Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

KADIAN (NDA-020616)

(MORPHINE SULFATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

Expand all

03/04/2021 (SUPPL-65)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Addiction, Abuse, and Misuse

Additions and/or revisions underlined:

… Patients at increased risk may be prescribed opioids such as KADIAN, but use in such patients necessitates intensive counseling about the risks and proper use of KADIAN along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].

5.3 Life-Threatening Respiratory Depression

Additions and/or revisions underlined:

… Accidental ingestion of even one dose of KADIAN, especially by children, can result in respiratory depression and death due to an overdose of morphine.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17)].

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.5)].

Newly added information:

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with KADIAN. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17)].

Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [see Warnings and Precautions (5.1, 5.5), Patient Counseling Information (17)].

5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Additions and/or revisions underlined:

… 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.

If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].

6 Adverse Reactions

Additions and/or revisions underlined in bulleted line listing:

Risks from Concomitant Use with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.5)]
Risks of Use in Patients with Gastrointestinal Conditions [see Warnings and Precautions (5.11)]
Increased Risk of Seizures in Patients with Seizure Disorders [see Warnings and Precautions (5.12)]

7 Drug Interactions

Table 1: Clinically Significant Drug Interactions with KADIAN

Benzodiazepines and Other Central Nervous System (CNS) Depressants

Under Intervention, the following language is added:

If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.1, 5.3, 5.5)].

Muscle Relaxants

Under Intervention, the following language is added:

Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3, 5.5)]

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Important information about KADIAN:

Additions and/or revisions underlined:

Get emergency help or call 911 right away if you take too much KADIAN (overdose). When you first start taking KADIAN, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Talk to your healthcare provider about naloxone, a medicine for the emergency treatment of an opioid overdose.

Before taking KADIAN, tell your healthcare provider if you have a history of:

abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems.

Tell your healthcare provider if you are:

living in a household where there are small children or someone who has abused street or prescription drugs

Get emergency medical help or call 911 right away if you have: …

PATIENT COUNSELING INFORMATION

Life-Threatening Respiratory Depression

Newly added information:

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with KADIAN. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see Dosage and Administrations (2.2), Warnings and Precautions (5.3)].Educate patients and caregivers on how to recognize the signs and symptoms of an overdose.

Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see Overdosage (10)].

If naloxone is prescribed, also advise patients and caregivers:

How to treat with naloxone in the event of an opioid overdose
To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency
To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do.

10/07/2019 (SUPPL-63)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Life-Threatening Respiratory Depression

Newly added information to end of subsection:

Additions and/or revisions underlined:

5.13 Withdrawal

Do not abruptly discontinue KADIAN in a patient physically dependent on opioids. When discontinuing KADIAN in a physically dependent patient, gradually taper the dosage. Rapid tapering of morphine in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain.

Additionally, avoid the use of mixed agonist/antagonist …

7 Drug Interactions

Table 1: Clinically Significant Drug Interactions with KADIAN

Serotonergic Drugs

Additions and/or revisions underlined:

Example: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined in bulleted information:

Important information about KADIAN:

Store KADIAN securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.

When taking KADIAN:

Dispose of expired, unwanted, or unused KADIAN by promptly flushing down the toilet, if a drug take-back option is not readily available. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.

PATIENT COUNSELING INFORMATION

Storage and Disposal:

Additions and/or revisions underlined:

Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store KADIAN securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving KADIAN unsecured can pose a deadly risk to others in the home.

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused KADIAN should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit

www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Newly added titled section:

Important Discontinuation Instructions

In order to avoid developing withdrawal symptoms, instruct patients not to discontinue KADIAN without first discussing a tapering plan with the prescriber.

09/18/2018 (SUPPL-62)

Approved Drug Label (PDF)

Boxed Warning

(Additions and/or revisions are underlined)

WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

KADIAN exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing KADIAN, and monitor all patients regularly for the development of these behaviors and conditions.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to

complete a REMS-compliant education program,
counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
consider other tools to improve patient, household, and community safety.

5 Warnings and Precautions

5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

(Additions and/or revisions are underlined)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:

Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.
To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.

12/16/2016 (SUPPL-57)

Approved Drug Label (PDF)

Boxed Warning

(Additions and/or revisions are underlined)

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES AND OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse

Life-Threatening Respiratory Depression

…Instruct patients to swallow KADIAN capsules whole or to sprinkle the contents of the capsule on applesauce and swallow immediately without chewing. Crushing, chewing, or dissolving the pellets in KADIAN capsules can cause rapid release and absorption of a potentially fatal dose of morphine.

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.

Reserve concomitant prescribing of KADIAN Injection 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.

4 Contraindications

(Additions and/or revisions are underlined)

KADIAN is contraindicated in patients with

Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days
Known or suspected gastrointestinal obstruction, including paralytic ileus

5 Warnings and Precautions

5.1 Addiction, Abuse, and Misuse

(Additions and/or revisions are underlined)

…Because extended-release products such as KADIAN deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of morphine present.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing KADIAN, and monitor all patients receiving KADIAN for the development of these behaviors and conditions…

5.10 Risks of Use in Patients with Gastrointestinal Conditions

(Revised subsection title; Additions and/or revisions are underlined)

KADIAN is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus…

5.11 Increased Risk of Seizures in Patients with Seizure Disorders

(Revised subsection title; Additions and/or revisions are underlined)

The morphine in KADIAN may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures…

5.13 Risks of Driving and Operating Machinery

(Revised subsection title)

5.2 Life Threatening Respiratory Depression

(Additions and/or revisions are underlined)

…Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases of KADIAN.

5.3 Neonatal Opioid Withdrawal Syndrome

(Additions and/or revisions are underlined)

…Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly…

5.4 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

(Revised subsection title; Additions and/or revisions are underlined)

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of KADIAN with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

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.

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 KADIAN is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs…

5.5 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

(Revised subsection title; Additions and/or revisions are underlined)

The use of KADIAN in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: KADIAN-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of KADIAN…

5.6 Interaction with Monoamine Oxidase Inhibitors

(Newly added subsection title; Additions and/or revisions are underlined)

Monoamine oxidase inhibitors (MAOIs) may potentiate the effects of morphine, including respiratory depression, coma, and confusion…

5.7 Adrenal Insufficiency

(Newly added subsection)

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.

5.8 Severe Hypotension

(Revised subsection title)

5.9 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

(Revised subsection title)

6 Adverse Reactions

(Additions and/or revisions are underlined)

The following serious adverse reactions are described, or described in greater detail, in other sections:

Interactions with Benzodiazepine or Other CNS Depressants
Adrenal Insufficiency
Severe Hypotension
Gastrointestinal Adverse Reactions
Withdrawal

6.2 Post-Marketing Experience

(Additions and/or revisions are underlined)

The following adverse reactions have been identified during post approval use of morphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.

7 Drug Interactions

(Additions and/or revisions are underlined)

Table 1 includes clinically significant drug interactions with KADIAN (Table has been added; please refer to label)

8 Use in Specific Populations

8.1 Pregnancy

(Pregnancy and Lactation Labeling Rule (PLLR) Conversion: Extensive changes; please refer to label)

8.2 Lactation

(Additions and/or revisions are underlined; Pregnancy and Lactation Labeling Rule (PLLR) Conversion)

Risk Summary

Morphine is present in breast milk. Published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine AUC ratio of 2.5:1 measured in one lactation study. However, there is insufficient information to determine the effects of morphine on the breastfed infant and the effects of morphine on milk production. Lactation studies have not been conducted with extended –release morphine, including KADIAN.

Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with KADIAN.

Clinical Considerations

Monitor infants exposed to KADIAN through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped.

8.3 Females and Males of Reproductive Potential

(Additions and/or revisions are underlined; Pregnancy and Lactation Labeling Rule (PLLR) Conversion)

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

In published animal studies, morphine administration adversely effected fertility and reproductive endpoints in male rats and prolonged estrus cycle in female rats.

8.5 Geriatric Use

(Additions and/or revisions are underlined)

…Elderly patients (aged 65 years or older) may have increased sensitivity to morphine. In general, use caution when selecting a dosage for an elderly patient, 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.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of KADIAN slowly in geriatric patients and monitor for signs of central nervous system and respiratory depression.

Morphine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Hepatic Impairment

(Newly added subsection)

Morphine pharmacokinetics have been reported to be significantly altered in patients with cirrhosis. Start these patients with a lower than usual dosage of KADIAN and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.

8.7 Renal Impairment

(Newly added subsection)

Morphine pharmacokinetics are altered in patients with renal failure. Start these patients with a lower than usual dosage of KADIAN and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instruction for use).

Addiction, Abuse, and Misuse

Inform patients that the use of KADIAN, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death…

Interactions with Alcohol

Instruct patients not to consume alcoholic beverages, or prescription and non-prescription products that contain alcohol, during treatment with KADIAN. The co-ingestion of alcohol with KADIAN may result in increased plasma levels and a potentially fatal overdose of morphine.

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications.

MAOI Interaction

Inform patients not to take KADIAN while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking KADIAN.

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms.

Important Administration Instructions

Instruct patients how to properly take KADIAN, including the following:

Swallow KADIAN capsules whole or sprinkling the capsule contents on applesauce and then swallow immediately without chewing
DO not crush, chew, or dissolve the pellets contained in the capsules due to a risk of fatal morphine overdose

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of KADIAN during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that KADIAN can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy.

Lactation

Advise patients that breastfeeding is not recommended during treatment with KADIAN.

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible.

For all medical inquiries contact: Allergan USA, Inc.

Medical Communications

1-800-678-1605

Distributed By: Allergan USA, Inc. Irvine, CA 92612

Medication Guide

(Additions and/or revisions are underlined)

Important information about KADIAN:

Taking KADIAN 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.

Tell your healthcare provider if you are:

breastfeeding. Not recommended during treatment with KADIAN

When taking KADIAN:

Do not change your dose. Take KADIAN exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.

Get emergency medical help if you have:

trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.