ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in
the labeling:
- Addiction, Abuse, and Misuse [see Warnings and Precautions ]
- Life-Threatening Respiratory Depression [see Warnings
and Precautions]
- QTc Prolongation [see Warnings and Precautions ]
- Neonatal Opioid Withdrawal Syndrome [see Warnings
and Precautions]
- Hypotensive Effects [see Warnings and Precautions ]
- Interactions with Other CNS Depressants [see Warnings
and Precautions]
- Application Site Skin Reactions [see Warnings and
Precautions ]
- Anaphylactic/Allergic Reactions [see Warnings and
Precautions]
- Gastrointestinal Effects [see Warnings and Precautions ]
- Seizures [see Warnings and Precautions]
Clinical Trial Experience
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical
trials of a drug cannot be directly compared to rates in the clinical
trials of another drug and may not reflect the rates observed in practice.
A total of 5,415 patients were treated
with BUTRANS in controlled and open-label chronic pain clinical trials.
Nine hundred twenty-four subjects were treated for approximately
six months and 183 subjects were treated for approximately one year.
The clinical trial population consisted of patients with persistent
moderate to severe pain.
The
most common serious adverse drug reactions (all <0.1%) occurring
during clinical trials with BUTRANS were: chest pain, abdominal pain,
vomiting, dehydration, and hypertension/blood pressure increased.
The most common adverse events (≥ 2%) leading
to discontinuation were: nausea, dizziness, vomiting, headache, and
somnolence.
The most common adverse
reactions (≥ 5%) reported by patients in clinical trials comparing
BUTRANS 10 or 20 mcg/hour to placebo are shown in Table 2, and comparing
BUTRANS 20 mcg/hour to BUTRANS 5 mcg/hour are shown in Table 3 below:
Table 2: Adverse Reactions Reported in ≥ 5% of Patients during
the Open-Label Titration Period and Double-Blind Treatment Period:
Opioid-Naïve Patients
| |
Open-Label
Titration
Period
|
Double-Blind
Treatment Period
|
| |
BUTRANS
|
BUTRANS
|
Placebo
|
|
MedDRA Preferred Term
|
(N = 1024)
|
(N = 256)
|
(N = 283)
|
| Nausea |
23% |
13% |
10% |
| Dizziness |
10% |
4% |
1% |
| Headache |
9% |
5% |
5% |
| Application site pruritus |
8% |
4% |
7% |
| Somnolence |
8% |
2% |
2% |
| Vomiting |
7% |
4% |
1% |
| Constipation |
6% |
4% |
1% |
Table 3: Adverse Reactions Reported in ≥ 5% of Patients during
the Open-Label Titration Period and Double-Blind Treatment Period:
Opioid-Experienced Patients
| |
Open-Label
Titration
Period
|
Double-Blind
Treatment Period
|
| |
BUTRANS
|
BUTRANS 20
|
BUTRANS 5
|
|
MedDRA Preferred Term
|
(N = 1160)
|
(N = 219)
|
(N = 221)
|
| Nausea |
14% |
11% |
6% |
| Application site pruritus |
9% |
13% |
5% |
| Headache |
9% |
8% |
3% |
| Somnolence |
6% |
4% |
2% |
| Dizziness |
5% |
4% |
2% |
| Constipation |
4% |
6% |
3% |
| Application site erythema |
3% |
10% |
5% |
| Application site rash |
3% |
8% |
6% |
| Application site irritation |
2% |
6% |
2% |
The following table lists adverse
reactions that were reported in at least 2.0% of patients in four
placebo/active-controlled titration-to-effect trials.
Table 4: Adverse Reactions Reported in Titration-to-Effect
Placebo/Active-Controlled Clinical Trials with Incidence ≥ 2%
|
MedDRA Preferred Term
|
BUTRANS
(N = 392)
|
Placebo
(N = 261)
|
| Nausea |
21% |
6% |
| Application site pruritus |
15% |
12% |
| Dizziness |
15% |
7% |
| Headache |
14% |
9% |
| Somnolence |
13% |
4% |
| Constipation |
13% |
5% |
| Vomiting |
9% |
1% |
| Application site erythema |
7% |
2% |
| Application site rash |
6% |
6% |
| Dry mouth |
6% |
2% |
| Fatigue |
5% |
1% |
| Hyperhidrosis |
4% |
1% |
| Peripheral edema |
3% |
1% |
| Pruritus |
3% |
0% |
| Stomach discomfort |
2% |
0% |
The adverse reactions seen in controlled
and open-label studies are presented below in the following manner:
most common (≥ 5%), common (≥ 1% to < 5%), and less common (<
1%).
The most common adverse
reactions (≥ 5%) reported by patients treated with BUTRANS in the
clinical trials were nausea, headache, application site pruritus,
dizziness, constipation, somnolence, vomiting, application site erythema,
dry mouth, and application site rash.
The common (≥ 1% to < 5%) adverse reactions reported
by patients treated with BUTRANS in the clinical trials organized
by MedDRA (Medical Dictionary for Regulatory Activities) System Organ
Class were:
Gastrointestinal
disorders: diarrhea, dyspepsia, and upper abdominal pain
General disorders and administration
site conditions: fatigue, peripheral edema, application site
irritation, pain, pyrexia, chest pain, and asthenia
Infections and infestations: urinary
tract infection, upper respiratory tract infection, nasopharyngitis,
influenza, sinusitis, and bronchitis
Injury, poisoning and procedural complications: fall
Metabolism and
nutrition disorders: anorexia
Musculoskeletal and connective tissue disorders: back pain, arthralgia, pain in extremity, muscle spasms, musculoskeletal
pain, joint swelling, neck pain, and myalgia
Nervous system disorders: hypoesthesia,
tremor, migraine, and paresthesia
Psychiatric disorders: insomnia, anxiety, and depression
Respiratory, thoracic and mediastinal
disorders: dyspnea, pharyngolaryngeal pain, and cough
Skin and subcutaneous tissue disorders: pruritus, hyperhidrosis, rash, and generalized pruritus
Vascular disorders: hypertension
Other less common adverse reactions, including
those known to occur with opioid treatment, that were seen in <
1% of the patients in the BUTRANS trials include the following in
alphabetical order:
Abdominal
distention, abdominal pain, accidental injury, affect lability, agitation,
alanine aminotransferase increased, angina pectoris, angioedema, apathy,
application site dermatitis, asthma aggravated, bradycardia, chills,
confusional state, contact dermatitis, coordination abnormal, dehydration,
depersonalization, depressed level of consciousness, depressed mood,
disorientation, disturbance in attention, diverticulitis, drug hypersensitivity,
drug withdrawal syndrome, dry eye, dry skin, dysarthria, dysgeusia,
dysphagia, euphoric mood, face edema, flatulence, flushing, gait disturbance,
hallucination, hiccups, hot flush, hyperventilation, hypotension,
hypoventilation, ileus, insomnia, libido decreased, loss of consciousness,
malaise, memory impairment, mental impairment, mental status changes,
miosis, muscle weakness, nervousness, nightmare, orthostatic hypotension,
palpitations, psychotic disorder, respiration abnormal, respiratory
depression, respiratory distress, respiratory failure, restlessness,
rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus,
urinary hesitation, urinary incontinence, urinary retention, urticaria,
vasodilatation, vertigo, vision blurred, visual disturbance, weight
decreased, and wheezing.
|
