MORPHINE SULFATE INJECTION USP SOLUTION

Canada - English - Health Canada

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Active ingredient:
MORPHINE SULFATE
Available from:
PFIZER CANADA ULC
ATC code:
N02AA01
INN (International Name):
MORPHINE
Dosage:
2MG
Pharmaceutical form:
SOLUTION
Composition:
MORPHINE SULFATE 2MG
Administration route:
INTRAMUSCULAR
Units in package:
10X1 ML
Prescription type:
Narcotic (CDSA I)
Therapeutic area:
OPIATE AGONISTS
Product summary:
Active ingredient group (AIG) number: 0104545008; AHFS: 28:08.08
Authorization status:
APPROVED
Authorization number:
00850314
Authorization date:
2018-10-03

Documents in other languages

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PRODUCT MONOGRAPH

INCLUDING PATIENT MEDICATION INFORMATION

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Morphine Sulfate Injection, USP

Sterile Solution

2 mg/mL, 10 mg/mL and 15 mg/mL

Narcotic Analgesic

Hospira Healthcare Corporation

17300 Trans-Canada Highway

Kirkland, Québec

H9J 2M5

Date of Revision:

March 9, 2018

Submission Control No: 211417

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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 .......................................................................22

DOSAGE FORMS, COMPOSITION AND PACKAGING .............................................22

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

PHARMACEUTICAL INFORMATION ..........................................................................23

PATIENT MEDICATION INFORMATION………………………………………………...24

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Morphine Sulfate Injection, USP

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form /

Strength

Nonmedicinal Ingredients

Intravenous,

Intramuscular, and

Subcutaneous:

2 mg/mL

10 mg/mL

15 mg/mL

Sterile solution

2 mg/mL

10 mg/mL

15 mg/mL

2 mg/mL, 10 mg/mL, 15 mg/mL:

Sodium metabisulfite, water for injection

INDICATIONS AND CLINICAL USE

Adults

Morphine Sulfate Injection, USP administered by slow intravenous injection, is indicated for the

relief of moderate to severe pain.

Morphine Sulfate Injection, USP is 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 (<12years of age)

The safety and efficacy of Morphine Sulfate Injection, USP has not been studied in the pediatric

population. Therefore the use of Morphine Sulfate Injection, USP is not recommended in

patients under 12 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.

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).

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Patients with suspected surgical abdomen (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.

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

cor pulmonale.

Patients with acute alcoholism, delirium tremens, and convulsive disorders, such as those

occurring in status epilepticus, tetanus, and strychnine poisoning.

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

head injury.

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

WARNINGS AND PRECAUTIONS

SERIOUS WARNINGS AND PRECAUTIONS

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 Sulfate Injection, USP 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 Sulfate Injection, USP 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 Sulfate Injection, USP and all patients should be monitored regularly for the

development of these behaviours or conditions (see WARNINGS AND PRECAUTIONS,

Abuse and Misuse). Morphine Sulfate Injection, USP 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

Sulfate Injection, USP. Infants exposed in-utero or through breast milk are at risk of life-

threatening respiratory depression upon delivery or when nursed.

Patients should be

monitored for respiratory depression, especially during initiation of Morphine Sulfate

Injection, USP 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 Sulfate Injection, USP especially by

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SERIOUS WARNINGS AND PRECAUTIONS

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 Sulfate Injection, USP 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 to patients who have been or

are taking alcohol. Morphine Sulfate Injection, USP 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 Sulfate Injection, USP 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

Do not use unless solution is clear and package is undamaged. 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.

Morphine Sulfate Injection, USP should be stored securely to avoid theft or misuse.

Morphine Sulfate Injection, USP 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 Sulfate Injection,

USP as it 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

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

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Abuse and Misuse

Like all opioids, Morphine Sulfate Injection, USP is a potential drug of abuse and misuse, which

can lead to overdose and death. Therefore, Morphine Sulfate Injection, USP 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 Sulfate Injection, USP 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 may product orthostatic hypotension in

ambulatory patients. These patients should be monitored for signs of hypotension after initiating

or titrating the dose of Morphine Sulfate Injection USP.

The use of Morphine Sulfate Injection, USP 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).

Caution should be used in patients with atrial flutter and other supraventricular tachycardias

due to a possible vagolytic action which may produce a significant increase in the ventricular

response rate.

Dependence/Tolerance

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

administration of Morphine Sulfate Injection, USP 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. However, psychic

dependence is unlikely to develop when morphine is used for a short time for the relief of pain.

Tolerance, as well as physical dependence, may develop upon repeated administration of

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opioids, and are not by themselves evidence of an addictive disorder or abuse.

Physical

dependence assumes clinically significant proportions only after several weeks of continued

opioid use, although some mild degree of physical dependence may develop after a few days of

opioid therapy. Tolerance is manifested initially by a shortened duration of analgesic effect, and

subsequently by decreases in the intensity of analgesia. The rate of development of tolerance

varies among patients.

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 lacrimation, rhinorrhea, dilated

pupils, irritability, body aches, diarrhea, goosebumps, loss of appetite, nausea, vomiting,

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. Treatment of the abstinence syndrome is primarily

symptomatic and supportive, including maintenance of proper fluid and electrolyte balance (see

ADVERSE REACTIONS; DOSAGE AND ADMINISTRATION, and Adjustment or

Reduction of Dosage).

Use in Drug and Alcohol Addiction

Morphine Sulfate Injection, USP is an opioid 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 Sulfate

Injection, USP; 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. Care should be exercised in patients with disorders of the biliary tract because

circulating morphine may induce smooth muscle hypertonicity resulting in biliary colic.

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

abdominal conditions (see CONTRAINDICATIONS).

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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.

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 Sulfate Injection, USP is not recommended to be used in pregnant women, unless, in

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

Injection, USP was used during pregnancy, special attention to NOWS is warranted.

Neurologic

Interactions with Central Nervous System Depressants (including benzodiazepines and

alcohol): Morphine sulfate 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 Sulfate Injection, USP is 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 Sulfate Injection, USP should not be administered if patients have been or are

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

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

DRUG INTERACTIONS).

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 convulsive disorders. Convulsions may occur in

individuals without a history of convulsive disorders if dosage is substantially escalated above

recommended levels because of tolerance development.

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. 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 Sulfate Injection, USP 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 Sulfate

Injection, USP 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 Sulfate Injection, USP is 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 Sulfate Injection, USP for at least 24 hours before the operation and

Morphine Sulfate Injection, USP 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 Sulfate Injection, USP is 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).

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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 Sulfate Injection, USP 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 Sulfate Injection, USP 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: 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 sulfate 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 Sulfate Injection, USP 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 Sulfate Injection, USP and following dose increases.

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 Sulfate

Injection, USP are essential. Overestimating the Morphine Sulfate Injection, USP 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 asthma and pulmonary emphysema may, due to its drying

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

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

should be used with great caution in patients having an acute asthmatic attack.

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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 for respiratory

depression, particularly when initiating therapy and titrating with Morphine Sulfate Injection,

USP as in these patients, even usual therapeutic doses of Morphine Sulfate Injection, USP may

decrease respiratory drive to the point of apnea. In these patients, use of alternative non-opioid

analgesics should be considered, if possible. The use of Morphine Sulfate Injection, USP is

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 a

history of alcohol and drug abuse and in a reduced dosage to debilitated patients, and in patients

with severely impaired hepatic or renal function, pulmonary function, Addison’s disease,

hypothyroidism, myxedema, toxic psychosis, prostatic hypertrophy or urethral stricture.

Pregnant Women: Studies in humans have not been conducted. Morphine Sulfate Injection,

USP crosses the placental barrier and is 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 of 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 even in its absence in the mother, presumably because of an

immature blood-brain barrier in the neonate. The comparative fetal and neonatal respiratory

depressant tendencies of equivalent analgesic doses of all drugs in this class have been

determined.

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 excreted in breast milk, Morphine Sulfate Injection, USP is 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 can occur in

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

of opioids, should be readily available if Morphine Sulfate Injection, USP is 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.

Pediatrics (< 12 years of age): The safety and efficacy of Morphine Sulfate Injection, USP have

not been studied in the pediatric population. Therefore, use of Morphine Sulfate Injection, USP

is not recommended in patients under 12 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 in these

conditions, particularly with repeated dosing.

Ambulatory Patients

Since opioid analgesics may impair the mental and/or physical abilities, patients should be

warned not to drive cars, or operate machinery, or unnecessarily expose themselves to

hazards.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Adverse effects of Morphine Sulfate Injection, USP (morphine sulfate injection) 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 major hazards associated with Morphine Sulfate Injection, USP include the following:

respiratory depression, apnea, and to a lesser degree, circulatory depression. Respiratory arrest, shock,

and cardiac arrest have occurred.

The most frequent adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting,

and sweating. These effects seem more prominent in ambulatory patients and in those who are not

suffering from severe pain. In such individuals, lower doses are advisable.

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Allergies

Pruritus, urticaria, other skin rashes, edema, and (rarely) hemorrhagic

urticaria. Wheal and flare over the vein with the intravenous injection

may occur. Anaphylactoid reactions have been reported following

intravenous administration. Thrombocytopenia has rarely been

reported.

Cardiovascular System

Orthostatic hypotension, fainting, flushing, supraventricular

tachycardias, atrial flutter, tachycardia, bradycardia, palpitation,

syncope, circulatory depression, peripheral circulatory collapse, and

cardiac arrest have occurred. Phlebitis following intravenous injection

has been reported.

Central Nervous System

Euphoria, delirium, weakness, headache, sedation, drowsiness, mental

clouding, dizziness, lethargy, impairment of mental and physical

performance, anxiety, convulsion, coma, insomnia, agitation, tremor,

uncoordinated muscle movements, confusion, visual disturbance,

transient hallucinations, disorientation, fear, miosis, dysphoria,

psychic dependence, and mood changes, and respiratory depression.

Gastrointestinal System

Dry mouth, anorexia, nausea, vomiting, increased pressure in the

biliary tract, biliary tract spasm, constipation. Patients with chronic

ulcerative colitis may experience increased colonic motility; toxic

dilatation has been reported in patients with acute ulcerative colitis.

Genitourinary System

Ureteral spasm, spasm of vesical sphincters, urinary retention or

hesitancy, oliguria, antidiuretic effect, reduced libido and/or potency

have been reported.

Other

Sweating, pruritus, 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

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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

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 Sulfate Injection, USP should not be consumed with

alcohol as it may increase the chance of experiencing dangerous side effects.

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.

The analgesic effect of morphine is potentiated by chlorpromazine and methocarbamol.

Morphine may increase the anticoagulant activity of coumarin and other anticoagulants.

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Concurrent administration of cimetidine and morphine has been reported to precipitate apnea,

confusion and muscle twitching.

Morphine Sulfate Injection, USP is incompatible with admixtures of soluble barbiturates,

chlorothiazide, aminophylline, heparin, meperidine, methicillin, phenytoin, sodium

bicarbonate, iodide, sulfadiazine and sulfisoxazole.

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,

potentially

life-threatening

condition

(see

WARNINGS

AND

PRECAUTIONS).

Drug-Lifestyle Interactions

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

General).

DOSAGE AND ADMINISTRATION

Morphine Sulfate Injection, USP 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 Sulfate Injection, USP 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 Sulfate Injection,

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

Morphine Sulfate Injection, USP, 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 Sulfate Injection, USP (see DOSAGE

AND ADMINISTRATION, Adjustment or Reduction of Dosage).

Dosing Considerations

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 Sulfate Injection, USP is not indicated for rectal administration

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

respiratory depression.

Recommended Dose and Dosage Adjustment

When administered intravenously, morphine sulfate should be given very slowly. Rapid

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intravenous injection increases the incidence of adverse reactions as described above. This

drug should be administered intravenously only if an opioid antagonist (i.e., naloxone) is

available. When morphine sulfate is given parenterally, especially intravenously, the patient

should be non-ambulatory.

Following are the equivalences of commonly used opioid 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)

Parenteral

Oral

Strong Opioid Agonists:

Morphine

Oxycodone

Hydromorphone

Anileridine

Levorphanol

Meperidine

Oxymorphone

Methadone

Heroin

5 (rectal)

10-15

Weak Opioid Agonists:

Codeine

Propoxyphene

Mixed Agonist-Antagonists

:

Pentazocine

Nalbuphine

Butorphanol

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

Evans

Pharmacological

management

chronic

pain:

review.

Aronoff

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.

2

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-

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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.

3

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

(a)

– I.M. OR S.C.

ADMINISTRATION

Non Proprietary (Trade) Names

Dose mg Equianalgesic to

10 mg of Morphine

(b)

Duration Compared

with Morphine

Morphine Sulfate

Same

Papaveretum (Pantopon)

Same

Hydromorphone hydrochloride

(Dilaudid)

Slightly shorter

Oxymorphone hydrochloride

(Numorphan)

Slightly shorter

Nalbuphine hydrochloride

(Nubain)

Same

Heroin, diamorphine

hydrochloride

Slightly shorter

Levorphanol tartrate (Levo-

Dromoran)

Same

Butorphanol tartrate (Stadol)

1.5 to 2.5

Same

Pentazocine lactate or

hydrochloride (Talwin)

Shorter

Meperidine pethidine

hydrochloride

(Demerol)

Shorter

Methadone hydrochloride

(Dolophine)

Same

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Beaver, W. T. Management of cancer pain with parenteral medication. JAMA 1980; 244; 2653-2657.

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

Morphine Sulfate Injection, USP 2 mg/mL

The usual adult dose is 1 mg, with a range of 0.1 mg to 5 mg per incremental dose.

Morphine Sulfate Injection, USP 10 mg/mL and 15 mg/mL

Usual Adult dose: 5 mg to 20 mg by intravenous, intramuscular or subcutaneous every 4 hours.

Not for intrathecal or epidural use.

Parenteral drug products should be inspected visually for particulate matter and discoloration

prior to administration. Do not use the injection if it is darker than pale yellow or discolored in

any other way, or it contains a precipitate (see PRECAUTIONS).

Use solution only if clear or pale yellow and contains no precipitate. Do not heat-sterilize.

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 Sulfate Injection, USP 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 Sulfate Injection, USP 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 Sulfate Injection, USP. 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.

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Following successful relief of moderate to severe pain, periodic attempts to reduce the opioid

dose should be made. Smaller doses or complete discontinuation may become feasible due to a

change in the patient’s condition or mental state. 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.

Opioid analgesics may only be partially effective in relieving dysesthetic pain, postherpetic

neuralgia, stabbing pains, activity-related pain and some forms of headache. That is not to say

that patients with advanced cancer suffering from some of these forms of pain should not be

given an adequate trial of opioid analgesics, but it may be necessary to refer such patients at an

early time to other forms of pain therapy.

Disposal

Morphine Sulfate Injection, USP should be kept in a safe place, out of the sight and reach of

children before, during and after use. Morphine Sulfate Injection, USP 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 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 opioids. The usual initial adult dose is 0.4 to 2

mg naloxone administered intravenously. If the desired degree of counteraction and

improvement in respiratory function is not obtained immediately following intravenous

administration, it may be repeated intravenously at 2- or 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.

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The usual initial pediatric dose is 0.01 mg/kg body weight, given intravenously,

intramuscularly or subcutaneously. 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.

Note:

In an individual physically dependent on opioids, the administration of the usual dose

of an opioid antagonist will precipitate an acute withdrawal syndrome. The use of

opioid antagonists in such individuals should be avoided, if possible. If an opioid

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 to one-fifth the usual dose administered.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Morphine, an opium alkaloid, is an opiate agonist 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 locus 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,

opioids 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.

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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.

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 intravenous injection. 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 12 years of age should not take Morphine Sulfate Injection, USP.

STORAGE AND STABILITY

Store between 20

C and 25

C. Protect from light and freezing.

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SPECIAL HANDLING INSTRUCTIONS

Not applicable.

DOSAGE FORMS, COMPOSITION AND PACKAGING

Morphine Sulfate Injection USP is a sterile, nonpyrogenic solution of morphine sulfate.

Composition:

Morphine Sulfate Injection, USP 2 mg/mL

Each mL contains morphine sulfate, pentahydrate 2 mg and sodium chloride 9.0 mg in water

for injection. May contain additional hydrochloric acid and/or sodium hydroxide for pH

adjustment. The pH is approximately 5.

Morphine Sulfate Injection, USP 10 mg/mL and 15 mg/mL

Each mL contains morphine sulfate, pentahydrate 10 mg (10 mg/mL) and 15 mg (15 mg/mL)

and sodium Metabisulfite 1mg in water for injection.

Packaging:

Morphine Sulfate Injection USP is supplied in single-use ampoule 1 mL: 2 mg/mL, 10 mg/mL

and 15 mg/mL.

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PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Proper name:

Morphine sulfate pentahydrate

Chemical name:

7,-8-Didehydro-4, 5α-epoxy-17-methylmorphinan-3, 6α-diol sulfate (2:1)(salt) pentahydrate

Molecular formula and molecular mass:

Molecular formula: (C

H

5H

Molecular mass: 758.83 g/mol

Structural formula:

Physicochemical Properties:

A fine, white powder. When exposed to air it gradually loses water of hydration, and darkens on

prolonged exposure to light. It is soluble in water and ethanol at room temperature.

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READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE

PATIENT MEDICATION INFORMATION

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Morphine Sulfate Injection, USP

Read this carefully before you start taking Morphine Sulfate Injection, USP. 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 Sulfate Injection, USP.

Serious Warnings and Precautions

Even if you take Morphine Sulfate Injection, USP 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 Sulfate

Injection, USP. 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 Sulfate Injection, USP taking even one

dose can cause a fatal overdose. This is especially true for children.

If you took Morphine Sulfate Injection, USP 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 Sulfate Injection, USP 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 is Morphine Sulfate Injection, USP used for?

Morphine Sulfate Injection, USP is an injection containing morphine sulfate (an opioid

analgesic) used to control your pain.

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How does Morphine Sulfate Injection, USP work?

Morphine Sulfate Injection, USP is a painkiller 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 Sulfate Injection, USP?

Medicinal ingredient: Morphine sulfate

Non-medicinal ingredients:

2 mg/mL, 10 mg/mL, 15 mg/mL: Sodium metabisulfite, water for injection

Morphine Sulfate Injection, USP comes in the following dosage form:

Solution for injection of 2 mg/ml, 10 mg/mL and 15 mg/mL

Do not use Morphine Sulfate Injection, USP if:

your doctor did not prescribe it for you

you are allergic to morphine sulfate or any of the other ingredients in Morphine Sulfate

Injection, USP

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 Sulfate Injection, USP. 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

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have problems with your thyroid, adrenal or prostate gland

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

suffer from migraines

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 Sulfate Injection, USP can then cause life-

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

determine if the benefits of using Morphine Sulfate Injection, USP outweigh the risks to your

unborn baby or nursing infant.

If you are pregnant and are taking Morphine Sulfate Injection, USP, 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 Sulfate

Injection, USP. 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 Sulfate Injection, USP. Morphine Sulfate

Injection, USP 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 Sulfate Injection, USP.

Serotonin Syndrome: Morphine Sulfate Injection, USP 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 Sulfate Injection, USP with certain anti-depressants or migraine medications.

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Serotonin Syndrome symptoms include:

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

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

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 Sulfate Injection, USP:

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

alcohol. Do not drink alcohol while you are taking Morphine Sulfate Injection, USP. 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 Sulfate

Injection, USP

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 Sulfate

Injection, USP 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

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How to take Morphine Sulfate Injection, USP:

Morphine Sulfate Injection, USP 2 mg/mL

The usual adult dose is 1 mg, with a range of 0.1 mg to 5 mg per incremental dose.

Morphine Sulfate Injection, USP 10 mg/mL and 15 mg/mL

Usual Adult dose: 5 mg to 20 mg by intravenous, intramuscular or subcutaneous every 4 hours.

Not for intrathecal or epidural use.

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 Sulfate Injection, USP for up to 7 days. If you need to take

Morphine Sulfate Injection, USP 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 Sulfate

Injection, USP. Be sure to use Morphine Sulfate Injection, USP 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 Sulfate

Injection, USP tell your doctor immediately.

Stopping your Medication

If you have been taking Morphine Sulfate Injection, USP 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 Sulfate Injection, USP. 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

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MORPHINE SULFATE INJECTION, USP

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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

restart at the last dose you took before you slowly stopped taking Morphine Sulfate Injection,

USP.

Refilling your Prescription for Morphine Sulfate Injection, USP:

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

Sulfate Injection, USP.

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 Sulfate Injection, USP 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 Sulfate Injection, USP?

These are not all the possible side effects you may feel when taking Morphine Sulfate Injection,

USP. 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

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MORPHINE SULFATE INJECTION, USP

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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 Sulfate Injection, USP.

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

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.

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MORPHINE SULFATE INJECTION, USP

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Reporting Side Effects

We encourage you to report serious or unexpected side effects to Health Canada. The

information is used to check for new safety concerns about health products. As a consumer,

your report contributes to the safe use of health products for everyone.

3 ways to report:

Online at MedEffect:

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

products/medeffect-canada.html

By calling 1-866-234-2345 (toll-free);

By completing a Consumer Side Effect Reporting Form and sending it by:

Fax to 1-866-678-6789 (toll-free), or

Mail to:

Canada Vigilance Program

Health Canada, Postal Locator 1908C

Ottawa, ON

K1A 0K9

Postage paid labels and the Consumer Side Effect Reporting Form are available

at MedEffect (https://www.canada.ca/en/health-canada/services/drugs-health-

products/medeffect-canada.html).

NOTE: Should you require information related to the management of side effects, contact your

health professional. The Canada Vigilance Program does not provide medical advice.

Storage:

Keep unused or expired Morphine Sulfate Injection, USP in a secure place to

prevent theft, misuse or accidental exposure.

Store between 20

C to 25

C. Protect from light and freezing.

Keep Morphine Sulfate Injection, USP 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 Sulfate Injection, USP, get emergency help right away.

If you want more information about Morphine Sulfate Injection, USP:

Talk to your healthcare professional

Find the full product monograph that is prepared for healthcare professionals and includes

this consumer 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 1-800-463-6001.

This leaflet was prepared by:

Hospira Healthcare Corporation

Kirkland, Québec H9J 2M5

Last Revised: March 9, 2018

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