DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Kadian (Morphine Sulfate) - Warnings and Precautions



KADIAN ® contains morphine sulfate, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. KADIAN ® can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing KADIAN ® in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.

KADIAN ® capsules are an extended-release oral formulation of morphine sulfate indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.

KADIAN® Capsules are NOT for use as a prn analgesic.

KADIAN ® 100 mg and 200 mg Capsules ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY.  Ingestion of these capsules or of the pellets within the capsules may cause fatal respiratory depression when administered to patients not already tolerant to high doses of opioids.  KADIAN ® CAPSULES ARE TO BE SWALLOWED WHOLE OR THE CONTENTS OF THE CAPSULES SPRINKLED ON APPLE SAUCE.  THE PELLETS IN THE CAPSULES ARE NOT TO BE CHEWED, CRUSHED, OR DISSOLVED DUE TO THE RISK OF RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE.



KADIAN ® Capsules are to be swallowed whole and are not to be chewed, crushed, or dissolved.  Taking chewed, crushed, or dissolved KADIAN ® Capsules leads to rapid release and absorption of a potentially fatal dose of morphine.

KADIAN ® 100 mg and 200 mg Capsules ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY.  This capsule strength may cause fatal respiratory depression when ingested or administered to patients who are not previously exposed to opioids. 

Care should be taken in the prescribing of this capsule strength.  Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death.

Misuse, Abuse and Diversion of Opioids

KADIAN® contains morphine an opioid agonist and a Schedule II controlled substance.  Opioid agonists have the potential for being abused and are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Morphine can be abused in a manner similar to other opioid agonists, legal or illicit.  This should be considered when prescribing or dispensing KADIAN® in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Abuse of KADIAN® by crushing, chewing, snorting or injecting the dissolved product will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND DEPENDENCE)

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.  Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Interactions with Alcohol and Drugs of Abuse

KADIAN® may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, and profound sedation or coma may result.

Impaired Respiration

Respiratory depression is the chief hazard of all morphine preparations.  Respiratory depression occurs more frequently in elderly and debilitated patients, and those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction (when even moderate therapeutic doses may significantly decrease pulmonary ventilation).

KADIAN® should be used with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve (e.g. severe kyphoscoliosis), hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of morphine may increase airway resistance and decrease respiratory drive to the point of apnea.  In these patients, alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of morphine with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increase in intracranial pressure. KADIAN® produces effects which may obscure neurologic signs of further increases in pressure in patients with head injuries.  Morphine should only be administered under such circumstances when considered essential and then with extreme care.

Hypotensive Effect

KADIAN® may cause severe hypotension.  There is an added risk to individuals whose ability to maintain blood pressure has already been compromised by a reduced blood volume, or a concurrent administration of drugs such as phenothiazines or general anesthetics. (See also PRECAUTIONS-Drug Interactions.) KADIAN® may produce orthostatic hypotension and syncope in ambulatory patients.

KADIAN®, like all opioid analgesics, should be administered with caution to patients in circulatory shock, as vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Interactions with other CNS Depressants

KADIAN® should be used with great caution and in reduced dosage in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, and alcohol because respiratory depression, hypotension, and profound sedation or coma may result.

Gastrointestinal Obstruction

KADIAN® should not be given to patients with gastrointestinal obstruction, particularly paralytic ileus, as there is a risk of the product remaining in the stomach for an extended period and the subsequent release of a bolus of morphine when normal gut motility is restored.  As with other solid morphine formulations diarrhea may reduce morphine absorption.


Although extremely rare, cases of anaphylaxis have been reported.



KADIAN® is intended for use in patients who require continuous, around-the-clock opioid analgesia for an extended period of time.  As with any potent opioid, it is critical to adjust the dosing regimen for KADIAN® for each patient, taking into account the patient's prior analgesic treatment experience.  Although it is clearly impossible to enumerate every consideration that is important to the selection of the initial dose of KADIAN®, attention should be given to the points under DOSAGE AND ADMINISTRATION.

Opioid analgesics have a narrow therapeutic index in certain patient populations, especially when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.

Selection of patients for treatment with KADIAN® should be governed by the same principles that apply to the use of any potent opioid analgesics.  Specifically, the increased risks associated with its use in the following populations should be considered: the elderly or debilitated and those with severe impairment of hepatic, pulmonary, or renal function; hypothyroidism; adrenocortical insufficiency (e.g., Addison's Disease); CNS depression or coma; toxic psychosis; prostatic hypertrophy, or urethral stricture; acute alcoholism; delirium tremens; kyphoscoliosis, or inability to swallow.

The administration of KADIAN® may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

KADIAN® may aggravate pre-existing convulsions in patients with convulsive disorders.


Patients taking KADIAN® who are scheduled for cordotomy or other interruption of pain transmission pathways should have KADIAN® ceased 24 hours prior to the procedure and the pain controlled by parenteral short-acting opioids. In addition, the post-procedure titration of analgesics for such patients should be individualized to avoid either oversedation or withdrawal syndromes.

Use in Pancreatic/Biliary Tract Disease

KADIAN® may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids may cause increases in the serum amylase level.

Tolerance and Physical Dependence

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist.  Physical dependence and tolerance are not unusual during chronic opioid therapy.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).

Special Risk Groups

KADIAN® should be administered with caution, and in reduced dosages in elderly or debilitated patients; patients with severe renal or hepatic insufficiency; patients with Addison's disease; myxedema; hypothyroidism; prostatic hypertrophy or urethral stricture.

Caution should also be exercised in the administration of KADIAN® to patients with CNS depression, toxic psychosis, acute alcoholism and delirium tremens, and convulsive disorders.

Driving and Operating Machinery

KADIAN® may impair the mental and/or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.  Patients must be cautioned accordingly.  Patients should also be warned about the potential combined effects of KADIAN® with other CNS depressants, including other opioids, phenothiazines, sedative/hypnotics and alcohol (see Drug Interactions).

Information for Patients

If clinically advisable, patients receiving KADIAN®, or their caregivers should be given the following information by the physician, nurse, or pharmacist:

  1. Patients should be advised that KADIAN® contains morphine and should be taken only as directed.
  2. Patients should be advised that KADIAN® capsules should be swallowed whole (not chewed, crushed, or dissolved). Alternately, KADIAN® capsules may be opened and the entire contents sprinkled on a small amount of apple sauce immediately prior to ingestion. KADIAN® capsules or the contents of the capsules must not be chewed or crushed due to a risk of fatal overdose.
  3. Patients should be advised that KADIAN® 100 mg and 200 mg Capsules are for use only in opioid-tolerant patients.  Special care must be taken to avoid accidental ingestion or use by individuals (including children) other than the patient for whom it was originally prescribed, as such unsupervised use may have severe, even fatal, consequences.
  4. Patients should be advised that the dose of KADIAN® should not be adjusted without consulting the prescribing health care provider.
  5. Patients should be advised to report episodes of breakthrough pain and adverse experiences occurring during therapy.  Individualization of dosage is essential to make optimal use of this medication.
  6. Patients should be advised that KADIAN® may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery).  Patients started on KADIAN® or whose dose has been changed should refrain from dangerous activity until it is established that they are not adversely affected.
  7. Patients should be advised that KADIAN® should not be taken with alcohol or other CNS depressants (sleeping medication, tranquilizers) except by the orders of the prescribing healthcare provider because dangerous additive effects may occur resulting in serious injury or death.
  8. Women of childbearing potential who become or are planning to become pregnant, should consult their prescribing healthcare provider prior to initiating or continuing therapy with KADIAN®.
  9. Patients should be advised that if they have been receiving treatment with KADIAN® for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the KADIAN® dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms.  Their prescribing healthcare provider should provide a dose schedule to accomplish a gradual discontinuation of the medication.
  10. Patients should be advised that KADIAN® is a potential drug of abuse.  They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
  11. Patients should be advised that severe constipation could occur as a result of taking KADIAN® and appropriate laxatives, stool softeners and other appropriate treatments should be initiated from the beginning of opioid therapy.
  12. Patients should be instructed to keep KADIAN® in a secure place out of the reach of children.  When KADIAN® is no longer needed, the unused capsules should be destroyed by flushing down the toilet.

Drug Interactions

CNS Depressants: Morphine should be used with great caution and in reduced dosage in patients who are concurrently receiving other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, other tranquilizers and alcohol because of the risk of respiratory depression, hypotension and profound sedation or coma.  When such combined therapy is contemplated, the initial dose of one or both agents should be reduced by at least 50%.

Muscle Relaxants: KADIAN® may enhance the neuromuscular blocking action of skeletal relaxants and produce an increased degree of respiratory depression.

Mixed Agonist/Antagonist Opioid Analgesics: Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as KADIAN®.  In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of KADIAN® and/or may precipitate withdrawal symptoms in these patients.

Monoamine Oxidase Inhibitors (MAOIs): MAOIs have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant depression of respiration or coma.  KADIAN® should not be used in patients taking MAOIs or within 14 days of stopping such treatment.

Cimetidine:  There is an isolated report of confusion and severe respiratory depression when a hemodialysis patient was concurrently administered morphine and cimetidine.

Diuretics:  Morphine can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.  Morphine may also lead to acute retention of urine by causing spasm of the sphincter of the bladder, particularly in men with prostatism.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate the carcinogenic potential of morphine have not been conducted. There are no reports of carcinogenic effects in humans. In vitro studies have reported that morphine is non-mutagenic in the Ames test with Salmonella, and induces chromosomal aberrations in human leukocytes and lethal mutation induction in Drosophila. Morphine was found to be mutagenic in vitro in human T-cells, increasing the DNA fragmentation. In vivo, morphine was mutagenic in the mouse micronucleus test and induced chromosomal aberrations in spermatids and murine lymphocytes. Chronic opioid abusers (e.g., heroin abusers) and their offspring display higher rates of chromosomal damage. However, the rates of chromosomal abnormalities were similar in nonexposed individuals and in heroin users enrolled in long term opioid maintenance programs.


Teratogenic Effects

(Pregnancy Category C)

Teratogenic effects of morphine have been reported in the animal literature. High parental doses during the second trimester were teratogenic in neurological, soft and skeletal tissue. The abnormalities included encephalopathy and axial skeletal fusions. These doses were often maternally toxic and were 0.3 to 3-fold the maximum recommended human dose (MRHD) on a mg/m2 basis. The relative contribution of morphine-induced maternal hypoxia and malnutrition, each of which can be teratogenic, has not been clearly defined. Treatment of male rats with approximately 3-fold the MRHD for 10 days prior to mating decreased litter size and viability.

Nonteratogenic Effects

Morphine given subcutaneously, at non-maternally toxic doses, to rats during the third trimester with approximately 0.15-fold the MRHD caused reversible reductions in brain and spinal cord volume, and testes size and body weight in the offspring, and decreased fertility in female offspring.  The offspring of rats and hamsters treated orally or intraperitoneally throughout pregnancy with 0.04- to 0.3-fold the MRHD of morphine have demonstrated delayed growth, motor and sexual maturation and decreased male fertility.  Chronic morphine exposure of fetal animals resulted in mild withdrawal, altered reflex and motor skill development, and altered responsiveness to morphine that persisted into adulthood.

There are no well-controlled studies of chronic in utero exposure to morphine sulfate in human subjects. However, uncontrolled retrospective studies of human neonates chronically exposed to other opioids in utero, demonstrated reduced brain volume which normalized over the first month of life.  Infants born to opioid-abusing mothers are more often small for gestational age, have a decreased ventilatory response to CO2 and increased risk of sudden infant death syndrome.  KADIAN® should only be used during pregnancy if the need for strong opioid analgesia justifies the potential risk to the fetus.

Labor and Delivery

KADIAN® is not recommended for use in women during and immediately prior to labor, where shorter acting analgesics or other analgesic techniques are more appropriate.  Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions.  However, this effect is not consistent and may be offset by an increased rate of cervical dilatation which tends to shorten labor.  Neonates whose mothers received opioid analgesics during labor should be observed closely for signs of respiratory depression.  A specific opioid antagonist, such as naloxone or nalmefene, should be available for reversal of opioid-induced respiratory depression in the neonate.

Neonatal Withdrawal Syndrome

Chronic maternal use of opiates or opioids during pregnancy coexposes the fetus. The newborn may experience subsequent neonatal withdrawal syndrome (NWS).  Manifestations of NWS include irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, weight loss, and failure to gain weight.  The onset, duration, and severity of the disorder differ based on such factors as the addictive drug used, time and amount of mother’s last dose, and rate of elimination of the drug from the newborn.  Approaches to the treatment of this syndrome have included supportive care and, when indicated, drugs such as paregoric or phenobarbital.

Nursing Mothers

Low levels of morphine sulfate have been detected in human milk.  Withdrawal symptoms can occur in breast-feeding infants when maternal administration of morphine sulfate is stopped.  Because of the potential for adverse reactions in nursing infants from KADIAN®, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety of KADIAN®, both the entire capsule and the pellets sprinkled on apple sauce, have not been directly investigated in pediatric patients below the age of 18 years.  The range of doses available is not suitable for the treatment of very young pediatric patients or those who are not old enough to take capsules safely.  The apple sauce sprinkling method is not an appropriate alternative for these patients.

Geriatric Use

Clinical studies of KADIAN® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Page last updated: 2013-02-08

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017