ADVERSE REACTIONS
Serious adverse reactions that may be associated with KADIAN® 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® 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® 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® 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® 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®, 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® 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® 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®
The safety of KADIAN® 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
®
is a mu-agonist opioid with an abuse
liability similar to other opioid agonists and is a Schedule II controlled
substance. KADIAN
®
and other opioids used in analgesia can be abused and are subject to
criminal diversion.
KADIAN® 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®, 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
®
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.
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