ADVERSE REACTIONS
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.
The following serious adverse reactions are discussed
elsewhere in the labeling:
- Cardiovascular thrombotic events [
see
Boxed Warning and Warnings and Precautions
]
- Gastrointestinal effects – risk of GI ulceration, bleeding,
and perforation [
see Boxed Warning and Warnings
and Precautions
]
- Hepatic effects [
see Warnings and Precautions
]
- Hypertension [
see Warnings and Precautions
]
- Congestive heart failure and edema [
see
Warnings and Precautions
]
- Renal effects [
see Warnings and Precautions
]
- Anaphylactoid reactions [
see Warnings
and Precautions
]
- Adverse skin reactions [
see Warnings and
Precautions
]
Clinical TrialsExperience
Adults
Osteoarthritis and
Rheumatoid Arthritis
The MOBIC Phase 2/3 clinical trial database includes
10,122 OA patients and 1012 RA patients treated with MOBIC 7.5 mg/day,
3505 OA patients and 1351 RA patients treated with MOBIC 15 mg/day.
MOBIC at these doses was administered to 661 patients for at least
6 months and to 312 patients for at least one year. Approximately
10,500 of these patients were treated in ten placebo- and/or active-controlled
osteoarthritis trials and 2363 of these patients were treated in ten
placebo- and/or active-controlled rheumatoid arthritis trials. Gastrointestinal
(GI) adverse events were the most frequently reported adverse events
in all treatment groups across MOBIC trials.
A 12-week multicenter, double-blind, randomized trial
was conducted in patients with osteoarthritis of the knee or hip to
compare the efficacy and safety of MOBIC with placebo and with an
active control. Two 12-week multicenter, double-blind, randomized
trials were conducted in patients with rheumatoid arthritis to compare
the efficacy and safety of MOBIC with placebo.
Table 1a depicts adverse events that occurred in ≥2%
of the MOBIC treatment groups in a 12-week placebo- and active-controlled
osteoarthritis trial.
Table 1b
depicts adverse events that occurred in ≥2% of the MOBIC treatment
groups in two 12-week placebo-controlled rheumatoid arthritis trials.
Table 1a Adverse Events (%) Occurring in ≥2% of MOBIC Patients
in a 12-Week Osteoarthritis Placebo- and Active-Controlled Trial
|
Placebo
|
MOBIC 7.5 mg daily
|
MOBIC 15 mg daily
|
Diclofenac 100 mg daily
|
No. of Patients
|
157
|
154
|
156
|
153
|
1 WHO preferred terms edema,
edema dependent, edema peripheral, and edema legs combined
2 WHO preferred terms rash, rash erythematous,
and rash maculo-papular combined |
Gastrointestinal
|
17.2 |
20.1 |
17.3 |
28.1 |
Abdominal pain |
2.5 |
1.9 |
2.6 |
1.3 |
Diarrhea |
3.8 |
7.8 |
3.2 |
9.2 |
Dyspepsia |
4.5 |
4.5 |
4.5 |
6.5 |
Flatulence |
4.5 |
3.2 |
3.2 |
3.9 |
Nausea |
3.2 |
3.9 |
3.8 |
7.2 |
Body as a Whole
|
|
|
|
|
Accident household |
1.9 |
4.5 |
3.2 |
2.6 |
Edema1
|
2.5 |
1.9 |
4.5 |
3.3 |
Fall |
0.6 |
2.6 |
0.0 |
1.3 |
Influenza-like symptoms |
5.1 |
4.5 |
5.8 |
2.6 |
Central and Peripheral Nervous System
|
Dizziness |
3.2 |
2.6 |
3.8 |
2.0 |
Headache |
10.2 |
7.8 |
8.3 |
5.9 |
Respiratory
|
|
|
|
|
Pharyngitis |
1.3 |
0.6 |
3.2 |
1.3 |
Upper respiratory tract infection |
1.9 |
3.2 |
1.9 |
3.3 |
Skin
|
|
|
|
|
Rash2
|
2.5 |
2.6 |
0.6 |
2.0 |
Table 1b Adverse Events (%) Occurring in ≥2% of MOBIC Patients
in two 12-Week Rheumatoid Arthritis Placebo-Controlled Trials
|
Placebo
|
MOBIC 7.5 mg daily
|
MOBIC 15 mg daily
|
No. of Patients
|
469
|
481
|
477
|
1 MedDRA high level term
(preferred terms): dyspeptic signs and symptoms (dyspepsia, dyspepsia
aggravated, eructation, gastrointestinal irritation), upper respiratory
tract infections-pathogen unspecified (laryngitis NOS, pharyngitis
NOS, sinusitis NOS), joint related signs and symptoms (arthralgia,
arthralgia aggravated, joint crepitation, joint effusion, joint swelling)
2 MedDRA preferred term: nausea, abdominal
pain NOS, influenza-like illness, headaches NOS, and rash NOS |
Gastrointestinal Disorders
|
14.1 |
18.9 |
16.8 |
Abdominal pain NOS2
|
0.6 |
2.9 |
2.3 |
Dyspeptic signs and symptoms1
|
3.8 |
5.8 |
4.0 |
Nausea2
|
2.6 |
3.3 |
3.8 |
General Disorders
and Administration Site Conditions
|
Influenza-like illness2
|
2.1 |
2.9 |
2.3 |
Infection and Infestations
Upper respiratory tract infections-pathogen class
unspecified1
|
4.1 |
7.0 |
6.5 |
Musculoskeletal and Connective
Tissue Disorders
Joint related signs
and symptoms1
|
1.9 |
1.5 |
2.3 |
Nervous System Disorders
|
Headaches NOS2
|
6.4 |
6.4 |
5.5 |
Skin and Subcutaneous Tissue Disorders
Rash NOS2
|
1.7 |
1.0 |
2.1 |
The adverse events that occurred
with MOBIC in ≥2% of patients treated short-term (4 to 6 weeks) and
long-term (6 months) in active-controlled osteoarthritis trials are
presented in Table 2.
Table 2 Adverse Events (%) Occurring in ≥2% of MOBIC Patients
in 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials
|
4 to 6 Weeks Controlled Trials
|
6 Month Controlled Trials
|
|
MOBIC 7.5 mg daily
|
MOBIC 15 mg daily
|
MOBIC 7.5 mg daily
|
MOBIC 15 mg daily
|
No. of Patients
|
8955
|
256
|
169
|
306
|
1 WHO preferred terms edema,
edema dependent, edema peripheral, and edema legs combined
2 WHO preferred terms rash, rash erythematous,
and rash maculo-papular combined |
Gastrointestinal
|
11.8 |
18.0 |
26.6 |
24.2 |
Abdominal pain |
2.7 |
2.3 |
4.7 |
2.9 |
Constipation |
0.8 |
1.2 |
1.8 |
2.6 |
Diarrhea |
1.9 |
2.7 |
5.9 |
2.6 |
Dyspepsia |
3.8 |
7.4 |
8.9 |
9.5 |
Flatulence |
0.5 |
0.4 |
3.0 |
2.6 |
Nausea |
2.4 |
4.7 |
4.7 |
7.2 |
Vomiting |
0.6 |
0.8 |
1.8 |
2.6 |
Body as a Whole
|
|
|
|
|
Accident household |
0.0 |
0.0 |
0.6 |
2.9 |
Edema1
|
0.6 |
2.0 |
2.4 |
1.6 |
Pain |
0.9 |
2.0 |
3.6 |
5.2 |
Central and Peripheral Nervous System
|
|
|
|
|
Dizziness |
1.1 |
1.6 |
2.4 |
2.6 |
Headache |
2.4 |
2.7 |
3.6 |
2.6 |
Hematologic
|
|
|
|
|
Anemia |
0.1 |
0.0 |
4.1 |
2.9 |
Musculoskeletal
|
|
|
|
|
Arthralgia |
0.5 |
0.0 |
5.3 |
1.3 |
Back pain |
0.5 |
0.4 |
3.0 |
0.7 |
Psychiatric
|
|
|
|
|
Insomnia |
0.4 |
0.0 |
3.6 |
1.6 |
Respiratory
|
|
|
|
|
Coughing |
0.2 |
0.8 |
2.4 |
1.0 |
Upper respiratory tract infection |
0.2 |
0.0 |
8.3 |
7.5 |
Skin
|
|
|
|
|
Pruritus |
0.4 |
1.2 |
2.4 |
0.0 |
Rash2
|
0.3 |
1.2 |
3.0 |
1.3 |
Urinary
|
|
|
|
|
Micturition frequency |
0.1 |
0.4 |
2.4 |
1.3 |
Urinary tract infection |
0.3 |
0.4 |
4.7 |
6.9 |
Higher doses of MOBIC (22.5 mg and
greater) have been associated with an increased risk of serious GI
events; therefore, the daily dose of MOBIC should not exceed 15 mg.
Pediatrics
Pauciarticular and
Polyarticular Course Juvenile Rheumatoid Arthritis (JRA)
Three hundred and
eighty-seven patients with pauciarticular and polyarticular course
JRA were exposed to MOBIC with doses ranging from 0.125 to 0.375 mg/kg
per day in three clinical trials. These studies consisted of two 12-week
multicenter, double-blind, randomized trials (one with a 12-week open-label
extension and one with a 40-week extension) and one 1-year open-label
PK study. The adverse events observed in these pediatric studies with
MOBIC were similar in nature to the adult clinical trial experience,
although there were differences in frequency. In particular, the following
most common adverse events, abdominal pain, vomiting, diarrhea, headache,
and pyrexia, were more common in the pediatric than in the adult trials.
Rash was reported in seven (<2%) patients receiving MOBIC. No unexpected
adverse events were identified during the course of the trials. The
adverse events did not demonstrate an age or gender-specific subgroup
effect.
The following is a list
of adverse drug reactions occurring in <2% of patients receiving
MOBIC in clinical trials involving approximately 16,200 patients.
Body as a Whole
|
allergic reaction, face edema, fatigue, fever, hot flushes, malaise,
syncope, weight decrease, weight increase |
Cardiovascular
|
angina pectoris, cardiac failure, hypertension,
hypotension, myocardial infarction, vasculitis |
Central and Peripheral
Nervous System
|
convulsions, paresthesia, tremor, vertigo |
Gastrointestinal
|
colitis, dry mouth, duodenal ulcer, eructation,
esophagitis, gastric ulcer, gastritis, gastroesophageal reflux, gastrointestinal
hemorrhage, hematemesis, hemorrhagic duodenal ulcer, hemorrhagic gastric
ulcer, intestinal perforation, melena, pancreatitis, perforated duodenal
ulcer, perforated gastric ulcer, stomatitis ulcerative |
Heart Rate and Rhythm
|
arrhythmia, palpitation, tachycardia |
Hematologic
|
leukopenia, purpura, thrombocytopenia |
Liver and Biliary System
|
ALT increased, AST increased, bilirubinemia, GGT
increased, hepatitis |
Metabolic and Nutritional
|
dehydration |
Psychiatric
|
abnormal dreaming, anxiety, appetite increased,
confusion, depression, nervousness, somnolence |
Respiratory
|
asthma, bronchospasm, dyspnea |
Skin and Appendages
|
alopecia, angioedema, bullous eruption, photosensitivity
reaction, pruritus, sweating increased, urticaria |
Special Senses
|
abnormal vision, conjunctivitis, taste perversion,
tinnitus |
Urinary System
|
albuminuria, BUN increased, creatinine increased,
hematuria, renal failure |
Post Marketing Experience
The following adverse reactions have been
identified during post approval use of MOBIC. 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. Decisions about whether to
include an adverse event from spontaneous reports in labeling are
typically based on one or more of the following factors: (1) seriousness
of the event, (2) number of reports, or (3) strength of causal relationship
to the drug. Adverse reactions reported in worldwide post marketing
experience or the literature include: acute urinary retention; agranulocytosis;
alterations in mood (such as mood elevation); anaphylactoid reactions
including shock; erythema multiforme; exfoliative dermatitis; interstitial
nephritis; jaundice; liver failure; Stevens-Johnson syndrome, and
toxic epidermal necrolysis.
|
REPORTS OF SUSPECTED MOBIC SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Mobic. The information is not vetted and should not be considered as verified clinical evidence.
Possible Mobic side effects / adverse reactions in 70 year old male
Reported by a health professional (non-physician/pharmacist) from Japan on 2011-10-03
Patient: 70 year old male
Reactions: Interstitial Lung Disease
Adverse event resulted in: hospitalization
Suspect drug(s):
Amlodipine Besylate
Dosage: 5 mg, unk
Mobic
Administration route: Oral
Other drugs received by patient: Pravastatin Sodium
Possible Mobic side effects / adverse reactions in 67 year old male
Reported by a health professional (non-physician/pharmacist) from Ireland on 2011-10-05
Patient: 67 year old male
Reactions: Renal Impairment
Adverse event resulted in: hospitalization
Suspect drug(s):
Mobicam
Indication: Postoperative Care
Mobic
Dosage: 15 mg
Administration route: Oral
Indication: Postoperative Care
Start date: 2009-03-01
Other drugs received by patient: NU-Seals 75mg Gastro-Resistant Tablets; Diovan HCT; Zanidip 20mg Film Coated Tablets; Nexium; Ventolin; Seretide 250 Evohaler 25/250ug/dose Pressure
Possible Mobic side effects / adverse reactions in 84 year old female
Reported by a physician from Japan on 2011-10-05
Patient: 84 year old female
Reactions: Peptic Ulcer
Suspect drug(s):
Loxonin
Dosage: 1 per 1 day
Administration route: Oral
Indication: Pain
Start date: 2009-07-01
End date: 2011-07-29
Mobic
Dosage: 1 per 1 day
Administration route: Oral
Indication: Pain
Start date: 2009-07-01
End date: 2011-08-31
Tramadol Hydrochloride/acetaminophen
Administration route: Oral
Indication: Pain
Start date: 2011-07-19
End date: 2011-08-31
|