STATEX TABLET 25MG

Canada - English - Health Canada

Buy It Now

Active ingredient:
MORPHINE SULFATE
Available from:
PALADIN LABS INC
ATC code:
N02AA01
INN (International Name):
MORPHINE
Dosage:
25MG
Pharmaceutical form:
TABLET
Composition:
MORPHINE SULFATE 25MG
Administration route:
ORAL
Units in package:
100
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:
00594636
Authorization date:
2009-04-03

Documents in other languages

PRODUCT MONOGRAPH

INCLUDING PATIENT MEDICATION INFORMATION

STATEX

®

morphine sulfate

Oral Drops –50 mg/mL

Suppositories – 5, 10, 20 and 30 mg

Oral Syrup – 1 and 5 mg/mL

Tablets – 5, 10, 25 and 50 mg

Opioid Analgesic

Paladin Labs Inc.

100 Alexis Nihon Blvd., Suite 600

St-Laurent, Quebec

H4M 2P2

Date of Preparation:

December 4, 1985

Date of Revision:

August 2, 2019

Version: 6.0

Submission Control No: 229677

Product monograph STATEX

®

Page 2 of 33

TABLE OF CONTENTS

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

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

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

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

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

DRUG INTERACTIONS ..................................................................................................13

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

OVERDOSAGE ................................................................................................................18

ACTION AND CLINICAL PHARMACOLOGY ............................................................19

STORAGE AND STABILITY ..........................................................................................20

SPECIAL HANDLING INSTRUCTIONS .......................................................................20

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

PART II: SCIENTIFIC INFORMATION ...............................................................................22

PHARMACEUTICAL INFORMATION ..........................................................................22

DETAILED PHARMACOLOGY .....................................................................................22

PART III: CONSUMER MEDICATION INFORMATION ..................................................25

Product monograph STATEX

®

Page 3 of 33

N

STATEX

®

morphine sulfate

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of

Administration

Dosage Form / Strength

Nonmedicinal Ingredients

Oral

Oral drop 50 mg/mL

Citric acid anhydrous, dextrose monohydrate,

glycerine, sodium benzoate, sodium

cyclamate, propylene glycol, water

Oral syrup 1 and 5 mg/mL

Unflavoured: citric acid anhydrous, dextrose

monohydrate, glycerine, sodium benzoate,

sodium cyclamate, propylene glycol, water

Orange flavour: citric acid anhydrous,

glycerine, orange extract, propylene glycol,

sodium benzoate, sucrose, water

Tablet 5, 10, 25 and 50 mg

FD&C Blue No.1 Lake 13% (5mg, 10mg),

FD&C red #3 Lake 15% (25mg, 50mg)

lactose monohydrate, lake blend yellow 17%

LB-111 (5mg, 50mg), magnesium stearate,

microcrystalline cellulose

Rectal

Suppository 5, 10, 20 and

30 mg

Wecobee M (hydrogenated vegetable oil)

For a complete listing see Dosage Forms, Composition and Packaging section.

INDICATIONS AND CLINICAL USE

Adults

STATEX is indicated for the symptomatic relief of severe chronic pain.

STATEX 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 (see ACTION AND CLINICAL

PHARMACOLOGY, Special Populations and Conditions, Geriatrics).

Product monograph STATEX

®

Page 4 of 33

Pediatrics (< 18 years of age)

The safety and efficacy of STATEX has not been studied in the pediatric population. Therefore

the use of STATEX is 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.

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 (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.

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).

Patients with cardiac arrhythmias.

Patients with emotional instability and/or suicidal ideation.

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, STATEX (morphine sulfate drops, suppositories, syrup and tablets)

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

STATEX 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 STATEX, and all

patients should be monitored regularly for the development of these behaviours or

conditions (see WARNINGS AND PRECAUTIONS). STATEX should be stored securely

to avoid theft or misuse.

Product monograph STATEX

®

Page 5 of 33

Life-threatening Respiratory Depression: OVERDOSE

Serious, life-threatening, or fatal respiratory depression may occur with use of STATEX.

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 STATEX or following a dose

increase.

STATEX tablets must be swallowed whole. Cutting, breaking, crushing, chewing, or

dissolving STATEX can lead to dangerous adverse events including death (see

WARNINGS AND PRECAUTIONS). Further, instruct patients of the hazards related to

taking opioids including fatal overdose.

Accidental Exposure

Accidental ingestion of even one dose of STATEX, 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 STATEX during pregnancy can result in neonatal opioid

withdrawal syndrome, which may be life-threatening (see WARNINGS AND

PRECAUTIONS).

Interaction with Alcohol

The co-ingestion of alcohol with STATEX 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 STATEX 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

Patients should be instructed not to give STATEX (morphine sulfate) to anyone other than

the patient for whom it was prescribed, as such inappropriate use may have severe medical

consequences, including death. STATEX should be stored securely to avoid theft or misuse.

STATEX should only be prescribed by persons knowledgeable in the continuous

administration of potent opioids, in the management of patients receiving potent opioids

Product monograph STATEX

®

Page 6 of 33

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 STATEX 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.

Abuse and Misuse

Like all opioids, STATEX is a potential drug of abuse and misuse, which can lead to overdose

and death. Therefore, STATEX 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 STATEX, 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.

STATEX drops, syrup and tablets are intended for oral use only. The tablets should be

swallowed whole, and not chewed or crushed. Abuse of oral dosage forms can be expected to

result in serious adverse events, including death.

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. These patients should be monitored for signs of

hypotension after initiating or titrating the dose of STATEX.

The use of STATEX in patients with circulatory shock should be avoided as it may cause

vasodilation that can further reduce cardiac output and blood pressure.

Dependence/Tolerance

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

administration of STATEX 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.

However, tolerance does not develop at an equal rate for all side effects. Cross-tolerance exists

with all opioids. In the wake of tolerance, the patient’s dosage might be increased if needed.

Product monograph STATEX

®

Page 7 of 33

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,

gooseflesh, 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

STATEX 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 STATEX; extreme caution and awareness

is 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)

STATEX is not recommended to be used in pregnant women unless, in the judgment of the

physician, the potential benefits outweigh the risks. If STATEX was used during pregnancy,

special attention to NOWS is warranted.

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

Product monograph STATEX

®

Page 8 of 33

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

by the newborn.

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

STATEX 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 with 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 of

overdose and death associated with the use of additional CNS depressants including alcohol and

illicit drugs (see DRUG INTERACTIONS).

STATEX should not be consumed with alcohol as it may increase the chance of experiencing

dangerous side effects, including death (see CONTRAINDICATIONS and 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.

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).

Product monograph STATEX

®

Page 9 of 33

Serotonin Syndrome: STATEX 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 serotonergic drug and/or STATEX 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. STATEX 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

STATEX 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 STATEX for at least 24 hours before the operation and STATEX should not be used

in the immediate post-operative period.

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

appropriate. Thereafter, if STATEX 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).

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.

STATEX 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

STATEX 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.

Product monograph STATEX

®

Page 10 of 33

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 STATEX, 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

STATEX 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 STATEX are

essential. Overestimating the STATEX 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 DOSAGE AND ADMINISTRATION).

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 STATEX, as in these patients,

even usual therapeutic doses of STATEX 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 STATEX 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 pulmonary function, Addison’s disease, hypothyroidism, myxedema,

toxic psychosis, prostatic hypertrophy or urethral stricture, hypopituitarism, reduced renal and/or

hepatic function, hypotension, biliary tract disorder, anemia, reduced blood volume and severe

malnutrition.

Product monograph STATEX

®

Page 11 of 33

Cancer Patients: Nausea and vomiting are symptoms frequently observed in terminal cancer

patients. If a phenothiazine drug is to be employed as an antiemetic agent, it should be

administered 30 minutes before morphine and not in the same preparation because of its

potentiating activity on morphine. The dose and choice of a phenothiazine drug will depend on

the individual patient, the disease, therapy/ies, and degree of sedation required.

Pregnant Women: Morphine has been demonstrated to be teratogenic in animals at very high

doses. Studies in humans have not been conducted. Morphine sulfate crosses the placental barrier

and is not recommended to be administered to pregnant women unless, in the judgment of the

physician, potential benefits outweigh the risks.

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, STATEX is not recommended to be used in nursing women and during

labour and delivery unless, in the judgment of the physician, the potential benefits outweigh the

risks. Life-threatening respiratory depression can 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

STATEX is used in this population.

Pediatrics (< 18 years of age): The safety and efficacy of STATEX have not been studied in the

pediatric population. Therefore, use of STATEX is 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 and ACTION AND

CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics).

Patients with Hepatic Impairment: Morphine should be administered with caution and in a

reduced dosage in patient with hepatic impairment.

Patients with Renal Impairment: Morphine should be administered with caution and in a

reduced dosage in patient with renal impairment.

Product monograph STATEX

®

Page 12 of 33

ADVERSE REACTIONS

Adverse Drug Reaction Overview

Adverse effects of STATEX (morphine sulfate) drops, suppositories, syrup and tablets 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 STATEX are sedation, nausea and vomiting,

constipation and sweating.

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 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.

The following adverse effects occur less frequently with opioid analgesics.

Product monograph STATEX

®

Page 13 of 33

Less Common Adverse Drug Reactions

Cardiovascular: Supra-ventricular tachycardia, postural hypotension, palpitations, faintness and

syncope.

Dermatologic: Pruritus, urticaria, other skin rashes and edema.

Endocrine: A syndrome of inappropriate antidiuretic hormone secretion characterized by

hyponatremia secondary to decreased free-water excretion may be prominent (monitoring of

electrolytes may be necessary).

Gastrointestinal: Dry mouth, anorexia, constipation, cramps, taste alterations and biliary tract

cramps.

CNS: Euphoria, dysphoria, weakness, insomnia, dizziness, confusional symptoms and

occasionally hallucinations.

Genitourinary: Urinary retention or hesitance, reduced libido or potency.

Withdrawal (Abstinence) Syndrome: Physical dependence with or without psychological

dependence tend to occur on chronic administration. An abstinence syndrome may be

precipitated when opioid administration is discontinued or opioid antagonists administered. The

following withdrawal symptoms may be observed after opioids are discontinued: body aches,

diarrhea, gooseflesh, loss of appetite, nervousness or restlessness, runny nose, sneezing, tremors

or shivering, stomach cramps, nausea, trouble with sleeping, unusual increase in sweating and

yawning, weakness, tachycardia and unexplained fever. With appropriate medical use of opioids

and gradual withdrawal from the drug, these symptoms are usually mild.

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

Overview

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

Product monograph STATEX

®

Page 14 of 33

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). STATEX should not be consumed with alcohol as it may increase

the chance of experiencing dangerous side effects.

Drug-Drug Interactions

Oral Anticoagulants: Morphine may enhance response to anticoagulants; however, short term

use does not likely have a significant effect.

Skeletal Muscle Relaxants: CNS depressant effect of morphine adds to the neuromuscular

blockade of muscle relaxants and atelectasis and increased respiratory depression may occur.

Exert great caution if used concurrently.

Antimuscarinics: May result in increased risk of severe constipation and/or urinary retention.

Levallorphan/Naloxone: Antagonize the analgesic, CNS and respiratory depressant effects of

opioid agonist analgesics and may precipitate withdrawal symptoms in physically dependent

patients: dosage of levallorphan or naloxone should be carefully titrated when used to treat

opioid overdosage in dependent patients.

Neuromuscular Blocking Agents: Respiratory depressant effects of neuromuscular blocking

agents may be additive to central respiratory depressant effects of opioid analgesics; caution is

recommended when an opioid drug is administered during surgery or in the immediate post-

operative period to a patient who has received a neuromuscular blocking agent.

Serotonergic agents: Co-administration of morphine sulfate 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-Food Interactions

Interactions with food have not been established.

Drug-Herb Interactions

Interactions with herbal products have not been established.

Drug-Laboratory Interactions

Morphine interferes with the diagnostic determination of cerebrospinal fluid pressure, the

concentrations of; plasma amylase, plasma lipase, serum alanine aminotransferase (SGPT),

serum aspartate aminotransferase (SGOT), serum bilirubin and serum alkaline phosphatase.

Product monograph STATEX

®

Page 15 of 33

Drug-Lifestyle Interactions

The concomitant use of alcohol should be avoided (see

WARNINGS AND PRECAUTIONS,

General

DOSAGE AND ADMINISTRATION

STATEX should only be used in patients for whom alternative treatment options are

ineffective or not tolerated (e.g., non-opioid analgesics).

STATEX tablets must be swallowed whole. Cutting, breaking, crushing, chewing, or

dissolving STATEX can lead to dangerous adverse events including death (see

WARNINGS AND PRECAUTIONS).

For opioid products used in acute pain, a maximum of 7 days treatment is recommended at

the lowest dose that provides adequate 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 the daily dose of STATEX not exceed 90 mg (90 morphine

milligram equivalent). Each patient should be assessed for their risk prior to prescribing

STATEX, 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 STATEX (see DOSAGE AND

ADMINISTRATION, Adjustment or Reduction of Dosage).

Dosing Considerations

STATEX (morphine sulfate drops, suppositories, syrup and tablets) 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).

STATEX drops, syrup and tablets are not indicated for rectal administration

STATEX may be taken with or without food.

STATEX tablets may be taken with a glass of water.

STATEX oral unflavoured drops and syrup may be diluted in a glass of fruit juice just prior to

ingestion if desired, to improve the taste.

STATEX suppositories should be placed against the rectal mucosa. The drug is not absorbed if

pushed into a mass of stool or if it is placed in the anal canal.

Recommended Dose and Dosage Adjustment

Adults: Individual dosing requirements vary considerably based on each patient's age, weight,

severity of pain, and medical and analgesic history.

Product monograph STATEX

®

Page 16 of 33

Patients Not Receiving Opioids at the Time of Initiation of Morphine Sulfate Treatment:

The usual initial adult dose is 10-30 mg q4h around the clock.

Because of the slower clearance in patients over 50 years of age, in elderly and debilitated

patients, and in those with impaired respiratory function or significantly decrease renal function,

an appropriate dose in those patient groups may be as low as half or less than the usual dose in

the younger age group.

Patients Currently Receiving Opioids: Having determined the total daily dosage of the present

analgesic, TABLE 1 can be used to calculate the approximate daily oral morphine sulfate dosage

that should provide equivalent analgesia. 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. It is

usually appropriate to treat a patient with only one opioid at a time.

Table 1: Opioid Conversion Table

a

Opioids

To convert to oral

morphine equivalent

To convert from oral

morphine multiply

by

Daily 90 mg MED

b

Morphine

90 mg/d

Codeine

0.15

6.67

600 mg/d

Hydromorphone

18 mg/d

Oxycodone

0.667

60 mg/d

Tapentadol

0.3-0.4

2.5-3.33

300 mg/d

Tramadol

0.1-0.2

Methadone

Morphine dose equivalence is not reliably established

*** The maximum recommended daily dose of tramadol is 300 mg - 400 mg depending on the formulation.

Adapted from the 2017 Canadian guideline for opioids for chronic non-cancer pain. McMaster University; 2017

MED: Morphine Equivalent Dose

Patients with Hepatic Impairment: Morphine should be administered with caution and in a

reduced dosage in patient with hepatic impairment.

Patients with Renal Impairment: Morphine should be administered with caution and in a

reduced dosage in patient with renal impairment.

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. STATEX should be initiated at a low dose and slowly

titrated to effect (see WARNINGS AND PRECAUTIONS and ACTION AND CLINICAL

PHARMACOLOGY).

Product monograph STATEX

®

Page 17 of 33

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. STATEX 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.

Higher doses may be justified in some patients to cover periods of physical activity.

Adjustment or Reduction of Dosage: During the first two or three days of effective pain relief,

the patient may exhibit drowsiness or sleep for prolonged periods. 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 at least three days before reduction,

provided the sedation is not excessive or associated with unsteadiness and confusional

symptoms, and respiratory activity and other vital signs are adequate. If excessive sedation

persists, the reason(s) for such an effect must be sought. Some of these are: concomitant sedative

medications, hepatic or renal failure, exacerbated respiratory failure, higher doses than tolerated

by an older patient, or the patient is actually more severely ill than realized. 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.

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

administration of opioids, including STATEX. Withdrawal (abstinence) symptoms may occur

following abrupt discontinuation of therapy. These symptoms may include body aches, diarrhea,

gooseflesh, 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.

Following successful relief of severe pain, periodic attempts to reduce the opioid dose should be

made. Smaller doses or complete discontinuation of the opioid analgesic may be feasible due to

changes in the patient's condition or improved 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 individualized 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.

Product monograph STATEX

®

Page 18 of 33

Opioid analgesics may only be partially effective in relieving dysesthetic pain, post-herpetic

neuralgia, stabbing pains, activity-related pain and some forms of headache. This 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 opiate analgesics, but it may be necessary to refer such patients at an

early time for other forms of pain therapy. Pain without nociception is usually not opioid-

responsive.

Disposal

STATEX should be kept in a safe place, out of the sight and reach of children before, during and

after use. STATEX should not be used in front of children, since they may copy these actions.

STATEX should never be disposed of in household trash. Disposal via a pharmacy take back

program is recommended. Unused or expired STATEX should be properly disposed of as soon

as it is no longer needed to prevent accidental exposure to others, including children or pets. If

temporary storage is required before disposal, a sealed child-proof container, such as a biohazard

waste container or a lockable medication box could be obtained from a pharmacy.

Missed Dose

If the patient forgets to take one or more doses, they should take their next dose at the next

scheduled time and in the normal amount.

OVERDOSAGE

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

Symptoms: Serious morphine overdosage is characterized by respiratory depression (reduced

respiratory rate and /or tidal volume: Cheyne-Stokes respiration; cyanosis), extreme somnolence

progressing to stupor or coma, hypotonia, dizziness, confusion, miosis, rhabdomyolysis

progression to renal failure, cold or clammy skin, and sometimes hypotension and bradycardia.

Pinpoint pupils are a sign of narcotic overdose, but are not pathognomonic (e.g. pontine lesions

of hemorrhagic or ischemic origin may product similar findings). Marked mydriasis rather than

miosis may be seen with hypoxia in the setting of morphine overdose. Severe over-dosage may

result in apnea, circulatory collapse, cardiac arrest and death.

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

exchange through the provision of a patent airway and controlled or assisted ventilation. The

opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression

due to overdosage or as a result of unusual sensitivity to morphine. An appropriate dose of the

antagonist should therefore be administered, preferably by the intravenous route. The usual

initial i.v. adult dose of naloxone is 0.4 mg or higher. Concomitant efforts at respiratory

resuscitation should be carried out. Since the duration of action of morphine may exceed that of

the antagonist, the patient should be under continued surveillance and doses of the antagonist

should be repeated as needed to maintain adequate respiration.

Product monograph STATEX

®

Page 19 of 33

An antagonist should not be administered in the absence of clinically significant respiratory or

cardiovascular depression. Oxygen, intravenous fluids, vasopressors and other supportive

measures should be used as indicated.

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

antagonists 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 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 by using dosage titration, commencing with

10 to 20% of the usual recommended initial dose.

Evacuation of gastric contents may be useful in removing unabsorbed drug.

ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Morphine sulfate is an opioid analgesic that acts as an agonist, interacting with stereo specific

receptor sites in the brain and other tissues.

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 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

Product monograph STATEX

®

Page 20 of 33

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.

Special Populations and Conditions

Pediatrics: Individuals under 18 years of age should not take STATEX.

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. STATEX should be initiated at a low

dose and slowly titrated to effect (see WARNINGS AND PRECAUTIONS and ACTION

AND CLINICAL PHARMACOLOGY).

Hepatic Impairment: Morphine should be administered with caution and in a reduced dosage in

patient with hepatic impairment.

Renal Impairment: Morphine should be administered with caution and in a reduced dosage in

patient with renal impairment.

STORAGE AND STABILITY

Store all preparations between 15-30

C in a well closed light resistant container.

SPECIAL HANDLING INSTRUCTIONS

Not applicable

Product monograph STATEX

®

Page 21 of 33

DOSAGE FORMS, COMPOSITION AND PACKAGING

Composition:

Statex Oral Drop 50 mg/ mL: Each 1mL of clear unflavored and colorless liquid contains 50 mg

of morphine sulfate. The non-medicinal ingredients are citric acid anhydrous, dextrose

monohydrate, glycerine, sodium benzoate, sodium cyclamate, propylene glycol, water. Calorie

content: 160 KCal/100 mL.

Statex Oral Syrup 1 mg/mL: Available as unflavored (clear) and orange flavored syrup. Each

mL contains 1 mg of morphine sulfate. The non-medicinal ingredients of the unflavoured syrup

are citric acid anhydrous, dextrose monohydrate, glycerine, propylene glycol, sodium benzoate,

sodium cyclamate, water. The non-medicinal ingredients of the orange flavoured syrup are citric

acid anhydrous, glycerine, orange extract, propylene glycol, sodium benzoate, sucrose, water.

Statex Oral Syrup 5 mg/mL: Available as unflavoured (clear) and orange flavoured syrup. Each

mL contains 5 mg of morphine sulfate. The non-medicinal ingredients of the unflavoured syrup

are citric acid anhydrous, dextrose monohydrate, glycerine, propylene glycol, sodium benzoate,

sodium cyclamate, water. The non-medicinal ingredients of the orange flavoured syrup are citric

acid anhydrous, glycerine, orange extract, propylene glycol, sodium benzoate, sucrose, water.

Statex Suppositories: Each white cone-shape suppository contains: morphine sulfate 5, 10, 20,

or 30 mg. The non-medicinal ingredient is wecobee M (hydrogenated vegetable oil).

Statex Oral Tablets: available as 5mg (green), 10 mg (blue), 25 mg (pink), 50 mg (orange)

round, scored on one side, identified with Paladin logo on the other side tablets. The non-

medicinal ingredients are FD&C Blue No.1 Lake 13% (5mg, 10mg), lactose monohydrate, lake

blend yellow 17% (5mg, 50mg), FD&C red#3, Lake 15% (25mg, 50mg), magnesium stearate,

microcrystalline cellulose.

Packaging:

Statex Oral Drops 50 mg/ mL: Available in 50 mL non-graduated bottles with calibrated

dropper, filled to deliver 1 mL (50 mg of Morphine Sulfate).

Statex Oral Syrup 1 mg/mL: Available in 250 and 500 mL graduated bottles in Pet or Pet G

bottles, and in uni-dose of 5, 10 and 15 mL (unflavoured only) in amber glass bottles.

Statex Oral Syrup 5 mg/mL: Available in 250 and 500 mL graduated bottles in Pet G bottles, and

in uni-dose of 5 and 10 mL (unflavoured only) in amber glass bottles.

Statex Suppositories: Available in boxes of 10.

Statex Oral Tablets: Available in bottles of 100 or control packs of 100 (4 x 25 tablets in blister).

Product monograph STATEX

®

Page 22 of 33

PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Proper name:

morphine sulfate

Chemical name:

morphinan-3, 6-diol,7,8-didehydro-4,5-epoxy-17-methyl-(5α , 6 α )-

sulfate(2:1) (salt), pentahydrate

Molecular formula:

O

Molecular mass:

668.76

Structural formula:

Physicochemical Properties:

Pentahydrate, white fine odorless, crystals or powder or cubical masses (with a bitter taste).

Looses some water at ordinary temperature, discolors on exposure to light. Soluble in water,

sparingly soluble in alcohol, insoluble in chloroform or ether.

DETAILED PHARMACOLOGY

Morphine alters both the perception of pain and the emotional response to pain. The spectrum of

actions of morphine due to its receptor affinity also include decreased gastrointestinal motility,

respiratory depression, nausea, vomiting, drowsiness, changes in mood, alterations of the

endocrine and autonomic nervous systems, and suppression of the cough reflex.

It has been proposed that there are multiple subtypes of opioid receptors, each mediating various

therapeutic and/or side effects of opioid drugs. The actions of an opioid analgesic may therefore

depend upon its binding affinity for each type of receptor and whether it acts as a full agonist or

a partial agonist or is inactive at each type of receptor. At least two of these types of receptors

(mu and kappa) mediate analgesia. A third type of receptor (sigma) may not mediate analgesia;

action at this receptor may produce the subjective and psychotomimetic effects characteristic of

opioids having mixed agonist/antagonist activity.

Product monograph STATEX

®

Page 23 of 33

Morphine Sulfate is absorbed from the gastrointestinal tract. Two thirds of an oral dose is

absorbed with maximum analgesic effect occurring after 60 minutes, however, the effect of a

given dose is variable. The time curve is often long by the oral route and peak plasma levels of

morphine occur 15 minutes post ingestion. The plasma half-life of morphine occurs at 2 to 3

hours post ingestion with large inter-subject variability.

Morphine sparingly crosses the blood brain barrier but appears in all tissues. Morphine is

metabolized in the liver via biotransformation. About 10% of a dose of morphine is excreted

through the bile into the faeces. The remainder is excreted via glomerular filtration in the urine

as conjugates or free morphine. Small quantities are excreted in breast milk and sweat. About

90% of a single dose of morphine is excreted in 24 hours with traces up to 48 hours.

Product monograph STATEX

®

Page 24 of 33

REFERENCES

"British National Formulary", 7th ed., British Medical Association and The Pharmaceutical

Society of Great Britain, London, England, 1984, pp. 163-167.

"Compendium of Pharmaceuticals and Specialties". 19th ed., C.M.E. Krogh, ed., Southam

Murray, Toronto, Ontario, 1984, p.403.

Davis. A.J.: Brompton's cocktail: Making good-byes possible. Am. J. Nurs.78:610-612, 1978.

"The Dispensatory of the United States of America", 24th ed., A. Osol et al, ed., J.B.

Lippincott Co., Philadelphia, Pa. 1950, pp. 714-720.

Drug Information for the Health Care Provider, Vol. I. USPDI, 5th ed., Mack Printing Co.,

Easton, Pa. 1984. pp. 887-901.

Interagency Committee on New Therapies for Pain and Discomfort. Report to the White

House:U.S. Dept. of Health, Education and Welfare, Public Health Service, National Institute

of Health, May 1979.

Lipman, A.: Drug Therapy in Chronic Pain, J. Cont. Ed. Clin. Hosp. Phar., 1, (Feb) 1979.

"Martindale:The Extra Pharmacopoeia", 28th ed. J.E.F. Reynolds, ed. Pharmaceutical Press,

London, England, 1982. pp. 1018-1021.

Melzack, R., Mount, B.M. and Gordon, J.M.: The Brompton mixture vs morphine solution

given orally: effects on pain. Can. Med. Assoc. J. 120:435-438 (Feb. 17 1979).

"The Merck Index". 10th ed., M. Windholz, Ed., Merck & Co. Inc., Rahway, N.J., 1983, pp.

898-899.

Mount, B.M.: Palliative Care of the Terminally Ill. Royal College Lecture (January 27,

1978).

Mount, B.M., Ajemian, I., and Scott, J.F.: Use of the Brompton mixture in treating the

chronic pain of malignant disease. Can. Med. Assoc. J. 115:112-124 (July 17, 1976).

"Physician's Desk Reference", 37th ed., Medical Economics Co. Inc., Oradell, N.J., 1983, pp.

1758-1759.

Twycross, R.G.: Value of cocaine in opiate containing elixirs, Br. Med. J. 2:1348 (Nov.

19)1977.

"The United States Pharmacopeia". 21st rev., Mack Publishing Company, Easton, Pa. 1984,

p. 701.

Product monograph STATEX

®

Page 25 of 33

READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE

PATIENT MEDICATION INFORMATION

STATEX

®

morphine sulfate oral drops, suppositories, oral syrup and tablets

Read this carefully before you start taking STATEX and each time you get a refill. 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

STATEX.

Serious Warnings and Precautions

Even if you take STATEX as prescribed you are at a risk for opioid addiction, abuse

and misuse. This can lead to overdose and death.

When you take STATEX tablets it must be swallowed whole. Do not cut, break, crush,

chew, dissolve the tablet. This can be dangerous and can lead to death or seriously

harm you.

You may get life-threatening breathing problems while taking STATEX. 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.

You should never give anyone your STATEX. They could die from taking it. If a

person has not been prescribed STATEX, taking even one dose can cause a fatal

overdose. This is especially true for children.

If you took STATEX 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.

You should not take STATEX with alcohol. This can be dangerous and can lead to

death or seriously harm you.

Taking STATEX 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.

Product monograph STATEX

®

Page 26 of 33

What is STATEX used for?

STATEX is used to manage your pain.

How does STATEX work?

STATEX 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 STATEX?

Medicinal ingredient: morphine sulfate

Non-medicinal ingredients:

Drops and unflavoured syrup: citric acid anhydrous, dextrose monohydrate, glycerine, sodium

benzoate, sodium cyclamate, propylene glycol, water.

Orange flavoured syrup: citric acid anhydrous, glycerine, orange extract, propylene glycol,

sodium benzoate, sucrose, water.

Suppositories: hydrogenated vegetable oil

Tablets: FD&C Blue No.1 Lake (5mg, 10mg), FD&C red #3 Lake (25mg, 50mg), lactose

monohydrate, lake blend yellow (5mg, 50mg), magnesium stearate, microcrystalline cellulose

STATEX comes in the following dosage forms:

STATEX is available in oral drops (50 mg/mL), suppositories (5, 10, 20, 30 mg), syrup (1, 5

mg/mL) and tablets (5, 10, 25 and 50 mg).

Do not use STATEX if:

your doctor did not prescribe it for you

you are allergic to morphine sulfate or any of the other ingredients in STATEX.

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.

Product monograph STATEX

®

Page 27 of 33

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

before you take STATEX. 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.

have a biliary tract disorder.

are pregnant or planning to become pregnant.

suffer from migraines.

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. STATEX can then cause life-threatening breathing

problems in your unborn baby or nursing infant. Your doctor will determine if the benefits of

using STATEX outweigh the risks to your unborn baby or nursing infant.

If you are pregnant and are taking STATEX, 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 STATEX. 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 STATEX. STATEX 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

Product monograph STATEX

®

Page 28 of 33

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 STATEX.

Serotonin Syndrome: STATEX 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 STATEX 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;

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 STATEX:

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

alcohol. Do not drink alcohol while you are taking STATEX. 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 STATEX;

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 STATEX 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;

warfarin (such as coumadin) and other anticoagulants (used for prevention or treatment

of blood clots);

Product monograph STATEX

®

Page 29 of 33

some heart medication (such as beta blockers);

antimuscarinic medicine;

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

St. John’s Wort.

How to take STATEX:

STATEX drops, syrup and tablets are not indicated for rectal administration

Swallow STATEX tablets whole. Do not cut, break, crush, chew or dissolve the tablet. This

can be dangerous and can lead to death or seriously harm you.

You can take your dose of STATEX with or without food. You can take you STATEX tablet

with a glass of water.

To improve the taste, you can dilute STATEX oral unflavoured drops and syrup in a glass of

fruit juice just before taking your dose.

You should place your STATEX suppository against the rectal mucosa. The medicine will not be

absorbed if you push the suppository into a mass of stool or if you place it in the anal canal.

Usual Adult Starting Dose:

Your dose is tailored/personalized just for you. Be sure to follow your doctor’s dosing

instructions exactly. Do not increase or decrease your dose without consulting your doctor.

Your doctor will prescribe the lowest dose that works to control your pain and 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 STATEX. Be sure to

use STATEX only for the condition for which it was prescribed.

If your pain increases or you develop any side effect as a result of taking STATEX, tell your

doctor immediately.

Stopping your Medication

If you have been taking STATEX 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 STATEX.

You should do it slowly to avoid uncomfortable symptoms such as having:

body aches;

diarrhea;

goosebumps;

loss of appetite;

Product monograph STATEX

®

Page 30 of 33

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;

an unexplained fever;

heart palpitations;

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 STATEX.

Refilling your Prescription for STATEX:

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

Therefore, it is important that you contact your doctor before your current supply runs out.

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 STATEX, 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;

cold or clammy skin;

low muscle tone.

Product monograph STATEX

®

Page 31 of 33

Missed Dose:

If you miss one dose, take your next dose at the scheduled time as usual. Do not take two doses

at once. If you miss several doses in a row, talk to your doctor before restarting your medication.

What are possible side effects from using STATEX?

These are not all the possible side effects you may feel when taking STATEX. 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

STATEX.

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,

Product monograph STATEX

®

Page 32 of 33

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.

Storage:

Store all preparations between 15-30

C in a well closed light resistant container.

Keep unused or expired STATEX in a secure place to prevent theft, misuse or

accidental exposure.

Keep STATEX 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 STATEX, get emergency help right away.

Product monograph STATEX

®

Page 33 of 33

Disposal:

STATEX should never be thrown into household trash, where children and pets may find

it. It should be returned to a pharmacy for proper disposal.

If you want more information about STATEX:

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); the manufacturer’s website www.paladinlabs.com,

or by calling 1-888-867-7426.

This leaflet was prepared by Paladin Labs Inc.

Last Revised: August 2, 2019.

Similar products

Search alerts related to this product

Share this information