rectal dose of morphine is six times the injectable dose. However, for chronic dosing,

clinical experience indicates that this ratio is 2-3:1 (i.e., 20-30 mg of oral or rectal morphine is equivalent to 10

mg of parenteral morphine).

Based on single entity oral oxycodone in acute pain.

Extremely variable equianalgesic dose. Patients should undergo individualized titration starting at an equivalent to 1/10

of the morphine dose.

Not recommended for the management of chronic pain.

Mixed agonist-antagonists can precipitate withdrawal in patients on pure opioid agonists.

Table 2: COMPARISON OF STRONG ANALGESICS AND STRUCTURALLY RELATED

DRUGS USED IN THE TREATMENT OF CANCER PAIN*

– I.M. OR S.C.

ADMINISTRATION

Non Proprietary (Trade) Names

Dose, mg Equianalgesic to 10 mg

of I.M. Morphine

**

Duration Compared with

Morphine

Morphine Sulfate

Same

Papaveretum (Pantopon)

Same

Hydromorphone hydrochloride

(Dilaudid)

Slightly shorter

Oxymorphone hydrochloride

(Numorphan)

Slightly shorter

Nalbuphine hydrochloride (Nubain)

Same

Diamorphine hydrochloride

(Heroine)

Slightly shorter

Levorphanol tartrate (Levo-

Dromoran)

Same

Butorphanol tartrate (Stadol)

1.5 - 2.5

Same

Pentazocine (Talwin) lactate or

hydrochloride

Shorter

Meperidine pethidine (Demerol)

hydrochloride

Shorter

Methadone hydrochloride

(Dolophine)

Same

Beaver WT. Management of cancer pain with parenteral medication. JAMA 1980: 244; 2653-2657.

In terms of the area under the analgesic time effect curve.

Morphine HP 25 and Morphine HP 50, administered subcutaneously or intramuscularly, when

required, should usually be given regularly around the clock, in most instances every 4 hours.

Directions for use: Morphine HP 25 and Morphine HP 50 must be diluted in a sterile area by a

pharmacist.

For I.V. Infusion with dilution: Morphine HP 25 and Morphine HP 50 may be diluted in

Dextrose 5%, in Water or Sodium Chloride Injection to the desired concentration (usually 0.1 to

0.5 mg/mL) and administered by I.V. infusion as required.

S.C. Infusion: If a patient has low muscle mass or is cachectic or has no accessible peripheral

veins, S.C. infusion using a portable pump can be tried. When switching from I.V. to S.C.

infusion, use same dose and monitor same parameters. The maximum dose that can be safely

given has not been defined but doses as high as 480 mg/24 hours have been given. Erythema

Morphine HP 25 / Morphine HP 50

Page 18 of 31

around the injection site may occur. Change needle site periodically (every 5 days, although

some clinicians prefer every 48 hours).

Morphine HP 25 and Morphine HP 50, as well as dilutions of Morphine HP 25 and Morphine HP

50 in Dextrose 5% in Water or Sodium Chloride Injection, can be stored in portable infusion

pump cassettes and PVC minibags. Protected from light and at room temperature, they will stay

stable for more than 15 days.

Morphine Dosage Reduction:

During the first 2 to 3 days of effective pain relief, the patient may sleep for many hours. This

can be misinterpreted as the effect of excessive analgesic dosing rather than the first sign of relief

in a pain exhausted patient. The dose, therefore, should be maintained for about 3 days before

reduction, if respiratory activity and other vital signs are adequate. Following successful relief of

severe pain, periodic attempts to reduce the narcotic dose should be made. Lower doses or

complete discontinuation of the narcotic analgesic may become feasible due to a physiological

change or the improved mental state of the patient.

Geriatrics:

Respiratory depression has occurred in the elderly following administration of large initial doses

of opioids to patients who were not opioid-tolerant or when opioids were co-administered with

other agents that can depress respiration. Morphine HP 25 and Morphine HP 50 should be

initiated at a low dose and slowly titrated to effect (see WARNINGS AND PRECAUTIONS and

ACTION AND CLINICAL PHARMACOLOGY).

Use with Non-Opioid Medications:

If a non-opioid analgesic is being provided, it may be continued. If the non-opioid is

discontinued, consideration should be given to increasing the opioid dose to compensate for the

non-opioid analgesic. Morphine HP 25 and Morphine HP 50 can be safely used concomitantly

with usual doses of other non-opioid analgesics.

Dose Titration:

Dose titration is the key to success with opioid analgesic therapy. Proper optimization of doses

scaled to the relief of the individual’s pain should aim at administration of the lowest dose

which will achieve the overall treatment goal of satisfactory pain relief with acceptable side

effects.

Dosage adjustments should be based on the patient’s clinical response.

Adjustment or Reduction of Dosage:

Physical dependence with or without psychological dependence tends to occur with chronic

administration of opioids, including Morphine HP 25 and Morphine HP 50. Withdrawal

(abstinence) symptoms may occur following abrupt discontinuation of therapy. These symptoms

may include body aches, diarrhea, goosebumps, loss of appetite, nausea, nervousness or

restlessness, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble

with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and

yawning.

Morphine HP 25 / Morphine HP 50

Page 19 of 31

Patients on prolonged therapy should be withdrawn gradually from the drug if it is no longer

required for pain control. In patients who are appropriately treated with opioid analgesics and

who undergo gradual withdrawal for the drug, these symptoms are usually mild (see

WARNINGS AND PRECAUTIONS). Tapering should be individualised and carried out under

medical supervision.

Patient should be informed that reducing and/or discontinuing opioids decreases their tolerance

to these drugs. If treatment needs to be re-initiated, the patient must start at the lowest dose and

titrate up to avoid overdose.

Disposal

Morphine HP 25 and Morphine HP 50 should be kept in a safe place, out of the sight and reach

of children before, during and after use. Morphine HP 25 and Morphine HP 50 should not be

used in front of children, since they may copy these actions.

OVERDOSAGE

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Symptoms: Overdosage with morphine is characterized by respiratory depression (a decrease in

respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), pinpoint pupils,

extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy

skin, and sometimes bradycardia and hypotension. In severe overdosage, particularly by the

intravenous route, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment: Primary attention should be given to the re-establishment of adequate respiratory

exchange through the provision of a patent airway and institution of assisted or controlled

ventilation. Naloxone hydrochloride is a specific and effective antagonist for respiratory

depression which may result from overdosage or sensitivity to narcotics. The usual initial adult

dose is 0.4 mg to 2 mg naloxone administered I.V. If the desired degree of counteraction and

improvement in respiratory function is not obtained immediately following I.V. administration, it

may be repeated intravenously at 2 to 3 minute intervals. Failure to obtain significant

improvement after 2 or 3 doses suggests that the condition may be due partly or completely to

other disease processes or nonopioid drugs. The usual initial dose in narcotic-induced respiratory

depression in neonates is 0.01 mg/kg body weight given I.V., I.M. or S.C. This dose may be

repeated in accordance with the adult administration guideline. If necessary, naloxone can be

diluted with Sterile Water for Injection, USP. Oxygen, intravenous fluids, vasopressors and other

supportive measures should be employed as indicated. An antagonist should not be administered

in the absence of clinically significant respiratory or cardiovascular depression. Morphine is not

dialyzable.

Toxic dose of morphine in humans by parenteral routes; a dose in excess of 30 mg rapidly

administered is likely to induce significant toxic effects in the nonaddicted adult who is not in

pain.

Morphine HP 25 / Morphine HP 50

Page 20 of 31

Note: If an individual is physically dependent on narcotics, the administration of the usual dose

of a narcotic antagonist will precipitate an acute withdrawal syndrome. The severity of this

syndrome will depend on the degree of physical dependence and the dose of antagonist

administered. The use of narcotic antagonists in such individuals should be avoided if possible. If

a narcotic antagonist must be used to treat serious respiratory depression in the physically

dependent patient, the antagonist should be administered with extreme care and only one-tenth

(10%) to one-fifth (20%) the usual dose administered.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Morphine, an opium alkaloid, is a narcotic analgesic and provides analgesia at a dose that does

not produce severe alterations in consciousness. Its principal therapeutic effect is relief of pain.

Its exact mechanism and focus of action are not known, but are believed to relate to the existence

of opiate receptors in the central nervous system. The drug affects both the initial perception of

pain and the emotional response to it and although pain relief is not usually complete, the level of

distress or suffering is markedly decreased. In addition to analgesia, narcotics produce

drowsiness, changes in mood, and mental clouding; however, neither sensory modalities nor

motor activity are blocked at therapeutic doses. There is no intrinsic limit to the analgesic effect,

but high dosages can produce adverse effects, such as respiratory depression, nausea and

vomiting, cough reflex depression, miosis, mild vasodilation and an increase in tone of the

gastrointestinal and genitourinary tracts.

Pharmacodynamics

Central Nervous System:

Morphine sulfate produces respiratory depression by direct action on brain stem respiratory

centres. The respiratory depression involves both a reduction in the responsiveness of the brain

stem centres to increases in CO

tension and to electrical stimulation.

Morphine sulfate depresses the cough reflex by direct effect on the cough centre in the medulla.

Antitussive effects may occur with doses lower than those usually required for analgesia.

Morphine sulfate causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid

overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin

may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in

the setting of morphine sulfate overdose.

Gastrointestinal Tract and Other Smooth Muscle: Morphine sulfate causes a reduction in

motility associated with an increase in smooth muscle tone in the antrum of the stomach and

duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are

decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased

to the point of spasm resulting in constipation. Other opioid-induced effects may include a

reduction in gastric, biliary and pancreatic secretions, spasm of the sphincter of Oddi, and

transient elevations in serum amylase.

Morphine HP 25 / Morphine HP 50

Page 21 of 31

Cardiovascular System:

Morphine sulfate may produce release of histamine with or without associated peripheral

vasodilation. Manifestations of histamine release and/or peripheral vasodilatation may include

pruritus, flushing, red eyes, hyperhidrosis and/or orthostatic hypotension.

Endocrine System:

Opioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes. Some changes that

can be seen include an increase in serum prolactin, and decreases in plasma cortisol and

testosterone. Clinical signs and symptoms may be manifest from these hormonal changes.

Immune System:

In vitro and animal studies indicate that opioids have a variety of effects on immune functions,

depending on the context in which they are used. The clinical significance of these findings is

unknown.

Concentration – Efficacy Relationships

Pain relief generally begins within several minutes after I.V administration. Higher doses provide

greater analgesic effect and longer duration of action but adverse effects limit the maximum

tolerated dose.

Pharmacokinetics

Morphine is detoxified in the liver by conjugation with glucuronic acid. Small amounts of the

free drug and larger amounts of conjugated morphine are found in the urine. These account for

most of the administered drug and 90% of the total excretion occurs within the first 24 hours.

Special Populations and Conditions

Pediatrics: Individuals under 18 years of age should not take Morphine HP 25 nor Morphine HP

STORAGE AND STABILITY

Store between 15 and 30°C. Protect from light. Discard unused portion. Do not autoclave.

LATEX-FREE STOPPERStoppers contains no dry natural rubber.

SPECIAL HANDLING INSTRUCTIONS

Not applicable.

DOSAGE FORMS, COMPOSITION AND PACKAGING

Morphine HP 25 / Morphine HP 50

Page 22 of 31

Morphine HP 25/Morphine HP 50 are clear, colourless or yellow isotonic, sterile, and

preservative free solution of morphine sulfate. No loss of analgesic potency and no increase in

toxicity have ever been demonstrated for discoloured solutions.

Morphine HP 25 (25 mg/mL)

Each mL contains: morphine sulfate 25 mg, sodium chloride for tonicity, sulfuric acid and/or

sodium hydroxide to adjust pH and water for injection. Available in single use amber vials of 1

mL, boxes of 10; and of 4 mL, boxes of 5.

Morphine HP 50 (50 mg/mL)

Each mL contains: morphine sulfate 50 mg, sodium chloride for tonicity, sulfuric acid and/or

sodium hydroxide to adjust pH and water for injection. Available in single use amber vials of 1

mL, boxes of 10; of 5 mL, boxes of 5; of 10 mL, boxes of 5; and 50 mL, boxes of 1.

Morphine HP 25 / Morphine HP 50

Page 23 of 31

PART II: SCIENTIFIC INFORMATION

REFERENCES

Morphine Forte, and Morphine Extra-Forte. Pfizer Canada ULC. Product Monograph. Control

Number: 220077. Date of Revision: August 6, 2018.

Morphine HP 25 / Morphine HP 50

Page 24 of 31

READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE

PATIENT MEDICATION INFORMATION

MORPHINE HP 25

MORPHINE HP 50

(Morphine sulfate injection USP)

Read this carefully before you start taking Morphine HP 25 and Morphine HP 50. This leaflet is

a summary and will not tell you everything about this drug. Talk to your healthcare professional

about your medical condition and treatment and ask if there is any new information about

Morphine HP 25 and Morphine HP 50.

Serious Warnings and Precautions

Even if you take Morphine HP 25 and Morphine HP 50 as prescribed you are at

a risk for opioid addiction, abuse and misuse. This can lead to overdose and

death.

You may get life-threatening breathing problems while taking Morphine HP 25

and Morphine HP 50. This is less likely to happen if you take it as prescribed by

your doctor. Babies are at risk of life-threatening breathing problems if their

mothers take opioids while pregnant or nursing.

If a person has not been prescribed Morphine HP 25 and Morphine HP 50

taking even one dose can cause a fatal overdose. This is especially true for

children.

If you took Morphine HP 25 and Morphine HP 50 while you were pregnant,

whether for short or long periods of time or in small or large doses, your baby

can suffer life-threatening withdrawal symptoms after birth. This can occur in

the days after birth and for up to 4 weeks after delivery. If your baby has any of

the following symptoms:

has changes in their breathing (such as weak, difficult or fast breathing)

is unusually difficult to comfort

has tremors (shakiness)

has increased stools, sneezing, yawning, vomiting, or fever

Seek immediate medical help for your baby.

Taking Morphine HP 25 and Morphine HP 50 with other opioid medicines,

benzodiazepines, alcohol, or other central nervous system depressants (including

street drugs) can cause severe drowsiness, decreased awareness, breathing

problems, coma, and death.

What are Morphine HP 25 and Morphine HP 50 used for?

Morphine HP 25 and Morphine HP 50 are injections containing morphine sulfate (an opioid

Morphine HP 25 / Morphine HP 50

Page 25 of 31

analgesic) used to control severe pain in patients who need an opioid administered by injection.

How does Morphine HP 25 and Morphine HP 50 work?

Morphine HP 25 and Morphine HP 50 are painkillers belonging to the class of drugs known as

opioids. It relieves pain by acting on specific nerve cells of the spinal cord and brain.

What are the ingredients in Morphine HP 25 and Morphine HP 50?

Medicinal ingredient: Morphine sulfate

Non-medicinal ingredients: Sodium chloride, sulfuric acid and/or sodium hydroxide and water

for injection

Morphine HP 25 and Morphine HP 50 comes in the following dosage forms:

Solution for injection of 25 mg/mL and 50 mg/mL

Do not use Morphine HP 25 and Morphine HP 50 if:

your doctor did not prescribe them for you

you are allergic to morphine sulfate or any of the other ingredients in Morphine HP 25 and

Morphine HP 50

you can control your pain by the occasional use of other pain medications. This includes

those available without a prescription

you have severe asthma, trouble breathing, or other breathing problems

you have any heart problems

you have bowel blockage or narrowing of the stomach or intestines

you have severe pain in your abdomen

you have a head injury

you are at risk for seizures

you suffer from alcoholism

you are taking or have taken within the past 2 weeks a Monoamine Oxidase inhibitor

(MAOi) (such as phenelzine sulphate, tranylcypromine sulphate, moclobemide or

selegiline)

you are going to have, or recently had, a planned surgery

To help avoid side effects and ensure proper use, talk to your healthcare professional

before you take Morphine HP 25 and Morphine HP 50. Talk about any health conditions

or problems you may have, including if you:

have a history of illicit or prescription drug or alcohol abuse

have severe kidney, liver or lung disease

have heart disease

have low blood pressure

have past or current depression

suffer from chronic or severe constipation

have problems with your thyroid, adrenal or prostate gland

have, or had in the past hallucinations or other severe mental problems

suffer from migraines

Morphine HP 25 / Morphine HP 50

Page 26 of 31

are planning to become pregnant

Other warnings you should know about:

Opioid dependence and addiction: There are important differences between physical

dependence and addiction. It is important that you talk to your doctor if you have questions or

concerns about abuse, addiction or physical dependence.

Pregnancy, nursing, labour and delivery: Opioids can be transferred to your baby through

breast milk, or while still in the womb. Morphine HP 25 and Morphine HP 50 can then cause

life-threatening breathing problems in your unborn baby or nursing infant. Your doctor will

determine if the benefits of using Morphine HP 25 or Morphine HP 50 outweigh the risks to your

unborn baby or nursing infant.

If you are pregnant and are taking Morphine HP 25 or Morphine HP 50, it is important that you

don’t stop taking your medication all of a sudden. If you do, it can cause a miscarriage or a still-

birth. Your doctor will monitor and guide you on how to slowly stop taking Morphine HP 25 or

Morphine HP 50. This may help avoid serious harm to your unborn baby.

Driving and using machines: Before you do tasks which may require special attention, you

should wait until you know how you react to Morphine HP 25 and Morphine HP 50. Morphine

HP 25 and Morphine HP 50 can cause:

drowsiness

dizziness or

lightheadedness

This can usually occur after you take your first dose and when your dose is increased.

Disorder of the adrenal gland: You may develop a disorder of the adrenal gland called adrenal

insufficiency. This means that your adrenal gland is not making enough of certain hormones.

You may experience symptoms such as:

nausea, vomiting

feeling tired, weak or dizzy

decreased appetite

You may be more likely to have problems with your adrenal gland if you have been taking

opioids for longer than one month. Your doctor may do tests, give you another medication, and

slowly take you off Morphine HP 25 and Morphine HP 50.

Serotonin Syndrome: Morphine HP 25 and Morphine HP 50 can cause Serotonin Syndrome, a

rare but potentially life-threatening condition. It can cause serious changes in how your brain,

muscles and digestive system work. You may develop Serotonin Syndrome if you take Morphine

HP 25 and Morphine HP 50 with certain anti-depressants or migraine medications.

Serotonin Syndrome symptoms include:

fever, sweating, shivering, diarrhea, nausea, vomiting;

muscle shakes, jerks, twitches or stiffness, overactive reflexes, loss of coordination;

Morphine HP 25 / Morphine HP 50

Page 27 of 31

fast heartbeat, changes in blood pressure;

confusion, agitation, restlessness, hallucinations, mood changes, unconsciousness, and

coma.

Sexual Function/Reproduction: Long term use of opioids may lead to a decrease in sex

hormone levels. It may also lead to low libido (desire to have sex), erectile dysfunction or being

infertile.

Tell your healthcare professional about all the medicines you take, including any drugs,

vitamins, minerals, natural supplements or alternative medicines.

The following may interact with Morphine HP 25 and Morphine HP 50:

Alcohol. This includes prescription and non-prescription medications that contain alcohol.

Do not drink alcohol while you are taking Morphine HP 25 and Morphine HP 50. It can

lead to:

drowsiness

unusually slow or weak breathing

serious side effects or

a fatal overdose

other sedative drugs which may enhance the drowsiness caused by Morphine HP 25 and

Morphine HP 50

other opioid analgesics (drugs used to treat pain)

general anesthetics (drugs used during surgery)

benzodiazepines (drugs used to help you sleep or that help reduce anxiety)

antidepressants (for depression and mood disorders). Do not take Morphine HP 25 and

Morphine HP 50 with MAO inhibitors (MAOi) or if you have taken MAOi’s in the last 14

days.

drugs used to treat serious mental or emotional disorders (such as schizophrenia)

antihistamines (drugs used to treat allergies)

anti-emetics (drugs used for the prevention of vomiting)

drugs used to treat muscle spasms and back pain

drugs used to treat migraines (e.g. triptans)

St. John’s Wort

How to take Morphine HP 25 and Morphine HP 50:

Morphine HP 25 and Morphine HP 50, used without dilution are indicated for the relief of severe

pain in narcotic-tolerant patients and therefore are not to be given to patients who are not already

receiving large doses of narcotics.

Morphine HP 25 and Morphine HP 50 are given under the skin, into the muscle or vein in doses

or concentrations that are higher than those usually needed.

Morphine HP 25 / Morphine HP 50

Page 28 of 31

The initial dosage should be based on the preceding (or previous) morphine or other narcotic

regimen used by the patient.

Usual Adult Starting Dose:

Your dose is tailored/personalized just for you.

Your doctor will prescribe the lowest dose that works to control your pain. It is recommended

that you only take Morphine HP 25 and Morphine HP 50 for up to 7 days. If you need to take

Morphine HP 25 and Morphine HP 50 for longer, your doctor will determine the best dose for

you to lower the risk of side effects and overdose. Higher doses can lead to more side effects and

a greater chance of overdose.

Review your pain regularly with your doctor to determine if you still need Morphine HP 25 and

Morphine HP 50. Be sure to use Morphine HP 25 and Morphine HP 50 only for the condition for

which it was prescribed.

If your pain increases or you develop any side effect as a result of taking Morphine HP 25 and

Morphine HP 50 tell your doctor immediately.

Stopping your Medication

If you have been taking Morphine HP 25 and Morphine HP 50 for more than a few days you

should not stop taking it all of a sudden. Your doctor will monitor and guide you on how to

slowly stop taking Morphine HP 25 and Morphine HP 50. You should do it slowly to avoid

uncomfortable symptoms such as having:

body aches

diarrhea

goosebumps

loss of appetite

nausea

feeling nervous or restless

runny nose

sneezing

tremors or shivering

stomach cramps

rapid heart rate (tachycardia)

having trouble sleeping

an unusual increase in sweating

heart palpitations

an unexplained fever

weakness

yawning

By reducing or stopping your opioid treatment, your body will become less used to opioids. If

you start treatment again, you will need to start at the lowest dose. You may overdose if you

Morphine HP 25 / Morphine HP 50

Page 29 of 31

restart at the last dose you took before you slowly stopped taking Morphine HP 25 or Morphine

HP 50.

Refilling your Prescription for Morphine HP 25 and Morphine HP 50:

A new written prescription is required from your doctor each time you need more Morphine HP

25 and Morphine HP 50.

Only obtain prescriptions for this medicine from the doctor in charge of your treatment. Do not

seek prescriptions from other doctors unless you switch to another doctor for your pain

management.

Overdose:

If you think you have taken too much Morphine HP 25 and Morphine HP 50, contact your

healthcare professional, hospital emergency department or regional Poison Control Centre

immediately, even if there are no symptoms.

Signs of overdose may include:

unusually slow or weak breathing

dizziness

confusion

extreme drowsiness

What are possible side effects from using Morphine HP 25 and Morphine HP 50?

These are not all the possible side effects you may feel when taking Morphine HP 25 and

Morphine HP 50. If you experience any side effects not listed here, contact your healthcare

professional.

Side effects may include:

Drowsiness

Insomnia

Dizziness

Fainting

Nausea, vomiting, or a poor appetite

Dry mouth

Headache

Problems with vision

Weakness, uncoordinated muscle movement

Itching

Sweating

Constipation

Low sex drive, impotence (erectile dysfunction), infertility

Talk with your doctor or pharmacist about ways to prevent constipation when you start using

Morphine HP 25 and Morphine HP 50.

Morphine HP 25 / Morphine HP 50

Page 30 of 31

Serious side effects and what to do about them

Symptom / effect

Talk to your healthcare

professional

Stop taking

drug and get

immediate

medical help

Only if

severe

In all cases

RARE

Overdose: hallucinations, confusion, inability

to walk normally, slow or weak breathing,

extreme sleepiness, sedation, or dizziness,

floppy muscles/low muscle tone, cold and

clammy skin.

Respiratory Depression: slow, shallow or

weak breathing.

Allergic Reaction: rash, hives, swelling of

the face, lips, tongue or throat, difficulty

swallowing or breathing

Bowel Blockage (impaction): abdominal

pain, severe constipation, nausea

Withdrawal: nausea, vomiting, diarrhea,

anxiety, shivering, cold and clammy skin,

body aches, loss of appetite, sweating.

Fast, Slow or Irregular Heartbeat:

heart palpitations.

Low Blood Pressure: dizziness, fainting,

light-headedness.

Serotonin Syndrome: agitation or

restlessness, loss of muscle control or muscle

twitching, tremor, diarrhea

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough

to interfere with your daily activities, talk to your healthcare professional.

Reporting Side Effects

You can report any suspected side effects associated with the use of health products to Health

Canada by:

Visiting the Web page on Adverse Reaction Reporting (https://www.canada.ca/en/health-

canada/services/drugs-health-products/medeffect-canada/adverse-reaction-

reporting.html) for information on how to report online, by mail or by fax; or

Calling toll-free at 1-866-234-2345.

NOTE: Contact your health professional if you need information about how to manage your side

effects. The Canada Vigilance Program does not provide medical advice.

Morphine HP 25 / Morphine HP 50

Page 31 of 31

Storage:

Keep unused or expired Morphine HP 25 and Morphine HP 50 in a secure place to

prevent theft, misuse or accidental exposure.

Store between 15°C to 30°C. Protect from light. Discard unused portion. Do not autoclave.

Keep Morphine HP 25 and Morphine HP 50 under lock, out of sight and reach of

children and pets.

Never take medicine in front of small children as they will want to copy you.

Accidental ingestion by a child is dangerous and may result in death. If a child

accidentally takes Morphine HP 25 or Morphine HP 50, get emergency help right

away.

If you want more information about Morphine HP 25 and Morphine HP 50:

Talk to your healthcare professional

Find the full Product Monograph that is prepared for healthcare professionals and includes

this Patient Medication Information by visiting the Health Canada website

(https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-

products/drug-product-database.html); or by calling 1-800-361-3062.

This leaflet was prepared by Sandoz Canada Inc.

110 rue de Lauzon

Boucherville, Quebec

J4B 1E6

Last Revised: May 17, 2019

Similar products

Search alerts related to this product

Share this information