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[see OVERDOSAGE WARNINGS
AND PRECAUTIONS (5) ].
The common adverse events seen on initiation of therapy with EMBEDA 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.
Short-Term (12-Week) Randomized
Study
Adverse reactions observed in at least 2% of subjects
treated with EMBEDA
This study utilized an enriched enrollment with a randomized withdrawal
design in which subjects were titrated to effect on open-label EMBEDA for up to
45 days. Once their pain was controlled, subjects were randomized to either
active treatment with EMBEDA or were tapered off EMBEDA using a double-dummy
design and placed on placebo. The Maintenance Period was 12 weeks. The most
common adverse reactions leading to study discontinuation were nausea,
constipation, vomiting, fatigue, dizziness, pruritus, and somnolence. Adverse
reactions, defined as treatment-related adverse events assessed by the
investigators, reported by greater than or equal to 2.0% of subjects in either the titration or
maintenance phase of the 12-week study are presented in Table 1.
Long-Term Open-Label Safety
Study
In the long-term open-label safety study, 465 patients with chronic
non-malignant pain were enrolled and 124 patients were treated for up to 1 year.
The distributions of adverse events were similar to that of the randomized,
controlled studies, and were consistent with the most common opioid related
adverse events. Adverse reactions, defined as treatment-related adverse events
assessed by the investigators, reported by greater than or equal to
2.0% of subjects are presented in Table 2.
Adverse Reactions Observed in the
Phase 2/3 Studies
Most common (greater than 10%): constipation, nausea, somnolence
Common (greater than or equal to 1% to less than 10%): vomiting, headache, dizziness, pruritus, dry mouth,
diarrhea, fatigue, insomnia, hyperhidrosis, anxiety, chills, abdominal pain,
lethargy, edema peripheral, dyspepsia, anorexia, muscle spasms, depression,
flatulence, restlessness, decreased appetite, irritability, stomach discomfort,
tremor, arthralgia, hot flush, sedation
Adverse Reactions Observed in the
Phase 2/3 Studies
Most common (greater than or equal to 10%):
Gastrointestinal disorders: constipation, nausea;
Nervous system disorders: somnolence.
Common (greater than or equal to 1% to less than 10%):
Gastrointestinal disorders: abdominal pain,
diarrhea, dry mouth, dyspepsia, flatulence, stomach discomfort, vomiting;
General disorders and administration site
conditions: chills, edema peripheral, fatigue, irritability;
Metabolism and nutrition disorders: anorexia,
decreased appetite;
Musculoskeletal and connective tissue disorders:
arthralgia, muscle spasms;
Nervous system disorders: dizziness, headache,
lethargy, sedation, tremor;
Psychiatric disorders: anxiety, depression,
insomnia, restlessness;
Skin and subcutaneous tissue disorders:
hyperhidrosis, pruritus;
Vascular disorders: hot flush.
Less Common (less than 1%):
Eye disorders: vision blurred, orthostatic
hypotension;
Gastrointestinal disorders: abdominal distension,
pancreatitis, abdominal discomfort, fecaloma, abdominal pain lower, abdominal
tenderness;
General disorders and administration site
conditions: malaise, asthenia, feeling jittery, drug withdrawal
syndrome;
Hepatobiliary disorders: cholecystitis;
Investigations: alanine aminotransferase
increased, aspartate aminotransferase increased;
Musculoskeletal and connective tissue disorders:
myalgia, muscular weakness;
Nervous system disorders: depressed level of
consciousness, mental impairment, memory impairment, disturbance in attention,
stupor, paraesthesia, coordination abnormal;
Psychiatric disorders: disorientation, thinking
abnormal, mental status changes, confusional state, euphoric mood,
hallucination, abnormal dreams, mood swings, nervousness;
Renal and urinary disorders: urinary retention,
dysuria;
Reproductive system and breast disorders: erectile
dysfunction;
Respiratory, thoracic and mediastinal disorders:
dyspnea, rhinorrhoea;
Skin and subcutaneous tissue disorders: rash,
piloerection, cold sweat, night sweats;
Vascular disorders: hypotension, flushing.
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