Source: FDA, National Drug Code (US) Revision Year: 2019
KADIAN is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Limitations of Use:
KADIAN should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
KADIAN 100 mg and 200 mg capsules, a single dose greater than 60 mg, or a total daily dose greater than 120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.
Instruct patients to swallow KADIAN capsules whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving the pellets in KADIAN capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].
Instruct patients who are unable to swallow KADIAN capsules to sprinkle the capsule contents on applesauce and immediately swallow without chewing [see Dosage and Administration (2.5)].
KADIAN is administered orally at a frequency of either once daily (every 24 hours) or twice daily (every 12 hours).
There has been no evaluation of KADIAN 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, begin treatment using an immediate-release morphine formulation and then convert patients to KADIAN as described below.
The starting dose for patients who are not opioid tolerant is KADIAN 30 mg orally every 24 hours.
Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.
Discontinue all other around-the-clock opioid drugs when KADIAN therapy is initiated.
There are no established conversion ratios from other opioids to KADIAN defined by clinical trials. Initiate dosing using KADIAN 30 mg orally every 24 hours.
It is safer to underestimate a patient’s 24-hour oral morphine dosage and provide rescue medication (e.g. immediate-release morphine) than to overestimate the 24-hour oral morphine dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and formulations.
Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to KADIAN.
Patients receiving other oral morphine formulations may be converted to KADIAN by administering one-half of the patient’s total daily oral morphine dose as KADIAN twice daily or by administering the total daily oral morphine dose as KADIAN once daily. There are no data to support the efficacy or safety of prescribing KADIAN more frequently than every 12 hours.
KADIAN is not bioequivalent to other extended-release morphine preparations. Conversion from the same total daily dose of another extended-release morphine product to KADIAN may lead to either excessive sedation at peak or inadequate analgesia at trough. Therefore, monitor patients closely when initiating KADIAN therapy and adjust the dosage of KADIAN as needed.
When converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to KADIAN, consider the following general points:
Parenteral to Oral Morphine Ratio:
Between 2 mg and 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of oral morphine that is three times the daily parenteral morphine requirement is sufficient.
Other Oral or Parenteral Opioids to Oral Morphine Ratios:
Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine.
Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.
Individually titrate KADIAN to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving KADIAN to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.
Patients who experience breakthrough pain may require a dosage adjustment of KADIAN, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the KADIAN dosage. In patients experiencing inadequate analgesia with once daily dosing of KADIAN, consider a twice daily regimen. Because steady-state plasma concentrations are approximated within 24 to 36 hours, KADIAN dosage adjustments may be done every 1 to 2 days.
If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
Do not abruptly discontinue KADIAN in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.
When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking KADIAN, there are a variety of factors that should be considered, including the dose of KADIAN the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist.
There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on KADIAN who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.13), Drug Abuse and Dependence (9.3)].
KADIAN capsules must be taken whole. Crushing, chewing, or dissolving the pellets in KADIAN capsules will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].
Alternatively, the contents of the KADIAN capsules (pellets) may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to:
The contents of the KADIAN capsules (pellets) may be administered through a French gastrostomy tube.
Do not administer KADIAN pellets through a nasogastric tube.
Acute overdosage with KADIAN can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.
In cases of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.
The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to morphine overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to morphine overdose.
Because the duration of reversal would be expected to be less than the duration of action of morphine in KADIAN, carefully monitor the patient until spontaneous respiration is reliably reestablished. KADIAN will continue to release morphine add to the morphine load for 24 to 48 hours or longer following ingestion, necessitating prolonged monitoring. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.
In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Dispense in a sealed tamper-evident, childproof, light-resistant container.
Store KADIAN securely and dispose of properly [see Patient Counseling Information (17)].
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
