İHALE DÜNYASI
İHALE DÜNYASI
KADIAN (R) (morphine sulfate) capsules are an opioid analgesic supplied in 10 mg, 20 mg, 30 mg, 50 mg, 60 mg, 80 mg, 100 mg, and 200 mg strengths for oral administration. Chemically, morphine sulfate is 7,8-didehydro-4,5 ?-epoxy-17-methyl-morphinan-3,6 ?-diol sulfate (2:1) (salt) pentahydrate and has the following structural formula: Morphine sulfate is an odorless, white, crystalline powder with a bitter taste and a molecular weight of 758 (as the sulfate). It has a solubility of 1 in 21 parts of water and 1 in 1000 parts of alcohol, but is practically insoluble in chloroform or ether. The octanol: water partition coefficient of morphine is 1.42 at physiologic pH and the pK b is 7.9 for the tertiary nitrogen (mostly ionized at pH 7.4). Each KADIAN (R) extended-release capsule contains either 10 mg, 20 mg, 30 mg, 50 mg, 60 mg, 80 mg, 100 mg, or 200 mg of Morphine Sulfate USP and the following inactive ingredients common to all strengths: hypromellose, ethylcellulose, methacrylic acid copolymer, polyethylene glycol, diethyl phthalate, talc, corn starch, and sucrose. The capsule shells contain gelatin, silicon dioxide, sodium lauryl sulfate, titanium dioxide, and black ink, D and C red #28, FD and C blue #1 (10 mg), D and C yellow #10 (20 mg), FD and C red #3, FD and C blue #1 (30 mg), D and C red #28, FD and C red #40, FD and C blue #1 (50 mg), D and C red #28, FD and C red #40, FD and C blue #1 (60 mg), FD and C blue #1, FD and C red #40, FD and C yellow #6 (80 mg), D and C yellow #10, FD and C blue #1 (100 mg), black iron oxide, yellow iron oxide, red iron oxide (200 mg). Structure Image
KADIAN (R) 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 (see CLINICAL PHARMACOLOGY ). KADIAN (R) Capsules are NOT intended for use as a prn analgesic. KADIAN (R) is not indicated for pain in the immediate postoperative period (the first 12-24 hours following surgery), or if the pain is mild or not expected to persist for an extended period of time. KADIAN (R) is only indicated for postoperative use if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate. (See American Pain Society guidelines.)
KADIAN (R) may be administered once or twice daily. KADIAN (R) capsules should be swallowed whole. The pellets in KADIAN (R) capsules should not be chewed, crushed, or dissolved due to the risk of rapid release and absorption of a potentially fatal dose of morphine. Alternatively, KADIAN (R) capsules may be administered as a sprinkle on apple sauce or through a 16 French gastrostomy tube (see ALTERNATIVE METHODS OF ADMINISTRATION section). The 100 mg and 200 mg capsules are for use only in opioid-tolerant patients. KADIAN (R) is not indicated for pre-emptive analgesia (administration pre-operatively for the management of post-operative pain), or for pain in the immediate post-operative period (the first 12 to 24 hours following surgery) for patients not previously taking the drug, because its safety in these settings have not been established. KADIAN (R) is only indicated for post-operative use if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Patients who are already receiving KADIAN (R) Capsules as part of ongoing analgesic therapy may be safely continued on the drug if appropriate dosage adjustments are made considering the procedure, other drugs given, and the temporary changes in physiology caused by the surgical intervention. Initiating Therapy with KADIAN (R) Capsules Physicians should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Health care professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring. It is critical to adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. In the selection of the initial dose of KADIAN (R) , attention should be given to: the total daily dose, potency and kind of opioid the patient has been taking previously; the reliability of the relative potency estimate used to calculate the equivalent dose of morphine needed (Note: potency estimates may vary with the route of administration); the patient's degree of opioid experience and opioid tolerance; the general condition and medical status of the patient; concurrent medication; the type and severity of the patient's pain. Care should be taken to use low initial doses of KADIAN (R) in patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications ( see PRECAUTIONS ). During periods of changing analgesic requirements including initial titration, frequent communication is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family. The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of an individual patient. Conversion from Other Oral Morphine Formulations to KADIAN (R) Patients on other oral morphine formulations may be converted to KADIAN (R) by administering one-half of the patient's total daily oral morphine dose as KADIAN (R) capsules every 12 hours (twice-a-day) or by administering the total daily oral morphine dose as KADIAN (R) capsules every 24 hours (once-a-day). KADIAN (R) should not be given more frequently than every 12 hours. Conversion from Parenteral Morphine or Other Parenteral or Oral Opioids to KADIAN (R) KADIAN (R) can be administered to patients previously receiving treatment with parenteral morphine or other opioids. While there are useful tables of oral and parenteral equivalents in cancer analgesia, there is substantial interpatient variation in the relative potency of different opioid drugs and formulations. For these reasons, it is better to underestimate the patient's 24-hour oral morphine requirement and provide rescue medication, than to overestimate and manage an adverse event. The following general points should be considered: Parenteral to Oral Morphine Ratio: It may take anywhere from 2-6 mg of oral morphine to provide analgesia equivalent to 1 mg of parenteral morphine. A dose of oral morphine three times the daily parenteral morphine requirement may be sufficient in chronic use settings. Other Parenteral or Oral Opioids to Oral Morphine Sulfate: There is lack of systematic evidence bearing on these types of analgesic substitutions. Therefore, specific recommendations are not possible. Physicians are advised to refer to published relative potency data, keeping in mind that such ratios are only approximate. In general, it is safest to give half of the estimated daily morphine demand as the initial dose, and to manage inadequate analgesia by supplementation with immediate-release morphine. (See discussion which follows.) The first dose of KADIAN (R) may be taken with the last dose of any immediate-release (short-acting) opioid medication due to the long delay until the peak effect after administration of KADIAN (R) . Use of KADIAN (R) as the First Opioid Analgesic There has been no evaluation of KADIAN (R) as an initial opioid analgesic in the management of pain. Because it may be more difficult to titrate a patient to adequate analgesia using an extended-release morphine, it is ordinarily advisable to begin treatment using an immediate-release morphine formulation. Individualization of Dosage The best use of opioid analgesics in the management of chronic malignant and non-malignant pain is challenging, and is well described in materials published by the World Health Organization and the Agency for Health Care Policy and. KADIAN (R) is a third step drug which is most useful when the patient requires a constant level of opioid analgesia as a "floor" or "platform" from which to manage breakthrough pain. When a patient has reached the point where comfort cannot be provided with a combination of non-opioid medications (NSAIDs and acetaminophen) and intermittent use of moderate or strong opioids, the patient's total opioid therapy should be converted into a 24 hour oral morphine equivalent. KADIAN (R) should be started by administering one-half of the estimated total daily oral morphine dose every 12 hours (twice-a-day) or by administering the total daily oral morphine dose every 24 hours (once-a-day). The dose should be titrated no more frequently than every-other-day to allow the patients to stabilize before escalating the dose. If breakthrough pain occurs, the dose may be supplemented with a small dose (less than 20% of the total daily dose) of a short-acting analgesic. Patients who are excessively sedated after a once-a-day dose or who regularly experience inadequate analgesia before the next dose should be switched to twice-a-day dosing. Patients who do not have a proven tolerance to opioids should be started only on the 10 mg or 20 mg strength, and usually should be increased at a rate not greater than 20 mg every-other-day. Most patients will rapidly develop some degree of tolerance, requiring dosage adjustment until they have achieved their individual best balance between baseline analgesia and opioid side effects such as confusion, sedation and constipation. No guidance can be given as to the recommended maximal dose, especially in patients with chronic pain of malignancy. In such cases the total dose of KADIAN (R) should be advanced until the desired therapeutic endpoint is reached or clinically significant opioid-related adverse reactions intervene. Alternative Methods of Administration In a study of healthy volunteers, KADIAN (R) pellets sprinkled over apple sauce were found to be bioequivalent to KADIAN (R) capsules swallowed whole with apple sauce under fasting conditions. Other foods have not been tested. Patients who have difficulty swallowing whole capsules or tablets may benefit from this alternative method of administration. Sprinkle the pellets onto a small amount of apple sauce. Apple sauce should be room temperature or cooler. The patient must be cautioned not to chew the pellets which could result in the immediate release of a potentially dangerous, even fatal dose of morphine. Use immediately. Rinse mouth to ensure all pellets have been swallowed. Patients should consume entire portion and should not divide apple sauce into separate doses. The entire capsule contents may alternatively be administered through a 16 French gastrostomy tube. Flush the gastrostomy tube with water to ensure that it is wet. Sprinkle the KADIAN (R) Pellets into 10 mL of water. Use a swirling motion to pour the pellets and water into the gastrostomy tube through a funnel. Rinse the beaker with a further 10 mL of water and pour this into the funnel. Repeat rinsing until no pellets remain in the beaker. THE ADMINISTRATION OF KADIAN (R) PELLETS THROUGH A NASOGASTRIC TUBE SHOULD NOT BE ATTEMPTED. Considerations in the Adjustment of Dosing Regimens If signs of excessive opioid effects are observed early in the dosing interval, the next dose should be reduced. If this adjustment leads to inadequate analgesia, that is, if breakthrough pain occurs when KADIAN (R) is administered on an every 24 hours dosing regimen, consideration should be given to dosing every 12 hours. If breakthrough pain occurs on a 12 hour dosing regimen a supplemental dose of a short-acting analgesic may be given. As experience is gained, adjustments in both dose and dosing interval can be made to obtain an appropriate balance between pain relief and opioid side effects. To avoid accumulation the dosing interval of KADIAN (R) should not be reduced below 12 hours. Cessation of Therapy When the patient no longer requires therapy with KADIAN (R) capsules, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient. Conversion from KADIAN (R) to Other Extended-Release Oral Morphine Formulations KADIAN (R) is not bioequivalent to other extended-release morphine preparations. Although for a given dose the same total amount of morphine is available from KADIAN (R) as from morphine solution or extended-release morphine tablets, the slower release of morphine from KADIAN (R) results in reduced maximum and increased minimum plasma morphine concentrations than with shorter acting morphine products. Conversion from KADIAN (R) to the same total daily dose of extended-release morphine preparations may lead to either excessive sedation at peak or inadequate analgesia at trough and close observation and appropriate dosage adjustments are recommended. Conversion from KADIAN (R) to Parenteral Opioids When converting a patient from KADIAN (R) to parenteral opioids, it is best to calculate an equivalent parenteral dose, and then initiate treatment at half of this calculated value. For example, to estimate the required 24 hour dose of parenteral morphine for a patient taking KADIAN (R) , one would take the 24 hour KADIAN (R) dose, divide by an oral to parenteral conversion ratio of 3, divide the estimated 24 hour parenteral dose into six divided doses (for a four hour dosing interval), then halve this dose as an initial trial. For example, to estimate the required parenteral morphine dose for a patient taking 360 mg of KADIAN (R) a day, divide the 360 mg daily oral morphine dose by a conversion ratio of 1 mg of parenteral morphine for every 3 mg of oral morphine. The estimated 120 mg daily parenteral requirement is then divided into six 20 mg doses, and half of this, or 10 mg, is then given every 4 hours as an initial trial dose. This approach is likely to require a dosage increase in the first 24 hours for many patients, but is recommended because it is less likely to cause overdose than trying to establish an equivalent dose without titration. Safety and Handling KADIAN (R) Capsules contain morphine sulfate which is a controlled substance under Schedule II of the Controlled Substances Act. Morphine, like all opioids, is liable to diversion and misuse and should be handled accordingly. Patients and their families should be instructed to flush any KADIAN (R) capsules that are no longer needed. KADIAN (R) may be targeted for theft and diversion by criminals. 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. KADIAN (R) consists of closed hard gelatin capsules containing polymer coated morphine sulfate pellets that pose no known handling risk to health care workers. KADIAN (R) Capsules are liable to diversion and misuse both by the general public and health care workers, and should be handled accordingly.
KADIAN (R) is contraindicated in patients with a known hypersensitivity to morphine, morphine salts or any of the capsule components, or in any situation where opioids are contraindicated. This includes in patients with respiratory depression (in the absence of resuscitative equipment or in unmonitored settings), and in patients with acute or severe bronchial asthma or hypercarbia. KADIAN (R) is contraindicated in any patient who has or is suspected of having paralytic ileus.
Serious adverse reactions that may be associated with KADIAN (R) therapy in clinical use are those observed with other opioid analgesics and include: respiratory depression, respiratory arrest, apnea, circulatory depression, cardiac arrest, hypotension, and/or shock (see OVERDOSAGE , WARNINGS ). The less severe adverse events seen on initiation of therapy with KADIAN (R) are also typical opioid side effects. These events are dose dependent, and their frequency depends on the clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid analgesia. The most frequent of these include drowsiness, dizziness, constipation and nausea. In many cases, the frequency of these events during initiation of therapy may be minimized by careful individualization of starting dosage, slow titration, and the avoidance of large rapid swings in plasma concentrations of the opioid. Many of these adverse events, will cease or decrease as KADIAN (R) therapy is continued and some degree of tolerance is developed, but others may be expected to remain troublesome throughout therapy. Management of Excessive Drowsiness Most patients receiving KADIAN (R) will experience initial drowsiness. This usually disappears within 3-5 days and is not a cause of concern unless it is excessive, or accompanied by unsteadiness or confusion. Dizziness and unsteadiness may be associated with postural hypotension, particularly in elderly or debilitated patients, and has been associated with syncope and falls in non-tolerant patients started on opioids. Excessive or persistent sedation should be investigated. Factors to be considered should include: concurrent sedative medications, the presence of hepatic or renal insufficiency, hypoxia or hypercapnia due to exacerbated respiratory failure, intolerance to the dose used (especially in older patients), disease severity and the patient's general condition. The dosage should be adjusted according to individual needs, but additional care should be used in the selection of initial doses for the elderly patient, the cachectic or gravely ill patient, or in patients not already familiar with opioid analgesic medications to prevent excessive sedation at the onset of treatment. Management of Nausea and Vomiting Nausea and vomiting are common after single doses of KADIAN (R) or as an early undesirable effect of chronic opioid therapy. The prescription of a suitable antiemetic should be considered, with the awareness that sedation may result (see Drug Interactions ). The frequency of nausea and vomiting usually decreases within a week or so but may persist due to opioid-induced gastric stasis. Metoclopramide is often useful in such patients. Management of Constipation Virtually all patients suffer from constipation while taking opioids, such as KADIAN (R) , on a chronic basis. Some patients, particularly elderly, debilitated or bedridden patients may become impacted. Tolerance does not usually develop for the constipating effects of opioids. Patients must be cautioned accordingly and laxatives, softeners and other appropriate treatments should be used prophylactically from the beginning of opioid therapy. Adverse Events Probably Related to KADIAN (R) Administration In clinical studies in patients with chronic cancer pain the most common adverse events reported by patients at least once during therapy were drowsiness (9%), constipation (9%), nausea (7%), dizziness (6%), and anxiety (6%). Other less common side effects expected from KADIAN (R) or seen in less than 3% of patients in the clinical studies were: Body as a Whole: Asthenia, accidental injury, fever, pain, chest pain, headache, diaphoresis, chills, flu syndrome, back pain, malaise, withdrawal syndrome Cardiovascular: Tachycardia, atrial fibrillation, hypotension, hypertension, pallor, facial flushing, palpitations, bradycardia, syncope Central Nervous System: Confusion, dry mouth, anxiety, abnormal thinking, abnormal dreams, lethargy, depression, tremor, loss of concentration, insomnia, amnesia, paresthesia, agitation, vertigo, foot drop, ataxia, hypesthesia, slurred speech, hallucinations, vasodilation, euphoria, apathy, seizures, myoclonus Endocrine: Hyponatremia due to inappropriate ADH secretion, gynecomastia Gastrointestinal: Vomiting, anorexia, dysphagia, dyspepsia, diarrhea, abdominal pain, stomach atony disorder, gastro-esophageal reflux, delayed gastric emptying, biliary colic Hemic and Lymphatic: Anemia, leukopenia, thrombocytopenia Metabolic and Nutritional: Peripheral edema, hyponatremia, edema Musculoskeletal: Back pain, bone pain, arthralgia Respiratory: Hiccup, rhinitis, atelectasis, asthma, hypoxia, dyspnea, respiratory insufficiency, voice alteration, depressed cough reflex, non-cardiogenic pulmonary edema Skin and Appendages: Rash, decubitus ulcer, pruritus, skin flush Special Senses: Amblyopia, conjunctivitis, miosis, blurred vision, nystagmus, diplopia Urogenital: Urinary abnormality, amenorrhea, urinary retention, urinary hesitancy, reduced libido, reduced potency, prolonged labor Post-marketing Adverse Events Probably Related to KADIAN (R) The safety of KADIAN (R) has been evaluated in a randomized, prospective, open-label, 4-week treatment period, post-marketing study consisting of 1418 patients ages 18-85 with chronic, non-malignant pain (e.g., back pain, osteoarthritis, neuropathic pain). No control arm was included in this study. The most common adverse events reported at least once during therapy were constipation (12%), nausea (9%) and somnolence (3%). Other less common side effects occurring in less than 3% of patients were vomiting, pruritus, dizziness, sedation, dry mouth, headache, fatigue and rash. DRUG ABUSE AND DEPENDENCE KADIAN (R) is a mu-agonist opioid with an abuse liability similar to other opioid agonists and is a Schedule II controlled substance. KADIAN (R) and other opioids used in analgesia can be abused and are subject to criminal diversion. KADIAN (R) is an opioid with no approved use in the management of addiction 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. Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. "Drug-seeking" behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated "loss" of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). "Doctor shopping" to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. KADIAN (R) , like other opioids, has been diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. KADIAN (R) is intended for oral use only. Abuse of chewed, crushed, or dissolved capsules or pellets poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances. Due to the presence of talc as one of the excipients in capsules, parenteral abuse can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
KADIAN (R) Capsules are to be swallowed whole and are not to be chewed, crushed, or dissolved. Taking chewed, crushed, or dissolved KADIAN (R) Capsules leads to rapid release and absorption of a potentially fatal dose of morphine. KADIAN (R) 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 (R) 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 (R) in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Abuse of KADIAN (R) 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 (R) 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 (R) 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 (R) 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 (R) 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 (R) may produce orthostatic hypotension and syncope in ambulatory patients. KADIAN (R) , 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 (R) 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 (R) 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. Other Although extremely rare, cases of anaphylaxis have been reported. --- BOXED WARNING: BOXED WARNING KADIAN (R) contains morphine sulfate, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. KADIAN (R) can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing KADIAN (R) in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion. KADIAN (R) 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(R) Capsules are NOT for use as a prn analgesic. KADIAN (R) 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 (R) 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.